TSHA

Okay, thank you for standing by. Welcome to the Taysha Gene Therapies first quarter 2026 financial results conference call. I would now like to hand the conference over to your first speaker today, Hayleigh Collins, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

Thank you. Good morning and welcome to Taysha's first quarter 2026 financial results and corporate update conference call. Earlier today, Taysha issued a press release announcing financial results for the quarter ended March 31st, 2026. A copy of this press release is available on the company's website and through our SEC filings. Joining me on today's call are Sean Nolan, Taysha's Chief Executive Officer, Sukumar Nagendran, President and Head of R&D, and Kamran Alam, Chief Financial Officer. We will hold a question and answer session following our prepared remarks.

On today's call, we will be making forward-looking statements, including statements concerning the potential of TSHA-102, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials,. Including with respect to functional milestones to positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development, and regulatory plans for our product candidates, including the timing of initiating additional trials, reporting data from our clinical trials, making regulatory submissions, timing or outcomes of communications with the FDA and the regulatory pathway for TSHA-102, the potential for the product candidate to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, our ability to realize benefits of Breakthrough Therapy designation for TSHA-102, our ability to drive long-term value for stockholders, and the market opportunity for our programs.

This call may also contain forward-looking statements relating to Taysha's growth, forecast of cash runway and future operating results, discovery and development of product candidates, strategic alliances and intellectual property, as well as matters that are not historical facts or information. Various risks may cause Taysha's actual results to differ materially from those stated or implied in such forward-looking statements. For a list and description of the risks and uncertainties that we face, please see the reports that we have filed with the SEC, including in our annual report on Form 10-K for the full year ended December 31st, 2025 that we filed on March 19th, 2026, and our quarterly report on Form 10-Q for the quarter ended March 31st, 2026 that we filed today.

This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast, May 6th, 2026. Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities law. With that, I would now like to turn the call over to our CEO, Sean Nolan.

Thank you, Hayleigh, and welcome everyone to our first quarter 2026 financial results and corporate update conference call. On today's call, I will begin with an update on our recent regulatory, clinical, and commercial readiness activities. Dr. Sukumar Nagendran, President and Head of R&D, will outline recently published preclinical data that continue to validate our novel TSHA-102 construct design and minimally invasive intrathecal route of administration. Kamran Alam, our Chief Financial Officer, will follow up with a financial update, and I will provide closing remarks and open the call for questions. We entered 2026 focused on a disciplined execution across our regulatory, clinical, and pre-commercialization activities for TSHA-102, with the goal of delivering a potentially transformative therapy to a broad population of patients with Rett syndrome who continue to face high unmet need.

Over the past several months, we have continued to advance our TSHA-102 clinical development program and made progress towards key clinical milestones anticipated in second quarter of 2026. On the regulatory front, we recently held an initial Breakthrough Therapy Type B multidisciplinary meeting with the FDA. During the meeting, we reaffirmed alignment on the planned pathway toward a BLA submission for TSHA-102, covering the pivotal trial design, endpoints, and BLA submission scenarios, including the potential to submit for approval based on a six-month interim analysis from the REVEAL pivotal trial. We believe our consistent constructive dialogue with the FDA continues to support our streamlined path toward a potentially expedited BLA submission.

In the first quarter of 2026, we held a Type C meeting with the FDA, where the FDA endorsed our proposed process performance qualification or PPQ campaign strategy in support of our planned BLA submission. I am pleased to share that we initiated the BLA-enabling PPQ campaign using our TSHA-102 commercial manufacturing process in April, we expect to complete execution by the fourth quarter of this year. We are confident that our CMC activities are on track to support our BLA submission in step with the pivotal data readout. The FDA previously agreed that TSHA-102 material produced from the clinical and final commercial manufacturing processes are comparable, therefore, may support our ability to utilize the clinical data across all clinical studies in our TSHA-102 development program in our BLA submission.

The ability to leverage the totality of evidence to support the long-term clinical benefit of TSHA-102 would strengthen the overall package and support a potentially expedited BLA submission based on the six-month interim analysis. Turning to our clinical progress, we further advanced dosing in the REVEAL pivotal trial with multiple patients dosed across multiple clinical trial sites. In parallel, enrollment in the ASPIRE trial is ongoing across multiple sites, and we remain on track to complete dosing in both trials this quarter. I am pleased to share that both high and low dose TSHA-102 continue to be generally well-tolerated with no treatment-related serious adverse events or dose-limiting toxicities observed in all patients treated across the REVEAL phase I/II and REVEAL pivotal trials as of the May 2026 data cutoff.

We look forward to reporting longer-term data from all 12 pediatric, adolescent, and adult patients treated in Part A of the REVEAL phase I/II trials later this quarter. Our pivotal development strategy is grounded on the rigor of our natural history analysis and Part A data collection and evaluation with trial design, endpoints, and statistical analyses developed based on discussions and written feedback from the FDA. Accordingly, developmental milestones in Part A are assessed using three structured criteria, all of which must be met in order for a developmental milestone to qualify as a gain or a regain post TSHA-102. First, all caregivers must complete the clinician-administered historical milestone questionnaire used in the natural history study.

This allows us to identify milestones eligible for gain or regain by confirming whether a milestone was never previously achieved or was lost long enough ago that the likelihood of a spontaneous gain or regain is less than 6.7%. Establishing a documented time since loss is fundamental to accurately differentiate a true regain from natural variability as each of the 28 milestones has its own determinant. A simple baseline assessment is not sufficient documentation to support a rigorous statistical assessment and is susceptible to false positives. Our approach ensures milestone history is captured accurately so that only true open milestones are counted as gains or regains. Second, the milestone gain must be captured by post-treatment video documentation. This provides evidence of milestone gains that can be objectively reviewed, which brings me to the third criterion.

Video evidence must be independently evaluated by multiple external raters using a pre-specified definition of achievement for each milestone from our pivotal trial protocol. We believe these criteria are essential for interpreting functional outcomes and provide a reliable assessment of TSHA-102's efficacy as we advance towards registration. We believe our Part A data accurately reflect the outcomes we expect to observe in the pivotal trial as they are evaluated using the same FDA-aligned criteria for the pivotal trial protocol. As a reminder, we presented data from Part A of the REVEAL phase I/II trials last year, demonstrating an 83% response rate at six months post-treatment, with five of the six patients treated with the high dose TSHA-102 gaining or regaining at least 1 developmental milestone. By 9 months post-treatment, the data demonstrated a 100% response rate across the six treated high-dose patients.

In addition to the 22 developmental milestones gained across the 10 patients treated with TSHA-102, patients also demonstrated a total of 165 additional functional skills and improvements across the core domains of Rett syndrome, an average of approximately 19 functional gains per patient. We observed a consistent pattern of early gains that were sustained, with additional gains seen over time, demonstrating the deepening of effect. In our upcoming Part A data readout, we expect to report longer-term follow-up, including at least 12 months of data from all 12 patients treated with TSHA-102. These results will include functional gains based on natural history-defined developmental milestones and additional functional skills and improvements impacting the activities of daily living that are meaningful to the caregivers and clinicians.

We will be hoping to see a consistent pattern of early responses that are sustained and deepen over time across functional gains and clinical outcome measures in the treated patients. We believe this longer-term follow-up will provide important context around the durability, deepening of effect, and consistency in responses. With FDA alignment on the potential to pool data across the full TSHA-102 development program in our BLA submission. We believe the longer-term Part A data has the potential to strengthen the overall BLA package and support an expedited submission. In parallel to our clinical and regulatory execution, we continue to build out our internal commercial infrastructure. We have strategically assembled a strong commercial leadership group, including senior hires who have deep expertise in commercial strategy, pre-commercial, and product launch planning, as well as payer and healthcare systems engagement within the gene therapy space.

With these key roles now in place, we are focused on developing a strategic commercial strategy to prepare for a potential launch, and we expect to share additional details on our commercial plans in the second half of the year. I would now like to turn the call over to Suku to discuss evidence that further validates the TSHA-102 program and route of administration in more detail. Suku?

Thank you, Sean. We have continued to make meaningful progress advancing TSHA-102 towards registration and remain confident in its differentiated potential. A key design attribute of TSHA-102 is its minimally invasive intrathecal route of administration, which market research shows is strongly preferred by clinicians and caregivers over direct-to-brain CNS delivery. This preference is driven by its familiarity, accessibility, and scalability, enabling broad access to treatment across institutions from major centers of excellence to regional and local sites. A peer-reviewed article was recently published by Frontiers in Medicine, Gene & Cell Therapy, which highlights preclinical data we previously presented at the 2025 International Rett Syndrome Foundation Rett Syndrome Scientific Meeting.

The data showed that intrathecal and direct to brain intracisterna magna administration demonstrated comparable, consistent, and widespread distribution of AAV9 vector throughout the brain and spinal cord in non-human primates. We believe this further validates lumbar intrathecal delivery as a potentially safe, effective, and minimally invasive approach to deliver a gene therapy to the central nervous system. In addition, on May 14th, we plan to present new preclinical data that further validates the construct design of TSHA-102 at the ASGCT 2026 annual meeting. Consistent with previously published vector comparisons, the data demonstrated that the self-complementary AAV9 vector enables significantly higher protein expression compared to single-stranded AAV9 in neuronal mouse cell models.

The 30-fold higher transduction efficiency demonstrated in this study, along with the improved genomic stability of self-complementary AAV9, supports our ability to effectively deliver TSHA-102 to the central nervous system using a minimally invasive lumbar intrathecal administration. In addition, the data showed that the miniMECP2 protein used in our TSHA-102 construct was functionally comparable to the full-length MECP2 protein across molecular and biochemical functions. We believe these data support the strategic TSHA-102 construct design and provides important translational context for the early, sustained, and deepening functional gains demonstrated across all patients previously reported in Part A of the REVEAL phase I/II trials.

We believe the supportive evidence of a continued FDA alignment on a registrational path and the clinical data generated to date support the potential for TSHA-102 to provide meaningful benefit to pediatric, adolescent, and adult patients with Rett syndrome using a minimally invasive delivery approach that is scalable. Our focus remains on clinical execution and data generation as we work to complete dosing in our REVEAL pivotal and ASPIRE trials and report long-term data from Part A of our REVEAL phase I/II trials this quarter. I would now like to turn the call over to Kamran to discuss financial results.

Thank you, Suku. Research and development expenses were $33.8 million for the three months ended March 31st, 2026, compared to $15.6 million for the three months ended March 31st, 2025. The $18.2 million increase was primarily driven by BLA-enabling PPQ manufacturing initiatives performed during the three months ended March 31st, 2026, and higher clinical expenses from the REVEAL Part A phase I/II, Part B pivotal, and ASPIRE trials. Compensation expenses, including non-cash stock-based compensation, also increased as a result of additional research and development headcount. General and administrative expenses were $9.7 million for the three months ended March 31st, 2026, compared to $8.2 million for the three months ended March 31st, 2025.

The increase of $1.5 million was primarily due to higher compensation expenses, including non-cash stock-based compensation expense and increases in consulting and professional fees, including commercial launch readiness initiatives. Net loss for the three months ended March 31st, 2026 was $42.4 million or $0.12 per share, compared to a net loss of $21.5 million or $0.08 per share for the three months ended March 31st, 2025. As of March 31st, 2026, Taysha had $276.6 million in cash and cash equivalents. We expect that our current cash resources will be sufficient to fund planned operating expenses into 2028. I will now turn the call over to Sean for his closing remarks. Sean?

Thank you, Kamran. Our confidence in our differentiated TSHA-102 gene therapy candidate continues to strengthen based on the developments highlighted today. We continue to believe TSHA-102 has the potential to deliver meaningful therapeutic benefit to a broad population of patients with Rett syndrome using a minimally invasive delivery approach. With a favorable tolerability profile demonstrated to date, dosing in the REVEAL pivotal and ASPIRE trials on track for completion in the second quarter of 2026, and a well-defined regulatory and commercial path, we're advancing toward potential registration with clarity as we work to bring a potentially transformative therapy to the Rett community. I will now ask the operator to begin our Q&A session. Operator?

Thank you. At this time, we will conduct the question-and-answer session. As a reminder, to ask a question, you need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question today comes from Kristen Kluska from Cantor Fitzgerald. Your line is open.

Hi. Good morning, everybody, and congrats on these updates. I wanted to ask you a little bit more about some of the data you're going to have at ASGCT. For the work you're doing that supports higher MECP2 protein expression with the self-complementary AAV9, can you tell us why this matters so much versus the obvious of just having more protein expression? Does this allow for a greater orchestra effect across more neurons? Does it mean a faster onset of action? What would you truly highlight here?

Thanks for the question, Kristen. I think Suku and I can tag team this. At a high level, I think what we wanted to do was really provide the why as to what the clinical result that we're generating is, right? I mean, from a clinical perspective, in every patient treated, whether it's a pediatric patient, adolescent patient, adult patient, everyone has been a responder. We're seeing, you know, multiple skills and improvements across all of these patients, and they happen quickly, and then they improve over time and get deeper. The question is, you know, why does that occur? I think what we're highlighting at ASGCT is the fact that the construct, which we purposefully utilize self-complementary technology, ultimately drives in this data set a 30x transduction efficiency or protein expression than single strand does.

That is a reason why you could potentially use a less invasive route of administration like intrathecal versus having to go with a closer to the brain approach. Usually you have to do that because of a single strand. The other thing too is just reinforcing the fact that the miniMECP2 gene, you know, continues to show comparability. You know, it's been published for over 15 years that this has been the case. Again, we just wanted to highlight that regardless of the genotype that we're seeing in these 12 patients that we've, you know, dosed to date and that we'll report on in a few weeks, they're all responding, and they're responding across clinical domains. The gene, the mini gene is very much a part of that because it essentially equals the full-length gene.

Again, the reason we use the mini gene was so we could package the self-comp. We're just trying to highlight the fact that the reason all the reasons that we put into building the construct are being demonstrated clinically, and that this allows us to use a particular route of administration that we know is strongly preferred out in the community. Suku, I don't know if there's more you might wanna add to that.

Yeah, Sean, I have a few more points to add. Kristen, thanks for that incredibly important question. What we've already shown with our REVEAL Part A program is that a simple lumbar puncture, a self-complementary mini-gene construct using TSHA-102, gives you incredibly important clinical results from an efficacy standpoint that translate into a significant improvement in activities of daily living. The clinical data at the present time from Part A now speaks for itself. Now when we work backwards and continue to further look at preclinical data, whether it's ours or from other companies, it is very clear that a self-complementary construct turns on very quickly once given into the central nervous system, i.e., via the CSF.

Once it turns on, it has rapid impact on one of the most important components of Rett syndrome, which is the autonomic dysfunction component, where we have impact pretty quickly, usually within a couple of weeks post-dosing. We've also shown repeatedly now in Part A that we have very positive clinical impact consistently, regardless of age, genotype, or phenotypic presentation of the patient with Rett syndrome, where there is an improvement in gross motor, fine motor skills or restoration of those skills which have been lost over time, but also improvement in the ability to communicate, as well as when it comes to social activities.

My point here is that a self-complementary stable construct turns on quickly, it persists, and it continues to persist and build on top of all the preclinical data that we have that shows that a lumbar puncture with the right product can have a simple but consistent positive clinical response for a post patient population that has significant unmet medical need, and in this case, Rett syndrome. I think we may have set the stage for an intrathecal lumbar puncture-based platform to treat difficult CNS diseases.

Thank you. One moment. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

Good morning. Regarding the BLA submission pathway for TSHA-102, can you walk through the different scenarios here and whether approval based on the six-month data should be considered the base case assumption and how you characterize the willingness of the FDA to approve based on six-month data sets and timelines around this? That'd be great. Thank you.

Yes, Salveen, great question. You know, we've been out talking with the investment community, you know, really since the beginning of the year, and this topic has come up. I think those that are on the call, this will sound very familiar. You know, we were very transparent with the FDA. You know, part of this meeting was trying to gain alignment, and we were walking them through various scenarios. And we told them point-blank that our preferred scenario would be a full approval at six months worth of data. You know, the argument for that, right, I mean, generally, they like the precedent of 12 months of data for gene therapy, which is arguably probably pretty arbitrary, to be honest, but that's generally what they've held to.

I think, you know, our perspective on that is understood, but if we continue to demonstrate comparability with Part A, we're gonna have years of data from those patients that we can use to support the durability. Their answer was essentially, look, you know, ultimately, this is gonna come down to the totality of the evidence. You know, this is something that if the company chooses to do, we will, you know, we are open to it, and we will review that in due course. Which is really the best answer you could possibly get, right? Which is the door is open, let the data speak for itself.

The second derivative of that in our view was basically if for whatever reason, you know, the FDA decides that Let's just say they wanna keep it as a precedent at 12 months, you know, we would push hard for a rolling review. You know, because the CMC modules would be done, the preclinical modules would be done, and we can have things updated where, you know, the six-month data is packaged in a way that they could look at that. Also, you know, then there's less to review when you would submit the final 12-month data, and that can pull things forward a couple quarters. Then obviously the third scenario would be, you know, they, you know, there may be nothing at all wrong with the data.

They just wanna see 12 months. We feel in any of those scenarios, number one, there continued to be a positive and constructive dialogue with the agency. There was no opposition to anything that we put forward. There was an openness to it. Clearly, it's gonna come down to the totality of the evidence, and their comfort level around the data package that's put forward. As we've said all along, the nice thing about this six-month interim is it creates the optionality for us to potentially get this to patients faster. You know, my personal opinion, I can be wrong, is that almost regardless of what we come back with, I know everyone would prefer it's the fastest time point and, you know, obviously, we're gonna do everything we can to facilitate that. We'll have clarity for the market.

Even in the scenario, and don't read into this, it's just even in the scenario where it's a 12-month ask, we can say that, and you know what our six-month data are, people can judge the probability of success, then it's an execution story. For all the reasons that we laid out in this call, you know, we feel that there is strong evidence to push for the six-month data. The fact that we've got comparability with the FDA on the CMC side is absolutely critical to this. That opens the door for us to pool the Part A data alongside the pivotal Part B, and in our opinion, really should alleviate any concerns on the durability piece. Ultimately, we'll leave it at that.

You know, the nice thing is we've got this option, you know, these options in front of us, thanks to the data that we've put forward today and also, the CMC quality that we've put forward today. We're in the best possible position we can be. We've got a couple cards that can fall our way, and we're excited about having this discussion with the FDA at the appropriate time.

Thank you.

Thank you.

Thank you for your question. Our next question comes from Biren Amin with Piper Sandler. Your line is open.

Yeah. Hi, guys. Thanks for taking my questions. Recently, the FDA commissioner announced a real-time clinical monitoring program that enables the FDA to evaluate data real time. Is that something that the company can leverage for REVEAL, given the high unmet need in Rett syndrome? Especially you know, Sean, with the six-month data and the agency potentially following patient data to 12 months during review under this program. I guess that's the first question. Second question for REVEAL, do you expect to stop enrollment at 15 patients or could you potentially over-enroll as is typically the case with clinical trial management and execution? If that's the case, how does the over-enrollment impact the effect size calculation for the study? Thank you.

Yeah. Just real quickly on the real-time piece. I'll ask Suku to comment on that. You know, I would say we're always keeping our eyes open for what we could potentially do. Like, the other one is the commissioner's voucher, right? Things are so dynamic up there. It can be difficult sometimes to tell what's afforded to you and what's not afforded to you. I think that, you know, what I just laid out in terms of scenarios, we feel very good about.

If there's an opportunity for us to lever one of these additional, you know, pathways, sure, we would try to do that. Again, I don't wanna try to make it sound like that's what we're attempting to do out of the gate here, just because it's not as formalized and crystallized in terms of, you know, the timelines, what you need to meet the hurdle bar, et cetera. I don't know if there's anything you'd add to that, Suku.

Yes. Sean, I mean, Biren Amin, thanks for that very interesting and important question because what the FDA has proposed, I think, could change the way clinical trials are overseen by the FDA with their direct hands-on experience and oversight. At the same time, as the real-time data pours in, I think, the regulators and the sponsors, clinical regulatory teams will have to work very closely to make sure appropriate interpretation is done when it comes to real-time safety data and efficacy data. Especially in the rare disease space, as we know, we are learning not only about the disease, but also the response to the therapeutic intervention at that point in time.

Sometimes the real-time decisions versus a more time process-oriented decision could have significantly impact and influence on programs. I hope that helps because at this time we are kind of watching the process interestingly, eventually the decision-making governance between the regulators and the sponsors are going to be critical to make sure real-time oversight of clinical trials will pay the dividends that the FDA hopes it will.

Yeah. Then, the question around the potential for over-enrollment. I would say that you're always trying to balance the, you know, getting the appropriate patients in screened, essentially, understanding that there could potentially be a screen fail. You know, like one of the criteria we have, right? There's a number of open milestones you must have, right? As an example. You know, you could go through the screening and then find out that that patient doesn't quite meet it. You're gonna wanna have more patients than 15, you know, going through the screening process. You know, if you do end up in a situation where you dose, you know, an extra patient or two, we would be certainly willing to do that.

I can just say the effects on the statistics are minimal. I mean, they would obviously look at the first 15 patients first and do the statistics on that. Then if you had another patient or two, they would do the statistics on that, but they really don't change much. Anything else you would add there, Suku?

No. The only thing I would add, Sean, is that as you said, the power and p-values for our patient sample size of 15, if it goes to 16 or 17 based on what Sean just described, it won't have major impact on power or p-value for the study itself. As you know from REVEAL Part A, we already have a 100% responder rate at nine months, with a small number of patients. Those observations, I think, are significant. As you know, all we need is a 33% responder rate for our REVEAL Part B study. Let us see what the eventual data pans out, but I think we are confident that the Part A data hopefully should be reproduced in Part B as well.

Yeah. I think the key, Biren, is just simply that the null hypothesis is so low.

Yeah.

It's effectively one per you know, one patient spontaneously having an effect. Because of that number being such a low aspect, the overall end doesn't really change things very, very much. Good question. Thank you.

Thank you very much. As a reminder, please do limit yourself to one question. Our next question comes from Tazeen Ahmad from Bank of America. Your line is open.

Hi, good morning. This is Wesley on for Tazeen. Thanks for your updates today. I had a question on sort of the mechanics of the Part B portion of the study compared to the Part A. You know, are the, like, assessments being done of the patients, the treated patients, you know, being done in the same way in Part B to Part A? Who is doing the, you know, the video recordings and, you know, and with regards to sort of the patients that you are currently screening and plan to dose, are those, you know, sort of sites and investigators similar between Part B and Part A? I'm just trying to, like, look for any color on sort of straight lines we can draw from, you know, the 12-month update you're gonna share soon, to what we can expect and how the Part B is running. Thank you.

Yeah. Thanks for the question. Suku, we can tag team this. You know, our view is that the read-through from the upcoming data review that we're going to put out should be pretty direct for all of you. That's why we've put so much emphasis around the rigor of the data collection in Part A. We spent a lot of time on the call talking about that. It starts with the fact that, you know, number one. So first of all of our milestones for the primary endpoint are pre-specified, right? There's clear definitions for those. Those demonstrations are from videos that are conducted in the study itself.

The way it's been working is that, you know, people doing the hand function test or the RMBA or the Mullen. If we have video of them doing a milestone, that video then goes outside the company and two of three raters have to adjudicate that as a milestone. The company has nothing to do with what is declared a milestone. I think that has been a big part of the reason why the agency has been open to our data set and the interim analysis, is that we had rigorous video evidence that was adjudicated outside the company. The other side of this coin is that the Mullen, which is another videotaped demonstration, and the RMBA are also supportive data sets that the agency sees. Again, those are on video.

The Mullen also gets centrally adjudicated, and the FDA and the RMBA is done in the clinic by the physician, right? There's no real way to be putting your thumb on a scale and, you know, making this data subjective. It's very objective. I think this is a good read-through to Part B. The only difference in Part B is that we're gonna have a standalone assessment of all of the milestones. I would argue that we're probably undercounting milestones in Part A, and that we have a better chance of counting more milestones in Part B because there's a standalone test. We spent a lot of time with the FDA developing this test. We have training modules around this test.

The test is conducted in the hospital by trained assessors at the hospital. This is not done at home. The parents aren't doing this. This is very prescriptive, and it's done in-house. Those videos then go outside the hospital to the raters, where they remain blinded until the six-month time period where they break the blind for all of the 15 patients and review those videos. The whole point of what we've been trying to emphasize since we began reporting data on milestones is clear definitions, rigorous baseline collection with videos assessed by central raters. It's gonna be very similar in Part B, but even more rigorous, and I think there's more ability to capture milestones because we now have a standalone test. Hopefully that gives you perspective there, but I think the read-throughs should be pretty direct when we update you in a few weeks.

Got it. Thanks for detail. Thank you.

You're welcome.

Thank you. Our next question is from Maury Raycroft with Jefferies. Your line is open.

Hi, this is James on for Maury. Thanks for taking our question. For the 12+ months of follow-up in the 2Q update, how are you setting expectations for the early milestones and skills deepening versus new, more complex milestones and skills appearing between six and 12 months? How do you plan to communicate that in the update relative to the last presentation last year? Also, should we expect a potential safety update from the REVEAL pivotal cohort around IRSF, or should we expect that update at a later point after IRSF?

Yeah. To answer your second question first, I mean, even today, when we said that the, as of the March safety cutoff, that was inclusive of the REVEAL Part A and also the pivotal trials and ASPIRE. That's all the studies that we're running right now. You just got a safety update on no treatment-related SAEs and DLTs. We'll continue to do that on a quarterly basis. The first part of the question, can you repeat that? I already lost it.

For the 12+ months follow-up in the 2Q update, how are you setting expectations?

Oh, okay. Yeah.

Yeah.

Yeah. I mean, to be very simple, I'll turn it over to Suku. You know, what we've seen on the reports that we did last time was that there's early responses. There's more responses that occur as time goes on relative to milestones, relative to skills and improvements. The things that you get better at, and you're also developing new milestones, new skills, and new improvements. That's what we would expect to see at 12 months.

Yeah, Sean, as you have emphasized, what we will communicate is the rapid, consistent, persistent clinical impact of TSHA-102 in patients with Rett syndrome, regardless of genotype, phenotype, or age. I would also emphasize that we hope that we can continue to show a significant collective improvement in skills, quote-unquote, that per patient could go above the 19 per patient that we disclosed this morning when Sean did his segment of the communication.

Just pay attention to that as well because I think a component of reaching developmental milestones in a validated manner, as we've already discussed and described, which the FDA truly likes, and I'm gonna emphasize these are done in a blinded reviewer, expert reviewer fashion and not done at home by caregivers, which usually the FDA, you know, has questions around. I hope that our 12-month+ data disclosure further enhances the confidence in what TSHA-102 can contribute potentially in a transformative manner to this patient population.

Yeah. I guess the last comment there, James, is that we don't expect to see any type of a plateau. We expect to continue to see improvements and new improvements over time based on the historical, disclosures. Thank you.

Thank you.

Our next question comes from Gil Blum from Needham & Company. Your line is open.

Good morning, thanks for taking our question. Maybe just another one on the six months, interim as a clarification. The FDA basically has not given clear feedback as to what it thinks about this six months interim. Would you say that what would dictate the, you know, decision here would be the data itself and the 12-month data that you're going to present at IRSF? Thank you.

Gil, can you repeat that? I honestly didn't quite get the point of the question.

The point is you haven't really gotten clear FDA feedback as it relates to the six-month interim. They're actually waiting for the data. Is that fair?

Yeah. I mean, I think that is fair. I think the clear feedback we got is that it's an option for us, and that's all you can ask for at this particular point in time. They've consistently said since we put that disclosure out, I guess it was June, you know, 25, where we started talking about that, it's always been something that's enabled. We just confirmed. We, we've gotten a lot of questions from investors like, "Hey, when's the last time you talked to the FDA?" It's like, well, we talked twice, you know, in the last, you know, few months here, once on CMC and once on our first Breakthrough meeting. We went back through, we got confirmation on the design, on the endpoints and our, and our scenarios that I went through.

They're like, "Yeah, I mean, that is an option for you. It's going to depend on the data in terms of approvability." You're never going to get anything better than that, which is why we were so with the outcomes from that meeting.

Okay. To summarize, they're open to it.

I didn't hear that.

Yes. They are open to the six month.

Oh, yeah. Yeah. It's in writing, by the way. I mean, it's as good as you can get. There was very much an open-mindedness to this, and it's an open door for us at this point in time, and it's going to be won by the data.

Thank you for the clarification. I appreciate it.

Thanks. Thanks, Gil.

As a reminder, to ask a question, please press star one one on your phone and wait for your name to be announced. Our next question is from Chris Raymond with Raymond James. Your line is open.

Yeah. Thanks. Maybe just two here. Just on the process performance campaign or the PPQ, you mentioned FDA's agreed on equivalency between the clinical and the commercial manufacturing. Maybe just can you give a little bit more color on what activities, you know, what are sort of the pinch points, I guess, in terms of getting to having something you can submit in Q4 between now and then? Then, you know, one of the things that kind of struck us, we've done some KOL work where people seem physicians, the physician community seems, you know, very aware that you have a broad range of ages in your data. Maybe just talk a little bit more about the importance of enrolling a broad age range and how that's being received by the clinical community from your perspective? Thanks.

Sure. So Chris, starting with the PPQ, you know, we aligned on comparability when we had the clinical lot that was in Part A, and then we ran our, call it our final commercial process. We ran a lot of that. It was one to one, and the FDA deemed that that was analytically comparable. What you have to continue to do as you produce more lots is demonstrate that those additional lots are also comparable. At this last meeting, we shared with them, you know, multiple additional lots that we'd run, and they continued to say that we're comparable. As you go into PPQ, you know, you're generally doing, you know, two or three additional runs, and then you share that data with the FDA.

We're in the process of doing those runs right now. Assuming those runs continue to be, you know, demonstrating comparability, that's when you're able to pool the data. The fact that we've been able to do it with multiple runs so far gives us a lot of confidence that there's strong alignment with the FDA. We take that data package, and the next time we meet with them, we share that with them and, you know, that's kind of the next step. We feel like we're in a really good position on the CMC side, and we have been for quite some time. It is not on the critical path to the BLA submission. That's that.

As it relates to the broad ages of enrollment, you know, if you think about the prevalent population, 85% of the prevalent population is over the age of 10. Demonstrating effect across pediatric, adolescent, and adults is very, very important because as we've done market research with both caregivers and with clinicians. They plan on offering it across the age spectrum, and they're planning to offer it because there's demonstrated effect across the age spectrum.

We feel that we're in a good position to serve the broad community who's requesting gene therapy because of the data that we've generated, and that's why we're being thoughtful about making sure that there's representation across the age spectrum in Part B. You know, our whole goal is to make this available for all patients with Rett syndrome, and the data continue to support that. I can tell you that the demand is high across the age groups based on what we've seen so far.

Great. Thank you.

Thank you.

Our next question is from Jack Allen with Baird. Your line is open.

Hey, congrats on the updates, and thanks for taking the questions. It sounds great to hear that enrollment is on track to be concluded in the 2nd quarter of this year. I guess my question is pretty simple in that I was wondering if you'd provide any additional color surrounding how far you are as it relates to completing enrollment, how many patients have been dosed in the study, and then if that's a little too direct, if you could just speak to the enthusiasm you're seeing from the patient community and the interest in the trial.

I think Suku can take the second part of the question. I mean, we're not gonna give specifics. I would just say, you know, the demand is super high. It's high across the age spectrum. Multiple sites. You know, we've got 10 sites that are active. Multiple patients have been dosed across multiple sites. Most of the sites have multiple patients. I mean, you wanna talk a little bit about the enthusiasm and the demand that we're seeing across the spectrum?

You know, absolutely. We have multiple Rett centers of excellence who are part of the clinical trial, and they all have, you know, hundred, 200+ patients. Many of the patients' caregivers and parents have been very enthusiastic about being screened and enrolling in our trial. I would say with confidence that we are over-enrolled, and we have more than enough patients to dose to meet the 15, the number of 15 or a little bit more. We will be meeting our commitment to complete dosing for both REVEAL Part B and ASPIRE by the end of the second quarter this year.

Great. Thanks much for calling.

Thanks, Jack.

Thank you. Our next question is from Whitney Ijem from Canaccord Genuity. Your line is open.

Hey, guys. Thanks for taking the question. Just thinking about durability, how often are patients assessed in Part A? I guess I'm just wondering if, you know, there's a scenario where later this year, either we or the FDA is getting, like, an eighteen-month update on those patients and then potential for longer-term updates going forward.

Yeah. Thanks for that question, Whitney. That's actually a very important question that you raised. Given that we have a Part B ongoing, and we have a agreement in with the FDA that the six-month interim analysis, once all 15 patients in Part B are dosed, would be considered based on the efficacy and safety data for potential full approval of our product. The REVEAL Part A long-term data from a clinical standpoint, safety and efficacy, I think could significantly also impact the six-month interim analysis from Part B, collectively driving towards the full approval. Sean clearly described that the FDA is aligned with us when it comes to the CMC process and the comparability technicalities between the Part A product and the Part B product.

To really answer your question on Part A, the long-term data, I think up to 18 months, being evaluated per the protocol, post-12 months, every quarter, I think is going to be also important to the collective six-month interim analysis. If the six-month interim analysis, you know, gives very useful clinical data, and Sean described the other scenario for Part B where you might need 12-month data as well, the REVEAL Part A persistence of effect long term will also, I think, influence further the confidence that our product will have immediate, consistent, and persistent effect long term as well in this patient community.

Yeah. The only thing I would add, Whitney, is when we report the data, we will also report the data that's greater than 12 months. You should have a real good sense of what's happening over time.

Got it. That's helpful. Thank you.

Thanks, Whitney.

Our next question is from Evan Seigerman with BMO Capital Markets. Your line is open.

Hi, Malcolm Hoffman on for Evan. Thanks for taking our question. Something about potential commercial manufacturing. I just wanted to ask, what redundancies exist across TSHA-102 manufacturing chain that could help if there were any disruptions to the process? Thank you.

Yeah. To answer the question, we currently are at Catalent's Baltimore, Maryland facility has obviously been inspected, and they have extensive gene therapy manufacturing experience. We feel really confident in the team that's at Catalent and our oversight of the team there. Importantly, as Sean mentioned earlier, we have ensured that based on our locked manufacturing process, CMC is not on the critical path to a potential BLA submission. As it pertains to, you know, downstream, you know, potential redundancy in manufacturing, that's something as we get closer to, you know, Part B interim data readout.

As we get closer to a potential BLA submission, that's something we will evaluate to mitigate any potential disruption to supply chain. We feel really confident given Catalent's manufacturing experience in that particular facility in Baltimore, that that facility can meet our ultimate commercial demand.

Yeah, Evan, that's where Sarepta is making ELEVIDYS as well. It's been FDA inspected and they're very familiar, as Kamran said, with gene therapy commercial scale. We feel very confident about that.

Appreciate it. Thanks, guys.

Thanks.

Thank you. Our next question is from Yanan Zhu with Wells Fargo. Your line is open.

Hey, this is Jeff on for Yanan. Thanks for taking our question. Today and in the last couple of months, market research has been touched on, indicating strong demand for gene therapy in Rett syndrome and a clear preference for intrathecal delivery, including a mentioning 80% of caregivers and clinicians are seeking gene therapy for their patients. Can you provide any additional color or details on this market research in terms of if you tested any product profiles for TSHA-102 and physician preference specifically for TSHA-102?

Yeah, I mean, there'll be more to come in the second half, deeper dives on the commercial aspect of things. You know, we essentially tested with physicians. It was about half the physicians were at centers of excellence, half were not at centers of excellence. We also separately ran a study, you know, with caregivers of Rett patients or, you know, children with Rett, you know, across the age spectrum. You know, we kept it pretty simple when we basically our product profile was, you know, our product profile that you've effectively seen, you know. The responder rate, the CGI, you know, scores on average, you know, with the duration of time that we've been testing these patients.

Think about the last, you know, data update we gave last year and the deck that we used. It was effectively that on a one-pager. We just toggled that with, you know, is it intrathecal or is it ICV? What would it matter, assuming the same set of data? You know, number one feedback consistently in both groups, physicians and the caregivers, was very high interest in gene therapy. They realize that you want something that treats the root cause. There's a very high interest in seeking that out, number one. Number two, what was interesting is it's also there's high treatment being sought across the age groups, including those over 30. That also is encouraging.

You know, when you distill this down to make it real simple, you know, we didn't wanna make it too technical, you know, at first. I think more has to be shown to get more precise on, you know, comparative product profiles. If all things are equal on safety and efficacy, you know, obviously there's a preference for the least invasive route, both in terms of perceived safety, but also just in terms of, you know, some of the physicians were making the point on throughput in the institutions, that it's a lot easier to put, let's just say, you had 100 patients at an institution.

It's easier to stage and manage those patients efficiently using intrathecally, versus if you have to you know, fight for OR time, neurosurgeon time, et cetera, it's harder to do that. You're gonna have more intrusions. You're gonna have more emergencies coming in that you're gonna have to, you know, work to allocate time. The scalability effect was something that was also, you know, quite top of mind for the physician group. Hopefully that gives you a little flavor for the data.

Yep. Got it. Thanks. Appreciate it.

Sure.

Thank you. Our next question comes from Silvan Tuerkcan with Citizens. Your line is open.

Yeah. Thank you so much for taking my question. I maybe just wanted to follow up on the intrathecal injection here. That is not a procedure, right? That can be done in the outpatient setting versus maybe some of, you know, other routes of administrations that may potentially come to the market as well. Can you just speak about that and potentially the cost differential between, you know, a full procedure that would require OR time and neurosurgery versus not? I don't know if you can comment on this, but do you know the screen fail rate that you currently have? Is that predominantly because of the strictness around the baseline measures? Thank you.

Yeah. In terms of the first question, you know, what we're doing is a 20-minute lumbar puncture administration with mild or no sedation. The patient can easily have this done and be out of the hospital, you know.

Same day.

Yeah, same day. You know, well within 24 hours. The ICV approach, you know, obviously you need to be in the OR for that. You have to have a neurosurgeon do the procedure. There is greater time and cost associated with that procedure. In terms of breaking it out, that's something we can talk more about in the second half. Just from an efficiency perspective, the ability to give someone a lumbar puncture, obviously you can do that in various, you know, spots throughout the hospital and do it safely. That's not the case with ICV. I mean, there are certain parameters that you're gonna have to have, certain staff that you're gonna have to have, including, you know, neurosurgeons to do the procedure itself. Keep in mind that the OR time is booked in advance.

You know, there's only so much OR space. There's only very few neurosurgeons to do these procedures. My point is that, and the point that the physicians were making, is that if you have a large number of patients, it would be much more efficient in the institution to be able to dose them on the via the intrathecal route for the reasons that I gave. The second question I didn't quite get, I don't know if anyone around the table got that or Silvan, if you could repeat that. I didn't get it.

Yeah. You know, obviously the trial's ongoing, so, but if you could just speak to the current screen fail rate, just to give a feel of, is there a significant patient population out there that just cannot qualify for this therapy because, let's say, they're too advanced or not advanced enough? Do you have any data points in that direction? Thank you.

Yeah. Silvan, you ask actually a very interesting and important question because, remember, Rett syndrome, there are multiple different genotypes. There is a very differentiated phenotypic presentation, meaning multiple phenotypes that present as Rett syndrome. You also have the complexity of mosaicism when it comes to central nervous system. It's a unique combination that eventually results in a complex clinical presentation. What we've shown in REVEAL Part A is that regardless of genotype or phenotypic presentation or age, our gene therapy given through a simple lumbar puncture consistently provides superior clinical efficacy with no major safety concerns at this point in time. When it comes to screen failure rates, in Part A, as far as I recall, there were no screen failures. In Part B, we have not discussed the screen failures publicly at this point in time.

They are minimal, and given that the common root to the disease is a lack of MECP2 or minimal MECP2 levels that have clinical efficacy or impact on the patient, restoration of MECP2 levels using TSHA-102, in general, addresses the lack of MECP2 and has superior clinical efficacy results up to now. My assumption here is as we experience and complete Part B REVEAL study and ASPIRE, that screen failure or loss of market, I guess, or clinical market access to a large group of patients is not an issue and will not be an issue. I hope that answers your question.

Yeah. Great. Very, very helpful. Thank you.

Thanks, Silvan.

This does conclude our question and answer session. I would now like to turn it back to Sean Nolan, Chairman and CEO.

Thanks to everyone who called in. I really appreciate the time and interest in Taysha. Have a great day.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Good day, and thank you for standing by. Welcome to the Taysha Gene Therapies, Inc.'s full-year 2025 financial results conference call. At this time, participants are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. You would then hear an automated message advising your hand is raised. To withdraw your question, please press 11 again. Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your speaker today, Hayleigh Collins, Senior Director of Corporate Communications and Investor Relations. Please go ahead. Thank you. Good morning, and welcome to Taysha Gene Therapies, Inc.'s full-year 2025 financial results and corporate update conference call. Earlier today, Taysha Gene Therapies, Inc. issued a press release announcing financial results for the full year ended December 31, 2025.

A copy of this press release is available on the company’s website and through our SEC filings. Joining me on today’s call are Sean Nolan, Taysha Gene Therapies, Inc.'s Chief Executive Officer; Sukumar Nagendran, President and Head of R&D; and Kamran Alam, Chief Financial Officer. We will hold a question-and-answer session following our prepared remarks. On today’s call, we will be making forward-looking statements, including statements concerning the potential of TSHA-102, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials, including with respect to functional milestones, to positively impact quality of life and alter the course of disease in the patients we seek to treat; our research, development, and regulatory plans for our product candidates, including the timing of initiating additional trials, reporting data from our clinical trials, and making regulatory communications with the FDA on the regulatory pathway for TSHA-102; the potential for the product candidate to receive regulatory approval from the FDA or equivalent foreign regulatory agencies; our ability to realize the benefits of Breakthrough Therapy designation for TSHA-102; our ability to drive long-term value for stockholders; and the market opportunity for our programs. This call may also contain forward-looking statements relating to Taysha Gene Therapies, Inc.'s growth, forecast cash runway and future operating results, discovery and development of product candidates, strategic alliances, and intellectual property, as well as matters that are not historical facts or information. Various risks may cause Taysha Gene Therapies, Inc.'s actual results to differ materially from those stated or implied in such forward-looking statements. For a list and description of the risks and uncertainties that we face, please see the reports we have filed with the SEC, including in our Annual Report on Form 10-K for the full year ended December 31, 2025, that we filed today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 19, 2026. Taysha Gene Therapies, Inc. undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities laws. With that, I would now like to turn the call over to our CEO, Sean Nolan.

Thank you, Hayleigh. On to our full-year 2025 financial results and corporate update conference call. On today’s call, we will begin with a brief update on recent clinical, regulatory, and commercial readiness activities. Then Dr. Sukumar Nagendran, our President and Head of R&D, will provide a clinical update on the TSHA-102 program. Kamran Alam, our Chief Financial Officer, will follow up with a financial update, and I will provide closing remarks and then open the call up for questions. 2025 was a year of significant execution for Taysha Gene Therapies, Inc. We announced compelling REVEAL Phase 1/2 data across pediatric, adolescent, and adult patients with Rett syndrome treated with TSHA-102, received FDA Breakthrough Therapy designation for TSHA-102, and secured written FDA alignment on our REVEAL pivotal and ASPIRE trial designs, paving the way for a potentially streamlined path toward BLA submission. This progress has set the stage for what we expect to be a transformative year ahead for Taysha Gene Therapies, Inc. as we focus on completing the pivotal development of TSHA-102 and bolstering our commercial readiness efforts as we advance towards potential registration. We have maintained ongoing, constructive dialogue with the FDA over the past two years, which has enabled alignment on a pathway that we believe reflects the rigorous, systematic data collection and well-controlled study design and endpoints required by the FDA for a robust, data-driven application. In 2025, we finalized alignment with the FDA on our REVEAL pivotal trial protocol and statistical analysis plan in support of our planned BLA submission, and we were pleased to initiate the pivotal trial in 2025 with the dosing of our first patient. Multiple patients have now been dosed in the trial, with enrollment advancing across multiple sites. We remain on track to complete dosing in 2026. Importantly, both high- and low-dose TSHA-102 continue to be generally well tolerated, with no treatment-related serious adverse events or dose-limiting toxicities observed in the patients treated in both the REVEAL Phase 1/2 and REVEAL pivotal trials as of the March 2026 data cutoff. In addition to initiating our REVEAL pivotal trial, we recently received FDA clearance to initiate the safety-focused ASPIRE trial, following written FDA alignment on the ASPIRE trial design and data for inclusion in our BLA submission to support a broad label for TSHA-102 for patients aged two years and older with Rett syndrome. ASPIRE will enroll three females with Rett syndrome aged two to less than four years, evaluating the safety and preliminary efficacy of a single intrathecal administration of the high dose of TSHA-102, 1e15 total vector genomes scaled to account for the lower brain volume in the two to less than four-year-olds. The written alignment we reached with the FDA outlines that our planned BLA submission will include a minimum of three months of ASPIRE safety data, while the efficacy in the two to less than six-year-old population will be extrapolated from the data collected in the REVEAL pivotal trial to support the broad label. We are on track to complete dosing for ASPIRE in 2026. We believe this recent FDA alignment on ASPIRE, together with the alignment on a six-month interim analysis for the REVEAL pivotal trial, potentially streamlines our path toward BLA submission for TSHA-102. In 2026, we attended a Type C meeting with the FDA and reached written alignment on the CMC requirements for our planned BLA submission. Specifically, we further aligned with FDA on our proposed comparability approach between TSHA-102 material derived from the clinical and final commercial manufacturing processes. The FDA agreed that the approach may support pooling data from the REVEAL Phase 1/2 trials with data from the ongoing REVEAL pivotal trial and the ASPIRE trial for the planned BLA submission. Importantly, we believe this creates flexibility and will further strengthen the overall dataset for the BLA package by including longer-term data and enabling a comprehensive assessment of safety and efficacy data that has been generated across the entire development program. Additionally, the FDA endorsed our proposed process performance qualification, or PPQ, campaign strategy to support process validation for the BLA submission. This included the stability data package, the potency assay strategy, and the execution of BLA-enabling PPQ lots using the commercial manufacturing process, which we expect to initiate in 2026. This feedback aligns with the agency’s January 2026 guidance aimed at increasing flexibility on requirements for cell and gene therapies to advance innovation. With this alignment, we are confident that our CMC activities are on track to support our planned BLA submission in step with the pivotal dataset readout. We truly appreciate the consistent, constructive, and collaborative interaction we have had with the FDA to date and believe our regulatory progress highlights the strength of our data-driven approach and further supports our goal to bring TSHA-102 to patients with Rett syndrome as safely and expeditiously as possible. We will continue to engage with the FDA as we prepare for our planned BLA submission. In addition to our clinical and regulatory progress, we have continued to bolster our commercial readiness activities. As a reminder, Rett syndrome is a devastating, rare, and progressive neurodevelopmental disease with high unmet need and a profound lifelong burden for patients and caregivers. It is well-characterized clinically, defined by impairments across multiple clinical domains, including fine and gross motor function, communication, autonomic function, and seizures. While Rett syndrome is a heterogeneous condition that presents with different levels of clinical severity based on each patient’s distinct genetic background, natural history data show that patients follow a common trajectory regarding the achievement of functional developmental skills, with the likelihood of spontaneous gain or regain of developmental milestones falling to approximately zero after six years of age. The multi-domain impairments result in loss of independence, with most individuals requiring 24/7 care and lifelong support for daily activities, such as eating or sitting up, severely impacting quality of life for patients and caregivers. This burden and the limitations of currently approved therapies, which focus on symptom management and do not address the underlying genetic root cause, have created strong urgency for new treatment options capable of delivering functional improvements. We believe this urgency, combined with the estimated 15,000 to 20,000 patients with Rett syndrome across the U.S., EU, and UK, underscores the substantial market opportunity for TSHA-102. Within the U.S. specifically, patient estimates range from 6,000 to 9,000 patients based on claims data and epidemiology data. Because Rett syndrome is a neurodevelopmental condition, and based on the Phase 1/2 data we have reported to date across pediatric, adolescent, and adult patients, we believe that most patients with Rett syndrome can meaningfully benefit from treatment. TSHA-102 is uniquely designed to address the root cause of Rett syndrome and, as such, has the potential to meaningfully alter the natural history of the disease and offer patients the opportunity to achieve functional milestones that would otherwise not be possible according to natural history. Recently completed market research reinforces this opportunity, as it demonstrated high anticipated demand from both clinicians and caregivers in the U.S. and a clear preference for intrathecal administration. The research findings are compelling for two main reasons. First, the research suggests that clinicians anticipate broad adoption of TSHA-102 across pediatric and adult patients with Rett syndrome. Caregivers similarly indicated that they would actively pursue an improved gene therapy with a target product profile consistent with TSHA-102. Caregivers emphasized that improvements in existing function or the achievement of new functional gains would be meaningful for individuals with Rett syndrome, as they translate into greater independence in daily living, such as speaking in phrases, walking with support, or finger feeding, which we have observed in patients treated with TSHA-102 in REVEAL Part A. Second, clinical outcomes will be the ultimate driver; however, market research indicated that clinicians and caregivers strongly prefer intrathecal administration over direct-to-brain CNS delivery, citing its familiarity, accessibility, and scalability, enabling the potential to safely and efficiently treat patients across institutions, from large centers of excellence to regional and local institutions. This facilitates broad patient access. Specifically, intrathecal administration, as it is used to deliver TSHA-102, is a routine, minimally invasive delivery approach that does not require a surgical suite or delivery by a neurosurgery expert. This enables the potential for TSHA-102 to be delivered as an outpatient procedure, which in turn may meaningfully expand the treatment footprint, given that administration in the commercial setting will not be limited only to centers of excellence. We believe this broader footprint would enable us to reach patients where they are already receiving care and support, and this is scalable as adoption and demand grow. Finally, as we advance towards registration, we are continuing to build out our internal commercial infrastructure. To that end, we recently appointed Brad Martin as Senior Vice President of Market Access and Value, further strengthening our commercial leadership team. Brad brings over two decades of leadership experience in market and commercial strategy, pre-commercial and product launch planning, as well as payer and health system engagement within the gene therapy space. He previously held senior roles at Neurotech Pharmaceuticals, Sarepta Therapeutics, and AveXis. At AveXis, he played a crucial role in securing market access for the blockbuster gene therapy Zolgensma, for the treatment of spinal muscular atrophy. We plan to continue to build out commercial capabilities as we prepare for a potential commercialization, and we expect to share additional details on our TSHA-102 commercial strategy in the second half of the year. I would now like to turn the call over to Sukumar to discuss progress on the clinical front in more detail. Suku? Thank you, Sean.

As Sean mentioned, we believe we have made significant progress on advancing our Phase 1/2 program and the FDA alignment. As a reminder, we presented data from Part A of the REVEAL Phase 1/2 trial last year, demonstrating a 100% response rate from the 10 treated patients in both low- and high-dose cohorts. An 83% response rate was seen at six months post-treatment, with five out of six patients gaining or regaining one or more milestones defined across the six treated high-dose patients. In addition to the 32 developmental milestones, an average of approximately 19 gains per patient as captured by validated clinical assessments. We have observed a consistent pattern of early gains that was sustained, with additional gains over time. We will provide the six-month interim analysis for the REVEAL pivotal trial and efficacy data across all 12 pediatric patients treated in REVEAL Part A in the second quarter of this year, and all patients will average 12-month follow-up time points across multiple clinical outcome measures, as well as continued well-tolerated safety profile. Today, on the trajectory of the gain, loss, and regain of development provided for TSHA-102, the combined likelihood of spontaneous milestone gain or regain drops to 6.3% after age six compared to rates as high as 85% between the ages of one and five years. These findings align with our own analysis, which allows us to generate data across the broader population while significantly mitigating statistical risk by enrolling 15 patients aged six to less than 52 years in the developmentally regressed population of Rett syndrome, the population with the most stable baseline and lowest spontaneous improvement rate. Importantly, this design enables us to test our response rate against the known hypothesis of 6.7% at age six and older. As Sean mentioned, we have dosed multiple patients in our REVEAL pivotal trial. Enrollment continues to advance across multiple clinical trial sites. We expect to complete dosing in the REVEAL and ASPIRE studies in 2026. We believe our ongoing dialogue with the FDA over the last two years supports the potential path to registration. Looking ahead, we remain focused on our clinical trial execution and data generation as we work to complete patient enrollment and advance towards registration. We believe the thoughtful, data-driven approach we have taken in designing and executing our pivotal development strategy positions us to deliver. I would now like to turn the call over to Kamran to discuss financial results. Thank you, Suku.

Research and development expenses were $86,400,000 for the year ended 12/31/2025 compared to $66,000,000 for the year ended 12/31/2024. The $20,400,000 increase was primarily driven by higher compensation expenses due to increased research and development headcount. Clinical trial and GMP expenses also increased during the year ended 12/31/2025 due to clinical trial activities in the REVEAL studies and BLA-enabling PPQ manufacturing initiatives. General and administrative expenses were $33,900,000 for the year ended 12/31/2025 compared to $29,000,000 for the year ended 12/31/2024. The increase of $4,900,000 was primarily due to higher compensation expenses and higher legal and professional fees, as well as debt issuance costs incurred in connection with the 2025 Trinity term loan that are recorded in general and administrative expense under the fair value option. Net loss for the year ended 12/31/2025 was $109,000,000, or $0.34 per share, compared to a net loss of $89,300,000, or $0.36 per share, for the year ended 12/31/2024. As of 12/31/2025, Taysha Gene Therapies, Inc. had $319,800,000 in cash and cash equivalents. During the fourth quarter, we raised an additional $50,000,000 in gross proceeds by utilizing our at-the-market, or ATM, equity offering program, with proceeds intended to support a potential commercial inventory build in 2027. We expect that our current cash resources will be sufficient to fund planned operating expenses into 2028. I will now turn the call over to Sean for his closing remarks.

Sean?

Thank you, Kamran. The progress we made in 2025 has set the stage for what we expect to be a transformative year ahead as we advance towards registration, and our confidence in a differentiated TSHA-102 gene therapy candidate continues to strengthen based on the recent developments highlighted today. With a favorable tolerability profile demonstrated to date, continued patient enrollment, and a well-defined regulatory and commercial path, we believe TSHA-102 has the potential to meaningfully address the genetic root cause of this devastating disease and provide meaningful benefit to a broad population of patients with Rett syndrome using a minimally invasive delivery approach. On behalf of the entire Taysha Gene Therapies, Inc. team, we remain committed to bringing a potentially transformative therapy to the Rett syndrome community. I will now ask the operator to begin our Q&A session.

Thank you. Star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press 11 again. Our first question comes from the line of Kristen Kluska with Cantor Fitzgerald. Your line is now open.

Hi, good morning everybody, and congratulations on all the progress. So you had a lot of comments about why the community might favor intrathecal administration. I wanted to first ask if you believe the community has a good understanding of why this route of administration gets to the brain. And then also, you listed several reasons why this might be more favorable. I am curious, both from the clinician standpoint as well as the parent or caregiver, if there is one item on that list that is standing out more than others. Thank you.

Yeah. Kristen, thanks for the question. You know, I would say that the support for IT, there were manifold reasons why people wanted to go down that route. The most obvious is everyone can relate to a lumbar puncture. Right? I mean, most of the moms out there have undergone that to some extent. People are familiar with it. They know it is not scary. And I think the most interesting thing is people are taking what I think is a very pragmatic approach. They are basically saying, hey, listen. The clinical data are going to be the most important thing, and if the data are, let us say, equal, then I am going to go do the least invasive approach I can for the person that I love, for the very simple reason that it does not involve drilling burr holes and going into the ICU and having a neurosurgeon involved. As they learn more about that, I think they are just like, hey, you know what? If all things are equal here, at a minimum, then I am going to take what I feel is the safest approach and the easiest approach. I think from the clinical perspective, it is the same kind of a logic set where they are saying, listen. Ultimately, it is going to be the clinical data that is going to carry the day. But based on what we know right now, it is easy for us to do this lumbar puncture. And when they start to talk about the practical logistics of the sites, the throughput necessary for intrathecal delivery done in an outpatient is much easier to manage. You do not have to schedule suite time, surgeon time, things like that. So they are saying, in terms of being able to broaden the reach, go to regional and local hospitals, and make sure that, broadly, the Rett community has access to this therapy, it is a much easier route of administration to administer and provide great care to their patients. Hopefully, that helps.

Okay. Thanks. And just on that point, they do understand that this route of administration is reaching the brain, right?

Yes. We did not get into—we did not explain to them the biodistribution. They are basically making the leap that if I administer it that way and the clinical data are good, it is going to where it needs to go. They do not care about biodistribution. They care about the fact that, is my loved one going to get better or not? And they are judging that based on the clinical data, which, you know, the product profile is just the data that we have shown to date. So we feel very—like, we were not surprised by these results at all, frankly. And I think it makes a lot of sense when you take a step back and just digest it all.

Thank you, Sean.

Thanks, Kristen. Thank you.

Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Good morning. Thanks for taking my questions. With the appointment of Brad Martin as Head of Market Access and Value, what will the first priorities be in this role? What are the key aspects of market access that Taysha Gene Therapies, Inc. should be focused on initially? And secondly, can you frame expectations for the update on longer-term safety and efficacy data from Part A? How many patients will we see, what kind of duration of follow-up, and what you are looking for in terms of the efficacy profile? Thank you.

Yeah. Thanks, Salveen. To start with the second part of the question first, what you can expect to see is—to take a step back—last time we reported data, it was 10 patients, and at the high dose, we had six months of data on five of the six patients. So what we are planning to do in the Q2 update, you will see data on all 12 Part A patients, and we will have a minimum of 12 months of data on all patients. The report out will be inclusive of the primary endpoint, which would be milestones. We are also going to give an update on the skills, the improvements. That is the data that we presented at CNS last year. You will see the CGIs. You will see the R-MBA. So you will get a very comprehensive picture of the dataset. And what we hope to show is what we have been able to demonstrate to date, which is that the early improvements are sustained and we continue to see deepening of response over the course of time. If you remember, the first patient we dosed, by the time we report this data, will be about three years post-dose. So we are starting to generate some nice durability data, which is fantastic. As it relates to what the market access team is doing, there are a lot of steps to take, of course. We generally begin by making sure we are mapping out where the patients are. And then, what is the mix of the payers, so how much commercial pay is there? How much Medicaid pay is there? And then what we will do is make sure from a site activation perspective that we are thinking about the right way to roll this out. So as an example, because of our market research and what we have seen on the route of administration, what is going to be really nice is that we are going to be able to essentially get to the regional and local hospitals. We want to make sure, though, that we roll this out in a very thoughtful manner and anyone using TSHA-102 is very educated on how to do this, knows how to manage gene therapy patients, and that we are comfortable with them and their institution doing that. So part of it is mapping all that out so that we have a good sequence to the flow. And then, you know, beginning to work with the payers and talking to them about the market size, talking to them about the clinical data. And the approach that we have taken historically, Salveen, has been get in early with the payers, be very transparent about what type of—what is the volume of patients that they could potentially see, educate them on the disease state, and educate them on your dataset, and really just take them along on the journey. So we look to build relationships with the payers, and that is what the nice thing about Brad is—he has those relationships. He has done this multiple times. And it is never too early to start on this. You really want to get in as early as you can to really pave the road so that there are no surprises on the back end.

Thank you. Our next question comes from the line of Biren Amin with Piper Sandler. Your line is now open.

Yeah. Hi, guys. Thanks for taking my questions. Congrats on all the progress. Sean, I noticed that the company had a successful Type C meeting with FDA this quarter on CMC for TSHA-102. So maybe on the BLA PPQ lots that you are initiating in the second quarter, when would these complete? And if the REVEAL interim data are positive, how soon do you think you can file the BLA after the interim data? Thanks.

Hey, Biren. Can you repeat the first question? Yeah. So on the BLA-enabling PPQ lots that are initiating in the second quarter of this year, when would these complete? Kamran, do you want to take that?

Yeah. Sure, Sean. So, Biren, nice to talk to you. Yeah. So the PPQ lots will be completed by end of this year. And in terms of the alignment with FDA, I will turn it over to Sean.

Yeah. I think, Biren, the plan we have would be we can do the analysis, the interim analysis, once all patients dosed in the pivotal are at six months. That is when the blind would get broken. Obviously, that is going to be dependent on the last patient dosed. Right? So that is going to happen sometime in the second quarter, based on everything that we are tracking to, which looks good. And then we have to adjudicate all that data. We have to make sure it is correct. The next step, we would sit down with the FDA, go through that data with them, and work to align them on what the next steps could potentially be. Right? And so, post that and post getting minutes, we would come back to the market and give you the update. The reason we do not want to say what the data are before we meet with the FDA is that that is only half the story. Right? So we think it is important to meet with the FDA. And I think there are a couple of potential avenues that could happen. Right? I mean, the best-case scenario would be the agency is very pleased with the data and they tell us to proceed to file on the six-month dataset, in which case we would work to do that immediately. So to be clear, what we are doing in the background—we are writing the CMC modules, the preclinical modules. Those will be in the can and done. So if we get the clearance on the clinical, that would be the only piece that we would have to write, and then we could file the BLA and things would move forward relatively quickly. Another scenario could be the agency says, look, we think the data are good. Historically, we have always liked to see 12 months of data. We would like to see 12 months of data. In that instance, we would make the case, well, okay. But then let us start the rolling submission because we have got all this other stuff done. You already know the primary endpoint has been met. You are looking for some additional time. Okay. Now we would have made the case that the durability from Part A we can now pool based on our recent update on CMC would help us with that case upfront, the six-month course of action. But if they want that, I think even in that scenario, again, the only thing that they would have to review would be the clinical module at the end. So that still pulls things up a couple of quarters. And then the last scenario would be they want to do things the traditional way and wait for 12 months. I think even in that scenario, the nice thing about the interim data—and again, we would share this with the market—is that I believe what we would be able to show is that the product works. You have met the endpoint. You have met the statistics of things. Now it is just time and execution, which I think the market would respond very favorably to as well. So the way I look at it is the FDA gave us the option to do the interim analysis. I believe it is based on the data that we showed in the early responses that we showed and the rigor in which the data were collected. So, look, we have got a few good cards to play here, and we are looking forward to it as we step it through 2026.

Perfect. Thanks for taking my questions.

Thanks, Biren.

Thank you. Our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is now open.

Hey. Good morning. Thanks for taking my questions. Can you talk about what you think the potential read-through from the recent negative opinion for Daybue from CHMP has for your program and also whether this changes what you think the commercial opportunity in Europe is? And related to that, what is your alignment currently with EU regulators on that?

Sure, Tazeen. I do not think there is a read-through based on what happened to Acadia. For those of you that have been around since Suku and I joined the management team here, back in the days when everyone talked about CGI and RSBQ, we were on the opposite side of that, if you remember. For gene therapy, you had to be able to demonstrate that the eye could see that truly had impact on the patient and the caregivers and it was unequivocal. And so, we feel the data that we are generating is very unique. And really no one has been able to demonstrate restoration of function in a neurodevelopmental disease before, and we are able to do that in multiple patients and across multiple clinical domains. And we have got natural history that is absolutely stellar. It is unequivocal. I think Jeff Neul’s paper reinforces everything that we have done from a strategic perspective and supports our thesis on things. And then if we are able to demonstrate what is happening with the primary endpoint and people gaining these milestones, but then beyond that, what we are trying to emphasize on the script is when you look at milestone gains outside the primary endpoint, and you look at improvements that people are having, it is almost 20 per patient so far. That is based on what we reported last year. So it is a significant impact that you cannot ignore. And the other thing too I would point to in the natural history data—there is R-MBA data. So we can demonstrate in multiple ways against natural history how we are changing the course of disease and how this is a transformational treatment, which then gives us the power to capture value through price in a very meaningful way and get reimbursed for it. If you take a look at what happened with Sarepta, up until they had some of the unfortunate safety things, their launch was going great. And I would argue that the data that we are generating is quite demonstrable. We are not having to talk about a scale. We are not having to talk about a one- or two-point change in the North Star or a one-point change in the CGI. The payers do not care. The payers want to see functional gains. They want to see concrete improvements. That is what is going to lead to getting you approved. Hope that helps.

Yeah, Sean. And maybe just a quick follow-up. On Europe again, usually there is a pretty deep discount on price. But, again, just given that there would be a lack of therapies available, do you think that strengthens your position on pricing when it comes time to that?

Yeah. I mean, I think we are going to be in a very strong position on price because of the data that we have and because of the high unmet need in the disease state. So we feel that—we are—obviously it is early days to get into what the actual price will be. But I think with where we sit and the data that we are capturing, and the fact that it is happening across multiple domains, and no matter what COA we are looking at, all the needles are moving in the right direction in a meaningful way, I think we will be able to capture the appropriate value.

Thank you.

Our next question comes from the line of Maury Raycroft with Jefferies LLC. Your line is now open.

Hi, good morning. Congrats on the progress and thanks for taking my question. For the REVEAL Part A update first half of this year, do you plan to provide a sub-analysis showing the proportion of patients that achieve more than one developmental milestone by 12 months? And are you planning to show any patient-level data with vignettes? And if so, how are you setting expectations for number of patients and milestone gains that you can show in that update?

Thanks, Maury. Yeah. To take the second part of your question first, we will likely highlight a couple of patient vignettes. And just to give you some perspective on why we show the data like we do, number one, we are going to have 12 patients’ worth of data. This drug is going to get approved or not approved in the aggregate. Right? The aggregate data is what you get approved on. So I think making sure it is clear—and we will share every endpoint that we are effectively capturing—and then the investor will get to judge the data and the probability of success in getting approved. So we think that is the most important thing. We think that is where the emphasis should be. I think highlighting a couple of patient vignettes would be helpful to basically show the early improvement and then the sustainability and the deepening of response over time, getting into more specifics about what is actually happening on a patient basis. So if we say that people are effectively gaining about 19 to 20 skills or milestones and improvements, let us tell you the story of what that looks like. Now if I did that for 12 patients, we would be on the call for five hours. So that is why we do not want to go through all 12 patients. We just want to highlight a couple things. And then, again, based on the aggregate, you can say, hey, I like this data or I do not like this data. But we think that is the right way to portray it. Can you remind me the first part of your question?

Yeah. Just some sort of a formal sub-analysis showing the proportion of patients that achieve more than one developmental milestone by 12 months.

We will take that into consideration. We are still working on the ultimate way to portray things. We have got a few ideas on how to get at—you know, we have gotten some feedback from investors on what they would like to see. So we will take all that into consideration, and we look forward to that update.

Got it. Likewise. Okay. Thanks for taking my questions.

Thanks, Maury.

Thank you. Our next question comes from the line of Gil Blum with Needham & Company. Your line is now open.

Good morning, and allow me also to add my congratulations on the progress. Just a couple ones from us. So as it relates to your recent update on the ASPIRE study, was this in line with prior expectations? Was this faster, or this is just, you know, run of course here? And our second question, it is good to see submissions using your RMAT designation of the CMC materials. This is a known issue in this space. Are you guys going to receive any feedback on what you have already submitted ahead of completing your filing, or is this just going to happen later? Thank you.

Okay. Let us take the ASPIRE. I would say—and Suku, jump in—I would say we got a pleasant surprise in that initially what we proposed to the FDA was a study of two to less than six-year-olds, and the FDA came back and said, listen, the brain volumes of a five-year-old and a four-year-old are effectively the same as a six-plus, so we feel that that data are already being captured and collected, and therefore they just wanted us to focus on the safety of the two- and three-year-old because they do have less brain volume. And so that was the experiment that they wanted us to run. We did recommend the three-month, and they agreed with that. I do not know, Suku, if there is anything else you found interesting about that whole thing?

No. I would add to that, Sean, that it is clear that the FDA is pretty comfortable with our safety and efficacy data up to a six-plus age group, and they are willing to let that dataset be used for the less than six. I mean, that two- to three-year-old, as you pointed out, because of the brain volume adjustment that is needed, they felt that was the appropriate age group for us to give them a small sample set on safety. And that could potentially be more than adequate for a complete BLA filing.

Yep. Yep. And, Gil, your question about the CMC—can you just restate that?

Yeah. Just wondering because you have an RMAT designation, is there any feedback the FDA could provide you on what you have submitted ahead of completing your filing, or is that not part of—thanks.

So, I mean, we have got—because of Breakthrough, it is an additional way to get access to the FDA. So we do have our first Breakthrough meeting with the agency coming up, and there will be more of those along the way. But we will use that to have a discussion around potential BLA submission scenarios and working to get at your question, which is, you have seen CMC, you have seen our preclinical—just working to gain alignment on the completeness of the packages that we are putting together and what we share with the FDA. So I think we are going to have really good line of sight to where we stand. CMC is a good example. We could not be in a better position right now. So back when we did our first commercial lot, the agency said they deemed that the clinical lot and the commercial lot were analytically comparable. Now that we have done more lots, they are continuing to say that. And now they are saying, if you continue to demonstrate this through PPQ, you can pool your data from Part A and from the pivotal and from ASPIRE because the product is the same. So that is the best you can possibly have right now, and I think that is an example of working closely with the agency. I know that they feel like there is nothing more on the preclinical side that needs to get done. It really is just generating the pivotal data and the ASPIRE data are going to be the last aspects of the submission package.

Excellent. Very helpful. Thank you.

Thanks, Gil.

Our next question comes from the line of Chris Raymond with Raymond James. Your line is now open.

Hey, thanks guys and congrats from us on the progress. Just have maybe a competitive two-part question, I guess, and maybe also wanted to drill down a bit on the BLA filing timing question. So Neurogene has made some comments in the past couple weeks to the effect that the six-month time endpoint—from—they have gotten word from FDA that that is not clinically meaningful. And, Sean, I think I have heard you say, you know, the difference here is you guys will have 12-month data from Part A to supplement, and that is kind of the difference maker. But I guess, is that the only difference maker or, you know, is there potentially something else, like maybe the risk-reward of the therapy or other factors? And then the second point is—you got my attention with some of your market research commentary. And I think it is an aspect that could be pretty important. You know, you are talking about intrathecal administration being able to reach patients outside of large centers of excellence, and being able to dose patients at the community center. Do you have any detail around the breakdown of patients between these centers of excellence and out in the community, and from just sort of the setup there commercially, just assuming both therapies are on the market at some point?

Yeah. I can say that the research we have done to date shows that about 50% of the Rett patients are associated with a center of excellence. That means that over the course of one year, there is one visit to the center of excellence. So that does not necessarily mean that it is the most convenient place for them to get the therapy. And put it another way, there are 50% more patients outside of the COEs. So we think it is very important to make sure that there is a network of care that gets to where the patients are. And so with the data we have, we are able to map where the patients are, and then we are going to take a very thoughtful approach about working through access to care and making sure that the people that are using this are well trained, the facility has the right mechanisms in place to support gene therapy and things of that nature. But what is nice about the intrathecal route is it allows us to broaden that footprint in a relatively straightforward manner. And getting access to patients is the most important thing. Suku, let us tag team the question on the meaningfulness of six months. I mean, I can just say the FDA never said that to us. So every case is unique. I guess the simplistic way I would answer that question is it depends what data you are generating in the first six months. And I think if those data are compelling from a clinical perspective, then the agency is going to take note.

Yeah. What I would add to that, Sean, is that I have not seen any data from Neurogene’s initial studies that show that they have actual clinical efficacy in the first six months post-dosing. And most of their clinical impact appears to come much later, maybe 10 months post-dosing. Usually, FDA looks at proof of concept before they agree to an earlier analysis. And we have six-month interim analysis from our Part A data that is more than convincing, that allowed them to say, yes, we can evaluate and bring the dataset in for actual review and approval if necessary. And then the second component is they always wind back to the construct because Neurogene’s construct is single-stranded. And single-stranded constructs usually take much longer to come together in the nucleus of the cell of interest and actually become efficacious from a protein production standpoint. So I think that may have played a role in also the six-month interim analysis being given to us while in that case there may have been some pushback.

Yeah. The other thing too, just to highlight, Chris, Daybue got approved on 12-week data. So I think it is really just what is being demonstrated at a point in time. Right? We—Yep. Hope that helps.

Yeah. Sure.

Thank you. In the interest of time, we ask that you please limit yourself to one question. Our next question comes from the line of Jack Allen with Baird. Your line is now open.

Congrats on the progress made over the course of 2025. I wanted to ask briefly about how enrollment is going in the pivotal studies and what aspects you are looking to screen these patients on the basis of. Can you talk a little bit about the pre-dosing period in the trial and how you are identifying patients that are really apt for the clinical studies that you are enrolling right now?

Well, Suku, we can tag team this. I would say, number one, Jack, there is consistency between Part A and Part B in that the severity of the patients is still a CGI-S between four and six. We did—one of the things we did—we have not provided the number—but one of the things we did put in the pivotal protocol is that, of the 28 milestones, there needs to be a certain number of open milestones to get into the study from a screening perspective. So that is probably the most interesting aspect of things that you are looking at. Suku, you want to talk about the enrollment and the progress that we are making?

Yeah. So, Jack, I mean, we have dosed multiple patients already. Multiple sites are active, and we are—frankly, I would say—we potentially have more patients than we need to actually screen and go forward. And we are well on our timeline when it comes to dosing all 15 patients and actually having results, hopefully, for the six-month interim analysis by the end of this year. I think that is where things are progressing at the present time.

Yeah. Jack, I think one thing that is really important is that the training at the sites is super important, meaning we have created a standalone DMA. Right? That is the Developmental Milestone Assessment—our name for that—call it a new COA that we developed to standardize the data collection of the milestones. And the FDA—that was really where they spent most of their time with us—was how are you going to systematize and make sure that the data collection are rigorous to make sure that we understand at baseline what a patient could and could not do and then you replicate that in a consistent manner every single time you conduct the DMA. So that is really—Suku’s team has done a stellar job in activating the sites and training the sites and getting them up and running. But that really is, in our discussions with the agency, a fundamental aspect that we wanted to make sure we had our hands tightly around.

Great. Congrats on all the progress.

Thanks, Jack.

Our next question comes from the line of Yanan Zhu with Wells Fargo. Your line is now open.

Hi. Thanks for taking our questions. Wanted to follow up on the pooling of data between the Phase 1/2 and the pivotal study, given that that sounds like something—you know, why you did—that is why you did the manufacturing comparability study. So in what form will the data be pooled? Are we talking about a supportive dataset separate from the top primary endpoint analysis, or could the two studies combine into one and give one number in a label? And then I have one additional question. Thanks.

I would, at a high level, say what the pooling allows you to do is multiple types of analyses looking at the totality of your data. So you can pool for safety. You can pool for efficacy. You can pool for age distribution. You can pool for a lot of different things. And the agency is going to do all those things anyway. The fact that you have got the ability to do that, though, does create the ability for you to support further your package because you have got different and, I would say, additive analytics that you can utilize to support the package that you are making. I do not know what else you would add to that, Suku.

Well, Sean, I would not add much else other than to say it gives us a comprehensive, large dataset in this rare disease of Rett syndrome that allows us to look at, as you said, multiple analyses, but also duration of efficacy, and impact on multiple milestone achievements over time. So I think it is a pretty comprehensive strategy that we have come up with. And frankly, the FDA agrees with us, given that they agree that, from a technical aspect, the clinical lots and the commercial lots that they are studying are both equitable. So I think it is a huge win for us to move this forward in a rapid manner.

Right. Thanks. Congrats for the ability to do that. And my follow-up question is on expectations for the upcoming data update. Now with 12 months of data on the milestones, what is the expectation for patients continuing to gain milestones between six and 12 months? And is there any chance to observe a loss of milestones, or is that captured in the data so that we have a sense of true durability? Thank you.

Yeah. Yanan, we would expect that there are continuous gains that happen, continuous improvements that occur over the course of time. So that is what we would anticipate seeing in this dataset. I would say, in terms of loss of gains and things like that, it is not what you would anticipate. I can say that, you know, sometimes on the day of assessment, you can see something may not be demonstrated. Like, if one of the girls has the flu or a UTI, it is very possible that they are not feeling well, and they are not going to demonstrate something. It does not mean they lost it. And I can just say in what we have reported on to date, we have never seen a loss of any gain. So we will work to highlight that when we give the update in the first half.

Thank you.

Our next question comes from the line of Whitney Ijem with Canaccord Genuity. Your line is now open.

Hey, guys. I am going to ask one ASPIRE question in two parts. First is just to double check on the language around the extrapolation, is there any nuance there or like math involved, or is it just that the REVEAL efficacy will be assumed for the ASPIRE population? And then the second question is just on dosing in ASPIRE. I think there was mention of a scaling based on brain volume. So any color you can give on that?

Yeah, Whitney. There is really no math on the extrapolation. It was really just whatever you see in the six-plus, that is going to get extrapolated into the younger age group. So that is where the alignment is with the agency. It is at a macro level. And then on the second part of the question on the scaling, yeah, it is a very consistent mathematical equation that you use from the preclinical to get to your human equivalent dose. And we will be using that same calculation in the two- to three-year-old. So, Suku, I do not know if there is anything more you would add to that.

All I would add, Sean, is that the calculation for the two- to four-year-olds is essentially equivalent to the 1e15 dose from an efficacy standpoint when we look at our preclinical models.

Right. So in terms of what they are getting—

Exactly.

Yes. Exactly.

So that makes sense, Whitney. So a two-year-old, even though they are getting less of a dose, it is equal to the 1e15 in a larger person. So they are getting the same therapeutic effect.

Effect. Right.

Yep. Understood. That makes sense. Thanks so much.

Thank you. Thank you. This concludes the question-and-answer session. I would now like to hand the call back over to Sean Nolan for closing remarks.

We appreciate everyone taking the time to listen to our 2025 update and corporate update as well, and look forward to making progress throughout the year and providing an update in Q2. Take care, everyone.

This concludes today’s conference. Thank you for your participation. You may now disconnect.