Taysha Gene Therapies Inc Aktie

Good day, and thank you for standing by. Welcome to the Taysha Gene Therapies First Quarter 2026 Financial Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your first speaker today, Hayleigh Collins, Senior Director of Corporate Communications and Investor Relations.

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 31, 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, forecasted 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 31, 2025, that we filed on March 19, 2026, and our quarterly report on Form 10-Q for the quarter ended March 31, 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 6, 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 laws.

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. Suku 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 the 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 6-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.

Additionally, 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, and we expect to complete execution by the fourth quarter of this year. As a result, we are confident that our CMC activities are on track to support our BLA submission in step with the pivotal data readout.

As a reminder, the FDA previously agreed that TSHA-102 material produced from the clinical and final commercial manufacturing processes are comparable, and therefore, they 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 6-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 3 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 prespecified 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 6 months post treatment with 5 of the 6 patients treated with the high-dose TSHA-102 gaining or regaining at least developmental milestone. By 9 months post treatment, the data demonstrated a 100% response rate across the 6 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 and 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 health care 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 central nervous system 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 and 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 intra-cisterna 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 14, 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 mini MECP2 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 this supportive evidence, our 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 trial 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 3 months ended March 31, 2026 compared to $15.6 million for the 3 months ended March 31, 2025. The $18.2 million increase was primarily driven by BLA-enabling PPQ manufacturing initiatives performed during the 3 months ended March 31, 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 3 months ended March 31, 2026 compared to $8.2 million for the 3 months ended March 31, 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 3 months ended March 31, 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 3 months ended March 31, 2025. As of March 31, 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. And 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?

[Operator Instructions] Our first question today comes from Kristen Kluska from Cantor.

Congrats on these updates. So 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 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. But 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 multiple skills and improvements across all of these patients and they happen quickly and then they improve over time and get deeper.

And so the question is why does that occur? And I think what we're highlighting at ASGCT is the fact that the construct, which we purposely utilize self-complementary technology ultimately drives in this data set, a 30x transduction efficiency or protein expression than single strand does. And so 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. And usually, you have to do that because of a single strand.

The other thing, too, is just reinforcing the fact that the mini MECP2 gene continues to show comparability. It's been published for over 15 years that this has been the case. But again, we just wanted to highlight that regardless of the genotype that we're seeing in these 12 patients that we've dosed to date and that we'll report on in a few weeks, they're all responding and they're responding across clinical domains. And the gene, the mini gene is very much a part of that because it essentially equals the full-length gene.

And again, the reason we use the mini gene was so we could package the self-comp. So 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 want to add to that.

Yes, Sean, I have a few more points to add. So 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 translates into a significant improvement in activities of daily living. So the clinical data at the present time from Part A now speaks for itself.

So now when we work backwards and continue to further look at preclinical data, whether it's us 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.

So 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. And I think we may have set the stage for an intrathecal lumbar puncture-based platform to treat difficult CNS diseases.

Our next question comes from Salveen Richter with Goldman Sachs.

Regarding the BLA submission pathway for 102, can you walk through the different scenarios here and whether approval based on the 6-month data should be considered the base case assumption? And how you characterize the willingness of the FDA to approve based on 6-month data sets and time lines around this, that would be great?

Yes, Salveen, great question. We've been out talking with the investment community really since the beginning of the year, and this topic has come up. And so I think those that are on the call, this will sound very familiar, but we were very transparent with the FDA. 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 6 months' worth of data.

And 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. And I think our perspective on that is understood. But if we continue to demonstrate comparability with Part A, we're going to have years of data from those patients that we can use to support the durability. And their answer was essentially, look, ultimately, this is going to come down to the totality of the evidence. And this is something that if the company chooses to do, we will -- 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 the FDA decides that let's just say they want to keep it as a precedent at 12 months, we would push hard for a rolling review because the CMC modules would be done, the preclinical modules would be done. And we can have things updated where the 6-month data is packaged in a way that they could look at that and also then there's less to review when you would submit the final 12-month data, and that can pull things forward a couple of quarters.

And then obviously, the third scenario would be there may be nothing at all wrong with the data. They just want to see 12 months. So we feel in any of those scenarios, number one, there continue 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 going to come down to the totality of the evidence and their comfort level around the data package that's put forward.

But as we've said all along, the nice thing about this 6-month interim is it creates the optionality for us to potentially get this to patients faster. And 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 obviously, we're going to do everything we can to facilitate that. But we'll have clarity for the market. And 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 6-month data are and people can judge the probability of success, and then it's an execution story.

So for all the reasons that we laid out in this call, we feel that there is strong evidence to push for the 6-month data. The fact that we've got comparability with the FDA on the CMC side is absolutely critical to this. And 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. So ultimately, we'll leave it at that. The nice thing is we've got this option -- 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. So we're in the best possible position we can be. We've got a couple of cards that can fall our way, and we're excited about having this discussion with the FDA at the appropriate time.

Our next question comes from Biren Amin with Piper Sandler.

Recently, the FDA Commissioner announced the 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 Sean, with the 6-month data and the agency potentially following patient data to 12 months during review under this program? So I guess that's the first question.

And then 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? And if that's the case, how does the over-enrollment impact the effect size calculation for the study?

Yes. Just real quickly on the real-time piece, I'll ask Suku to comment on that. But 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 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 pathways, sure, we would try to do that. But again, I don't want to 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 the time lines, 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, 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. But 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, because 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. And sometimes the real-time decisions versus a more time process-oriented decision could have significant impact and influence on programs.

So I hope that helps, because at this time, we are kind of watching the process interestingly. And you mentioned 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.

Yes. And then the question around the potential for over-enrollment, I would say that you're always trying to balance the -- getting the appropriate patients in screened essentially, understanding that there could potentially be a screen fail. Like one of the criteria we have, right, there's a number of open milestones you must have, right, as an example. You could go through the screening and then find out that, that patient doesn't quite meet it. So you're going to want to have more patients than 15 going through the screening process. And if you do end up in a situation where you dose an extra patient or 2, we would be certainly willing to do that. I can just say that 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. And then if you had another patient or 2, 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 there, Sean, is that as you said, the power and p-values for a patient sample size of 15, if it goes to 16 or 17 based on what Sean just described, it won't have a major impact on power or p-value for the study itself. And as you know, from REVEAL Part A, we already have 100% responder rate at 9 months with a small number of patients. And those observations, I think, are significant. And as you know, all we need is a 33% responder rate for our REVEAL Part B study. So 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.

Yes. I think the key, Biren, is just simply that the null hypothesis is so low. It's effectively 1 patient spontaneously having an effect. So because of that number being such a low aspect, the overall end doesn't really change things very, very much. But good question. Thank you.

[Operator Instructions] And our next question comes from Tazeen Ahmad from Bank of America.

This is Wesley on for Tazeen. I had a question on sort of the mechanics of the Part B portion of the study compared to the Part A. Are the like assessments being done of the patients, the treated patients being done in the same way in Part B to Part A? Who is doing the video recordings? And with regards to sort of the patients that you are currently screening and plan to dose, are those 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 the 12-month update you're going to share soon to what we can expect and how the Part B is running.

Thanks for the question. And Suku, we can tag team this. 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. And 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. And it starts with the fact that, number one, what we rate is -- so first of all, all of our milestones for the primary endpoint are prespecified, right? There's clear definitions for those. And those demonstrations are from videos that are conducted in the study itself.

So when people -- the way it's been working is that people are 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 2 of 3 raters have to adjudicate that as a milestone. So the company has nothing to do with what is declared a milestone. And 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.

Now the other side of this coin is that the Mullen, which is another video tape 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? So there's no real way to be putting your thumb on a scale and making this data subjective. It's very objective. So I think this is a good read-through to Part B.

The only difference in Part B is that we're going to have a standalone assessment of all of the milestones. So 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. So 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 they break -- until the 6-month time period where they break the blind for all of the 15 patients and review those videos.

So 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 going to 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. So hopefully, that gives you a perspective there, but I think the read-through should be pretty direct when we update you in a few weeks.

Our next question is from Maury Raycroft with Jefferies.

This is James on for Maury. For the 12-plus 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 6 and 12 months? And how do you plan to communicate that in the update relative to the last presentation last year? And also, should we expect a potential safety update from the REVEAL pivotal cohort around IRSF or how should -- or should we expect that update at a later point after IRSF?

Yes. To answer your second question first, I mean, even today, when we said that as of the March safety cutoff, that was inclusive of the REVEAL Part A and also the pivotal trials and ASPIRE. So that's all the studies that we're running right now. You just got a safety update on no treatment-related SAEs and DLTs. And we'll continue to do that on a quarterly basis.

And the first part of the question, could you repeat that? I already lost it.

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

Yes. I mean to be very simple, and I'll turn it over to Suku, 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. And that the things that you had, 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.

Yes, 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. And I would also emphasize that we hope that we can continue to show a significant collective improvement in "skills" that per patient could go above the 19 per patient that we disclosed this morning when Sean did his segment of the communication.

So 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 going to emphasize these are done in a blinded reviewer, expert reviewer fashion and not done at home by caregivers, which usually the FDA has questions around. So I hope that our 12-month plus data disclosure further enhances the confidence in what TSHA-102 can contribute potentially in a transformative manner to this patient population.

Yes. I guess 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.

Our next question comes from Gil Blum from Needham & Company.

Maybe just another one on the 6 months interim, as a clarification, the FDA basically has not given a clear feedback as to what it thinks about this 6-month interim. Would you say that what would dictate the decision here would be the data itself and the 12-month data that you're going to present at IRSF?

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 6-month interim. They're actually waiting for the data. Is that fair?

Yes. 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 '25 where we started talking about that. It's always been something that's enabled. We just confirmed, and we've gotten a lot of questions from investors like, hey, when was the last time you talked to the FDA? It's like, well, we talked twice in the last few months here, once on CMC and once on our first breakthrough meeting. And we went back through, we got confirmation on the design, on the endpoints and our scenarios that I went through. And they're like, yes, I mean that is an option for you. It's going to depend on the data in terms of approvability. So you're never going to get anything better than that, which is why we were so with the outcomes from that meeting.

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

I didn't hear that.

Yes, they are open to the 6-month...

Yes, yes. And it's in writing, by the way. I mean, so 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.

[Operator Instructions] Our next question is from Chris Raymond with Raymond James.

Maybe just 2 here. Just on the Process Performance Campaign or PPQ. You mentioned FDA has agreed on equivalency between the clinical and the commercial manufacturing. Maybe just can you give a little bit more color on what activities, 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? And then one of the things that kind of struck us, we've done some KOL work where people seems physician -- the physician community seems 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?

Sure. So Chris, starting with the PPQ, 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. And so it was 1:1, and the FDA deemed that, that was analytically comparable. And what you have to continue to do as you produce more lots is demonstrate that there's -- those additional lots are also comparable. So at this last meeting, we shared with them multiple additional lots that we'd run, and they continue to say that we're comparable.

Now as you go into PPQ, you're generally doing 2 or 3 additional runs and then you share that data with the FDA. So we're in the process of doing those runs right now. Assuming those runs continue to be demonstrating comparability, that's when you're able to pool the data. So the fact that we've been able to do it with multiple runs so far gives us a lot of confidence. There's a strong alignment with the FDA. And then we take that data package and the next time we meet with them, we share that with them, and that's kind of the next step. So 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. So that's that.

As it relates to the broad ages of enrollment, if you think about the prevalent population, 85% of the prevalent population is over the age of 10. So 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. So we feel that we're in a good position to serve the broad community who is 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. So our whole goal is to make this available for all patients with Rett syndrome and the data continue to support that. And I can tell you that the demand is high across the age groups based on what we've seen so far.

Our next question is from Jack Allen with Baird.

Congrats on the updates. It sounds great to hear that enrollment is on track to be concluded in the second quarter of this year. I guess my question is pretty simple, and that I was wondering if you could 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 maybe 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?

Yes. I think Suku can take the second part of the question. I mean we're not going to give specifics. I would just say the demand is super high. It's high across the age spectrum, multiple sites -- we've got 10 sites that are active. Multiple patients have been dosed across multiple sites. Most of the sites have multiple patients.

So I mean, do you want to talk a little bit about the enthusiasm and the demand that we're seeing across the spectrum?

Absolutely. So we have multiple centers of excellence who are part of the clinical trial, and they all have 100, 200-plus patients. Many of the patients' caregivers and parents have been very enthusiastic about being screened and enrolling in our trial. So 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. So we should be -- 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.

Our next question is from Whitney Ijem from Canaccord Genuity.

Just thinking about durability, how often are patients assessed in Part A? And I guess I'm just wondering if there's a scenario where later this year, either we or the FDA is getting like an 18-month update on those patients and then potential for longer term updates going forward?

Yes. Thanks for that question, Whitney. That's actually a very important question that you raised. So given that we have a Part B ongoing, and we have an agreement with the FDA that the 6-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 6-month interim analysis from Part B collectively driving towards the full approval. And 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.

So 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 it's going to be also important to the collective 6-month interim analysis. And if the 6-month interim analysis 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.

Yes. 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. So you should have a real good sense of what's happening over time.

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

Malcolm Hoffman on for Evan. Thinking 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?

Yes. So to answer the question, so we currently are at Catalent, and Catalent's Baltimore, Maryland facility has obviously been inspected and they have extensive gene therapy manufacturing experience. And we feel really confident in the team that's at Catalent and our oversight of the team there. And importantly, as Sean mentioned earlier, we have ensured that based on our lock manufacturing process, CMC is not on the critical path to a potential BLA submission.

And as it pertains to downstream potential redundancy in manufacturing, that's something as we get closer to Part B interim data readout. And as we get closer to a potential BLA submission, that's something we will evaluate to mitigate any potential disruption to supply chain. But we feel really confident given Catalent's manufacturing experience in that particular facility in Baltimore that, that facility can meet our ultimate commercial demand.

And Evan, that's where Sarepta is making Elevidys as well. And so it's been FDA inspected, and they're very familiar, as Kamran said, with gene therapy commercial scale. So we feel very confident about that.

Our next question is from Yanan Zhu with Wells Fargo.

This is Jeff on for Yanan. Today and in the last couple of months, market research has been touched on, indicating strong demand for gene therapy in Rett and a clear preference for intrathecal delivery, including 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 patient -- physician preference specifically for TSHA-102?

Yes. I mean -- and there'll be more to come in the second half, deeper dives on the commercial aspect of things. But we essentially tested with physicians. So it was about half the physicians were at centers of excellence, half were not at centers of excellence. And then we also separately ran a study with caregivers of Rett patients or children with Rett across the age spectrum. And we kept it pretty simple. I mean we basically -- our product profile was -- our product profile that you've effectively seen, the responder rate, the CGI scores on average with the duration of time that we've been testing these patients. Think about the last data update we gave last year and the deck that we used, it was effectively that on a one pager. And then we just toggle that with is it intrathecal or is it ICV? What would it matter, assuming the same set of data?

And so 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. So 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. So that also was encouraging. And then when you distill this down to make it real simple, and again we didn't want to make it too technical at first. I think more has to be shown to get more precise on comparative product profiles.

But if all things are equal on safety and efficacy, obviously, there's a preference for the least invasive route, both in terms of perceived safety, but also just in terms of 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 fight for OR time, neurosurgeon time, et cetera, it's harder to do that. You're going to have more intrusions, you're going to have more emergencies coming in that you're going to have to work to allocate time. So the scalability effect was something that was also quite top of mind for the physician group. So hopefully, that gives you a little flavor for the data.

Our next question comes from Silvan Tuerkcan with Citizens.

I maybe just wanted to follow-up on the intrathecal injection here. So that is not a procedure, right? So that can be done in the outpatient setting versus maybe some of 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 a full procedure that would require OR time in neurosurgery versus not? And then I don't know if you can comment on this, but do you know the screen fail rate that you currently have? And is that predominantly because of the strictness around the baseline measures?

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

Same day.

Yes, same day, well within 24 hours. The ICV approach, obviously, you need to be in the OR for that. You have to have a neurosurgeon do the procedure. And so 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. But just from an efficiency perspective, the ability to give someone a lumbar puncture, obviously, you can do that in various spots throughout the hospital and do it safely.

That's not the case with ICV. I mean there are certain parameters that you're going to have to have, certain staff that you're going to have to have, including neurosurgeons to do the procedure itself. And keep in mind that the OR time is booked in advance. There's only so much OR space. There's only very few neurosurgeons to do these procedures. So 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. So I don't know if anyone around the table got that or Silvan, if you could repeat that, I didn't get it.

Yes. And obviously, the trial is ongoing. So -- but if you could just speak to the current screen fail rate, just to give a feel of are there -- 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 or do you have any data points in that direction?

So Silvan, you asked 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. And then you also have the complexity of mosaicism when it comes to central nervous system. So it's a unique combination that eventually results in a complex clinical presentation. And 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. But they are minimal. And given that the common route 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. So my assumption here is as we experience and complete Part B REVEAL study and ASPIRE that screen failure or loss of market, I guess, a 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.

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 Full Year 2025 Financial Results Conference Call. [Operator Instructions] 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, Corporate Communications and Investor Relations. Please go ahead.

Thank you. Good morning, and welcome to Taysha's Full Year 2025 Financial Results and Corporate Update Conference Call. Earlier today, Taysha 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'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 and 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 submissions; timing or outcomes of 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's growth, forecasted 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 we have filed with the SEC, including in our annual report on Form 10-K for the full year 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 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 [Audio Gap] to our full year 2025 financial results and corporate update conference call. On today's call, I will begin with a brief update on our recent clinical, regulatory and commercial readiness activities. Then Dr. Suku 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. We announced compelling REVEAL Phase I/II 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 as we focus on completing the pivotal development of TSHA-102 and bolstering our commercial readiness efforts as we advance towards potential registration. We've maintained ongoing constructive dialogue with the FDA over the past 2 years, which has enabled alignment on a pathway that we believe reflects the rigorous systematic data collection and well-controlled study design and endpoint selection 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 the fourth quarter of 2025 with the dosing of our first patient. Multiple patients have now been dosed in the trial, with enrollment across -- advancing across multiple sites. We remain on track to complete dosing in the second quarter of 2026. Importantly, both high- and low-dose TSHA-102 continues 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 I/II and REVEAL pivotal trial 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 2 years and older with Rett syndrome. ASPIRE will enroll 3 females with Rett syndrome aged 2 to less than 4 years, evaluating the safety and preliminary efficacy of a single intrathecal administration of the high dose of TSHA-102, [ 1 ] of the 15 total vector genomes, scaled to account for the lower brain volume in the 2 to less than 4-year olds. The written alignment we reached with the FDA outlines that our planned BLA submission will include a minimum of 3 months of ASPIRE safety data, while the efficacy in the 2 to less than 6-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 the second quarter of 2026. We believe this recent FDA alignment on ASPIRE, together with the alignment on a 6-month interim analysis for our REVEAL pivotal trial, potentially streamlines our path toward BLA submission for TSHA-102.

In the first quarter of 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 I/II 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 data set for the BLA package by including longer-term data and enabling a comprehensive assessment of safety and efficacy data that's 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 the second quarter of 2026. This feedback aligns with the agency's January 2026 guidance aimed at increasing flexibility and 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 data set readout.

We truly appreciate the consistent, constructive and collaborative interaction we have held 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 continue 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 0 after 6 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 do not address the underlying genetic root cause, have created a 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 U.K., 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 I/II data we've 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, adolescent 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 emphasize 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 the 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 a scalable adoption as demand grows.

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 2 decades of leadership experience in market access 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 that commercial capability to prepare for 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 Suku 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 TSHA-102 program towards registration. We are encouraged by the data previously shared from Part A of our REVEAL trial and the FDA alignment on a clear pathway to potential BLA submission. As a reminder, we presented data from Part A of the REVEAL Phase I/II trial last year, demonstrating a 100% response rate across our 10 treated patients in both dose cohorts. In the high-dose cohort, an 83% response rate was seen at 6 months post treatment, with 5 of 6 patients gaining or regaining [ 1 natural history defined ] developmental milestones. By 9 months post treatment, the data demonstrated a 100% response rate across the 6 treated high-dose patients.

In addition to the developmental milestones gained, patients also demonstrated a total of 165 other [ still gains ] and improvements across the core domains of Rett syndrome, an average of approximately 19 gains per patient, as captured by validated clinical assessments. We have observed a consistent pattern of early gains that were sustained with additional gains over time, demonstrating a deepening [ of effect ]. We believe these data enable our alignment with the FDA on the 6-month interim analysis for the REVEAL pivotal trial and supported by the FDA [ mission ] to grant Breakthrough Therapy designation to TSHA-102 in September 2025. We look forward to reporting longer-term safety and efficacy data across all 12 pediatric, adolescent and adult patients treated in REVEAL Part A in the second quarter of this year, with our patients developing [ 12-month follow-up time points ]. We'll be looking to see a consistent early response that over time across multiple clinical outcome measures, as well as continued well-tolerated safety profile.

Recently, [indiscernible] of the NIH funded [indiscernible] study, part of a publication describing the most comprehensive [ long ] view to date on the trajectory of the gain, loss and regain developmental milestones in Rett syndrome. We believe this analysis across [indiscernible] milestones provide an important validation of our development strategy for TSHA-102, where we are focused on a set of 28 milestones identified as the most clinically meaningful to caregivers [indiscernible].

The publication demonstrates that the combined likelihood of spontaneous milestone gain or regain [indiscernible] milestones dropped to 6.3% [indiscernible] compared to record high of [ 85% ] between the ages of 1 and 5 years. These findings align with our own analysis of the natural history data and provide strong external validation of our 2-study strategy, which allows us to generate data across the broader population while significantly mitigating statistical risk associated with a single-arm study measuring gain or regain of developmental milestones in the natural history derived control.

Our FDA aligned REVEAL pivotal trial is enrolling 15 patients aged 6 to less than 2 years in the developmental plateau population of Rett syndrome, the population with the most stable baseline and spontaneous improvement rate. Importantly, this design enables us to test our response rate against the [ known ] hypothesis of 6.7%, requiring a minimum 33% response rate to demonstrate efficacy. The aim of our ASPIRE trial is [indiscernible] patients to support the potential broad label for TSHA-102 in individuals aged 2 years and older with Rett syndrome.

As Sean mentioned, we have dosed multiple patients in our REVEAL pivotal trial. Additional enrollment continues to advance across multiple clinical trial sites. We expect to complete dosing in REVEAL and ASPIRE in the second quarter of 2026. We maintain that the safety and efficacy data we have generated to date from Part A of our REVEAL trial are differentiating factors and believe our ongoing dialogue with the FDA over the last 2 years supports the potential of TSHA-102 to provide meaningful benefits to patients with Rett syndrome.

Looking ahead, we remain focused on our clinical trial execution and data generation as we work to complete patient enrollment and advance toward registration. We believe the thoughtful data-driven approach we've taken in designing and executing our pivotal developmental strategy position us to deliver as well as broad label on TSHA-102.

I would now like to turn the call over to Kamran to discuss financial results.

Thank you, Suku. Research and development expenses were $86.4 million for the year ended December 31, 2025, compared to $66 million for the year ended December 31, 2024. The $20.4 million 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 December 31, 2025 due to clinical trial activities in the REVEAL studies and BLA-enabling PPQ manufacturing initiatives.

General and administrative expenses were $33.9 million for the year ended December 31, 2025, compared to $29 million for the year ended December 31, 2024. The increase of $4.9 million 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 December 31, 2025, was $109 million or $0.34 per share compared to a net loss of $89.3 million or $0.36 per share for the year ended December 31, 2024.

As of December 31, 2025, Taysha had $319.8 million in cash and cash equivalents. During the fourth quarter, we raised an additional $50 million 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 plant 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 the 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 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. Operator?

[Operator Instructions] Our first question comes from the line of Kristen Kluska with Cantor Fitzgerald.

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'm curious, both from the clinician standpoint as well as the parent or caregiver, if there's one item on that list that's standing out more than others?

Yes. Kristen, thanks for the question. I would say that the support for IT, there were manyfold reasons why people wanted to go down that route. The most obvious is I think 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's not scary.

And I think the most interesting thing is people are taking what I think is a very pragmatic approach. They're basically saying, hey, listen, if the data -- the clinical data are going to be the most important thing. And if the data are, let's say, equal, then I'm going to go do the most least invasive approach I can for the person that I love for the very simple reason that it doesn't involve as much drilling Burr holes and going to the ICU and having a neurosurgeon involved. As they learn more about that, I think they're just like, hey, you know what, if all things are equal here at a minimum, then I'm going to take the safest, what I feel is the safest approach and the easiest approach.

I think from the clinical perspective, it's the same kind of a logic set where they're saying, listen, ultimately, it's going to be the clinical data that's going to carry the day. But based on what we know right now, it's easy for us to do this lumbar puncture. And when they start to talk about the practical logistics of the sites, just the throughput necessary for intrathecal delivery done in an outpatient is much easier to manage. You don't have to schedule suite time, surgeon time, things like that. So they're 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's a much easier route of administration to administer and provide great care to their patients. Hopefully, that helps.

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

Yes. We didn't get into -- we didn't explain to them, the biodistribution. They're basically making the leap that if I administer it that way and the clinical data are good, it's going to where it needs to go. Like they're not -- they don't care about biodistribution. They care about the fact that -- is my loved one going to get better or not. And they're judging that based on the clinical data, which -- the product profile is just the data that we've shown to date. So we feel very -- like we weren't 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.

Our next question comes from the line of Salveen Richter with Goldman Sachs.

With the appointment of Brad Martin as Head of Market Access and Value, what will the first priorities be in this role? And what are the key aspects of market access that Taysha will 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're looking for in terms of the efficacy profile?

Yes. 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 6 months of data on 5 of the 6 patients. So what we're planning to do in the Q2 update, you'll see data on all 12 Part A patients, and we'll 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're also going to give an update on the skills, the improvements. That's the data that we presented at CNS last year. You'll see the CGI-S, you'll see the R-MBA. So you'll get a very comprehensive picture of the data set. And what we hope to show is what we've 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 out 3 years post-dose. So we're starting to generate some nice durability data, which is fantastic.

As it relates to what the market access team is doing, there's a lot of steps to take, of course. We generally begin by making sure we're mapping out where the patients are and then what's the mix of the payers. So how much commercial pay is there, how much Medicaid pay is there. And then what we'll do is make sure from a site activation perspective, that we're thinking about the right way to roll this out.

So as an example, because of our market research and what we've seen on the route of administration, what's going to be really nice is that we're 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're comfortable with them and their institution doing that. So part of it is mapping all that out so that we've got a good sequence to the flow. And then 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've taken historically, Salveen, has been get in early with the payers, be very transparent about what type of -- what's the volume of patients that they could potentially see, educate them on the disease state and educate them on your data set and really just take them along on the journey. So we look to build relationships with the payers. And that's what -- the nice thing about Brad is he has those relationships. He's done this multiple times. And it's 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's no surprises on the back end.

Our next question comes from the line of Biren Amin with Piper Sandler.

Sean, I noticed that the company had a successful Type C meeting with the FDA this quarter on CMC for TSHA-102. So maybe on the BLA, PPQ lots that you're 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?

Biren, can you repeat the first question?

Yes. 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?

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

Yes. 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 6 months. That's when the blind would get broken. Obviously, we would -- that's going to be dependent on the last patient dose, right? So that's going to happen sometime in the second quarter based on everything that we're tracking to, which looks good. And then we have to adjudicate all that data. We have to make sure it's correct.

The next step, we would sit down with the FDA, go through that data with them and work to align with 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 don't want to say what the data are before we meet with the FDA is that, that's only half the story, right? So we think it's important to meet with the FDA. And I think there's 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 6-month data set. In which case, we would work to do that immediately.

So to be clear, what we're doing in the background, we're 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'd 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've always liked to see 12 months of data. We'd like to see 12 months of data." In that instance, we would make the case, well, okay, but then let's start the rolling submission because we've got all this other stuff done. You already know the primary endpoint has been met. You're looking for some additional time, okay. Now we would have made the case that the durability from Part A, which we can now pool, based on our recent update on CMC would help us with that case upfront on the 6-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'd be able to show is that the product works, you've met the endpoint, you've met the statistics of things. Now it's 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's based on the data that we showed and the early responses that we showed and the rigor in which the data were collected. So look, we've got a few good cards to play here, and we're looking forward to it as we step through 2026.

Our next question comes from the line of Tazeen Ahmad with Bank of America.

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 what you think that, if at all, it 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 don't think there is a read-through, based on what happened to Acadia. I think 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 something 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're generating is very unique. And really, no one has been able to demonstrate restoration of function in a neurodevelopmental disease before. And we're able to do that in multiple patients and across multiple clinical domains. And we've got natural history that is absolutely stellar. It's unequivocal. I think Jeff Newell's paper reinforces everything that we've done from a strategic perspective and supports our thesis on things.

And then if we're able to demonstrate, look what's happening with the primary endpoint and people gaining these milestones. But then beyond that, what we're trying to emphasize in the script is when you look at milestone gains outside the primary endpoint and you look at improvements that people are having, it's almost 20 per patient so far. That's based on what we reported last year. So it's a significant impact that you can't 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're 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.

So I mean, 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're generating is quite demonstrable. We're not having to talk about a scale. We're not having to talk about a 1- or 2-point change in the North Star or a 1-point change in the CGI. The payers don't care. The payers want to see functional gains. They want to see concrete improvements, and that's what's going to lead to getting you approved. I hope that helps.

Yes, Sean. And maybe just a quick follow-up on Europe again, usually, there's 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?

Yes. I mean I think we're 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're -- obviously, it's early days to get into what the actual price will be. But I think with where we sit and the data that we're capturing and the fact that it's happening across multiple domains and no matter what colo we're looking at, all the needles are moving in the right direction in a meaningful way. I think we'll be able to capture the appropriate value.

Our next question comes from the line of Maury Raycroft with Jefferies LLC.

Congrats on the progress. For the REVEAL Part A update in first half of this year, do you plan to provide a sub-analysis showing the proportion of patients that achieved more than 1 developmental milestone by 12 months? And are you planning to show any -- in your data update, are you planning to show any patient level data with vignettes? And if so, how are you setting expectations for a number of patients and milestone gains that you can show in that update?

Thanks, Maury. Yes, 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're 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's clear, and we'll share every endpoint that we're effectively capturing, you and the investors will get to judge the data and the probability of success in getting approved. So we think that's the most important thing. We think that's 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 and 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's tell you the story of what that looks like.

Now if I did that for 12 patients, we would be on the call for 5 hours. So that's why we don't want to go through all 12 patients. We just want to highlight a couple of things. And then again, based on the aggregate, you can say, "Hey, I like this data," or "I don't like this data." But we think that's the right way to go ahead and to portray it. Can you remind me the first part of your question about the Part A?

Yes, just some sort of a formal sub-analysis showing the proportion of patients that achieved more than one developmental milestone by 12 months.

We'll take that into consideration. We're still working on what the ultimate way to portray things. We've got a few ideas on how to get it. We've gotten some feedback from investors on what they'd like to see. So we'll take all that into consideration, and we look forward to that update.

Our next question comes from the line of Gil Blum with Needham & Company.

Allow me also to add my congratulations on the progress. Just a couple of ones from us. So as it relates to your recent update on the ASPIRE study, was this in line with prior expectations? Was it faster? Or this is just run of course here?

And our second question, it's good to see submissions using your RMAT designation of the CMC materials, which is a known issue in the space. Are you guys going to receive any feedback on what you've already submitted ahead of completing your filing? Or is this just going to happen later?

Okay. Let's 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 2 to less than 6-year olds. And the FDA came back and said, listen, I mean, the brain volumes of a 5-year-old and a 4-year-old are effectively the same as a 6-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 2- and 3-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 3 month, and they agreed with that. I don't know, Suku, if there's anything else you found interesting or -- about that whole thing.

No, what I would add to that, Sean, is that it's clear that the FDA is pretty comfortable with our safety and efficacy data up to the 6-plus age group, and they're going to let that data set to be used for the less than 6. And in that 2- to 3-year old, as you pointed out, because of the brain volume adjustment that's 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.

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

Yes. 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 it?

So I mean, I would put it [Audio Gap] we've got -- because of Breakthrough, we've got -- it's an additional way to get access to the FDA. So we do have our first Breakthrough meeting with the agency coming up, and there'll be more of those along the way. But we'll use that to have a discussion around potential BLA submission scenarios and working -- to get at your question, which is you've seen CMC, you've seen our preclinical, just working to gain alignment on the completeness of the packages that we've -- that we're putting together and what we shared with the FDA. So I think we're 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 deem that the clinical lot and the commercial lot were analytically comparable. Now that we've done more lots, they're continuing to say that. And now they're 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's the best you can possibly have right now. And I think that's an example of working closely with the agency. I know that they feel like there's nothing more on the preclinical side that needs to get done. It really is just generating that the pivotal data and the ASPIRE data are going to be the last aspects of the submission package.

Our next question comes from the line of Chris Raymond with Raymond James.

Just maybe a competitive 2-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 of weeks to the effect of the 6-month time endpoint is that -- they've gotten word from FDA that that's not clinically meaningful. And Sean, I think I've heard you say the difference here is you guys will have 12-month data from Part A to supplement, and that's kind of the difference maker. But I guess, is that the only difference maker? Or 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's an aspect that could be pretty important. You're 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 like both therapies are on the market at some point?

Yes. I can say that the research we've done to date show that about 50% of the Rett patients are associated with a center of excellence. That means that over the course of 1 year, there's 1 visit to the center of excellence. So that doesn't necessarily mean that it's the most convenient place for them to get the therapy. And put another way, there's 50% more patients outside of the COEs. So we think it's 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're able to map where are the patients, and then we're 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's 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's tag team the question on the meaningfulness of 6 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're generating in the first 6 months. And I think if those data are compelling from a clinical perspective, then the agency is going to take note.

Yes. What I would add to that, Sean, is that I haven't seen any data from Neurogene's initial studies that show that they have actual clinical efficacy in the first 6 months post dosing. And most of their clinical, in fact, appears to come much later, maybe 10 months post dosing. And usually, the FDA looks at proof of concept before they agree to an earlier analysis. And we have 6 month interim analysis from our Part A data that is more than convincing that allows them to say, yes, we can evaluate and bring that data set in for actual review and approval if necessary.

And then the second component is they always point 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 6-month interim analysis being given to us, while in that case, there may have been some pushback.

Yes. The other thing, too, just to highlight, Chris, Daybue got approved on 12-week data. So I think it's really just what is being demonstrated at a certain point in time, right. Hope that helps.

[Operator Instructions] Our next question comes from the line of Jack Allen with Baird.

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

Suku, we can tag team this. I would say, number one, Jack, there's consistency between Part A and Part B in that the severity of the patients is still a CGI-S between 4 and 6, right? We did -- one of the things we did -- we haven't 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's probably the most interesting aspect of things that you're looking at. Suku, do you want to talk about the enrollment and the progress that we're making?

Yes. So Jack, I mean, we have dosed multiple patients already. Multiple sites are active, and we are, frankly, I would say, have the potential to have more patients than we need to actually screen and dose. And we are well on time lines when it comes to dosing all 15 patients and actually having results, hopefully, for the 6-month interim analysis by the end of this year. I think that's where things are progressing at the present time.

Yes, Jack, I think one thing that's really important is that the training at the sites is super important, meaning we've created a stand-alone DMA, right? That's -- the developmental milestone assessment is our name for that. So it's -- call it, it's a new colo that we developed to standardize the data collection of the milestones. And the FDA was -- that was really where they spent the 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 couldn't do. And then you replicate that in a consistent manner every single time you conduct the DMA. So that's 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.

Our next question comes from the line of Yanan Zhu with Wells Fargo.

I wanted to follow up on the pooling of data between the Phase I/II and the pivotal study, given that, that sounds like something why you did -- that's why you did the manufacturing comparability study. So in what form will the data be pooled? Are we talking about a supportive data set separate from the top primary endpoint analysis? Or could the 2 study combine into 1 and give 1 number in the label? And then I have one additional question.

At a high level, I would say what the pooling allows you to do is multiple types of analysis, 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've got the ability to do that, though, does create the ability for you to support further, your package because you've got different, and I would say, additive analytics that you can utilize to support the package that you're making. I don't know what else you'd add to that, Suku?

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

Right. Congrats for the ability to do that. And my follow-up question is on expectation for the upcoming data update. Now with 12 months data on the milestones, what is the expectation for patients continuing to gain milestones between 6 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?

Yes, Yanan, we would expect that there are continuous gains that happen, continuous improvements that occur over the course of time. So that's what we would anticipate seeing in this data set. I would say in terms of loss of gains and things like that, it's not what you would anticipate. I can say that [Audio Gap] you can see something may not be demonstrated. Like if one of the girls has the flu or a UTI, it's very possible that they're not feeling well and they're not going to demonstrate something. It doesn't mean they lost it. And we -- I can just say in what we've reported on to date, we've never seen a loss of any gain. So we'll work to highlight that when we give the update in the first half.

Our next question comes from the line of Whitney Ijem with Canaccord Genuity.

I'm 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 can you -- any color you can give on that?

Yes, Whitney, there's really no math on the extrapolation. It was really just whatever you see in the 6 plus, that's going to get extrapolated into the younger age group. So that's where the alignment is with the agency. It's at a macro level.

And then on the second part of the question on the scaling, yes, I mean, it's a very consistent mathematical equation that you use from the preclinical to get to your human equivalent dose. And we'll be using that same calculation in the 2- to 3-year old. So Suku, I don't know if there's anything more you'd add to that?

All I would add, Sean, is that the calculation for the 2- to 4-year olds is essentially equivalent to the [ 1 in 15 ] dose from an efficacy standpoint when you look at our preclinical models.

Right. So in terms of what they're getting.

Exactly. Exactly. Yes.

That make sense. So a 2-year-old, even though they're getting less of a dose, it's equal to the 1 into the 15 in a larger person. So they're getting the same therapeutic...

Effect.

Effect. Right.

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.

Good day, everyone and welcome to The Taysha Gene Therapies Third Quarter 2025 Earnings Call. [Operator Instructions] Please note, this call may be recorded and I will be standing by if you should need any assistance.

It is now my pleasure to turn the conference over to Hayleigh Collins. Please go ahead.

Thank you. Good morning and welcome to our Third Quarter 2025 Financial Results and Corporate Update Call. Earlier today, Taysha issued a press release announcing financial results for the third quarter ended September 30, 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'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 submissions; timing or outcomes of 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 regulatory agencies; our ability to realize the benefits of Breakthrough Therapy designation for TSHA-102; and the market opportunity for our programs.

This call may also contain forward-looking statements relating to Taysha's growth, forecasted 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 December 31, 2024, that we filed February 26, 2025, and our quarterly report on Form 10-Q for the quarter ended September 30, 2025, that we filed today.

This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 4, 2025. 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 laws.

With that, I would now like to turn the call over to our CEO, Sean Nolan.

Thank you Haley and welcome everyone to our third quarter conference call. I will begin with an update of our recent corporate activities and progress across our TSHA-102 Rett syndrome program. Suku will then discuss the new supplemental analysis from Part A of our REVEAL Phase I/II trials. Kamran will follow up with a financial update, and I will provide closing remarks before opening the call to questions.

In the quarter, we believe we made meaningful progress that sets the stage for what could be a transformative period ahead for Taysha. The recent regulatory clarity and progress we've achieved, which was enabled by the strength of our REVEAL Part A data set, rigorous data evaluation methodology, and our natural history data analysis allows us to focus on executing our REVEAL pivotal trial and advancing towards BLA submission with clarity and confidence.

A major milestone was the receipt of FDA Breakthrough Therapy designation for TSHA-102 at the end of September. This designation is designed to expedite the development and review of therapies for serious conditions that have demonstrated preliminary clinical evidence of substantial improvement over available treatments in one or more clinically meaningful endpoints. TSHA-102 received Breakthrough Therapy designation based on the FDA's review of available safety and efficacy data from all 12 pediatric, adolescent, and adult patients treated with TSHA-102 in Part A of our REVEAL Phase I/II trials, including clinical data from the previously disclosed May 2025 data cutoff.

Receiving Breakthrough designation highlights the FDA's recognition of both the significant unmet medical need among the 10,000 patients suffering from Rett syndrome in the U.S. and the therapeutic potential of TSHA-102 to redefine the treatment paradigm for this devastating disease. Notably, over 80% of programs with Breakthrough Therapy designation that proceeded to file for approval have ultimately received FDA approval. We look forward to continued engagement with the FDA as we advance toward potential registration.

In September, we finalized alignment with FDA on our REVEAL pivotal trial protocol and statistical analysis plan in support of our planned BLA submission for TSHA-102, following resolution of remaining clinical and statistical queries. Importantly, our previously aligned-upon key design elements remain unchanged. In line with FDA's guidance for cell and gene therapy programs that was issued in September, we believe that the prospectively aligned by -- that by prospectively aligning with FDA on the statistical analysis plan for our pivotal trial helps ensure that the data set collected will be considered reliable and suitable for BLA submission. We are enrolling 15 patients in the developmental plateau population of Rett syndrome with a primary endpoint of response rate which is defined as the percentage of patients who gain or regain one or more of the 28 natural history defined developmental milestones.

A response rate of 33%, equivalent to 5 out of 15 patients, is the minimum threshold for success sufficient to achieve our primary endpoint. Notably, we've observed a 100% response rate across the 10 patients in Part A of our REVEAL trials. Additionally, we aligned with the FDA on a 6-month interim analysis that may serve as the basis for BLA submission, potentially accelerating our planned BLA submission by at least 2 quarters.

As previously disclosed, the data from Part A of the REVEAL trials demonstrated an 83% response rate at 6 months post treatment, with 5 of the 6 patients treated with the high-dose TSHA-102 achieving a developmental milestone. We observed a consistent pattern of sustained milestone gains with a deepening of effect or additional milestone gains over time. By 9 months post treatment, the data demonstrated a 100% response rate across the 6 treated high-dose patients in Part A. We believe these data support both the suitability of the 6-month time point to demonstrate clinically meaningful efficacy and that the 6-month efficacy data may be representative of treatment effects at 12 months. We believe this enabled our alignment with FDA that a 6-month interim analysis may serve as the basis for BLA submission.

It's important to understand that we believe we received Breakthrough Therapy designation and achieved FDA alignment largely due to the results of the rigorous clinical evaluation methodology applied to our video-evidenced developmental milestone data from Part A of the REVEAL Phase I/II trials. In Part A, videos were centrally rated by multiple independent reviewers using milestone definitions from the pivotal trial protocol to ensure an objective, consistent evaluation of milestone gain and regain in the developmental plateau population where these gains are not expected to spontaneously occur.

By adhering to rigorous milestone evaluation criteria based on natural history, this approach minimizes bias and avoids overcounting milestones by ensuring the milestones are truly eligible for gain or regain. As a result, this provides a reliable reflection of TSHA-102's disease-modifying therapeutic effect and ensures that the pivotal trial is well powered to demonstrate efficacy. We will continue to have frequent and consistent interactions with the FDA.

We presented our REVEAL Part A data from the May 2025 data cutoff, including the new supplemental analysis, which provides supportive evidence that further reinforced TSHA-102's consistent, multidomain impact on activities of daily living at the Child Neurology Society Annual Meeting in October. Suku will discuss these results shortly.

With the strength of our Part A clinical data and a clear FDA-aligned path to potential registration, we believe we are strongly positioned to initiate our REVEAL pivotal trial and accelerate execution towards BLA submission. Dosing of the first patient in our REVEAL pivotal trial is scheduled and on track for this quarter, with additional patient enrollment expected to continue across multiple sites this quarter.

On the heels of our strong clinical and regulatory progress, we are thrilled to have regained full global rights to our TSHA-102 Rett syndrome program. We regained these rights in October following the expiration of our 2022 option agreement with Astellas, which had granted Astellas an exclusive option to enter into a negotiation period to license TSHA-102 and certain rights with respect to change in control transactions. We appreciate the collaborative relationship we've had with Astellas and the unencumbered rights to TSHA-102 that we now hold enable us to focus on driving long-term value with full strategic flexibility and optionality. We continue to build out our infrastructure to support advancing TSHA-102 toward late-stage development and potential commercialization, if approved.

This September we strengthened our commercial leadership team with the appointment of David McNinch as Taysha's Chief Commercial Officer. David brings over 2 decades of experience in global commercialization and strategic market development across multiple therapeutic areas. Most recently he served as Chief Business Officer at Encoded Therapeutics, where he led the commercial and partnering strategy across the company's gene therapy portfolio. He previously held senior commercial roles at Prothena as well as InterMune, where he led the launch of Esbriet, the first FDA-approved treatment for idiopathic pulmonary fibrosis, and supported the company's acquisition by Roche.

David reports to Sean McAuliffe, Taysha's Chief Business Officer. Previously at AveXis, Sean led the development and execution of the commercial launch of Zolgensma for spinal muscular atrophy, the first FDA-approved gene therapy for the treatment of a monogenic CNS disease, which has reached blockbuster status. With an estimated 15,000 to 20,000 patients with Rett syndrome across the U.S., EU, and U.K., compelling clinical data from Part A of our REVEAL trials, and a minimally invasive, commercially advantageous delivery approach, we see a significant opportunity to address a profound unmet medical need and drive long-term value. We believe our strong balance sheet, team with proven gene therapy experience, and the clear path to registration strongly position us to initiate our REVEAL pivotal trial and accelerate execution toward BLA submission.

I will now turn the call over to Suku to discuss our clinical progress in more detail. Suku?

Thank you, Sean. As Sean mentioned, the regulatory progress we've achieved to date was enabled by the strength of our REVEAL Part A data and our natural history data analysis that allows us to objectively measure developmental milestone gain and regain in the developmental plateau population using each patient as their own control.

At the Child Neurology Society Annual Meeting in October, we presented a comprehensive review of our Part A data set using the evaluation frame point and endpoints of our pivotal trial. As previously reported, 100% of the 10 patients in Part A achieved 1 or more natural history-defined developmental milestones following treatment with TSHA-102, with a consistent pattern of early gains that are sustained and new achievements continuing to emerge over time following TSHA-102 treatment. These milestones were all video evidenced and assessed by independent central raters according to the definition of milestone achievement from our pivotal trial protocol. These criteria enabled a reliable, objective, and consistent assessment of TSHA-102's efficacy, and importantly, show that our pivotal trial is well powered to establish the therapeutic impact of TSHA-102.

Additionally, we presented a new supplemental analysis of REVEAL Part A data that captured supportive evidence of additional skill gains and improvements outside of the 28 natural history-defined milestones. These gains are derived from the Adapted Mullen Scales of Early Learning, the Revised Motor Behavior Assessment or RMBA, and the observer reported communication ability assessment, which are Rett-validated, structured assessments that evaluated prespecified skills and quantifiable improvements. The results show that in addition to the developmental milestones achieved across the treatment cohort in Part A, patients consistently gained multiple additional skills and improvements in core disease characteristics across the domains of autonomic function, communication, fine motor, and gross motor areas. We believe these findings reinforce the consistent, broad therapeutic impact of TSHA-102 on activities of daily living that are important to caregivers and clinicians.

As we continue to prioritize safety, I am pleased to share that TSHA-102 continues to be generally well tolerated, with no treatment-related serious adverse events or dose-limiting toxicities across the 12 pediatric, adolescent, and adult patients treated with the high and low doses of TSHA-102 in Part A of our REVEAL trials as of the October 2025 data cutoff. We are encouraged by the data we've collected from Part A of our REVEAL trials, which we believe support the potential of TSHA-102 to provide meaningful benefit to children, adolescents, and adults living with Rett syndrome. We look forward to reporting longer-term Part A clinical data in the first half of 2026.

I will now turn the call over to Kamran to discuss financials. Kamran?

Thank you, Suku. Research and development expenses were $25.7 million for the 3 months ended September 30, 2025, compared to $14.9 million for the 3 months ended September 30, 2024. The increase was driven by BLA-enabling process performance qualification, or PPQ, manufacturing initiatives, REVEAL clinical trial activities, and higher compensation expenses as a result of increased headcount during the 3 months ended September 30, 2025.

General and administrative expenses were $8.3 million for the 3 months ended September 30, 2025, compared to $7.9 million for the 3 months ended September 30, 2024. The increase of $0.4 million was primarily due to debt issuance costs incurred in connection with the refinancing of our existing loan and security agreement with Trinity Capital that are recorded in general and administrative expense under the fair value option and was partially offset by lower legal and professional fees. Net loss for the 3 months ended September 30, 2025, was $32.7 million, or $0.09 per share, compared to a net loss of $25.5 million, or $0.10 per share, for the 3 months ended September 30, 2024.

As of September 30, 2025, Taysha had $297.3 million in cash and cash equivalents. We expect that our current cash resources will support planned operating expenses and capital requirements into 2028.

I will now turn the call over to Sean for his closing remarks. Sean?

Thank you, Kamran. With Breakthrough Therapy designation and finalized FDA alignment, together with our strong balance sheet and full strategic control of TSHA-102, we believe we are entering the pivotal phase of development with focus and confidence in our ability to redefine the treatment landscape for Rett syndrome while driving long-term value. We remain on track to dose the first patient in our REVEAL pivotal trial with additional enrollment expected at multiple sites this quarter. Additionally, we expect to report longer-term clinical data from Part A of our REVEAL Phase I/II trials in the first half of 2026. We look forward to providing further updates as we initiate our REVEAL pivotal trial and advance TSHA-102 towards BLA submission.

I will now ask the operator to begin our Q&A session. Operator?

[Operator Instructions] We'll take our first question from Kristen Kluska with Cantor.

Just curious, this time around in the pivotal trial, you have a lot more evidence going for you. So can you talk about the pipeline of interest and demand for being in this trial and then your thoughts about how long it could take to fully enroll?

Kristen, thanks for the question. I would say unequivocally that the demand to be in the trial is exceptionally high. I think the fact that we've been relatively consistently putting out both safety and efficacy data as we have maturation occur in the study and keeping close contact with the advocacy group, centers of excellence, and KOLS has led to a strong demand.

So with that as a backdrop, let me just turn it over to Suku to give a little bit more flavor and then maybe just give time line parameters around when we expect enrollment could potentially take.

Thanks for that question, Kristen. So as Sean highlighted, we have multiple sites -- more than 15 sites identified for our clinical trials program Part B. All of these sites are at centers of excellence. And very interestingly, many of these sites have 100-plus patients per site who have the diagnosis of Rett syndrome. And many of these patients could qualify for a Part B trial. And this includes pediatric, adolescent, and adult patients who will be part of the process.

Now furthermore, let me highlight that in the best case scenario, we could potentially enroll and recruit all 15 patients within a 3-month time period, and a more conservative time line could be between 3 to 6 months. And as I said, many of these sites already have multiple patients identified. And there's significant interest in our gene therapy program due to the efficacy already and safety already disclosed in the Part A trial and the ease of route of administration that we have to deliver a gene therapy that already shows significant clinical impact. Thank you.

Yes. And maybe just one more thing to add. We highlighted it in the press release. But to Suku's point, we've got dosing schedules for the first patients already scheduled this quarter, and we expect other patients to enroll at multiple sites this quarter as well. So I think that speaks to both the demand and the alacrity at which the sites have worked to initiate the pivotal trial.

And Kristen, one more point I should emphasize is many of these sites may be able to dose more than 1 patient in a staggered parallel fashion. So we might be able to get 1, 2, or 3 patients 2, 3 weeks apart at some of these sites, which would further accelerate our timelines and hopefully make the submission of the BLA time line even shorter and make this product available to deserving patients who have Rett syndrome.

Our next question comes from Salveen Richter with Goldman Sachs.

I was just wondering if you could touch on expectations for the longer-term data in the first half of next year and also help us understand in the context of your discussions with the FDA what they have signed off on in terms of that minimum threshold for success here that's sufficient for filing.

Thanks for the question, Salveen. For the first part of the question, relative to what updates will we give in the first half of next year, I think it'll be consistent with what you've seen. As the data matures, we've tried to look at things as a full cohort. So ultimately we want to get to, we have all 12 patients at 12 months, and I think that'll be very important data to look at relative to the 6-month time point, where are we at 12 months with these patients. And so we'll do that.

In addition to that, I think it's important to continue to provide updates relative to the safety profile. So we want a little bit of flexibility here that we could potentially give an update in the first quarter with almost 12 months of data, we could do -- we could wait for the second quarter, but we want to -- we just want to make sure that the market is aware of the fact that we do plan to give further updates both in terms of safety and efficacy that we think will be very enlightening and informative relative to the predictability of the approval of the pivotal trial. So that's number one.

Number two, as it relates to FDA alignment, we highlighted in the script and I think it's really important that back in September the FDA put out guidance that's very consistent with everything we've done to date in our interactions with them, which is very specifically, they want alignment on your SAP before you start your clinical trial. Like that is the highly recommended path to take. And that's exactly what we've done. We submitted the SAP going back as far as January. When we got the okay to go ahead and submit the final SAP and the clinical protocol by the end of the second quarter without an end-of-phase meeting, we did that. We've answered all the then subsequent queries from the statistical analysis plan question and clinical questions. And we actually even reached out to the FDA because we had believed we'd answered all their questions, and we sent them a note and said, "We just want to confirm that there's no other outstanding statistical or clinical questions." And they said, "Confirmed."

So we feel everything that we've just presented with the [ NF15 ], the threshold of a responder being the gain or regain of 1 milestone and crossing the threshold of having a 33% response rate, all ties to the statistical plan that we've submitted. So we feel we're very much in alignment with the FDA. And the other thing I would just note is that per the FDA's internal SOPs, these milestone meetings where you're talking about the final protocol, the SAP internally, the Directors are at those meetings. So I can't give you specific names who are there, but that is the protocol. So we feel, again, supremely confident at this particular point in time. We've done everything that this FDA has asked us to do. We've been in full alignment with them the entire way. And I would argue, we were in full alignment with the Peter Marks regime as well. And I think that's all because of the integrity of the data and the quality and rigor of the data collection that we've put forward. So we think we've checked all the boxes, we've double checked, and we're told we're good to go. And that's why it's full steam ahead on patient enrollment right now.

Our next question comes from Tazeen Ahmad with Bank of America.

I wanted to get a little bit more color on how you're thinking about the way we should all be thinking about the data from the younger patients, meaning the 2- to 6-year-olds, relative to the 6-plus-year-olds as it relates to efficacy in particular. And then on safety, should we be expecting to see a staggered release of safety data on that younger population relative to the older population? Basically, when could we expect to see data start to come in from that cohort base?

Thanks for the questions, Tazeen. Number one, I think the headline is our goal is to ensure that by the time we submit the BLA under any circumstance that these 2- to 5-year-old population is included in that, so that we would have a very broad 2-plus label effectively. And so the way we're stepping through that is this quarter we'll be having dialog with the FDA. We've submitted the protocol to them, so we'll be getting some feedback on that. It is a safety focused study. We have had discussions with the FDA, formal meetings with the FDA, where we've basically made the following request, that for this population, we want to establish safety, number one. We will collect some efficacy data, of course, but what we proposed was that we could extrapolate efficacy from the 6-plus population and that that would be sufficient for getting this younger group into the label. And the FDA agreed to that.

So that's how we're going to step through it. We would anticipate beginning to dose these patients once we have alignment with the FDA, probably towards the middle of 2026. Again, because it's safety, we think the trains will align on time in terms of BLA submissions, and then we'll follow efficacy over the course of time in this patient population to see if there's things that are unique there. And if appropriate, we could certainly update the label with any new data we have. But again, to just restate the primary goal is that, at approval you would have a label of 2-plus with no specific constraints relative to efficacy that's been collected. It's the full population that you're getting approval on.

Our next question comes from Gil Blum with Needham & Company.

So maybe just another one on protocols here. How much leeway do you think the agency provides regarding the method of video review and is it fair to assume that all companies in the space receive the same guidance on that?

Yes, Gil, I would say in our experience, the most time we spent in dialog with the FDA was around the rigor of the data collection for the primary endpoint. They were very much focused on how we were going to do that, that there was high fidelity in the data, and that there was high inter-rater reliability. And in fact, what we did to further bolster our case with the FDA is we actually ran a pilot at multiple sites testing the DMA with multiple central raters, and we submitted that as part of our data package to get the protocol approved and also in the Breakthrough Therapy package as well.

And so all I can say is that like anything, you're as good -- in our space, you're as good as the data that you're collecting. FDA was super focused on that. So I'm assuming anyone going into a pivotal trial would be held to the standard of a minimum of video evidence and having it centrally adjudicated. I think the question is have you run the experiment and do you know that the methodology you're employing is going to give you the result that you anticipate. And what we feel good about is we've run that result. We've collected the data from our Part A study, and we've done central raters with that. But then the pilot study, which you really haven't talked too much about, but we ran that in the background again at multiple sites, and that gives us the confidence, and hopefully gave the FDA confidence that what we're putting forward is highly rigorous, high-end fidelity, and high-end inter-rater reliability.

Our next question comes from Biren Amin with Piper Sandler.

This is [ Michael ] on for Biren. Are there any updates on your plans in Europe or discussions with the EMA on the applicability of Part B? And separately, is the bar for the interim analysis similar to that for the final 12-month analysis?

Thanks, Michael. Thanks for the question. First and foremost, our focus has been and will be on the U.S., number one, two, and three. That's the biggest market out there. We've been historically resource constrained, both financially as well as human resource capital wise.

We're in a better position now, but we've really worked to make sure that we are as aligned as possible, with the highest probability possible to get things approved as safely and as quickly as we can in the U.S. We will continue, and what we've been doing, Michael, with, with Europe and the U.K. is working to enable them, so stepping through regulatory dialogs and things of that nature. We think that as we further generate data in Part A and also get into Part B, that will further inform those discussions and will give us even clearer line of sight to what the options we have.

We know we're going to have multiple options to go into Europe. There's some that we've taken in the past that would be the most efficient and make the most sense for all parties involved. We want to see if we can work to enable that.

The other thing too is from a policy perspective, I think, we all know the challenges on both sides of the pond. We want to make sure we focus here at home and lock in those things. And we can also take the time while we're collecting the data to see how policy also shakes out from an ex-U.S. perspective as well. So the long-term goal is to enable Europe for sure. It's just a question of stepping through it in a very thoughtful manner.

Our next question comes from Maury Raycroft with Jefferies.

Congrats on the progress. Wondering if you'd tell us anything additional about timelines for IRB approval for the additional 2 to 5 sites that you'll need for the pivotal. And just when thinking about enrollment for this study, is there anything more you could say about number of patients you could potentially have enrolled by end of this year? Just helping provide some line of sight to potentially getting to data from the pivotal by the end of next year.

Yes, Maury, it's a great question. I think we can provide more information in either Q1 or sometime in the springtime, I think, as we have better line of sight. Again, just from how we're stepping through it, we've submitted protocol to the FDA, we've got a -- waiting for their feedback on that. That'll certainly inform things. We're doing -- I would say, contextually, we're doing for the pivotal trial, 15 patients. This is a smaller subset of patients. So we would anticipate the number of patients to be less than 15 in this study. I think that from a IRB perspective, it will be a new protocol.

So it'll have to go through the process of contracting IRB approval, ethics, all the things that you have to do. I can tell you that there are, as you would anticipate, multiple sites, of course, that want to be a part of this. So I don't think that's going to be an issue. We just want to make sure that, number one, we get alignment first and foremost with the FDA on the protocol and the associated statistical plan that we're putting forward. And then number two, that from an operational perspective, we're doing things in a manner that is most efficient and doesn't by any way impede the enrollment of the 6-plus population.

So the way we see this, based on the fact that the primary endpoint in the little kids study, is safety -- we think the 2 trains are going to come back together. And again, just to make the point that we do anticipate including that data along with the 6-plus pivotal data in the BLA submission with the goal of getting a broad label.

Our next question comes from Jack Allen with Baird.

Congrats on all the progress made over the course of the quarter. I guess my first one was on the broader sentiment of the FDA. There was quite a bit of news over the weekend and Monday morning [ driving ] CBER and some changes outside CDER. And I just wanted to get a sense for any thoughts that the team has as it relates to management interactions with the agency, whether the agency is functioning as expected and what your plans are going forward to interact.

And then briefly on the younger patient cohort, I also wanted to ask about how you're thinking about dose. As you go into younger patients, you could theoretically increase the relative exposure if you're treating smaller patients with a fixed dose. I'm just curious if you have any plans to address that potential issue.

Yes, Jack, let me start with the second part of your question on dose. It's going to be 1x10 15 total vg, but we're going to adjust for brain volume. So we want to make sure that none of those younger kids get any more dose on a per-kilogram basis than anyone we've dosed so far safely. So we've given that a lot of thought. The clin dev team has done a super job. Again, we've got that in front of the FDA. So we're being very thoughtful about that safety perspective. So more to come on that once we have the protocol finalized.

As it relates to the FDA, what we can point to is a couple of things. And I said this earlier. We had good alignment with Nicole Verdun. Nothing that we've changed -- we've done nothing since the new regime's been in that's different in terms of our natural history assessment, our proposed endpoints, et cetera. And I've used this term before, but no one has pushed us off the ball. And the reason we believe that is because we have levered data collected in a very rigorous manner to make our case with the FDA.

Number two, the approach that we're taking is exactly what the FDA wants. So that's why we referenced this FDA guidance from September where they're basically saying, "Hey, [indiscernible] for gene and cell therapies, we want alignment on your protocol and your SAP before you start the study."

So what are we doing? We've taken our first-in-human study. We've learned from that. We've done the natural history analysis. And now what we're saying is, based on what we've learned, we're going to propose a prospective pivotal trial with the following endpoint and the following statistical analysis plan. And we've worked with the FDA to get that into a situation where they've signed off on that. So we've done exactly what they wanted.

Our understanding is any of these milestone meetings like signing off on a protocol or Breakthrough designation, which I can talk about in a second. But internally the Directors are in those meetings. So we've checked and double-checked to make sure we're not misinterpreting things. We've gotten confirmation of that. We feel like we've done everything that the FDA has asked us to do.

And more importantly, we're not asking them to do something that's out of course. What we're not doing is we're not taking the Part A data and saying, "Oh, you know what, we want you guys to go back and we're going to propose now that we're doing a DMA, and we're going to do these developmental milestones. So we want you to approve our data based on a statistical plan we put in front of you after the fact." That is not something that we've done. We're taking a more traditional approach and starting a new study. Suku wants to add some information?

Yes, one thing I would add, Sean, is that under Dr. Vinay Prasad and Vijay Kumar's current leadership of CBER, they have -- their team has followed the spirit of the RMAT designation in CBER and the Breakthrough designation that we have achieved. So our interactions have been very fluid and very constructive and very useful. So I just wanted to emphasize that.

Yes, I mean, Jack, one last thing on Breakthrough to the point Suku is making. The internal SOP at FDA for Breakthrough is that when a Breakthrough request comes in, the Directors are made aware of it. They then send it to the review team and assign them to review it and let them know the recommendation. And so that means that eyes are on things. And again, we've done the best that we can to be data driven in all of our requests.

And therefore, again, we feel the fact that the Breakthrough was granted in September under this current regime in the manner that they like. We've followed their guidance that they've issued in September in terms of protocol for pivotals as well as SAP. We've tried to step through it in exact manner that they want and, I would argue, the exact manner based on data that any administration would want. So that's why I went back into the Wayback Machine with the Peter Marks' group. But it is important, and I do think it's relevant, to say they agreed with what we were doing as well, based on the way that we were going through it. So I've always said data drives -- is the currency of the realm. And we believe that's the case.

We're just going to keep moving forward and be as transparent as we can with the agency. And as a result of having Breakthrough, we now can set up even additional meetings with them, which we've already done, to start to talk about BLA submission process and things of that nature.

Our next question comes from Chris Raymond with Raymond James.

Just a couple of commercial questions here maybe. So you're starting the commercial buildout now with the hiring of a Chief Commercial Officer. Maybe talk about the footprint you'll need, how it will look, and maybe the milestones that we should expect in terms of, I guess, access progress. And then maybe a related question. Of the 28 developmental milestones, are there any that you think matter more, be it communication, fine motor, or gross motor milestones in terms of clinical acceptance among the physician community, or in terms of ease of access that we should be thinking about?

Yes. I think to start with your second question, all of the 28 milestones that we selected, we did in concert with KOLs and with the advocacy community. So if you were talking to some of the KOLs, they would talk about higher order milestones. So there's 51 milestones, Chris, in the natural history database. You'll hear like that language, because these are the milestones that, from a clinical and from a functional perspective, really do matter across the 3 different domains. So I wouldn't say anyone rises to the level more than anyone else. It's all relevant to the particular situation of each individual patient. I will say that when you talk to the parents communication is top of mind with them.

They want to know what hurts, what do they want, are they hungry, how can they make them feel better, those kinds of things, which make a lot of sense. But that's why we feel we've reached that agreement with the FDA that any 1 of those 28 is relevant. And I think what we're also trying to show is that over time, not only are there more milestones being gained of the 28, but the whole purpose of the supplemental analysis was to show that outside of that -- the 28 are a mechanism for us to get approval, but outside of that, in multiple scales, whether it be done from the clinicians or rated independently like the Mullen or the ORCA, which is the parents and what they're saying that they're noticing. The point of that was to say, beyond the 28 that we've talked about, there's a lot of other things happening that are great. And we're seeing good things, the parents are seeing things, the clinicians are seeing improvements in function, and all of that is going to be what we put forward to the FDA in the final package and would also be part of what we discuss with payers. Suku?

Yes, thanks, Sean. And one more thing I would add is that -- Chris, is that as our trial design is patient as their own control, every milestone matters. So it doesn't matter what the milestone is out of the 28, to the patient, to the parent, or the caregiver, all of them actually matter, and all of them have impact on activities of daily living. And given our Part A data set, my hope as a physician and clinician is that there will be no patient left behind over time as we gather more data from Part B.

Yes. And then the first part of your question, Chris, about commercial, I'd say a couple things. First, you're definitely on the leading edge of the curve here. We think starting in the first quarter, we really are going to put more color around how we see the commercial opportunity. I think, for starters, it really is underappreciated how large the patient population is. So we're doing a lot of work relative to claims data analysis and things of that nature to put finer points on things. We're also looking at the launch of Daybue. That's going to be a good surrogate for potential uptake.

And the more that we're digging into things, the more robust we think the opportunity truly is, particularly in a situation where the data set that we're going to be able to discuss with payers and also get the treating clinicians and the families hopefully excited about what they're seeing is that no one's been able to demonstrate functional gains before in a neurodevelopmental disease, even in adults. So that opens up a really significant opportunity. And we also have known from the get-go that using CGI (sic) [ CGI-I ] and RSBQ and those type of scales is going to mean absolutely nothing to the payers. They do not care what a CGI (sic) [ CGI-I ] score actually is. They want to know what they're paying for. And what they're going to be paying for is going to be improvements in function or gains of function that haven't been demonstrated, which is why we feel so strongly that this endpoint for a gene therapy is the right way to go.

An example is in Canada, the HTA denied Daybue being reimbursed because they couldn't determine the clinical relevance of a 0.3 change in CGI (sic) [ CGI-I ]. So again, I think we're going to be on really strong ground with the data set that we're putting forward in a very significant patient population. And the other thing I'll say just in terms of the team, David McNinch is our new Chief Commercial Officer. He's got a ton of experience. He and I work together at InterMune on the launch of Esbriet, which was a big success. David was also recently at Encoded. He knows gene therapy very well.

He reports to Sean McAuliffe, who's our Chief Business Officer. Sean was on the Zolgensma launch team. So we've got a very stacked group internally and, I would say, on the Medical Affairs team, our Head of Medical Affairs, Alain, ran Med Affairs in Canada for Acadia. So we feel like the field team and the commercial team, call it, the external-facing group, we've got just a stellar all-star team, and we'll continue to put out more perspective on that as we generate the data and move towards the BLA submission. Great question.

Our next question comes from Yanan Zhu with Wells Fargo Securities.

Wanted to dig into the statistical plan a little bit. Thanks for all the color so far on the call regarding alignment and the FDA. Given that the trial design is novel and there is not an external control arm, per se, wonder how the p-value is derived. And also in terms of the interim analysis, how unambiguous or subjective the threshold is for triggering filing based on interim? In other words, do you run any risk if you file on interim? Just wondering with regard to the actual data and the p-value in making that decision.

So that's a good question. I'll try to answer that for you in very simple, straightforward terms. So the evaluations are not subjective, they're actually quite objective, because remember, we have a natural history that is very tightly analyzed and the FDA accepted our natural history analysis. But it's very clear once these patients get above 6 years of age, they do not gain new milestones, or they do not regain milestones. And our evaluation process for achievement of new milestones or regain of milestones is video recorded. And as Sean has pointed out earlier, it's very rigorously evaluated by blinded central reviewers. And there are different reviewers for the 6-month interim analysis as well as the 12-month interim analysis. So you have to keep that in mind as well.

Now remember, also the 6-month interim analysis, all 15 patients dosed have to reach that 6-month time point before we break the blind on the video evaluations and before we share the information or the data with the FDA for potentially filing on the BLA as we complete the study at 12 months. And that data set will also be available at the final filing of the BLA. So what we do is by the 6-month interim analysis process, we have the opportunity to shorten the time line of filing of the BLA by two quarters more. So again, the 6-month interim analysis also does not really have significant impact on the p-value nor the power of the study, given that the loss of the alpha is actually minimal, and it's a 33% responder rate is all that's needed really to meet our primary endpoint, whether it's a 6-month or 12-month analysis.

And keep in mind that usually none of these patients at 6 months reach a new milestone or regain a lost milestone. Therefore, any milestone gained even by 1 patient is miraculous. So I will leave it at that. From a clinician's perspective, I think we have something that I hope that we can gather the data quickly and get our data set to the FDA so that we can make this therapy available to patients as soon as possible. I hope that answers your question, Yanan.

Our next question comes from Joon Lee with Truist Securities.

This is Mahdi on for Joon. So the question is, I just wanted to ask you to please remind us what is the actual definition of regaining again. And assuming that at the 6-month interim data is positive, how soon you can start filing for BLA?

Yes, thanks for that question. So this is Suku, and I'll respond to that question because it's -- thanks because it's important that it's clearly defined and the audience understands what it means. So remember again, natural history, once patients with Rett syndrome reach the age of 6 and above, they do not regain a lost milestone. So I'll give you an obvious one.

Let's assume a patient before 6 years of age with Rett syndrome can sit up without support and they lose it completely and now cannot sit up without support. Post treatment with TSHA-102, our gene therapy through lumbar puncture, if that patient now again is able to sit without support, that is a regain of a lost milestone. A gain of a new milestone is something where the patient before the age of 6, for example, can never use their fingers due to significant stereotactic movements and therefore cannot pick up a teaspoon or a cup to feed themselves. Post treatment, this milestone is now achieved where the patient can actually use their fingers, which they've never done before, can pick up a spoon or a cup and feed themselves. That is the gain of a new milestone.

So it's very almost black and white, which actually makes it very easy both for the clinicians who are evaluating the patients, the video reviewers who are blinded, as well as when the FDA hopefully sees our videos, it will make it obvious that our product actually works. And keep in mind that this entire process of video recording, central raters, blinding, et cetera, came from our AveXis experience many years ago. And we have most of the team here at Taysha that will continue to execute on this program and hopefully reproduce what we were able to do for SMA population using AVXS-101, which is now Zolgensma.

It appears we have no further questions at this time. I'll turn the program back to the speakers for any additional or closing remarks.

We appreciate everyone taking the time this morning to join us. Have a good day. Thank you.

This concludes today's program. Thank you for your participation and you may disconnect at any time.

[Operator Instructions] Ladies and gentlemen, good morning, and welcome to Taysha Gene Therapy's Second Quarter 2025 Earnings Conference Call. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Haleigh Collins, Director, Head of Corporate Communications. Please go ahead.

Thank you. Good morning, and welcome to our second quarter 2025 financial results and corporate update conference call. Earlier today, Taysha issued a press release announcing financial results for the second quarter ended June 30, 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's Chief Executive Officer; Sukumar Nagendran, President and Head of R&D; Kamran Alam, Chief Financial Officer; and Dr. Elsa Rossignol, Director of the Integrated Rett Syndrome Clinic at St. Justin in Montreal and principal investigator of the REVEAL Phase I/II trials. We will be presenting slides to accompany our prepared remarks today, which will be available on our website after the call. We will host a question-and-answer session following our prepared remarks.

Please note that Dr. Rossignol will be available to take questions until 9:20 a.m. Eastern Time, after which she will be stepping away for her clinic commitments. 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 and to our other product candidates 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 submissions; timing or outcomes of communications with the FDA in Health Canada on the regulatory pathway for TSHA-102 the potential for product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies and the market opportunity for our programs.

This call may also contain forward-looking statements relating to Taysha's growth, forecasted 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 we face, please see the reports we filed with the SEC, including in our annual report on Form 10-K for the full year ended December 31, 2024, that we filed February 26, 2025. Our quarterly report on Form 10-Q for the quarter ended June 30, 2025, we filed today. This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast, August 12, 2025. Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this 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, and welcome, everyone, to our second quarter conference call. I will begin with an update on our recent activities and regulatory progress for our lead TSHA-102 Rett syndrome program, including new details of our FDA-aligned pivotal trial design and our registrational pathway. Next, Suku will discuss our natural history data analysis, which underpins our REVEAL pivotal trial design. I've invited Dr. Elsa Rossignol, Director of the Integrated Rett Syndrome Clinic at St. Justine in Montreal and a principal investigator of the REVEAL trials to present the previously disclosed Part A clinical data from our REVEAL Phase I/II trials that she presented at the International Rett Syndrome Foundation Scientific Meeting in June. Those who attended may recall how impactful her presentation was to the audience.

Today, we're excited to expand its reach to the broader community as these data have been central to our clinical discussions with regulators in preparation for our pivotal trial. Kamran will then follow up with a financial update, and I will provide closing remarks before opening the call to questions. We have continued to make strong progress supporting the advancement of our TSHA-102 program. This included obtaining alignment with the FDA and Health Canada to proceed with initiating our REVEAL pivotal trial, reporting positive clinical data supporting the therapeutic potential of TSHA-102 and strengthening our balance sheet. We believe this meaningful progress sets us on a clear and efficient path towards the potential registration of TSHA-102.

In May, we announced that we had reached alignment with FDA on key design elements of our REVEAL pivotal trial and next steps for enabling study initiation. Subsequently, we submitted our IND application amendment to the FDA and CTA amendment to Health Canada. I am now pleased to report that we have officially commenced the site activation for our REVEAL pivotal trial in accordance with the key design elements we previously aligned on with FDA following receipt of no objection letter from Health Canada and feedback from the FDA. As a result of this progress, we anticipate beginning patient enrollment for our pivotal trial in the fourth quarter of this year. Our frequent and constructive dialogue with the FDA through the RMAT mechanism has been instrumental in enabling us to navigate this novel regulatory pathway, which I will discuss in more detail shortly.

Rett syndrome is a rare, progressive and debilitating neurodevelopmental disease, affecting an estimated 15,000 to 20,000 patients across the U.S., Europe and U.K. It often necessitates 24/7 care and lifelong support. Despite the severity, there are no currently approved therapies that treat the underlying genetic root cause of this disease, underscoring the urgency for new therapeutic advancements. TSHA-102 is highly differentiated gene therapy candidate designed to target the genetic root cause of Rett syndrome. With key attributes that intend to support safety and potential commercial viability, we believe TSHA-102 is poised to redefine the treatment landscape for Rett syndrome. Specifically, it leverages the clinically and commercially proven AAV9 vector, which is a well-characterized safety profile that's been demonstrated in studies for other third-party gene therapies across multiple indications.

Another important distinction is that TSHA-102 is administered via lumbar intrathecal injection, which is a routine minimally invasive delivery approach. Commercially, this can be advantageous in that it does not require a surgical suite or neurosurgery expert delivery, and it can be performed as a routine outpatient procedure. Additionally, intrathecal administration delivers the vector directly to the cerebrospinal fluid, which facilitates widespread biodistribution and transduction within the CNS, while limiting systemic circulation. This reduces peripheral tissue exposure that may help lower the risk of off-target effects, including immune responses and systemic toxicities, thereby potentially contributing to a more favorable safety profile. From the outset, our clinical development strategy has been deeply data-driven with a focus on defining the most objective, clinically meaningful way to assess TSHA-102 across a broad patient population.

Our robust analysis of the Rett syndrome natural history data set demonstrated that after the age of 6 years, the likelihood of achieving defined developmental milestones across the core functional domains of Rett syndrome is approximately 0%. This established a developmental plateau population. These important findings underpin our FDA-aligned pivotal trial design and allow us to objectively measure the functional aspects of TSHA-102 on essential activities of daily living. As I mentioned, we are pleased to have commenced site activation for our REVEAL pivotal trial, which will assess the percentage of patients in the developmental plateau population who gain or regain one or more development milestones as part of the primary endpoint with each patient serving as their own control.

Based on the Part A data from our REVEAL 1/2 trials, it's encouraging that all 10 patients treated with TSHA-102 gained or regained or more developmental milestones, corresponding to a 100% response rate for the pivotal trial primary endpoint based on the May 25 data cutoff. With safety at the forefront, we are pleased to share the low and high dose of TSHA-102 continue to be generally well tolerated with no treatment-related serious adverse events or dose-limiting toxicities in the 12 patients treated as of August 2025 data cutoff. Lastly, we recently completed a public follow-on offering that resulted in total gross proceeds of $230 million, including full exercise of the underwriter's option to purchase additional shares, extending our cash runway into 2028. With our balance sheet strengthened, our pivotal trial underway and a defined path to registration, we believe we are well positioned to advance TSHA-102 to benefit patients living with this devastating disease.

Our REVEAL clinical development program was designed to support the future approval of TSHA-102 for the treatment of females aged 2 years and older with Rett syndrome. Recall, Part A was our dose escalation phase where we treated 12 patients aged 6 to 21 years in our 2 Phase I/II REVEAL trials with 1 of the 2 dose levels. The totality of the Part A data helped inform our discussions with the FDA and Health Canada on the optimal trial design for Part B, the pivotal phase of our trials. Our REVEAL pivotal Part B trial will evaluate developmental milestone gain and regain in the developmental plateau population. In parallel, we previously announced we are aligned with the FDA on an extrapolation approach in a separate safety focused study evaluating TSHA-102 in the pre-developmental plateau population of females aged 2 to less than 6 years.

Given the high incidence of spontaneous milestone gains in this population, safety will be the primary focus and efficacy will be extrapolated from the developmental plateau population. Importantly, we believe this 2-study approach allows us to generate safety and efficacy data across the broad Rett syndrome population while mitigating disease heterogeneity risk. Leveraging a pivotal trial design focused on targeted enrollment of patients within the developmental plateau population provides high statistical confidence given the approximately 0% likelihood of spontaneous milestone achievement in this population. From a CMC perspective, the pivotal TSHA-102 product has been released and cleared for use in our REVEAL pivotal trial. As previously disclosed, the FDA approved the use of the pivotal lot, which is manufactured from the planned commercial manufacturing process and agreed that it was comparable with the clinical material used in Part A. This achievement supports product consistency and quality, which are essential pillars of safety.

Furthermore, this streamlines our path to initiating the pivotal trial and underscores our CMC readiness to support a future BLA submission. Our REVEAL pivotal trial for TSHA-102 will reflect a single-arm open-label pivotal trial design with each patient serving as their own control. The high dose of TSHA-102 of 1E of the 15 total vector genomes will be evaluated, and we will enroll 15 females between the ages of 6 and less than 22 years in the developmental plateau population. As mentioned, the primary endpoint will assess the percentage of patients who gain or regain one or more developmental milestones from the list of 28 milestones across the core functional domains of communication, fine motor and gross motor.

Importantly, this responder definition was supported by the FDA in Health Canada as part of our recent feedback. With this established, we continue to believe Part A of our REVEAL trial supports the pivotal trial is well powered to establish efficacy. We plan to conduct a 6-month interim analysis in addition to a 12-month primary analysis, which could potentially expedite BLA submission by 2 to 3 quarters. Key secondary endpoints include the average number of total developmental milestones gain or regain per patient following TSHA-102 as well as clinician-assessed outcomes, including the RMA and the CGI-I. These secondary endpoints are designed to capture the broad therapeutic outcomes across the domains of communication, fine motor, gross motor and autonomic function that are central to the burden of disease.

We are focused on site activation, which we anticipate will enable us to begin patient enrollment in the fourth quarter of this year. Importantly, our pivotal trial primary endpoint is an objective, clinically meaningful and individualized assessment of function in the developmental plateau population. It was supported by caregiver research and natural history and has been aligned on with the FDA. As such, we believe achievement of this endpoint has the potential to redefine expectations and expand the possibilities of gene therapy for patients with Rett syndrome. With the pivotal trial now underway, it is important to understand the data-driven approach we took to defining this novel regulatory pathway, which was informed by the natural history and our REVEAL Part A clinical data. I will now turn the call over to Suku to discuss this. Suku?

Thank you, Sean. The longitudinal NIH-funded IRSF natural history study data represents the largest global Rett syndrome natural history data set in which patients were assessed by direct examination. This included longitudinal data on the gain, loss and regain of developmental milestones in the co-functional domains of Rett syndrome. These data were collected via clinician conducted interviews with primary caregivers at 6- to 12-month intervals. We selected a large cohort of approximately 1,100 females with up to 14 years of follow-up who closely aligned with our REVEAL trial enrollment criteria. We use this data to build age and time-based cumulative incidence curves, which demonstrate the likelihood of gaining a new milestone based on age and the likelihood of regaining a milestone that was lost based on time since loss.

These models showed clear age and time-based trends in developmental milestone acquisition that have strengthened the field's understanding of longitudinal disease progression. -- substantiated the disease-modifying potential of TSHA-102 and informed our discussions with the FDA on our proposed pivotal trial design. As seen on the slide, we built a tool that predicts the likelihood of a developmental milestone gain based on age and regain based on time since loss. Importantly, these incidence models demonstrated that the likelihood of gaining or regaining any of the 28 defined developmental milestones for our primary endpoint is highly predictable in patients 6 years of age or older. Here, you will see 3 examples of milestone gains across the 3 core domains, demonstrating that when an untreated patient achieved these milestones, it occurred before the age of 6. After the age of 6, the curve flattens with approximately 0% likelihood of an individual gaining these milestones.

We leverage these findings to establish the developmental plateau population, which is the population of age 6 years and older, at which the likelihood of milestone gain and regain becomes predictable. And as mentioned, this is the core population we are enrolling in our pivotal trial. This slide highlights the 28 developmental milestones selected for inclusion in our primary endpoint, each meeting predefined criteria, that is they are meaningful to caregivers, represent activities of daily living and demonstrated between 0 and less than 6% likelihood of spontaneous achievement in untreated individuals aged 6 years and older. This illustrative graphic helps put these findings into context, -- our natural history analysis uncovered the developmental plateau population of patients aged 6 years and older, where there's an exceedingly low chance of 2 things: number one, gaining new developmental milestones; and number two, regaining developmental milestones that were lost after a defined number of years.

Therefore, the gain of new or restoration of previously lost milestones presents an objective, clinically meaningful and data-driven way to assess the efficacy of TSHA-102 in a broad population. We applied a rigorous evaluation criteria to our Part A developmental milestone data to enable a reliable, objective and consistent assessment of TSHA-102's efficacy. As a first-in-human study, we evaluated a range of clinical outcome assessments in Part A to generate a robust data set to inform our pivotal trial design. As such, select developmental milestones were captured through video recorded evaluations, clinical outcome assessments, caregiver assessments and clinician notes. We applied structured evaluation criteria to the available video evidence milestones.

To qualify as a milestone achievement following TSHA-102, there were 3 criteria that had to be met. First, the milestones have either never been gained or was lost sufficiently long ago such that the likelihood of spontaneous gain regain was less than 6.7% based on reviews of patients' medical history and available baseline video data. Second, there had to be video documentation of the milestone achievement post TSHA-102 treatment. Third, this video evidence was independently evaluated by multiple external central raters who use prespecified definitions of achievement for each of the 28 milestones based on the pivotal trial protocol to determine whether a milestone was demonstrated. By leveraging this criteria, we believe the Part A of our REVEAL trials is a reliable reflection of TSHA-102's impact on developmental milestone achievement well beyond what's statistically probable for these patients.

And importantly, that our pivotal trial is well powered to establish the therapeutic impact of TSHA-102. Beyond the video evidence milestone data, we collected data that further demonstrate developmental milestone achievements and functional improvements in activities of daily living across the core domains of the disease, which we look forward to sharing in the fourth quarter of this year to further support the broad therapeutic impact. With that, I'm pleased to turn the call over to Dr. Elsa Rossignol to present the previously disclosed Part A data. Elsa?

Thank you, [indiscernible] . So it's a pleasure to be here and to describe what we, as Suku said, already presented in the IRSF meeting in June. And so next slide, please. Okay. So, as we're moving on, we've observed, as Suku was mentioning -- I'm sorry, do you hear me? Can you move the slide? Are you guys hearing me?

Yes, we can hear you.

Okay. Very good. So please move the slides. Thank you. All right. So as Suku was mentioning, the data from Part A was reanalyzed using independent central raters to assess gains or regains of any developmental milestones that were part of these 28 milestones isolated by -- based on the natural history study data. And all of these milestones, I remind you, are typically never gained or regained past the age of 6. And so all of the data that we currently had in the trial was reanalyzed based on video. So, it was a very strict detection of gain or regain using predefined primary criteria. And so we were very pleased to see that all patients treated so far in the cohort have reached this criteria of gaining at least one milestone or regaining at least while milestones. and many patients actually gained more than 1 milestone as you will observe in the next slide.

But before we go on, I just want to point out that in the data we're presenting here for the clinical assessments, we're describing 10 patients. The 2 other patients were below the 3-month cutoff. So we didn't have yet the clinical assessments to detect and conduct this evaluation. I also want to point out, when you look at the data that, of course, the longer follow-up were for the low-dose cohort. And so for the high-dose cohorts, we have a shorter follow-up and many of them were still adolescent. And so we're eager to see the development of this data moving forward with the 12 months and 18 months cutoff for the high-dose patients. And so looking at the gains that we've observed in the cohort so far, out of the 10 patients that were treated, next slide.

Out of the 10 patients that were treated, we've observed a gain of 22 developmental milestones, and these were across multiple domains of the disease as illustrated here. And patients that gained milestones in one domain often gain also in other domains, so it's not restricted to one single domain. And so 22 milestones out of 10 patients suggest that many patients gain more than one. The domains that we've observed with gains or regains are, for instance, in communication. We saw patients that are now able to use phrases to communicate things like, okay, by mom, where before they would use sparse words here and there or one single word very infrequently. We've also seen patients learning to use words who had previously been nonverbal for communication.

Many patients also gained the ability to follow command with a gesture or without the gesture. So more reactive to conversations around them and expectations, which really helps the daily routine of things like going to brush a heat or eating meal or it's time to prepare for school or nothing. Some patients have gained the ability to point to things they want or to identify body parts. This may seem like just a basic task for anyone who has a typical development. But for patients with Rett, this is really critical because they've finally been able to point what they really want. So it really clarifies their needs and helps communication with the family and caregivers for identifying body parts.

This is very helpful when patients are more cranky or crying and it's very difficult to know where they're -- if they have pain somewhere, if they can point that it's the head or it's the tooth or it's the belly, it's very helpful for caring for these patients. So communication was key, both receptive and expressive. In terms of fine motor, we've seen patients gaining the ability to hold a bottle on prop. So a real gain in autonomy and independence so that they would eventually be able to drink by themselves. To finger feed, once again, with pencil grip, this is a huge improvement in independence. -- reaching for a toy and transferring objects from one hand to the other, which very much helps manipulating objects when you're holding or stabilizing with one hand, you can manipulate with the other hand. And eventually, once you're stabilized, then participate to the task with both hands, which is really key for independence and purposeful hand use.

In terms of gross motor scales, we've seen patients starting to be able to walk with support to stand while holding up, to pull to a standing position or to sit without support. All of these show real gains in terms of independence and mobility, and it reduces the physical burden of caregivers. And I'll give you an example in the next slide, please. So as we were discussing clinical evolution with patients at each visit, we're filming many of these assessments. And so from these films on the next slide, we could capture quotes from the family and caregivers, which are illustrated here. And basically, these really show how impactful these new gains were for these families.

And so one patient told us all of our days are better, her improvements are much beyond anything we had expected or hoped for. So it's so transformative that it really was across multiple aspects of their life. She gained multiple words, no, yes, mom, dad and is making consistent sounds with meaning and even says some phrases, okay, bye, no more. And so it's really a clear progress in communication for a child who previously was using a single word once in a while. Another family told us she's a lot easier to care for. She can point a lot more deliberately to make choices and to show us what she wants, and she will keep gesturing until we get it for her. She pushes away what she doesn't want. And this is really, really key because on daily living, when they can finally really show what they actually want or mean, it reduces stress. It reduces anxiety and it makes all interactions so much more pleasant for the kid and for the family.

The ability to stand while holding on is really important. So this family told us it has been a good fan when it comes to toileting while out in the community because now I can have her stand and hang to my arm to toilet and wipe her. So of course, this is really helpful if a child can finally stand by their own even through holding. And the consistency of keeping her hands down without constant stereotypies allows us to practice more tasks such as using a walker, which has been huge. So once again, better hand use can transfer into gross marker skill gains as well, where even this might not show up in the developmental gain skills that was described earlier, it is still a gain in practice because walking around with a walker is much more convenient than with somebody holding you and holding the trunk as you're trying to move a few steps.

Another family said her hands are more relaxed and she tries to grab everything with a racking graph. She can follow directions in a snap like if we say, let's go, she gets up and she heads to the door. She's babbling now, which didn't do before, and it definitely is trying to tell us something. So you can see just from a few of these quotes, how striking and broad the gains were. So it's not restricted to one single domain. The next slide, please.

As we're looking at the data to -- across the various assessments, it became very clear that our high-dose patients are performing better than the low dose. So they're making their gains much faster. And so you can see from the green line here that 100% of the cohort of high dose reached at least one milestone within 9 months and whereas it took a bit longer for the low-dose patients. So the pace is much increased. And you can imagine that these lines are still growing. And so these patients are still being followed. And presumably, we could expect that they're still making progress, whereas the data we're presenting is that the was made. And so this quicker gain may lead to better improvement on the long term as well. Next slide.

Apart from the developmental milestone evaluation that we described, we've done many other scales, both clinical scales and questionnaires to family. And so the next slide, please, is the one on the RMBA scale. And this is one of the scale that I personally really like because it's a large broad scale of 24 items that goes much beyond what we see for the RSBQ. So the RSBQ tends to be focused on communication and breathing and irritability and things like that. But the RMBA, please go back to the previous slide. RMBA is really 24 items across multiple domains, motor function, functional skills, social skills, apparent behavior and breathing, and it's a total of 96 points. So now on this slide that you're showing, what we've observed across the cohort is a clear gain on this maximum of 96 points.

We've seen a gain of 11 points at 6 months and 12.8 points at 12 months in the cohort, suggesting a very drastic improvement that is, of course, beyond sickle domain because this scale really assessed very broadly multiple aspects of the disease. And when we compare to the natural history, this gain of 11 points at 6 months and of 12.8 points at 12 months is very, very striking. Please show the slide that I'm describing, which is the next one. Yes, this is the one where we see the score, 11 points improvement compared to natural history and 12.8 points at 12 months compared to natural history. So this is really unheard of and very striking in terms of the depth of the improvement. Next slide.

The next scale that we're showing is results from the CGI-I. And the CGI-I is this clinical global impression improvement scale. And this is a global impression that clinicians will share after taking into account everything that has been done at this visit, including the RMBA, the physical exam, the SSBQ, the hand function test and all of the other assessments. And we're really looking for changes across the 7 domains of the disease, so motor, fine motor, language, communication, breathing, autonomic dysfunction, epilepsy. And so it's also a very broad scale. And so next slide, what we've observed in our cohort is an improvement in all patients on this scale. And once again, the high-dose patients overperformed compared to the low-dose patients.

So the high-dose patients reached 1, which is a scale that suggests very much improved by 9 months of follow-up, whereas in the low-dose patients, we were around 3 and eventually 2, so 2 being much improved and 3 is minimally improved. So we do see gains in all the cohorts, even in adolescents and adults, even treated with a low dose, but the depth of the gain and the rapidity of the gain is greater in the patients treated with a high dose. The next slide, please. This slide summarizes the full data set comparing the low dose and the high dose that really illustrates many of the points that I've shared today.

First of all, all of the patients were responder based on this developmental milestone assessment, 100% of low dose and high-dose cohort reached at least 1 milestone, and this was achieved faster in the high-dose cohort. In terms of the ANDA, as I mentioned, all of them improved and improved quite strikingly. So we see in the low dose at 6 months, 9.8 points and at 9 months, 11.5 points on a 96-point scale, which is a very striking improvement. In the high dose, you can see that the depth of improvement is even greater. So we're reaching an 18-point improvement at more than 9 -- then in terms of CGI-I, as I mentioned, all patients improved. So at the cutoff, we had 75% of patients in the low dose that had improved on the CGI-I scale and 100% of the high dose.

And as a mean, we're observing at 6 months, 2.3 and at 9 months, 2.8 in the low dose, and those are much improved -- between the much improved and minimally improved grades. -- whereas for the high dose, we're reaching a much-improved grade at 6 months and very much improved grade at more than 9 months. So we are gaining even more. Now in terms of the CGI-IS, this is the severity score, which once again looks at 7 aspects of the disease and grades the ability of the patients in a broader fashion. And it's usually very hard to change grades of the CGI-S because you need very striking gains to switch one item out of that grid. And so we observed 33% of the high-dose cohort changing severity to a better grade and 25% changing also in the low dose. So in both cohorts, we've observed patients improving so much that they were able to switch scores for the CGI-S.

Last slide. So in total, we've observed that TSHA-102 has been generally very well tolerated, both in the low and the high dose. There has been no dose-limiting toxicities or treatment-induced serious adverse events. We've observed, of course, some treatment-induced adverse events associated to TSHA-102. Most of them were in the mild, some were in the moderate and severity range. The most frequent ones were elevated liver enzymes. And when we saw those, the majority were beyond -- below 2x the upper limit of normal and a few patients did have more acute excursions above 5x, but they all responded to steroid treatment and recovered without sequelae. Other side effects that were observed and associated with TSHA-102 are side effects expected for AAV therapy, so fever, less RBC after the lumbar puncture treatment and increase in protein in the CSF. Overall, seizures were well controlled in this cohort. So I'm done with my slides, and I'm moving the call back to the Taysha team.

Thank you, Dr. Rossignol. Research and development expenses were $20.1 million for the 3 months ended June 30, 2025, compared to $15.1 million for the 3 months ended June 30, 2024. The $5 million increase was driven by BLA enabling process performance qualification manufacturing initiatives, REVEAL clinical trial activities and higher compensation expenses as a result of increased headcount during the 3 months ended June 30, 2025. General and administrative expenses were $8.6 million for the 3 months ended June 30, 2025, compared to $7.3 million for the 3 months ended June 30, 2024. The increase of $1.3 million is primarily due to higher legal and professional fees.

Net loss for the 3 months ended June 30, 2025, was $26.9 million or $0.09 per share compared to a net loss of $20.9 million or $0.09 per share for the 3 months ended June 30, 2024. As of June 30, 2025, Taysha had $312.8 million in cash and cash equivalents. This reflects gross proceeds of $230 million from the May 2025 follow-on financing, which includes the full exercise of the underwriters' option to purchase additional shares. We also refinanced our existing loan and security agreement with Trinity Capital from the original $40 million, which was paid in full to a new debt facility equal to $50 million upfront. The refinanced loan defers debt principal payments by more than 2.5 years, lowers our interest rate and provides access to nondilutive capital. Importantly, there continue to be no financial liquidity covenants or warrants associated with the new refinance loan with Trinity.

We look forward to our continued partnership with the Trinity Capital team. We expect our current cash resources to support planned operating expenses and capital requirements into 2028. I will now turn the call over to Sean for his closing remarks. Sean?

Thanks, Kamran. I'm pleased with the progress we have continued to make to advance our TSHA-102 program. With a strengthened balance sheet, our FDA-aligned pivotal trial underway and compelling clinical data from Part A, we are moving forward with confidence as we work to deliver on our anticipated near-term milestones. This includes beginning patient enrollment for our pivotal trial in the fourth quarter of this year. We also plan to report new supplemental clinical data from Part A of our REVEAL Phase I/II trials supporting the broad therapeutic impacts of TSHA-102 in the fourth quarter of this year. We truly appreciate the collaborative interactions with the FDA in Health Canada to date and believe this progress advances our goal to bring TSHA-102 to patients with this devastating disease as expeditiously and safely as possible. I will now ask the operator to begin our Q&A session. Operator?

[Operator Instructions] We take the first question from the line of Salveen Richter from Goldman Sachs.

This is Lydia on for Salveen. I guess given there was a 100% response rate for the pivotal trial primary endpoint in the Part A of the study, is this the bar for Part B in your view?

I think that the results we've seen in Part A are exceptionally compelling. I think 100% is always a difficult standard to keep. I think what's the most important thing is how we built the statistical plan for Part B. And keep in mind that we're using a null hypothesis of 6.7%, which was the highest percentage of a gain regain per milestone that we're evaluating. And when you take that into account with a 15-patient population, that would mean 1 patient out of 15 would spontaneously have a potential gain or regain. So the statistical bar to get over is relatively low. All things speaking, it's approximately 33% based on our submission of the SAP. So, what gives us a lot of confidence is that the numbers that we're seeing so far play out in Part A are consistent and significantly above that threshold. Thank you.

We take the next question from the line of Kristen Kluska from Cantor Fitzgerald.

I'll ask my question for Dr. Rossignol. So it was encouraging to hear that other milestones have been reported that weren't necessarily as part of the video assessments. But can you help us understand, is there a certain time point where all these milestones are occurring by? Are you seeing them -- additional ones occur over the long span of time? Just trying to get a sense of whether or not you think the benefits of the gene therapy have plateaued yet.

Also, please feel free to take that.

Yes. So thank you for the question. If you look at the data that we have so far up to the cutoff, we were seeing increasing improvement as we were following the patients. And so we're expecting a similar increase in gains over the time course since that last cutoff. And so this does not occur just in one visit, and we do see gains usually at most visits in follow-up. And when we were mentioning the gains that are not observed or quantified in this developmental milestone assessment, what I meant by that is if you're now able to walk with a walker, that doesn't give you a point on the developmental milestone scales because you would need to walk independently. So, we can have critical gains that improve daily functioning that are not captured in this skill set but are still major and critical improvements.

We take the next question from the line of Tazeen Ahmad from Bank of America.

I wanted to maybe talk about the differentiation of your gene therapy versus your competitor. In particular, maybe I could get the doctor's view on study design. So you're looking at a smaller cohort and you're also looking at a single primary endpoint. Can you talk about the differences in these studies and how you think this could lead to differentiation between the 2 programs?

Yes. Thanks, Tazeen. It's good to hear from you. Suku, maybe we can tag team this. I think first and foremost is the fact that the way we conducted the Part A trial was to cast a broad net. It was really the first-in-human trial to let us explore what are some of the different efficacy measures that would make a lot of sense. And all along the way, we've always been of the mind that with the gene therapy, you really have to show something clinically meaningful and objective that's going to impact activities of daily living, i.e., you can go back 2 years and hear Suku talk about small gains and scales are not going to be the mark that we're looking for. And so, I think the fact that we've been working with the regulators to establish a completely new paradigm in assessing clinical efficacy, which is the gain and regain of milestones.

This is functional gains that have never been achieved before in this disease. And so we're redefining a, how we're going about defining what truly is impactful from a clinical perspective and from a patient and caregiver perspective. And I think the approach that we're taking is exceptionally unique. We've been very enthused by the -- I would say that just the support we've got, the excitement that we've gotten from the KOLs that participated in the natural history, people participating in the study, advocacy, everyone is just very excited because they see how this can truly impact their quality of life. So I think when you look at things broadly, Tazeen, we're in a situation where we're capturing milestones where we can clearly show an effect. And that's going to mean a lot with payers as well.

And then the additional endpoints that we're looking at relative to RMBA, CGI, again, we can benchmark RMBA to the natural history, and it's exceptionally compelling. I mean effectively, natural history is about 0, right? It just doesn't move. It doesn't get any better. And we're showing that it's better. Again, that's going to help with the excitement in the community. That's going to help with the payers and supporting them. And I think you combine the efficacy impact that you're seeing with the safety that we've been able to generate to date, and we think that is very much attributed to 2 things.

One is CMC quality and two would be the route of administration really minimizes the amount of systemic exposure that these patients receive. So, we think for all those reasons, this is going to be a very enticing offer to patients, and they're going to want to do what's easiest and safest for their kids and also, that demonstrates a significant effect that can change the way that their daily life is lived. Anything else to add?

Sean, I would add one more thing, Tazeen the way, nice to hear your voice. I just wanted to again emphasize at Taysha, we are clearly committed to the patients with Rett syndrome, and that's what we've done, really paying attention to safety and clinical meaningfulness of our product with a minimally invasive route of administration. So having said that, and you've already seen the data that Dr. Elsa Rossignol presented and what Sean just said, as far as commenting on NeuroGen's protocol, I would say for full disclosure and disclaimer, I really don't know what their protocol is yet other than what's in the public domain. It appears to be a single-arm study. They had a composite endpoint for their primary, but it's not clear that that's still the case based on what was disclosed just this week.

I would also go further to say that the natural history data set that we have, I have never seen such a comprehensive and a large natural history data set to do an appropriate assessment and it's a 14-year period. So given our experience in looking at this data set, it's very clear that once you get above the age of 6 and you do a therapeutic intervention such as TSHA-102, and as Sean highlighted and Dr. Rossignol highlighted, when you see a gain of a new skill or regain of a lost scale, the odds very likely it's the Taysha gene therapy intervention. And we've seen patients actually change their lives by gaining these skills or developmental milestones and having an improvement in the activities of daily living. Things that I would say that I take for granted like getting up in the morning, brushing my teeth, feeding myself and putting my shirt on most of these patients, whether they're young or old, cannot do.

So having the ability to change their lives in such a manner and work with the advocacy groups and the physicians or experts in this field and the regulators such as the FDA gives us a lot of satisfaction having come back to do this for TSHA-102 in the patient population. So thank you.

The next question comes from the line of Gil Blum from Needham & Company.

This is Ethan on for Gil. Congratulations on the progress this quarter. So your competitor recently received regulatory feedback that a 6-month endpoint would not be considered clinically meaningful in their case. Obviously, your study designs are slightly different, but would you expect any pushback on using your interim readout to support BLA filing? Or was that already discussed with the FDA as well?

Yes. It was part of our submission. And I would say a couple of things. And we can only speak to the Taysha interactions and feedback. But one of the things that we really tried to highlight in Suku's presentation, Elsa's presentation is that we've taken a very data-driven approach. And so, when you think about what underlies our interim analysis approach is the fact that it's based on the proof-of-concept analysis of the Part A data, which provides very robust support for the primary endpoint at both 6 and 12 months. And then when you apply the data that also went through against the statistical plan that we talked about, there's a clear difference between what the statistical threshold for success would be at 6 months and what we're actually seeing. So recall, one of the slides that also went through showed at 6 months at the high dose, there was an 83% responder rate at 6 months, and then that improves and deepens over the course of 12 months.

So, it's something that I think from a data perspective, we really leverage with the FDA as the rationale as to why you could do a 6-month interim I can tell you, we've had discussions with them. It's really, at this point, focused on further refinements of the actual analysis, but we have not been pushed off the ball about doing a 6-month interim. It's more the particulars of the assessments. So we feel good about where we stand at this particular point in time.

The next question comes from the line of Maury Raycroft from Jefferies.

This is James on for Maury. Congratulations on the progress this quarter. Can you talk about expectations for the new supplemental REVEAL Part A data in Q4? Could we get additional data points like more granular information on the number of video documented milestones gained across the high and the low dose or individual CGII data points? Do you anticipate that the data will be at a medical conference or a company update?

I can see it being at both a medical conference and a company update. And we'll provide more specifics over the coming weeks and months leading into it, James. But there's a lot of information that we captured, as I mentioned earlier, and we cast a pretty wide net. And some of that net also included additional videos that we haven't talked about different ways to get at the milestone gain. And so we want to share with the community additional milestones and what those look like, how those translate into activities of daily living. And I think it will give a more fulsome picture of just exactly how the milestones are translating to improvements in activities of daily living and improvements of quality of life of the patients that have been treated thus far.

The next question comes from the line of Biren Amin from Piper Sandler.

Can you maybe characterize any changes from the Part A CMC material batch to Part B CMC material with, I guess, a specific emphasis on full empty capsid ratio across both batches? And with the commercial scale of material, what are your thoughts in terms of how many patients you can supply into the market when approval comes in?

Yes, Biren, as you know, it's a massive opportunity, right? I mean, just in the U.S., if we're talking around 10,000 patients, it's a massive, massive unmet need. So, it's very important from our perspective, and we've been working as a team. And fortunately, we have an excellent leader, Fred Porter, leading the effort for us to, a, make sure we're making the highest quality product; and b, that we're doing it at scale. And so, I think first and foremost, it's important to note that we've aligned with the FDA, I think we said this a few quarters ago that the Part A and the pivotal material are analytically comparable, which is very important. We've already made the product for the pivotal trial. We've shared that with the FDA.

That's made with the commercial process at scale. And the FDA has said you can go into the clinic with that. So certainly, one of the things that we did with -- in our thinking about this is we could have extended our cash runway into mid-2028 because of the combination of the raise that we did and Kamran's good work with reworking the Trinity loan. But what we opted to do was to just basically keep -- send the guidance into 2028. So in the situation where we're able to move things forward more quickly with regulators, we could really work to begin to build the commercial inventory that we need. So we've got that as a contingency. We've got the funds to do it, and we feel very strongly that we're in a good position on the CMC side at this point.

We take the next question from the line of Jack Allen from Baird.

On the update here, very holistic update. I guess I wanted to ask just more specifically on your recent interactions with regulators. It seems like you have sign off from the Canadian authorities. But I wanted to understand where it sits as it relates to the IND amendment with the FDA and any ongoing discussions there. What are the points of conversation as it relates to those conversations, if they're ongoing or have you achieved a formal signoff? Where do things sit there? And then any additional color around European regulatory discussions would be interesting as well.

Yes, Jack, great question. So a couple of things, and Suku check me on this. But basically, number one, there's a difference just in process. So, with Health Canada, we did an amendment to the CTA, and they have a 37-day review period and you -- if there's no issues, you get what's called a no objection letter or an NOL. And we got a no objection letter on day 37 with no comments. That means you're good to go. It means Elsa is working through things with the site right now as an example. And that's the process up in Canada.

In the U.S., with the FDA, because we did an IND amendment, there's no official correspondence that you get. There's no letter that you get. There's generally been an unofficial 30-day if you don't hear something, you can proceed. We were told early on, this would have been back in early, I guess, July, we received correspondence that there was no clinical hold concerns and we could proceed at our discretion. Subsequently, we've had interactions with the FDA with information requests and things of that nature. And I would characterize it as the -- our view is that really, it's like further alignment is what we're looking for, that the ongoing FDA dialogue is focusing on how do we position the program for success versus getting into overturning any key trial design elements or things of that nature. So it's been very constructive and supportive.

As it relates to Europe, we do have a scientific advice meeting scheduled for this early fall, and we're continuing to work to enable that geography. So we should have more information when we give our next earnings call. Thanks for the question.

Ladies and gentlemen, we take that as the last question and conclude the question-and-answer session. I will now hand the conference over to Mr. Sean Nolan for his closing comments.

Just want to thank everyone for their time this morning, including our special guest, Dr. Elsa Rossignol, and we wish you all a great week. Take care, and we'll talk soon.

Thank you. Ladies and gentlemen, the conference of Taysha Gene Therapies has now concluded. Thank you for your participation. You may now disconnect your lines.