Ladies and gentlemen, good morning and welcome to Taysha Gene Therapy's second quarter 2025 Earnings Conference call. At this time, all participants are in listen-only mode. A brief question and answer session will follow the formal presentation. If anyone requires operator assistance during the conference, please signal the operator by pressing star and zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Haley 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, Tayshia 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, Tayshia's Chief Executive Officer, Ducumar Nagandrin, President and Head of the R&D, Cameron Alam, Chief Financial Officer, and Dr. Elsa Rosignol, Director of the Integrated Rett Syndrome Clinic at St. Justine in Montreal and Principal Investigator of the VEAL Phase 1-2 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. Rosignol 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 TASHA-102, including the reproducibility and durability of any favorable results initially seen in patients' dose 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 our outcomes of communications with the FDA and Health Canada on the regulatory pathway for TASHA 102, the potential for product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and a market opportunity for our programs. This call may also contain forward-looking statements relating to TASHA'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 TASHA'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, and 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. Tayshia undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this call, except if may be required by applicable securities laws. With that, I would now like to turn the call over to our CEO, Sean Nolan.

To our second quarter conference call. I will begin with an update on our recent activities and regulatory progress for our lead Tayshia 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 Rosenall, 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. The attendant may recall how impactful her presentation was to the audience. Today, we're excited to expand its reach to the broader community through our clinical discussion update, and I will provide closing remarks before opening the call to questions. Strong progress supporting the advancement of our TASIA-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 TASIA-102, and strengthening our balance sheet. We believe this meaningful progress sets us on a clear and efficient path towards the potential registration of TASIA-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 site activation for our Revealed Pivotal Trial. In accordance with the key design elements we previously reached on with FDA and feedback from the FDA. ...enrollment for our Pivotal Trial in the fourth quarter of this year, 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. 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. In reality, there are no currently approved therapies that treat the underlying genetic root, storing the urgency for new therapeutic advances. ...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 TASHA-102 is poised to redefine the treatment landscape for Rett syndrome. It leverages the clinically and commercially proven AAV9 vector, which is a well-characterized safety profile that's been demonstrated in studies. Another important distinction is that TASHA-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 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 program. At any outset, our clinical development strategy has been deeply data-driven, with a focus on defining the most objective, clinically meaningful way to assess TASIA-102 across a broad patient population. Our robust analysis of the Rett syndrome natural history data set demonstrated that after the age of six years, the likelihood of achieving defined developmental milestones across the core functional domains of Rett syndrome is approximately zero percent. This established the developmental plateau population. These important findings underpin our FDA-aligned pivotal trial design and allow us to objectively measure the functional aspects of TASIA-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 developed milestones as part of the primary endpoint, with each patient serving as their own control. Based on the Part 8 data from our Reveal 1-2 trials, it's encouraging that all 10 patients treated with TASIA-102 gained or regained one or more developmental milestones corresponding to a 100% response rate for the pivotal trial primary endpoint based on the May 25th continue to be generally well-tolerated with no treatment-related serious adverse events or dose-limiting toxin August 2025 data cutoff. As of the underwriter's adoption of our cash runway into 2028. With our balance sheet strengthened, we are well positioned to advance TASHA-102 to benefit patients living with females aged two years and older with Rett syndrome. Recall, Part A was our dose escalation phase where we treated 12 patients, two reveal trials with one of the two 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 of our trials. I will evaluate developmental milestone gain and regain in the developmental plateau population, lined with the FDA on an extrapolation approach in a separate safety-focused study evaluating TASIA-102 in the pre-developmental plateau population of females age 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 two-study approach allows us to generate safety and efficacy data across the broad threat 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 TASIA-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. This streamlines our path to initiating the pivotal trial and underscores our CMC readiness to support a future BLA. So the pivotal trial for TASIA-102 will reflect a single-arm, open-label pivotal trial design with each patient serving as their own control. The high dose of TASIA-102 of 1E to the 15 total vector genomes will be evaluated, and We will enroll 15 females between the ages of 6 in 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 and Health Canada as part of our recent feedback. With this established, we continue to believe Part A of the pivotal trial is well-powered to establish efficacy. We plan to conduct a six-month interim analysis, primary analysis, with three quarters. Key secondary endpoints include the average number of total developmental milestones gained or regained for patient following TASHA-102, as well as clinician-assessed outcomes, including the RMBA and the CGII. 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 based on site activation, which we anticipate will enable us to begin patient enrollment in the fourth quarter. 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. The achievement of this end point 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 revealed part A clinical data. I will now turn the call over to Suku to discuss this. Suku?

The data represents the largest global test by direct examination. Developmental milestones in the co-functional domains of RET enrollment criteria, cumulative in the incident of gaining a new milestone based on age, and the likelihood of acquisition of longitudinal disease-modifying potential of TESHA-102, and informed our discussions with the FDA on our proposed pivotal trial design. Developmental milestones, but the likelihood of gaining or regaining any of the 28 defined developmental milestones for our primary endpoint is highly predictable in patients six years of age or older. Here you'll see three examples of milestone gains across the three core domains, demonstrating that when an untreated patient achieved these milestones, it occurred before the age of six. After the age of six, the curve flattens individuals gaining these milestone plateau population, which is the population of age six years and older, we are enrolling in our pivotal trial. 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%. Exceedingly low chance of developmental milestones that were lost after a defined number of years. A previously lost milestone population and clinician knows that the likelihood of spontaneous gain and regain was less than 6.7% based on reviews of patient's medical history. Each of the 28 milestones based on the pivotal trial protocol to determine whether a milestone was demonstrated. The collection of TESHA-102's impact on developmental milestone achievement well beyond what's statistically probable for these patients and importantly that our pivotal trividence milestone day functionally have improvements in activities of daily living across the core domains of the disease here to further support the broad therapeutic impact. Over to Dr. Elsa Rosignol, Sparte Data.

Thank you. Thank you, Diyu. So it's a pleasure to be here and to describe what we've, as Suku said, already presented in the IRSS 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 slides?

Are you guys hearing me?

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 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 six. 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 regained using predefined binary 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 one milestone. And many patients actually gained more than one milestone, as you will observe in the next slides. 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 two other patients were below the three-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 cohort, we have a shorter follow-up, and many of them were still adolescents, and so we're eager to see the development of this data moving forward with the 12 months and 18 months cut off for the high-dose patients and so looking at the gains that we've observed in the cohort before out of the ten patients that were treated and next slide out of the ten patients that were treated we've observed the 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 in 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 by 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 and for communication and 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 your teeth 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 RAD, 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 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 unpropped, so real gain in autonomy and independence. so that they would eventually be able to drink by themselves. To finger feed, once again, with pencil grafts, 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 growth motor skills, 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, yeah, 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 god friend 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 stereotypes 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 motor 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 grasp. She can follow directions in a snap like if we say let 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 So 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 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 nine months, 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 of the cutoff of May. 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 families. 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 it 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, Our MBA is really 24 items across multiple domains, motor function, functional skills, social skills, aberrant 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 maximal of 96 points. we've seen a gain of 11 points at six months and 12.8 points at 12 months in the cohort, suggesting a very drastic improvement that is, of course, beyond one single 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 six 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 the 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 RSBQ, the hand function test, and all of the other assessments. And we're really looking for changes across the seven 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 one, which is a scale that suggests very much improved by nine months of follow-up. Whereas in the low-dose patients, we were around three and eventually two. So two being much improved and three 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. So 100% of low-dose and high-dose cohorts reach at least one milestone, and this was achieved faster in the high-dose cohort. In terms of the RMDA, as I mentioned, all of them improved, and improved quite strikingly. So we see in the low-dose at six months, 9.8 points, and at nine 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 nine months. Then in terms of CGII, as I mentioned, all patients improved. So at the cutoff, we had 75% of patients in the low dose that had improved on the CGII scale and 100% of the high dose. And as a mean, we're observing at six months, 2.3, and at nine 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 six months and a very much improved grade at more than nine months. So we are gaining even more. Now, in terms of the CGIIS, this is the severity score, which once again looks at seven 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 CGIIS 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 CGIS. Last slide. So in total, we've observed that TASHA-102 has been generally very well tolerated, both in the low and the high dose. There has been no dose-limiting specificities or treatment-induced serious adverse events. We've observed, of course, some treatments-induced adverse events associated to TASHA-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 below two times the upper limit of normal, and a few patients did have more acute excursions above five times, but they all responded to steroid treatment and recovered without a sickle lab. Other side effects that were observed and associated with TASHA-102 are side effects expected for AAV therapies, so fever, lethargy 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 TASHA team. share for the three months ended June 30th 2024.

As of June 30th 2025, Tayshia 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 underwriter's 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 up front. The refinance loan defers debt principal payments by more than two and a half years, lowers our interest rates, and provides access to non-dilutive 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. I'll now turn the call over to Sean for his closing remarks. Sean? Thanks, Cameron.

I'm pleased with the progress we have continued to make to advance our TASIA 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 1-2 trials, supporting the broad therapeutic impacts of TASIA-102 in the fourth quarter of this year. We truly appreciate the collaborative interactions with the FDA and Health Canada to date and believe this progress advances our goal to bring TASHA-102 to patients with this devastating disease as expeditiously and safely as well. I'll ask the operator to begin our Q&A session. Operator?

Thank you. Ladies and gentlemen, we will now begin the question and answer session. If you would like to ask a question, please press star and 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star and 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Ladies and gentlemen, we request you to limit yourself to one question per participant. We take the first question from the line of Salveen Richter from Goldman Sachs. Please go ahead.

Hi. Good morning. This is Lydia on for Salveen. Thanks so much for taking our question. 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? Thanks so much.

Using a null hypothesis, gain-regain per milestone to spontaneously have a potential gain or regain. My confidence is that the numbers that we're seeing so far play out in Part A are consistent and significantly above that.

Thank you. We take the next question from the line of Christian Kluska from Canterphys Jeral. Please go ahead.

Hi, good morning. I'll ask my question for Dr. Rossengol. 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.

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 improvements 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 skills 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.

Thank you. We take the next question from the line of Tazeen Ahmad from Bank of America. Please go ahead.

Hi, guys. Thanks for taking my question. 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 two programs?

Yeah, thanks, Tazina. Let us explore, you know, what are some of the different clinically meaningful not going to be. And so I think the fact that, you know, we've been working with the regulators to establish a completely new pair that have never been achieved before in this disease. And I think the approach that we're taking is exceptionally unique. We've been very enthused. I think when you look at things, 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 a zero, 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 pain. 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 two things, minimizes the most reasons offered 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.

I just wanted to again emphasize, you know, at Taysha, 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 I've already seen the data that Dr. Elsa Rosignol, you know, presented and what Sean just said. As far as commenting, you know, on NeuroGene'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, about the age of six. And as Sean highlighted and Dr. Rosenjohn highlighted, when you see a gain of a new skill or regain of a lost skill, the odds are very likely it's the TASIA gene therapy intervention. And we've seen patients actually change their lives by gaining these skills or developmental milestones and having an improvement in their activities of daily living. You know, things that I would say that I take for granted by 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 that ability to change their lives in such a manner and work with the advocacy groups and the physicians who are experts in this field and the regulators such as the FDA, you know, gives us a lot of satisfaction having come back to do this for Teshawana. to end the patient population. So thank you.

Thank you. The next question comes from the line of Gil Blum from Needham and Company. Please go ahead.

Hey guys, this is Ethan Anand for Gil. Congratulations on the progress this quarter. So your competitor recently received regulatory feedback that a six-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.

Thank you. ...showed a six-monitor rate at six 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 six-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 six-month interim. It's more the particulars of the assessments.

Thank you. The next question comes from the line of Maury Raycroft from Jefferies. Please go ahead.

Good morning. This is James Ahm from Maury. Congratulations on the progress this quarter, and thanks for taking our questions. 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 CGI data points? Do you anticipate that the data will be at a medical conference or a company update?

I can conference on a company update. And, you know, we'll provide more specifics over the coming weeks and months leading into it, James. But, you know, there's a lot of information that we captured, as I mentioned earlier, and we cast a pretty wide net. And some of that, and that also included additional videos that we haven't talked about, different ways to get it. So we want to share with the community, give a more fulsome picture of improvements.

Thank you. The next question comes from the line of Birin Amin from Piper Sandler. Please go ahead.

Thanks for taking my questions. 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-to-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?

Well, it's a massive offer 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, you know, I think first for the pivotal trial, we've shared that with the FDA. That's made with the commercial process at scale. And the FDA is certainly a combination of the raise that we did and Cameron's good work with reworking the mission on the CMC.

Thank you. We take the next question from the line of Jack Allen from Baird. Please go ahead.

Great. Thanks for taking the questions, and congrats on the update here. very holistic update uh i guess i wanted to ask just more specifically on your your recent interactions with regulators it seems like you have sign off from the the canadian authorities um 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 uh as it relates to those those conversations if they're ongoing or you have you achieved a formal sign off where do things sit there, and then any additional color around European regulatory discussions would be interesting as well. Thank you so much.

Yeah, Jack, great question. So a couple things. There's no letter and things of that nature, and I would characterize it as it's like further alignment is what we're looking for, that the ongoing, you know, FDA dialogue is focused success versus getting into overturning any key, you know, trial design elements or things of that nature. So it's been very, you know, 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, you know, when we give our next earnings call. Thanks for the question.

Thank you. Thank you. 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.

I just want to thank everyone for their time this morning, including our special. We wish you all a great week.

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.