Taysha Gene Therapies Q2 2025 Earnings Report

Taysha Gene Therapies EPS Results

• Actual EPS: -$0.09
• Consensus EPS: -$0.07
• Beat/Miss: Missed by -$0.02
• One Year Ago EPS: N/A

Taysha Gene Therapies Revenue Results

• Actual Revenue: $1.99 million
• Expected Revenue: $1.61 million
• Beat/Miss: Beat by +$381.00 thousand
• YoY Revenue Growth: N/A

Taysha Gene Therapies Announcement Details

• Quarter: Q2 2025
• Date: 8/12/2025
• Time: Before Market Opens
• Conference Call Date: Tuesday, August 12, 2025
• Conference Call Time: 8:30AM ET

Taysha Gene Therapies (NASDAQ:TSHA), a gene therapy company, focuses on developing and commercializing adeno-associated virus-based gene therapies for the treatment of monogenic diseases of the central nervous system. It primarily develops TSHA-120 for the treatment of giant axonal neuropathy; TSHA-102 for the treatment of Rett syndrome; TSHA-121 for the treatment of CLN7 disease; TSHA-118 for the treatment of CLN1 disease; TSHA-105 for the treatment of for SLC13A5 deficiency; TSHA-113 for the treatment of tauopathies; TSHA-106 for the treatment of angelman syndrome; TSHA-114 for the treatment of fragile X syndrome; and TSHA-101 for the treatment of GM2 gangliosidosis. Taysha Gene Therapies, Inc. has a strategic partnership with The University of Texas Southwestern Medical Center. Taysha Gene Therapies, Inc. was incorporated in 2019 and is headquartered in Dallas, Texas.

Taysha Gene Therapies Q2 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Company has secured FDA and Health Canada alignment on its REVEAL pivotal trial design, commenced site activation, and expects to begin patient enrollment in Q4 2025.
• Positive Sentiment: In Part A of REVEAL, all 10 treated patients (100%) gained or regained one or more developmental milestones with no treatment-related serious adverse events, underscoring the candidate’s potential efficacy and safety.
• Positive Sentiment: Completed a public follow-on offering raising $230 million and refinanced debt to extend the cash runway into 2028, bolstering the company’s financial runway.
• Neutral Sentiment: Robust natural history analysis showed ~0% likelihood of milestone gain/regain after age six, defining the “developmental plateau” and informing an objective primary endpoint.
• Positive Sentiment: Pivotal⁠-batch CMC material has been released and deemed comparable to clinical lots, demonstrating readiness for future BLA submission.

Presentation

[Operator]

Ladies and gentlemen, good morning, and welcome to Tasia Gene Therapy's Second Quarter twenty twenty five Earnings Conference Call. At this time, all participants are in listen only mode. A brief question and answer session will follow the formal presentation. 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.

[Hayleigh Collins, Senior Director - Corporate Communications & IR at Taysha Gene Therapies Inc]

Thank you. Good morning, and welcome to our second quarter twenty twenty five financial results and corporate update conference call. Earlier today, Tatia issued a press release announcing financial results for the second quarter ended 06/30/2025. 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 Zukumar Nagandran, President and Head of R and D Cameron Alam, Chief Financial Officer and Doctor.

[Hayleigh Collins, Senior Director - Corporate Communications & IR at Taysha Gene Therapies Inc]

Elsa Rosignol, Director of the Integrated Rett Syndrome Clinic at St. Justine in Montreal and Principal Investigator of the VEAL Phase onetwo 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 Doctor.

[Hayleigh Collins, Senior Director - Corporate Communications & IR at Taysha Gene Therapies Inc]

Rosignol will be available to take questions until 09:20 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 TATIA-one hundred two, 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 also the course of disease in the patients we seek to treat, our research development and regulatory plans for our product candidates including the timing initiating additional trials, reporting data from our clinical trials and making regulatory submissions. Timing or outcomes of communications with the FDA and Health Canada on the regulatory pathway for TATIA-one hundred two, the potential for product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies and the market opportunity for our programs.

[Hayleigh Collins, Senior Director - Corporate Communications & IR at Taysha Gene Therapies Inc]

This call may also contain forward looking statements relating to TAETIA'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 Teixa'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 ks for the full year ended 12/31/2024 that we filed 02/26/2025 and our quarterly report on Form 10 Q for the quarter ended 06/30/2025 we filed today. This conference call contains time sensitive information that's accurate only as of the date of this live broadcast, 08/12/2025. 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.

[Hayleigh Collins, Senior Director - Corporate Communications & IR at Taysha Gene Therapies Inc]

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

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Thank you, Haley, 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 TATIA-one hundred two Rett syndrome program, including new details of our FDA aligned pivotal trial design and our registrational pathway. Next, Sukhu will discuss our natural history data analysis which underpins our REVEAL pivotal trial design. I've invited Doctor. Elsa Rosenau, Director of the Integrated Rett Syndrome Clinic at St.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Justine in Montreal and a Principal Investigator of the REVEAL trials to present the previously disclosed Part A clinical data from our REVEAL Phase onetwo 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. Cameron 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 TATIA-one 102 program.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 TATIA-one 102 and strengthening our balance sheet. We believe this meaningful progress sets us on a clear and efficient path towards the potential registration of TATIA-one hundred two. 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 REVEAL pivotal trial.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 fifteen thousand to twenty thousand patients across The U. S, Europe and UK.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

It often necessitates 20 fourseven 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. TATIA-one hundred two 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 TATIA-one hundred two 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Another important distinction is that TATIA-one hundred two 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 TATIA-one hundred two across a broad patient population.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Our robust analysis of the Rett syndrome natural history dataset 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 TATIA-one 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 A data from our REVEAL 1.2 trials, it's encouraging that all 10 patients treated with TATIA-one hundred two gained or regained one or more developmental milestones corresponding to a one hundred percent response rate for the pivotal trial primary endpoint based on the May 25 data cut off.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

With safety at the forefront, we are pleased to share the low and high dose of TATIO-one hundred two continue to be generally well tolerated with no treatment related serious adverse events or dose limiting toxicities in the twelve patients treated as of August 2025 data cut off. Lastly, we recently completed a public follow on offering that resulted in total gross proceeds of $230,000,000 including full exercise of the underwriters 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 TATIA-one hundred two to benefit patients living with this devastating disease. Our REVEAL clinical development program was designed to support the future approval of TATIA-one hundred two for the treatment of females aged two years and older with Rett syndrome. Recall Part A was our dose escalation phase where we treated 12 patients aged six to 21 years.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

In our two Phase onetwo REVEAL trials with one of the two dose levels. The totality of the Part A data help 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 TATIA-one hundred two in the pre developmental plateau population of females aged two to less than six 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Importantly, we believe this two 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 zero percent likelihood of spontaneous milestone achievement in this population. From a CMC perspective, the pivotal TATIA-one hundred two 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Furthermore, the streamlines are passed to initiating the pivotal trial and underscores our CMC readiness to support a future BLA submission. Our REVEAL pivotal trial for TATIA-one hundred two will reflect a single arm open label pivotal trial design with each patient serving as their own control. The high dose of TATIA-one hundred two of 1e to the 15 total vector genomes will be evaluated and we will enroll 15 females between the ages of six 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 and Health Canada as part of our recent feedback.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

With this established, we continue to believe Part A of our REVEAL trial supports the pivotal trial as well powered to establish efficacy. We plan to conduct a six month interim analysis in addition to a twelve month primary analysis, which could potentially expedite BLA submission by two to three quarters. Key secondary endpoints include the average number of total developmental milestones gained or regained per patient following TATIA-one hundred two as well as clinician assessed outcomes including the rMVA 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 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 define 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 Sukhu to discuss this. Sukhu?

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

Thank you, Sean.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

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 six to twelve month intervals. We selected a large cohort of approximately 1,100 females with up to fourteen years of follow-up who closely aligned with our REVEAL trial enrollment criteria. We used 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.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

These models showed clear age and time based trends in developmental milestone acquisition that have strengthened the field understanding of longitudinal disease progression, substantiated the disease modifying potential of TACHA-one hundred two 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 six years of age or older. Here you will 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 with approximately zero percent likelihood of an individual gaining these milestones.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

We leverage these findings to establish the developmental plateau population, which is the population of age six years and older, at which the likelihood of milestone gain and regain becomes predictable. And as mentioned, this is the co 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 zero percent and less than six percent likelihood of spontaneous achievement in untreated individuals aged six years and older. This illustrative graphic helps put these findings into context. Our natural history analysis uncovered the developmental plateau population of patients aged six years and older, where there's an exceedingly low chance of two things: number one, gaining new developmental milestones and number two, regaining developmental milestones that were lost after a defined number of years.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

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 TESHA-one hundred two 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 TESHA-one hundred two'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.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

To qualify as a milestone achievement following TAESA-one hundred two, there were three criteria that had to be met. First, the milestone had either never been gained or was lost sufficiently long ago such that the likelihood of spontaneous gainregain was less than six point seven percent based on reviews of patients' medical history and available baseline video data. Second, there had to be video documentation of the milestone achievement post TACHA-one hundred two treatment. Third, this video evidence was independently evaluated by multiple external central raters who use pre specified 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 TASHA-one hundred two'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 TACHA-one hundred two.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

Beyond the video evidence milestone data, we collected data that further demonstrate developmental milestone achievement 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 Doctor. Elsa Rosigno to present the previously disclosed Part A data. Elsa?

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

Thank you. Thank you. So it's a pleasure to be here and to describe what we've, as Sukou said, already presented in the IRFS meeting in June. And so next slide, please. Okay.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

So as we're moving on, we've observed, as Sukhu was mentioning I'm sorry. Do you hear me? Can you move the slide? Are you guys hearing me?

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Yeah, we can hear you.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

Okay, very good. So please move the slides. Thank you. All right, so as Sukka 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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 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 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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 adolescents. So we're eager to see the development of this data moving forward with the twelve months and eighteen months cutoff for the high dose patients. And so looking at the gains that we've observed in the cohorts 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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, bye, mom, whereby 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 gain 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, you know, going to brush your feet or eating meal or it's time to prepare for school or nothing.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

Some patients have gained the ability to point to things they want or to identify body parts. This may seem like, you know, 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 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, you know, caring for these patients. So communication was key, both receptive and expressive.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

In terms of fine motor, we've seen patients gaining the ability to hold a bottle unpropped, 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 pincer grasp, this is a huge improvement in independence. Reaching for a toy and transferring objects from one hand to the other, 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 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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 slides, 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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, 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 godsend 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 is really helpful if a child can finally stand by them all their own even through holding. And the consistency of keeping our hands down without constant stirratippies allows us to practice more tasks such as using a walker, which has been huge.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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 striking and broad the gains were, so it's not restricted to one single domain.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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 one hundred percent 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 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 cutoff was made.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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 scales 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 RRSPQ.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

So the RRSPQ tends to be focused on communication and breathing and irritability and things like that. But the RMBA, please go back to the previous slide. RNBA 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 twelve months in the cohort, suggesting a very drastic improvement that is, of course, beyond one sickle domain because this scale really assessed very broadly multiple aspects of the disease.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

And when we compare it to the natural history, this gain of 11 points at six months and of 12.8 points at twelve months is very, very striking. Please show the slide that I'm describing, which is this next one. Yes, this is the one where we see the score, 11 points improvement compared to natural history and 12.8 points at twelve months compared to natural history. So this is really unheard of and very striking in terms of the depth of the improvement. Next slide.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

The next scale that we're showing is results from the CGI I, and the CGI I is this Clinical Global Impression Improvement Scale. This is the global impression that clinicians will share after taking into account everything that has been done at this visit, including the RMA, the physical exam, SBQ, 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 the scale.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

And once again, the high dose patients overperform 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 dataset comparing the low dose and the high dose that really illustrates many of the points that I've shared today.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

First of all, all of the patients were responder based on this developmental milestone assessment, so one hundred percent of low dose and high dose cohort reached at least one milestone, and this was achieved faster in the high dose cohort. In terms of the RNDA, 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 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 improvement at more than nine months. Then in terms of CGI I, as I mentioned, all patients improved.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

So at the cutoff, we had seventy five percent of patients in the low dose that had improved on the CGI I scale and one hundred percent 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 very much improved grade at more than nine months. So we are gaining even more. Now in terms of the CGI IS, this is the severity 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 CGI F because you need very striking gains to switch one item out of that grid.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

And so we observed thirty three percent of the high dose cohort changing severity to a better grade and twenty five percent 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 Tysha102 has been, you know, 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

We've observed, of course, some treatments induced adverse events associated to PSHA-one hundred two. Most of them were in the mild, some were in the moderate severity range. The most frequent ones were elevated liver enzymes, 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 sequel life. Other side effects that were observed associated with TAESA-one hundred two are side effects expected for AAV therapies, so fever, lethargy after the lumbar puncture treatment, and increase in protein in the CSF. Overall, were well controlled in this cohort.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

So I'm done with my slides and I'm moving the call back to the Tasia team.

[Kamran Alam, CFO at Taysha Gene Therapies Inc]

Thank you, Doctor. Rosenkull. Research and development expenses were $20,100,000 for the three months ended 06/30/2025, compared to $15,100,000 for the three months ended 06/30/2024. The $5,000,000 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 three months ended 06/30/2025. General and administrative expenses were $8,600,000 for the three months ended 06/30/2025 compared to $7,300,000 for the three months ended 06/30/2024.

[Kamran Alam, CFO at Taysha Gene Therapies Inc]

The increase of $1,300,000 is primarily due to higher legal and professional fees. Net loss for the three months ended 06/30/2025 was $26,900,000 or $09 per share compared to a net loss of $20,900,000 or $09 per share for the three months ended 06/30/2024. As of 06/30/2025, Tasi had $312,800,000 in cash and cash equivalents. This reflects gross proceeds of $230,000,000 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 $40,000,000 which was paid in full to a net new debt facility equal to $50,000,000 upfront.

[Kamran Alam, CFO at Taysha Gene Therapies Inc]

The refinance loan defers debt principal payments by more than two point five 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.

[Kamran Alam, CFO at Taysha Gene Therapies Inc]

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?

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Thanks, Cameron. I'm pleased with the progress we have continued to make to advance our TATIA-one hundred two program.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 onetwo trials supporting the broad therapeutic impacts of TATIA-one hundred two 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 TATIA-one hundred two to patients with this devastating disease as expeditiously and safely as possible. I will now ask the operator to begin our Q and A session. Operator?

[Operator]

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Session. We take the first question from the line of Salveen Richter from Goldman Sachs. Please go ahead.

[Lydia Erdman, Biotech Equity Research Analyst at Goldman Sachs]

Hi, good morning. This is Lydia on for Salveen. Thanks so much for taking our question. I guess given there was 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 build the statistical plan for Part B and keep in mind that we're using a null hypothesis of six point seven percent, which was the highest percentage of a gain regain per milestone that we're evaluating. And when you take that into account with a fifteen patient population that would mean one patient out of fifteen would spontaneously have a potential gain or regain. So, the statistical bar to get over is relatively low.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

All things speaking, it's approximately thirty three percent 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.

[Operator]

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

[Kristen Kluska, Equity Research Analyst at Cantor Fitzgerald]

Hi, good morning. I'll ask my question for Doctor. Rothengel. 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?

[Kristen Kluska, Equity Research Analyst at Cantor Fitzgerald]

Are you seeing 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Elsa, please feel free to take that.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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. 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.

[Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine]

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.

[Operator]

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

[Tazeen Ahmad, MD - US Equity Research at Bank of America]

Hi, guys. Good morning. 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.

[Tazeen Ahmad, MD - US Equity Research at Bank of America]

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? Thanks.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Yes. Thanks, Stacy. It's good to hear from you. Sukum, 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 at 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 two years and hear Sukou 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 that's going to mean a lot with payers as well.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

And then the additional endpoints that we're looking at relative to rMDA CGI, again we can benchmark RMBA to the natural history and it's exceptionally compelling. I mean effectively natural history is about 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 payers and supporting them.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

And I think you combine the efficacy impact that you're seeing with the safety that we've been able to generate today and we think that is very much attributed to two 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.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

Sean, would add one more thing to Azim. By the way, nice to hear your voice. I just want to again emphasize at Taecia, 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 Doctor. Elsa Rosignol presented and what Sean just said.

[Sukumar Nagendran, President & Head - Research & Development at Taysha Gene Therapies Inc]

As far as commenting on Neuogen's protocol, 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 of and it's a fourteen year period. So given our experience in looking at this data set, it's very clear that once you get above the age of six and you do a therapeutic intervention such as TACHA-one hundred two and as Sean highlighted and Doctor. Rozinjal highlighted, when you see a gain of a new skill or regain of a lost skill, the odds are very likely it's the patient 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 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 gives us a lot of satisfaction having come back to do this for TAEUSH one hundred two and the patient population. So thank you.

[Operator]

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

[Ethan Markowski, Equity Research Associate at Needham & Company]

Hey guys, this is Ethan on 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Yes, it was part of our submission and I would say a couple of things and we can only speak to the Taeja interactions and feedback. But one of the things that we really try to highlight in Sukou'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 of both six and twelve 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 six months and what we're actually seeing. So recall one of the slides that also went through showed at six months of the high dose there is an eighty three percent responder rate at six months and then that improves and deepens over the course of twelve months.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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. So we feel good about where we stand at this particular point in time.

[Operator]

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

[Analyst]

Good morning. This is James on for 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?

[Analyst]

Do you anticipate that the data will be at a medical conference or a company update?

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

I can see it being at both medical conference and the 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.

[Operator]

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

[Biren Amin, MD & Senior Research Analyst at Piper Sandler Companies]

Yes. Hi, guys. 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? Thanks.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Yes, Biren, as you know, it's a massive opportunity, right. I just in The U. S. If we're talking around 10,000 patients, it's a massive unmet need. So, it's very important from our perspective and we've been working as a team.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Unfortunately, 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 very important. We've already made the products 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

So certainly, one of the things that we did with and are thinking about this is, we could have extended our cash runway into mid-twenty twenty eight, because of the combination of the raise that we did and Cameron'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.

[Operator]

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

[Jack Allen, Senior Research Analyst - Biotechnology at Baird]

Great. Thanks for taking the questions and congrats on the update here, very whole holistic update. I guess I wanted to ask just more specifically on your recent interactions with regulators. It seems like you have signed 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?

[Jack Allen, Senior Research Analyst - Biotechnology at Baird]

If they're ongoing or 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

Yes, Jack, great question. So a couple of things and Sukhu checked 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 thirty seven 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.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

I mean, also is working through things with our 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 is no official correspondence that you get, there is no letter that you get. There is generally an unofficial thirty day, if you don't hear something you can proceed.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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 that 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 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 we position the program for success versus getting into overturning any key trial design elements or things of that nature. So it's very constructive and supportive.

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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.

[Operator]

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

[Sean Nolan, CEO & Chairman at Taysha Gene Therapies Inc]

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

[Operator]

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

Participants

Executives

• Hayleigh Collins, Senior Director - Corporate Communications & IR
• Sean Nolan, CEO & Chairman
• Sukumar Nagendran, President & Head - Research & Development
• Kamran Alam, CFO

Analysts

• Elsa Rossignol, Pediatric Neurologist at CHU Sainte-Justine
• Lydia Erdman, Biotech Equity Research Analyst at Goldman Sachs
• Kristen Kluska, Equity Research Analyst at Cantor Fitzgerald
• Tazeen Ahmad, MD - US Equity Research at Bank of America
• Ethan Markowski, Equity Research Associate at Needham & Company
• Analyst
• Biren Amin, MD & Senior Research Analyst at Piper Sandler Companies
• Jack Allen, Senior Research Analyst - Biotechnology at Baird