Taysha Gene Therapies Q3 2026 Earnings Call Transcript

Taysha Gene Therapies (NASDAQ:TSHA) reported third-quarter financial results on Thursday. The transcript from the company’s third-quarter earnings call has been provided below.

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Summary

Taysha Gene Therapies reported a net loss of $39.1 million for Q3 2026, with increased R&D and G&A expenses driven by clinical trial costs and commercial readiness efforts.

The company completed dosing in the REVEAL and ASPIRE trials, with all patients clearing the acute post-dosing safety monitoring period, indicating a favorable safety profile for Taysha 102.

A major manufacturing milestone was achieved with the completion of the BLA-enabling PPQ manufacturing campaign for Taysha 102, supporting potential future commercialization.

Taysha remains on track for a potential BLA submission based on the REVEAL pivotal trial six-month interim analysis, with FDA feedback expected in the first half of 2027.

The company plans to nominate an additional gene therapy candidate targeting a CNS disorder in the first half of 2027, aiming to expand its genetic medicines franchise.

Full Transcript

OPERATOR

Thank you for standing by, and welcome to Taysha Gene Therapies Third Quarter 2026 Financial Results Conference Call. Currently, all participants are in a listen-only mode. After the speaker’s presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press Star 11 on your telephone to remove yourself from the queue. You may press Star 11 again. I would now like to hand the call over to Stephanie Webster.

Please go ahead.

Stephanie Webster (Investor Relations)

Thank you. Good morning, and welcome to Taysha Gene Therapies’ third quarter 2026 financial results and corporate update conference call. Earlier today, Taysha Gene Therapies issued a press release announcing financial results for the quarter ended September 30, 2026. A copy of this press release is available on the company’s website and through our SEC filings. Joining me on today’s call are Sean Nolan, Taysha’s Chair and Chief Executive Officer; Sukumar Nagendran, President and Head of R&D; and Kamran Alam, Chief Financial Officer. We will hold a question-and-answer session following our prepared remarks on today’s call.

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

This call may also contain forward-looking statements relating to Taysha’s growth, forecasted cash runway and future operating results, discovery and development of product candidates, including our potential nomination of an additional gene therapy candidate in the first half of 2027, manufacturing and commercial readiness activities, strategic alliances and intellectual property, as well as matters that are not historical facts or information. Various risks may cause Taysha’s actual results to differ materially from those stated or implied in such forward-looking statements.

For a list and description of the risks and uncertainties that we face, please see the reports we have filed with the SEC, including in our Annual Report on Form 10-K for the full year ended December 31, 2025 that we filed on March 19, 2026. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 12, 2026. Taysha Gene Therapies undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities laws.

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

Sean Nolan (Chief Executive Officer)

Thank you, Stephanie, and welcome, everyone, to our third quarter 2026 financial results and corporate update conference call. On today’s call, I will begin with an update on our recent clinical, manufacturing, and commercial readiness activities. Dr. Suku Nagendran, President and Head of R&D, will then provide an update on the Taysha 102 program. Then Kamran Alam, our Chief Financial Officer, will follow up with a financial update, and finally I will provide closing remarks before opening the call up to questions.

During the Q&A, Dr. Fred Porter, Chief of Staff and Technical Operations Officer, will also be available for questions. The third quarter marked another period of strong execution for Taysha, during which we made meaningful progress across our clinical, manufacturing, and commercial readiness activities, supporting a potential BLA submission and the potential future commercialization of Taysha 102. As we round out the year, we remain focused on building upon the robust data set generated thus far in preparation for a potentially catalyst-rich period ahead, including topline data from the REVEAL pivotal trial six-month interim analysis and potential FDA feedback on the BLA submission pathway expected in the first half of 2027.

I’ll first touch on our clinical progress, which Suku will elaborate on later on the call. Following the completion of dosing in both the REVEAL pivotal and ASPIRE trials, we are pleased to announce that all 33 patients dosed with Taysha 102—29 in the REVEAL Phase 1/2 and pivotal trials and 4 in the ASPIRE trial—have cleared the acute post-dosing safety monitoring period associated with AAV gene therapies. The last pivotal trial patient was dosed over four and a half months ago, and the last ASPIRE patient was dosed over three months ago.

We are very encouraged by our clearance of the acute safety window, which continues to demonstrate that Taysha 102 is well tolerated in all patients. This represents a key milestone for our program and gives us further confidence in the favorable safety profile observed to date and the continued advancement of Taysha 102 toward a potential BLA submission and potential future commercialization. As a reminder, once all patients in the REVEAL pivotal trial complete six months of follow-up, we will conduct an interim analysis, which may serve as the basis of our planned BLA submission and potentially accelerate our submission timeline by at least two full quarters relative to filing on the 12-month data. We continue to expect to report both topline data from the interim analysis and potential feedback from the FDA on next steps in the BLA submission pathway in the first half of 2027.

Both high- and low-dose Taysha 102 continue to be generally well tolerated. Notably, across the broader Taysha 102 clinical program, which began over three years ago, 33 patients spanning a broader range of ages, genotypes, and disease severities have been treated with no severe treatment-related serious adverse events or dose-limiting toxicities reported as of the November 2026 data cutoff, supporting a favorable and consistent safety profile for trial participants across the program.

I also want to touch on our commercial readiness efforts and the achievement of a major manufacturing milestone in the fourth quarter of 2026 with successful completion of our BLA-enabling Process Performance Qualification, or PPQ, manufacturing campaign for Taysha 102. Recall, following a Type C meeting in January 2026, we aligned with the FDA on our proposed PPQ strategy, including the production of commercial-scale drug product batches required to validate our final Taysha 102 commercial manufacturing process in support of our planned BLA submission.

We have now completed the BLA-enabling PPQ manufacturing campaign for Taysha 102, with all process parameters and analytical results meeting the predefined product specifications as well as comparability criteria for commercial product and clinical material. In addition, our assessment of comparability between PPQ commercial product and the clinical trial material conducted under the FDA-aligned strategy supports the potential inclusion of the REVEAL Part A data in the planned BLA submission, further supporting the potential for a BLA submission based on the pivotal six-month trial interim analysis.

We are also very pleased with the yield and the number of finished good doses manufactured from each of our PPQ batches, which we believe should translate to efficient and favorable cost of goods sold to support our potential commercial launch. Additionally, the commercial manufacturing process consistently achieved a single-digit empty capsid percentage—an important indicator of product quality that contributes to patient safety. These results demonstrate our ability to consistently manufacture high-quality product at the scale required to support the potential commercial demand and potential commercialization.

We look forward to sharing these data and finalizing our CMC plan with FDA at a Type B meeting expected later in this fourth quarter. Beyond manufacturing, we also continue to advance our broader commercial readiness efforts during the third quarter, further building out our commercial organization and advancing key market access initiatives, including expanding our payer team, conducting pre-approved information exchange discussions with payers, progressing site readiness activities at institutions, and advancing trade and distribution readiness activities to support the potential launch of Taysha 102.

We believe the progress made across clinical, manufacturing, and commercial readiness efforts has positioned us well for multiple key upcoming regulatory interactions. In the fourth quarter, we plan to discuss the manufacturing data with the FDA to further strengthen the CMC package. Thereafter, we plan to engage with the FDA on next steps in a potential BLA submission pathway and will share the feedback from this meeting along with the topline data from the six-month interim pivotal trial analysis in the first half of 2027.

With multiple potential milestones on the horizon for Taysha’s Rett program, we continue to leverage our expertise in CNS genetic medicines, and as we begin to position Taysha as a broader genetic medicines franchise, we expect to nominate an additional gene therapy development candidate targeting a CNS disorder with high unmet medical need and robust commercial opportunity and commence preclinical development activities in the first half of 2027.

With that, I’ll turn the call over to Suku.

Sukumar Nagendran (President and Head of R&D)

Thank you. As Sean highlighted, we achieved several important milestones this quarter that we believe further strengthen the foundation of TSHA-102 and its path towards potential registration. As a reminder, 33 patients have been treated with TSHA-102 in the REVEAL Phase 1/2, REVEAL Pivotal, and ASPIRE trials across studies, dose levels, and a broad patient population. TSHA-102 continues to be generally well tolerated with no severe treatment-related serious adverse events or dose-limiting toxicities observed as of the November 2026 data cutoff.

Notably, this favorable safety profile includes the ASPIRE trial, where no treatment-related serious adverse events have been reported amongst participants as young as 2 and 3 years of age. As Sean mentioned, all patients in the REVEAL and ASPIRE trials have now cleared the acute post-dosing safety monitoring period commonly associated with AAV gene therapy. With all patients in the REVEAL Pivotal and ASPIRE trials now beyond this period, and no severe treatment-related serious adverse events or dose-limiting toxicities identified across all 33 patients, the growing safety dataset continues to support the favorable and consistent safety profile observed across our TSHA-102 program, and the benefit-risk profile continues to remain highly favorable.

In the third quarter, we further highlighted the scientific foundation supporting TSHA-102 through multiple encore presentations at the 55th Child Neurology Society annual meeting. Daisha’s oral presentation and three poster presentations featured data previously presented at the International Rett Syndrome Foundation scientific meeting highlighting longer-term REVEAL Part A data, natural history analysis, and psychometric validation work, all of which support the clinical and regulatory foundation for TSHA-102.

Taken together, the growing safety dataset, durability and consistency of clinical responses observed to date, along with continued progress across the TSHA-102 scientific foundation, further strengthen our confidence in the TSHA-102 program and our potential regulatory pathway. I will now turn the call over to Kamran.

Kamran Alam (Chief Financial Officer)

Thank you, Suku. Research and development expenses were $28.8 million for the three months ended September 30, 2026, compared to $25.7 million for the three months ended September 30, 2025. The $3.1 million increase was primarily driven by higher clinical expenses from the REVEAL Phase 1/2, REVEAL Pivotal, and ASPIRE trials. Compensation expenses, including non-cash stock-based compensation, also increased as a result of additional research and development headcount.

General and administrative expenses were $13.1 million for the three months ended September 30, 2026, compared to $8.3 million for the three months ended September 30, 2025. The increase of $4.8 million was primarily due to higher compensation expenses, including non-cash stock-based compensation expense, and increases in consulting and professional fees, including commercial launch readiness initiatives. Net loss for the three months ended September 30, 2026, was $39.1 million, or $0.10 per share, compared to a net loss of $32.7 million, or $0.09 per share, for the three months ended September 30, 2025.

As of September 30, 2026, Taysha Gene Therapies had $422.8 million in cash and cash equivalents. We expect that our current cash resources will support planned operating expenses and capital requirements into the second half of 2028. I will now turn the call over to Sean for his closing remarks.

Sean Nolan (Chief Executive Officer)

Thank you, Kamran. We believe the progress made this quarter further strengthens the clinical, manufacturing, and regulatory foundation supporting TSHA-102 as we advance toward a potential BLA submission and work to bring this potentially transformative therapy to the Rett syndrome community. With all patients in the REVEAL and ASPIRE trials dosed and past the acute post-dosing monitoring period, and the BLA-enabling PPQ campaign complete, we remain focused on generating a rigorous dataset and preparing for upcoming FDA interactions next year.

We expect FDA feedback following our CMC Type B meeting in the first quarter and plan to report top-line data from the REVEAL Pivotal six-month interim analysis, along with FDA feedback on the planned BLA submission pathway, in the first half of 2027. We continue to see a potential path to a BLA submission based on either the six-month interim or the 12-month Pivotal trial data and expect to provide greater clarity on the planned submission pathway in the first half of 2027.

In parallel, we plan to continue to advance our long-term vision of building a broader CNS genetic medicines franchise with the nomination of an additional gene therapy candidate in the first half of 2027. I would like to recognize the expertise and vigilance of our participating principal investigators, the rigorous training and oversight provided by our clinical development and clinical operations teams, as well as our CRO and CDMO partners, and, importantly, the commitment of the patients and caregivers whose participation in the trials and dedication help ensure the best possible outcome for the Rett syndrome community. With that, I will now ask the operator to begin our Q&A session.

OPERATOR

Thank you. As a reminder, to ask a question, you will need to press star-11 on your telephone to remove yourself from the queue. You may press star-11 again. You will be limited to one question to allow everyone the opportunity to participate. Please stand by while we compile the Q&A roster. Our first question comes from the line of Kristen Kluska of Cantor. Your line is open.

Kristen Kluska (Analyst)

Hi, good morning, everybody. Congrats on the progress, and thanks for taking my question. The question I had for you is we understand what the bar needs to be for the upcoming readout in order for the trial to be deemed statistically significant and successful, but how are you thinking about the clinical bar, perhaps to make this competitive at a six-month analysis? And then, assuming you are in a position where you can file, will we still get to see the 12-month data at some point?

Thank you.

Sean Nolan (Chief Executive Officer)

Thanks a lot, Kristen. Appreciate that. I think we’ll start with your second part of your question. The short answer is yes. I mean, we would definitely share the 12-month data that would ultimately become part of the product label. So I don’t see that there’s any competitive challenges with leading with the six-month data. In fact, I think getting to market first is critically important, and if we’re able to do that, I think that positions us well.

If our six-month data are strong enough for us to be able to submit on that, based on the discussions we’ve had with payers thus far, things are lining up nicely in terms of reimbursement broadly, and I think that will only be strengthened as we then augment the label with the 12-month data. But so far, in our discussions with the payers, there’s no impediment to going with six months with the full approval versus waiting for the 12 month in terms of securing proper reimbursement.

So again, we see the six month as all upside and the potential to get to market even faster.

OPERATOR

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

Elizabeth (Analyst)

Great. Good morning, guys. Thanks for taking our question. This is Elizabeth on for Salveen. You mentioned that you will nominate an additional candidate targeting a CNS disorder and start preclinical activities in the first half of next year. Wanted to see if you could give us any more color on where you think Taysha’s capabilities and just expertise in this space would be best suited in terms of an indication or using your delivery platform. Thank you.

Sean Nolan (Chief Executive Officer)

Thanks, Elizabeth. Appreciate the question, and I’ll take that and then certainly open up to Suku to give his perspective as well. I think, number one, we’re going to focus on CNS genetic medicines. I think that is our core expertise. Suku himself has a steeped history in CNS gene therapy development. The team that he has surrounded himself with, both the MDs on our staff as well as the medical affairs teams and the clinical operations group, are all very experienced in CNS and, in particular, CNS genetic medicine.

So I think that’s directly in our wheelhouse. The other thing I would highlight is, I think one of our core competencies, in addition to the clinical and regulatory strengths we have, is on the CMC side. And the work that Fred Porter, Gretchen Smith, the whole team have done is truly outstanding. And I think those of you that have known us over the course of the last decade or so know we’ve really worked to put a premium around the quality of the CMC, and the fact that we’re at commercial scale and single-digit empty-to-full ratio is something that Fred really set as a goal and drove the team, and Gretchen drove the teams, to get there—which we think reduces the amount of dose that the patients are exposed to and hopefully improves and enhances the safety profile.

So I think the combination of those things, along with the relationships on the regulatory side that we’ve developed with the CNS team in genetic medicines at FDA and the credibility that we’ve built, are reasons why we want to continue to expand our footprint in that particular space. Suku, I’m not sure if there’s anything else you might want to add to that.

Sukumar Nagendran (President and Head of R&D)

Yes, Sean. What I would emphasize is, basically as you said, we have a very strong team on the CMC and translational research side under Fred Porter, and we have a very strong regulatory team. I would remind folks that when we were at AveXis, the work we did with the FDA helped set the draft guidance for neurodegenerative disorders for the FDA. I would also say that the work we’ve done at Taysha in the neurodevelopmental disorder space with Rett syndrome has also helped mature the neurodevelopmental guidance that has come out from the FDA in draft form.

Furthermore, we also have significant clinical experience in taking our CMC product—where the empty capsids are now in the single digits—which translationally could have significant potential clinical impact for us across the board. We also look at commercial opportunities with large patient populations for the future, where we can use our preclinical experience on the translational side, looking at animal models of a disease state that translate to the CNS rare disorder space with large commercial populations.

That can not only help pivot Taysha beyond the lead program of Rett syndrome to other relevant commercial opportunities and clinical opportunities in the CNS space. So we are looking forward to doing what we have to do to further progress our pipeline.

OPERATOR

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

Biren Amin (Analyst)

Yeah, thanks for taking my questions, and congrats on all the progress. On the FDA meeting where you discuss the interim data at six months—I think that’s going to happen early next year—how much data will be shared with FDA from the Part A patients, and the correlation of activity from six months to longer-term follow-up that allows FDA read-through on the duration of response with the six-month interim? And then on the CMC Type B meeting, FDA recently finalized CMC guidance 10 days ago on cell and gene therapy.

How does your PPQ campaign align with that final guidance? Thank you.

Sean Nolan (Chief Executive Officer)

Yes. So on the first question, we will update the FDA on the part A data that we have. I think it would be a data cut post certainly well beyond 12 months. I know that. And we’ll share any safety data that we have over the course of time with them, which is like the update you just got with no severe treatment-related SAEs or DLTs. That’ll continue to get updated for the FDA from a safety perspective as well. So they’ll definitely see the part A data.

We will share all of the primary endpoint and secondary endpoint data with them at that meeting as well so they can get a fulsome look at the totality of the evidence and how things are lining up at six months. And it’s our belief that if the part B data continue to move forward and resemble what we saw in part A, the combination of the pivotal data plus the long-term part A data is going to be very helpful and very well may facilitate us being able to file on the six-month data set.

As it relates to CMC, I think the best person to answer how the guidance from the FDA stacks up against our PPQ results is Fred Porter. So Fred, would you mind taking that question, please?

Fred Porter (Chief of Staff and Technical Operations Officer)

Yes, John, I’m happy to. Thanks for the question. Yes, the recent guidance that got finalized around potency assay strategy is kind of a key part of the conversation we intend to have with the agency later this year. We’ve been talking to the agency over the course of this program about our potency assay strategy, really leveraging that matrix approach, and what we hope to do on this final meeting ahead of our BLA submission is really solidify our final commercial potency release strategy, leveraging all the elements of that guidance.

And so we’re very well aligned with that finalized guidance that just came out and really look forward to sharing that data with the agency and getting their feedback. Thanks for the question.

OPERATOR

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

Wesley (Analyst)

Hi, good morning, this is Wesley on for Tazeen. Thanks for the updates today. I had a question on the sequence of events coming forward the second half of next year. When you do the six-month interim, do you plan to announce — I know you’re not going to share the data before the FDA meeting — but do you plan to announce when that interim analysis is finished, and then will you sort of hold everything until, for like one release with the FDA interaction information as well as the primary endpoint data?

Thank you.

Sean Nolan (Chief Executive Officer)

Yeah, Wesley, the way we’re thinking of this is, you know, the trigger for the interim analysis is going to be the last patient hitting their six-month assessment. Right. And right now that’s scheduled within the month of December. So once that occurs, there’s a whole process that takes place where the blind gets broken. Then all the videos have to be reviewed by the blinded raters. So there’s time around that and then we’ll get the top-line data followed by the secondary endpoints.

We’ll request the Type B meeting with the FDA. If things hold on the timeline — again, assuming nobody gets the flu and has to have their appointment delayed or something like that — we would be thinking the FDA meeting would likely occur later in the first quarter, and then the minutes coming, you know, either that same quarter or into early in the second quarter. So that’s why we guided to the first half was just to give flexibility because some of it’s outside of our control, both in terms of the, you know, the patients’ visits and then ultimately, you know, the timing of the FDA minutes, which is normally 30 days, but sometimes it can extend.

So we just wanted to make sure we had the flexibility on that once we have the data. So, you know, sometime in the month of January, you know, the management team will go dark, right? We’re going to have to, you know, stay out of, you know, public discussions until we have that meeting with the FDA and get back. So that’s the sequence of events. The logic behind it, again, is we felt if we put the data out ahead of the FDA feedback, I think we’re going to have a lot of — everyone’s going to have their own opinion of how good it is, you know, should it receive the six-month review or what have you. So we just felt really the opinion that matters the most here is going to be the FDA’s, and we want to be respectful of them. And so therefore we thought it was best to keep it, you know, out of the public eye and then have that discussion with them and then come back and say, look, here’s the data, here’s how the FDA sees the data, and here’s the next steps.

And hopefully in any scenario there, you know, Wes, we’re in a situation where we’re providing, you know, clear line of sight to the market and hopefully, you know, it’s the six-month review, which would be breaking precedent for the FDA. I mean, we feel strongly that if the data are similar to what we saw in part B, that there’s an absolute case for that. If they want to stick to their precedent and go with 12 months, we could explain that to people.

But you’d also get to look at the data. So it really becomes an execution and a timing situation. But the probability of approvability would be high. And then it’s the focus on the commercialization efforts, which our team is well advanced on. So hopefully that gives you a little color as to how we’re stepping through this.

OPERATOR

Thank you. Our next question comes from the line of Maury Raycroft of Jefferies. Your line is open.

Maury Raycroft (Analyst)

Hi, good morning. Congrats on the progress and thanks for taking my question as well. Just checking, besides potency release strategy, is there anything else that you need to clarify in the CMC front in the 4Q Type B meeting? And you expanded the Catalent partnership to commercial supply at Harmans in second quarter, the same quarter when the PPQ test began. Were the PPQ batches made at Harmans?

Sean Nolan (Chief Executive Officer)

Yeah. Again, the best person here would be Fred. Do you mind taking both of those questions, Fred?

Fred Porter (Chief of Staff and Technical Operations Officer)

Sure, I don’t mind at all. A great question around the topics of this meeting are around a few things. One is we wanted to share the results from that PPQ campaign — the performance results, the analytical testing results, and the comparability data like Sean mentioned in the intro. That’s going to be a key discussion with them. We feel like the data we’re going to share aligns with our pre-aligned strategy with them around comparability. But we also want to look forward and position ourselves really strongly for our BLA filing to try to get ahead of any area of uncertainty before we start building our BLA for submission next year. So that’s really the plan, including final specifications, some other key activities that would help enable our commercial readiness and BLA readiness as well.

In terms of where the batches were manufactured, you’re right. We signed our commercialization agreement last year ahead of our PPQ campaign, and we have manufactured our lots at the commercial Harmans facility in Maryland. So thank you for the question.

OPERATOR

Thank you. Our next question comes from the line of Gil Bloom of Needham. Your question, please, Gil.

Gil Bloom (Analyst)

Good morning, everyone, and allow me to add my congratulations on completing dosing and passing the safety interims — very important. Just one from us then. So I’m sure you guys heard some of the reported cases of malignant transformations with Zolgensma. I mean this is kind of a longer-term safety question given it’s a similar strategy as it relates to CNS indications. Just wondering how you guys are thinking of that as a risk and whether you think this is related to just total dose effect of AAV or vector or whatever you guys think could be the cause here.

Thank you.

Sean Nolan (Chief Executive Officer)

Yeah, Gil, I’ll take a real high-level stab at that and then turn the call over to Suku. But I think right now with the amount of information that’s publicly available, it’s difficult. Right? I mean, it looks like there’s nine cases that have been reported. One of the cases was unrelated with a benign tumor. The two others, looks like there was some mutagenesis that had happened. So I think there’s more to tell there. What we don’t know is some of the background rate on some of these tumors and things of that nature in each of the disease states.

So there’s more to come. I think we have to just be patient for that. You know, I would say at a very high level, in our preclinical and clinical data with TSHA-102, we’ve had no evidence of any type of tumor formation. I think you all know we use MRIs at baseline and then at times throughout the study. So, you know, I think we’re in a good situation there and it would have flagged something if we would have seen it thus far. And so I can report on the 33 patients that we’ve dosed to date, we have not had any indication of that kind of situation.

The other thing that seems to be playing out here — you mentioned total dose — this was from an IV dose administered versus a fixed dose directly into the CNS. So that could potentially be a bit of a contributing factor here. And also the construct, you know, I think it’s important — we do not use a widely acting promoter. We use something that’s very focused in the CNS as opposed to a ubiquitous promoter. And our construct doesn’t have any introns in it, which can potentially, theoretically, lead to some type of vector integration.

So I think for all those reasons, you know, right now our view is this is more likely a program-specific kind of a situation. You know, I think we’ll have more data unfold as it occurs, but we don’t see any read-through directly to us. Doesn’t seem to be an AAV9 phenomenon. It may be unique to, again, construct design and potentially biology of the disease itself. But let me pause there and turn it over to Suku to see if he may have additional perspective to share.

Sukumar Nagendran (President and Head of R&D)

Yeah, thanks, Sean. Hey, Gil, that’s a good question. I mean, so keep this in mind though. With gene therapy, usually when you treat the root cause of the disease, especially with lethal central nervous system disorders such as what Zolgensma was approved for, SMA type 1. You know, SMA type 1 kids, usually by 20 months of age, 95% of these children are either not alive or they are on permanent respiratory support. So if you consider that lethality and you look at the number of patients dosed with Zolgensma IV, I think Novartis reported over 6,000 patients had been dosed so far since its approval in 2019.

And out of those 6,000 patients dosed, there were nine cases of tumors reported. I mean, nine patients by Novartis. And out of those nine patients, six patients, the actual history of the disease or the tumors are unclear because Novartis hasn’t given us the details yet. But the three patients who the details are somewhat clear, one of those was a benign astrocytoma, I think in the spinal cord, and there was no evidence of insertional mutagenesis.

The other two cases were thought to be malignant, and there seems to be evidence of insertional mutagenesis of the associated promoter, which I think was a CAG chicken beta-actin promoter. And it appears that the GLI1 tumor suppressor gene may have been activated. But the issue is this. What the product has done, Zolgensma, is it has changed the epidemiologic course of SMA type 1 by now allowing these children to live much longer and potentially healthier lives. And in presymptomatic children, it appears that it’s preventing the disease from occurring from at least the data that I’ve seen. So basically, the epidemiology of the disease has been altered with SMA type 1.

And given that Zolgensma is being used to treat the disease and we’re not sure what the predisposition of this patient population is to tumors, whether benign or malignant, so collectively speaking, the benefit, I think, far outweighs the risk for this patient population with Zolgensma and, frankly, Visma, which is approved for over two years of age, and the number needed to treat for a positive outcome I think is far greater than the number needed to harm in this specific population.

So I would say as a physician and a clinician, I’m pretty comfortable with Zolgensma and Iclisma continuing to do what it does in this highly lethal, high-risk patient population. I hope that it helps address your question, Gil.

OPERATOR

Thank you. Our next question comes from the line of Jack Allen of R.W. Baird. Your line is open, Jack.

Jack Allen (Analyst at R.W. Baird)

Great. Thanks for taking the questions and congrats on all the progress made over the course of the quarter. I wanted to ask about the patients enrolled in REVEAL Part B. I was curious if we get any additional incremental color ahead of 1H ’27 update from the six-month data there. I believe there had been previous discussion of potentially having more open milestones in the REVEAL Part B patients. Any context you can provide as it relates to the differences between Part A and Part B patients would be very helpful here.

Sean Nolan (Chief Executive Officer)

Yeah, Jack, I can take a stab at that and turn it to Suku as well. In general there’s a lot of similarities, right? I mean the baseline severity scores of the TGISS are in the 4 to 6 range. The ages are going to be 6 years to 21 years of age. So that’s very consistent. The distribution of ages, it’s a nice distribution. We’ve got a good mix of pediatric kids, adolescent kids and then young adults. So I think we’ve got a good spectrum there. We got a good spectrum of severities at baseline like we talked about and we took all genotypes again.

So I’d say there’s a lot of consistencies there. Your point about the open milestones is a good one, which is in Part A we didn’t have a threshold of the number of open milestones you had to have. Right. So obviously the more open milestones you have, the greater the probability that you might actually hit one. In Part B, we haven’t said what it was, but we did keep a number of—there was a threshold of open milestones that you had to have open. So our hope there is that it gives patients more opportunity to demonstrate benefit potentially than what we saw in Part A. Suku, I don’t know in terms of any other baseline characteristics, is there any other color you want to provide?

Sukumar Nagendran (President and Head of R&D)

Yeah, Sean, what I would add and just remind folks on the call is that Part A was a first-in-human safety study with efficacy measurements being hypothesis. So essentially we were evaluating multiple different efficacy parameters, which included milestones versus the natural history from the IRSF database, to allow us to choose appropriate efficacy milestones to be the primary endpoint. And obviously we have developmental milestones based on the IRSF database for the ages above 6 and also based on CDC guidelines.

So having said that, the number of open milestones are actually truly clinically relevant for the Part B study because it also enables us to evaluate more accurately and more concisely the global impact of our product across the age ranges studied, which is pretty broad and adequately represented, but also regardless of genotype or phenotype, hopefully reproduce the results that we saw in Part A, which was basically a 100% responder rate. And also the baseline characteristics between Part A and Part B is that we have accurate baseline evaluations in Part B that are even more consistent than Part A, which I think further increases our confidence in hitting the primary endpoint with success and hopefully bring this product to the patients who deserve it based on the six-month interim analysis from Part B.

OPERATOR

Thank you. Our next question comes from the line of Yanan Ju of Wells Fargo. Your line is open. Yanan, great.

Yanan Ju (Analyst)

Thanks for taking our questions and thanks for all the very helpful updates on this call. Was wondering about, for the discussion with FDA on the interim data, what aspects of the data could inform the agency’s decision to whether allowing or not on the six-month data. I think you’ve mentioned in the past the bar on response rate. Can you comment on is that the main factor or could there be other layers of the data that could increase or decrease the likelihood of interim filing on interim.

Thank you.

Sean Nolan (Chief Executive Officer)

Yeah, and good question. And Suku and I can also tag team this one. You’re correct. I mean the statistics at six months and 12 months are the same. Right. So it’s essentially that 30, about a third of patients need to respond to make sure that from a statistical perspective you’ve hit that particular threshold. I would say in general that’s why—now we’re asking them to do something that they haven’t done before. Right. I mean we’re basically saying I know that you generally wanted to look at 12 months of data before, but we think six months is sufficient.

And obviously our case for that, assuming that we continue to demonstrate the comparability from Part A, is that we do have long-term Part A data to show durability. And if the Part B data at six months looks encouraging, we know from Part A that it generally should just get better over the course of time. And so, you know, we have a logic. The FDA understands our logic. I think the question is going to come down to the totality of the evidence and, you know, does the FDA want to look at potentially changing precedents and how comfortable are they with that?

I think that’s why we’re having the meeting, to get their perspective on things. And that’s where again, I feel from a market perspective, we really believe if the data are good at six months, we have a great case for the six-month full approval and submission. And we’ve shared that with the FDA. They clearly understand our view on that, and they’ve said let’s have that discussion when we see the data. So I think things have lined up as well as they could, and then ultimately it’s going to be looking at the tea leaves and then getting comfortable with, again, potentially changing precedent.

I just go back to a comment earlier. We think six months is right, if the data are strong, for the community and the patients and getting things out sooner rather than later, particularly if safety has been demonstrated. But if the FDA is concerned about a precedent—and to be very clear to everybody, they’ve never expressed this to us; they have not, I am just giving you my opinion because we are asking them to do something different—if they want to stick with 12 months, my view is at least we share that with you along with the data, and you can definitely get a sense of the probability of success and the strength of the label.

And then, you know, I see that as a positive scenario too. But we’re going to put our best foot forward on the six-month. Again, they are very open-minded to it. It’s just going to be a function of everything they see and how they feel about precedent. Suku, I’m not sure if there’s anything else you might want to comment on there.

Sukumar Nagendran (President and Head of R&D)

Yeah, thanks, Sean. One thing I would again remind the audience here is that when you look at the natural history, which helped us set the stage for the Part B design, what you remember is the age group studied in Part A was 6 to 21 years of age and in Part B for 6 to 22 years of age, and that any spontaneous gain of a milestone that was never achieved above the age of six, or a spontaneous regain after a loss of a milestone, is literally negligible.

And we also ran Monte Carlo simulations of 15 patients times 10,000 sequences. So I guess the point I’m emphasizing is the clinical response that you see in every patient in Part B after the age of 6, post TSHA-102 dosing, has to be due to the product. So even a 30% responder rate is not a statistical number; it is a truly clinically meaningful number. So the question is, can we reproduce a 30% response rate in Part B, given that we had a 100% responder rate in Part A, and I think if you do the statistical odds, I think we should be able to hit the statistical number needed for the Part B primary endpoint. But also clinically meaningful is the fact that in Part A we’ve shown that TSHA-102 gene therapy given intrathecally works very quickly within two weeks. It helps address autonomic dysfunction, which is consistent almost amongst all patients dosed, and also it helps address communication and loss of social skills very quickly, as well as achievement of gross and fine motor milestone function.

And it’s consistent across the age groups studied and the genotypes identified, as well as severity of disease. So if you can reproduce all of that from Part A in Part B, the six-month interim analysis I think will truly be clinically meaningful for the FDA to seriously consider changing the paradigm from a regulatory process for gene therapy approval.

OPERATOR

Thank you. Our next question comes from the line of Jack Allen of Baird. Your line is open, Jack.

Jack Allen (Analyst at R.W. Baird)

Great. Thanks so much for taking the follow-up question. I just wanted to ask one more briefly on the design of the Reveal study. I know you have the more robust baseline measures. I think there are as many as two video assessments at baseline. But when we think about the number of video assessments within the six-month period, I’m just curious how many on-study video assessments there might be. And then as it relates to the six-month analysis, is it going to be the first six months of data from all these patients or will it be at least six months of data from each patient when you take that data cut essentially in the December/January timeframe.

Sean Nolan (Chief Executive Officer)

Yeah, Jack. So the first question would be, you’re right, there’s two videos that are done pre-dosing to set the baseline, and then there are three videos done post-dosing in the first six months. And so those five videos for each patient are what is going into the, call it, the blinded review. And at six months, when we do the interim, we’re only going to look at six months of data for all patients. So anyone who’s at nine months or 12 months or whatever, we’re not looking at that data.

That’s going to continue to be blinded for the 12-month assessment. I hope that makes sense.

OPERATOR

Thank you. Our next question comes from the line of Evan Segerman of BMO. Your line is open. Evan.

Evan Segerman (Analyst at BMO Capital Markets)

Hi, guys. Thank you so much for taking my question. So, Sean, you said something earlier interesting about the commercial batches in terms of the quality with single-digit empty vectors and a potential kind of safety benefit for patients. Have you actually seen that kind of in the real world? And are you able to demonstrate that or include that in labeling or use that as kind of a marketing component in your messaging? That’s a very interesting thing and I think could be very important.

Love for you to expand on that.

Sean Nolan (Chief Executive Officer)

Yeah, I mean, I think it is critically important if you’re able to do it, right. I mean, if you just make it real simple, there’s gene therapies out there that could be 50% empties or more. And so in the case of 50% empties, you’re doubling the dose to get the therapeutic effect. So number one, from a patient safety perspective, you’re exposing patients to more dose because you have such a percentage of empty capsids, and there’s obviously a potential risk associated with that based on the total vector load that one may be giving.

Now, we think we’re mitigating that by our route of administration and giving a fixed dose as opposed to using a systemic dose. But even getting into the single digits, which has been a goal of ours internally, we feel is the right thing from a product purity perspective that can potentially translate into, again, less exposure to the patients. The other benefit to that is the cost of goods. I mean, you’re more efficient in your process, your yields are going to be better, and that obviously is a benefit as well.

Whether that gets into the label, I would say probably doesn’t. But I think if we’re able to continue to sustain that, and we have every reason to believe we would as we’ve run multiple batches at commercial scale at this point, I think it is something, from a messaging perspective, we would definitely want to share with the clinicians so that they have that information and they can use that to inform their patients as they talk about benefit-risk.

Hope that makes sense.

OPERATOR

Thank you. Our next question comes from the line of Silvan Turkjohn of Citizens. Your line is open. Sylvan,

Silvan Turkjohn (Analyst at Citizens)

Good morning. Congrats on the safety update here, and thanks for taking my question. I just had two quick ones. Maybe could you just give us maybe a follow-on on that reported Grade 2 peripheral neuropathy event that you were seeing in one of the girls here. I know it resolved, but how’s that girl been doing? I don’t know if you can comment on that. And then on ESGCT, there was a poster by one of your competitors on the ability of the transcript expression control via the regulatory element. And the data that they posted seems to show that with miRARE there is some dampening of overall expression levels. What do you make of that preclinical data? Thank you.

Sean Nolan (Chief Executive Officer)

Yeah, I mean, I’d say, look, at a high level at this point in development to be talking about the preclinical data seems like we’re, you know, missing the forest through the trees. But to be very specific on your question, Silvan, I would say the following. You know, we’ve published data on our miRARE. All the preclinical work we did, the non-human primate work we did, and that’s been published in peer-reviewed journals, and it clearly shows the ability to manage expression on a cell-by-cell basis.

Keep in mind, too, that the non-human primate data, those are all wild-type animals, and the safety profile was fantastic. That was all submitted to the FDA. They never asked us a question about it. They did ask for a cell-based assay to confirm the in vivo work, which we did. The cell-based assay clearly shows the control with and without miRARE. So that data is all with the FDA. They’ve never asked us another question around expression control.

And, you know, I can’t speak to the work that others have done, but it’s certainly not the work that we’ve done with our own construct. As it relates to your first question on the PNS patient, I guess, Suku, you’re the best person to take this, if you don’t mind.

Sukumar Nagendran (President and Head of R&D)

Yeah, thanks, Sean. So just to refresh everyone’s memory, when it comes to Rett syndrome, it’s thought that 50% to 70% of Rett patients have peripheral neuropathies that already pre-exist. And this patient did have evidence of underlying clinical evidence of sensory neuropathy. And if you recall, this patient had some worsening of symptoms and, per hospital protocol, had to be admitted for treatment and was discharged in less than 18 hours post-treatment, which obviously per the FDA guidance made this an SAE.

And this patient started recovering pretty quickly post-treatment, I think within 24 to 48 hours, and I would say is now getting pretty close to getting back to her baseline prior to treatment, even though she’s not exactly there yet. Thanks.

OPERATOR

Thank you. Our next question comes from the line of Whitney Ijam of Canaccord. Please go ahead, Whitney.

Angela (Analyst)

Hi, thank you, guys, for taking our question. This is Angela on for Whitney. Just thinking through again, assuming success with the six-month endpoint, how are you guys thinking about commercial readiness to potentially capitalize on the market lead there? And then can you also just give us a sense of how many doses you would plan to have available at launch, whether that be if you are filing on six months or 12 months? Thank you.

Sean Nolan (Chief Executive Officer)

Yeah, Angela. On the doses, Fred and his team and Kamran have worked out with Catalent a commercial supply agreement, and so we have a good estimate range of what we think demand is going to be in the first 12 months. And we’ve worked through that with Catalent, so we don’t see that there’s going to be any supply constraint to the market. I think that’s an important piece. As it relates to getting ready, you know, we’ve built a very experienced commercial team, and I would say over the last year, if you want to think about the basics of what is the marketing strategy, what’s the go-to-market strategy look like, you know, we’ve got that complete. You’re talking about the messaging, what are the strategic imperatives that we have to accomplish, what are the targets that we’re going to go after first, both in terms of centers of excellence and how do we broaden the reach over the course of time—we’ve been through that.

What’s the target audience of physicians that we want to work through? How do we coordinate with the advocacy groups and make sure, from a disease education campaign and gene therapy education, that we’ve got the right materials in place and we can stage that accordingly? So all of that has been ongoing, and we feel very, very good about that. What’s the sales force sizing look like? All of that—working with the SP, selecting your 3PL—all those kinds of things we’ve either done or are almost completed. With the market access piece, we’ve really invested heavily in both bringing on an experienced team in gene therapy, which is critically important. And we’ve been, as I mentioned in the call, doing a lot of work with the payers—in terms of pre-approval information sharing, talking to them about profiles, potential.

We’ve been doing pricing work, and I tell you, the feedback we’ve gotten is great. They like the conversations to begin as early as we’re doing, and we started them, you know, actually in 2025. But they like them a couple years in advance so they can plan for it. They just want no surprises, and they want to do the right thing. And, you know, we’ve had very good interface with them. So we’ve got a very good plan in place for how we’re stepping through it.

You can see on our expense side, some of the SG&A bump has been on the commercial and medical affairs teams. And I would just say that we’re very confident about where we are and how we’re going to position the product, which is why we really want to be first to market, and we’re going to be ready to do that should the opportunity arise.

OPERATOR

Thank you, ladies and gentlemen. This concludes our question-and-answer session. I’ll turn the call back to Mr. Nolan for his final remarks.

Sean Nolan (Chief Executive Officer)

Thank you very much. We appreciate everyone’s time this morning and look forward to providing updates in the first half of next year. Take care, everyone. Have a good day.

OPERATOR

Thank you, ladies and gentlemen. This concludes today’s presentation. Thank you once again for your participation. You may now disconnect your lines.

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