Taysha Gene Therapies - Earnings Call - Q1 2025

Executive Summary

• Q1 2025 beat on both revenue and EPS vs S&P Global consensus: revenue $2.30M vs $1.35M consensus (+71%), EPS ($0.08) vs ($0.09) consensus; beats driven by collaboration/deferred revenue recognition with disciplined OpEx control. Bold beat on both lines [*S&P Global].
• Regulatory inflection: Written FDA alignment on key elements of the pivotal Part B design for TSHA-102; FDA advised submitting the protocol/SAP as an IND amendment (no end-of-phase meeting), potentially accelerating initiation; submission expected in Q2 2025.
• Safety/tolerability remains favorable: Across 10 patients (high dose n=6; low dose n=4), no treatment-related SAEs or DLTs as of Apr 10, 2025; management reiterated confidence in high-dose profile and trajectory to pivotal.
• Near-term catalysts: Part B protocol/SAP submission (Q2 2025), pivotal initiation activities (Q3 2025), and comprehensive program update (pivotal design, natural history analysis, and REVEAL cohorts) alongside the IRSF Scientific Meeting in Q2 2025.

What Went Well and What Went Wrong

• What Went Well

  • FDA alignment: “We obtained written alignment from the FDA on key elements of our pivotal Part B trial design... FDA advised us to proceed directly to submitting our pivotal trial protocol and... SAP as an amendment to the IND... eliminating the need for a formal end-of-phase meeting.” — CEO Sean Nolan.
  • Safety maintained at scale: No treatment-related SAEs/DLTs across 10 patients (high n=6; low n=4) in REVEAL; high/low dose generally well tolerated.
  • Visibility into pivotal path: Management emphasized objective, non–effort-based primary endpoint with blinded, video-based assessments; single-arm framework with robust bias mitigation discussed on the call.

• What Went Wrong

  • Year-over-year revenue decline: Q1 revenue fell to $2.30M from $3.41M in Q1 2024 as collaboration/deferred revenue cadence moderated.
  • Operating costs up sequentially: Total operating expenses rose to $23.72M from $21.95M in Q4 2024 as programs advanced toward pivotal, though down vs Q3 2024 which included an impairment.
  • Continued net losses: Q1 net loss was ($21.53)M; though improved YoY, TSHA remains dependent on external capital over time despite runway into Q4 2026.

Transcript

Operator (participant)

Greetings, and welcome to the Taysha Gene Therapies First Quarter 2025 Earnings Call. At this time, all participants are in listen-only mode. The question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star then zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Hayleigh Collins, Director, Head of Corporate Communications. Please go ahead.

Hayleigh Collins (Director and Head of Corporate Communications)

Thank you. Good morning, and welcome to Taysha's First Quarter 2025 Financial results and corporate update conference call. Earlier today, Taysha issued a press release announcing financial results for the first quarter ended March 31, 2025. A copy of this press release is available on the company's website and through our SEC filings. Joining me on today's call are Sean Nolan, Taysha's Chief Executive Officer, Sukumar Nagendran, President and Head of R&D, and Kamran Alam, Chief Financial Officer. We will hold a question-and-answer session following our prepared remarks.

Please note that 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 the patients dosed to date in clinical trials 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 additional trials and reporting data from our clinical trials. Advice from 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. The market opportunity for our programs. Our current cash resources supporting our planned operating expenses and capital requirements into the fourth quarter of 2026.

This call may also contain forward-looking statements relating to Taysha's growth, forecasted cash runway and future operating results, discovery and development of product candidates, strategic alliances, and intellectual property, as well as matters that are not historical facts or information. Various risks may cause Taysha's actual results to differ materially from those stated or implied in such forward-looking statements. For a list and description of the risks and uncertainties that we face, please see the reports that we have filed with the SEC, including in our annual report on Form 10-K for the full year ended December 31, 2024, that we filed on February 26, 2025, and our quarterly report on Form 10-Q for the quarter ended March 31, 2025, that we filed today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 15, 2025.

Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities laws. With that, I would now like to turn the call over to our CEO, Sean Nolan.

Sean Nolan (CEO)

Thank you, Hayleigh, and welcome everyone to our first quarter 2025 financial results and corporate update conference call. I will begin with a brief update on our recent activities. Then Sukumar Nagendran, President and Head of R&D of Taysha, will provide an update on our lead Taysha 102 gene therapy program and clinical development for Rett syndrome. Kamran Alam, our Chief Financial Officer, will follow up with a financial update, and I will provide closing remarks and open up the call for questions. This year has been marked by strong execution across our Taysha 102 program and clinical evaluation for pediatric, adolescent, and adult patients suffering from Rett syndrome. We are pleased with the significant regulatory and clinical progress that we believe continue to support a clear path to registration.

Importantly, our analysis of the natural history data, coupled with the longer-term clinical data from our low-dose cohort and interim high-dose data that we have collected across a broad range of ages and stages of patients with Rett syndrome in our two REVEAL phase I, II trials, have further informed the therapeutic potential of Taysha 102 and supported our alignment with the U.S. FDA on key elements of our development plan for part B, the pivotal phase of our trials.

In February, we shared that we completed dosing of the 10 patients in part A, the dose escalation portion of the reveal phase I-II adolescent-adult trial and the reveal phase I-II pediatric trial, with six patients in cohort two evaluating the high dose of Taysha 102 of 1.0 x 10^15 total vector genomes and four patients in cohort one evaluating the low dose of Taysha 102 of 5.7 the 14 total vector genomes. As our data further mature, we're pleased that Taysha 102 continues to be generally well tolerated across the high and low-dose cohorts, with no treatment-related serious adverse events or dose-limiting toxicities as of the April 10, 2025, data cutoff.

Recall, patients being evaluated in our reveal phase I-II trials are in the post-regression period of the disease, where functional gains or restoration of lost function are not expected to occur in the untreated population. Previously, we shared clinical data from the low-dose cohort in our reveal trials, where pediatric and adult patients with advanced disease not only showed clinical improvements but also gained functional skills across the domains of fine motor, gross motor, and socialization and communication, which represent improvements in activities of daily living. This included beginning to use eating utensils, sitting independently, standing up from a chair independently, and the ability to use an eye gaze communication device. Each of these functional gains reflects meaningful skills that can significantly improve a patient's quality of life by affording greater independence and autonomy.

These functional gains, which are not expected to occur in the untreated population of patients with Rett syndrome based on natural history data and the additional clinical data we have collected since from our Reveal trials, have supported our interactions with the FDA regarding the optimal regulatory pathway for Taysha 102. Over the past 18 months, we have maintained frequent ongoing discussions with a broad FDA review team, including senior leadership through the Regenerative Medicine Advanced Therapy, or RMAT, mechanism. These discussions, which have been rooted in robust data-driven findings, have been aimed at advancing Taysha 102 toward a pivotal trial design in which clinically meaningful functional gains are assessed in a rigorous and bias-mitigated manner across a broad patient population. To date, we believe our interactions with the FDA have consistently been productive and supportive of our development approach.

As such, I'm pleased to share that we have obtained written alignment from the FDA on key elements of our pivotal part B trial design for Taysha 102 and next steps to enable the initiation of the pivotal trial. Importantly, the FDA advised us to proceed directly to submitting our pivotal trial protocol and associated statistical analysis plan as an amendment to the Investigational New Drug or IND application, which we expect to submit in the current quarter. This approach eliminates the need for a formal end-of-phase meeting, which may expedite study initiation and registration. We truly appreciate the clear, constructive, and collaborative interactions with FDA to date and believe this progress on our registrational pathways supports the strength of our data-driven approach and further enables our goal to bring Taysha 102 to patients with this devastating disease as expeditiously as possible.

We are focused on finalizing the details of our protocols and statistical analysis plan as we prepare to submit the IND amendment this quarter. In the coming weeks, we plan to provide a fulsome update on our pivotal part B trial design, our Rett syndrome natural history data analysis, and the clinical data from part A of our Reveal trials as part of a Taysha 102 program update in conjunction with the International Rett Syndrome Foundation's 2025 Rett Syndrome Scientific Meeting taking place June 9th through the 11th. At the IRSF meeting, we will deliver three oral presentations related to Taysha 102, including one focused on our clinical data. As we approach these critical milestones, our confidence in our differentiated gene therapy candidate continues to strengthen based on the recent developments highlighted today.

We believe Taysha 102 has the potential to provide meaningful benefit to a broad population of patients with Rett syndrome using a minimally invasive delivery approach with a clear path to registration based on the critical alignment reached with FDA. I will now turn the call over to Suku to provide more context on these advancements that further support a clear path to registration. Suku.

Sukumar Nagendran (President and Head of R&d)

Thank you, Sean, and good morning, everyone. As Sean mentioned, we believe we have made significant progress on advancing our Taysha 102 program towards registration. Recall, we have two ongoing phase I-II reveal trials evaluating Taysha 102, an adolescent and adult trial taking place in Canada and the U.S. for females aged 12 and older with Rett syndrome, and a pediatric trial taking place in the U.S., the U.K., and Canada, females five to eight years old with Rett syndrome.

We are currently evaluating two dose levels of Taysha 102 in part A, the dose escalation portion of both trials. Our approach from the outset has been to utilize part A to generate a dataset that informs the key elements of our pivotal part B trial. There are several key aspects of Rett syndrome that have shaped our development approach for Taysha 102 as we've worked to align with the FDA on key elements of our pivotal trial design. Rett syndrome is a devastating, rare, and progressive neurodevelopmental disease that leads to complications in fine and gross motor function, socialization and communication, autonomic function, and seizures. The functional impairments and disease features often necessitate 24/7 care and lifelong assistance, leading to a significant caregiver burden and severe impact on quality of life. There is a significant unmet medical need.

Additionally, while Rett syndrome is a heterogeneous condition with different levels of clinical severity based on each patient's distinct genetic background, patients generally follow a common trajectory regarding the achievement of functional developmental skills. Following a period of regression, affected individuals typically enter a plateau period around the age of five or six, during which they're highly unlikely to gain new functional skills or regain skills that have been lost to disease progression. As we think about gene therapy for patients in the post-regression population of Rett syndrome, we've already developed the hallmark characteristics of the disease. The ultimate goal is restoration of function and improvement in activities of daily living. Taysha 102 is designed as a one-time gene therapy that aims to address the underlying cause of Rett syndrome by restoring MECP2 protein expression on a cell-by-cell basis across the central nervous system.

Therefore, we believe Taysha 102 may provide the opportunity for patients with the advanced stage of Rett syndrome to develop new functional skills. Rett syndrome requires an increase in MECP2 protein to activate the neural circuits necessary for gaining function, as well as time for patients to strengthen these reactivated circuits and learn skills that are affected by the disease. Therefore, we believe that early clinical benefit is a strong indicator that MECP2 protein has reached therapeutic levels that, in turn, create the opportunity for patients to strengthen their neural network over time and learn complex skills. In both our reveal trials, we have consistently seen early clinical improvements and functional gains post-treatment that persisted and strengthened over time. That could be highly unlikely based on natural history data.

This has been highly encouraging since patients being evaluated in our Reveal phase I-II trials are in the post-regression period of the disease, where, as Sean noted, functional gains or restorations of lost function are not expected to occur in the untreated population. As we prepare to report long-term low-dose data and preliminary high-dose data across the pediatric, adolescent, and adult patients in our two reveal trials, we hope to see a consistent pattern of early response that deepens over time across a broad population of patients with varying genotypes. We believe this could further support the broad treatment potential of Taysha 102 and move us closer to our goal of bringing a potentially transformative treatment to all patients with Rett syndrome.

Overall, these functional outcomes seen thus far in patients treated with Taysha 102 have supported our ability to reach alignment with the FDA on key elements of the pivotal trial design for Taysha 102 and next steps to enable study initiation. Based on our data-driven findings and ongoing discussions with the FDA, we remain steadfast in our conviction that functional outcomes are the most relevant, objective, and clinically meaningful assessments of the treatment effect of Taysha 102 in patients with Rett syndrome. I will now turn the call over to Kamran to discuss our financial results. Kamran.

Kamran Alam (CFO)

Thank you, Suku. Research and development expenses were $15.6 million for the three months ended March 31, 2025, compared to $20.7 million for the three months ended March 31, 2024.

The $5.1 million decrease was driven by good manufacturing practices, or GMP, batch activities, with the intended commercial manufacturing process for Taysha 102 performed during the three months ended March 31, 2024. The decrease in expenses was partially offset by higher compensation expenses for R&D employees as a result of increased headcount. General and administrative expenses were $8.2 million for the three months ended March 31, 2025, compared to $7.1 million for the three months ended March 31, 2024. The increase of $1.1 million was primarily due to higher compensation expenses and increases in legal and professional fees. Net loss for the three months ended March 31, 2025, was $21.5 million, or $0.08 per share, compared to a net loss of $24.1 million, or $0.10 per share, for the three months ended March 31, 2024. As of March 31, 2025, Taysha had $116.6 million in cash and cash equivalents.

We continue to expect that our current cash resources will support planned operating expenses and capital requirements into the fourth quarter of 2026. I will now turn the call back over to Sean for his closing remarks. Sean.

Sean Nolan (CEO)

Thanks, Kamran. We are pleased with the significant regulatory and clinical progress made across our Taysha 102 Rett syndrome program that continues to support a clear path to registration. With written alignment from the FDA on key elements of our part B pivotal trial design and next steps to enable study initiation, we believe we are strongly positioned for success as we work to rapidly advance our Taysha 102 gene therapy program toward the pivotal trial and bring us closer to our mission of delivering on Taysha 102 to the Rett syndrome community as expeditiously as possible.

In the coming weeks, we look forward to providing a fulsome update on our pivotal Part B trial design, our Rett syndrome natural history data analysis, and the clinical data on both the high and low-dose cohorts of our reveal trials during a program update in conjunction with the IRSF scientific meeting. With that, I will now ask the operator to begin our Q&A session. Operator.

Operator (participant)

Thank you, Sean. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star then one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star and then two if you would like to remove your question from the queue. Please note participants are limited to one question and one follow-up at a time.

The first question we have comes from Kristen Kluska of Cantor. Please go ahead.

Kristen Kluska (Equity Research Analyst)

Good morning. I'm looking forward to IRSF in a few short weeks here. One question we've been getting is what signals can potentially point to there being a dose response given this is a highly heterogeneous syndrome? Should we be thinking about the time to treatment onset? Are there any specific endpoints or anecdotes where the effects might be easier to measure to see if that dose response is there?

Sean Nolan (CEO)

Yeah, Kristen, good question. Suku, feel free to jump in on this. I think there's a couple of things we can look at. One is, as you mentioned, a temporal aspect.

As we think about gains of function, we think about some of the improvements we see on a more qualitative level using metrics like RMBA and CGI that in what we've reported to date, you see early improvements and strengthening over time. We think there could be differentiation at the high dose in terms of the time period to see that and also the magnitude of the response that we're seeing. Again, assuming the safety continues to look like we've seen thus far, we've always had the view that the high dose would be the right dose. We will talk through that in more fulsome manner once we go through the data, but that's how we're thinking of it. Suku is there anything you'd add to that?

Sukumar Nagendran (President and Head of R&d)

Yeah, Sean, what I would also add is that there is the translational dataset, right?

The animal-to-human translation when it comes to motor function and respiratory function, we've seen some improvement there between the doses. The other thing is, obviously, we are reviewing all the clinical data, and obviously, over time, we think it's going to mature and get better between the doses. Logically, the higher dose also, I think, should add a further advantage purely because the further MECP2 or the higher the levels are in this heterogeneous complex disease, neurologically, we think that will also have a better clinical impact in that patient population as well.

Kristen Kluska (Equity Research Analyst)

Thank you.

Operator (participant)

The next question we have comes from Salveen Richter of Goldman Sachs. Please go ahead.

Lydia Gould (Global Investment Research Analyst)

Hi, this is Lydia on for Salveen. Thanks so much for taking our question and congrats on the update today.

Acknowledging your plan to provide an update later this quarter, could you just frame the bar for success and kind of how you're thinking about that in light of the recent regulatory feedback just in terms of the data that we can expect here? Thanks so much.

Sean Nolan (CEO)

Sure. I think what's going to be very helpful for the market is to, number one, see what the natural history analysis that we've conducted highlights. I think that's something that's been missing, frankly, for the disease state for quite some time. We'll step through our analysis of that natural history. Truly, that underlies both the regulatory strategy and the clinical strategy. The reason we want to package everything together is to start with just a clear baseline on what would you expect to see in the natural course of the disease.

Even though the disease is heterogeneous, the patients really, at a certain point, have a very clear type of a trajectory, let's say. Secondly, we'll then explain what the regulatory details are. We've reached alignment on key framework, which, what does that mean? That means we've reached alignment on what the trial design is. We've reached alignment on the primary endpoint. We've reached alignment on the study population. We've reached alignment on the estimated number of patients that we'll need to achieve statistical significance. We'll work to share that with all of you. With that, we'll go through the clinical data, both the long-term low-dose data and the high-dose data, looking through primarily the lens that the FDA has agreed to as a primary endpoint, which we think will be very predictive of what the success looks like in the pivotal trial.

I think it'll give people a very good insight into the probability of success and also then the timeline to a potential BLA submission. There'll be a lot there. That's why we wanted to share with everybody today. Reaching this congruence with the FDA is fantastic. It obviates the need for an end-of-phase meeting, which when you add it all up, could take potentially another quarter to get that wrapped up. We've already reached that alignment. Now that we can step right into the protocol submission, that effectively is a 30-day clock. Assuming there's no issues, we would be able to then proceed with site activities and initiation. A lot to update at the IRSF meeting, but very exciting times for the program. We're poised to step into part B and move this closer to BLA.

Lydia Gould (Global Investment Research Analyst)

Thanks so much.

Sean Nolan (CEO)

Thank you.

Lydia Gould (Global Investment Research Analyst)

Thank you.

Sean Nolan (CEO)

The next question we have comes from Gil Blum of Needham and Company. Please go ahead.

Gil Blum (Senior Biotech Analyst)

Good morning again. Let me add my congratulations on the progress here. You kind of mentioned the timeline in the previous question. Is there any specific feedback that the FDA may provide still post this 30-day period on the study protocol and SAP?

Sean Nolan (CEO)

Yeah, Gil. Suku and I can tackle this one. I would say that I'll just start with the framework that the end-of-phase meeting purpose is generally to align on things or you have a misalignment with the FDA and a meeting is needed to reconcile that. The good news is we've reached alignment with the FDA on really the key aspects of the trial design, right? We've got written agreement that the trial design is good.

We've gotten written agreement that the primary endpoint is a go, the study population. We've talked about the statistical analysis plan. We're in very good shape there. At this point, it's putting the detail into the protocol and making that submission. Suku, I'd like you to comment on if we're at this stage, there could be potentially a little back and forth, but they wouldn't have told us to submit the protocol if there was something that could really be a showstopper.

Sukumar Nagendran (President and Head of R&d)

Yeah. Your correction, Sean, I mean, they would have asked us to come back to further review the protocol, etc., if they were uncomfortable with what had been originally proposed. The odds are that it's highly unlikely that they will have significant further comment.

There could be some correspondence if they had a question or two, but it's highly unlikely at this point.

Gil Blum (Senior Biotech Analyst)

Thank you.

Sean Nolan (CEO)

Thank you.

Operator (participant)

The next question we have comes from Maury Raycroft of Jefferies. Please go ahead.

Maury Raycorft (Equity Research)

Hi, good morning. Congrats on the update and thanks for taking my questions. Realizing there are more details to come on the trial design, can you at least talk about what the primary endpoint will be and if it would include standardized clinical video showing milestone or functional gain? I don't know if there's anything additional you could say about the statistical analysis plan as it relates to the endpoints at this point.

Sean Nolan (CEO)

Yeah.

I mean, I would say that you can expect that the primary endpoint is going to be consistent with what we've been focused on over the last 18 months or so, which has been working towards an endpoint that is objective. It's clinically meaningful. It's very easy to measure. And it's important both to the patients, the caregivers, and the clinicians. Again, without getting too far ahead of ourselves, I would just say we've always wanted to be in a position where you could have a very efficient, robust clinical study. We've always thought that a placebo was not necessary, that a single arm could work here with the right controls. If that's the case, you would want to make sure that there would be mechanisms in place where you would have appropriate bias mitigation measures, video assessments, and raters and adjudicators that would be appropriately blinded.

I think those are the details that we'll provide. We're in good shape on all of that in terms of the alignment that we've obtained with the FDA.

Maury Raycorft (Equity Research)

Got it. That's really helpful. Okay. Thanks for taking my question.

Sean Nolan (CEO)

Thanks, Maury.

Operator (participant)

The next question we have comes from Yanan Zhu of Wells Fargo. Go ahead. Great.

Yanan Zhu (Senior Analyst and Biotechnology Equity Research)

Thanks for taking our questions. I was wondering how does the aligned design compare with your proposal or your desired design going into the meeting? Also, it sounds like natural history will be playing an important role. Just wanted to perhaps ask whether this is a single-arm design. I have one follow-up. Thanks.

Sean Nolan (CEO)

Yeah, Yan. I would say that the design that the company put forward is the design that the FDA endorsed.

We had some discussions around the previous question from Maury, making sure that from a process perspective, everyone was comfortable with what we were going to do, and we achieved that. There was never any pushback from the agency. They've always been very constructive and open-minded to what we've put in front of them. They've only requested data, which is obviously very justified. The data was in two areas. One was we told them our premise with the natural history data and what that might show, and we've put that in front of them. They've, I would say, agreed with what we've put in front of them. The second piece was the clinical data. As our data have evolved, we've continued to update them on what we're seeing.

It was really the combination of those two aspects of data that got us to this point where we had the alignment and obviated the need for the end-of-phase meeting.

Yanan Zhu (Senior Analyst and Biotechnology Equity Research)

Oh, great. Yeah. Actually, I would—oh, sorry.

Sean Nolan (CEO)

I was going to ask you, what was the second part of your question?

Yanan Zhu (Senior Analyst and Biotechnology Equity Research)

Right. I was going to ask what might be the role of any data that might have played into the lack of a need for an end-of-phase meeting. I think you kind of answered that. Let me also ask, is the lack of the end-of-phase meeting having anything to do with FDA resource capacity? Also, is it a general action on the indication, which means for other sponsors, this could also be the case? Lastly, do you expect harmonization of the endpoints across sponsors? Thank you.

Sean Nolan (CEO)

Yeah.

In terms of FDA resources, what I can tell you is we've received written alignment before the announcements with Peter Marks and the departures. We subsequently have had interactions with the FDA where they've maintained that posture. We think that there's no relation between not having an end-of-phase meeting and resources. I go back to Suku comment earlier, which is the reason for an end-of-phase meeting is generally to either get congruence or you are in opposition. You're not aligned on a key aspect. You need to have a meeting to discuss that. Because we've had RMAT, we've already interacted with the FDA three times this year, multiple times last year. We've had a very consistent and progressive discussion with them. We've been working towards this for 18 months. The reality is we got there with them through this RMAT mechanism.

There was no need for them to take the time to have an official meeting. To us, it highlights the robustness of the data that we have put in front of the FDA, both in terms of natural history and our clinical data to support what we wanted in terms of trial design, endpoints, etc. We look forward to continuing to move things forward. It is super exciting. Again, I think keep in mind that usually if you are doing an end-of-phase meeting, I want to say it is a 70-day clock or so. We are now able to submit the protocol, which we say we are going to do this quarter. There is a 30-day wait period. They could ask us for a couple of clarifying requests, which we would do expeditiously, or they could say nothing.

In a very short period of time, we would anticipate being able to initiate site activities, get the pivotal trial up and running, and we're on a very exciting pathway to get to a potential BLA.

Yanan Zhu (Senior Analyst and Biotechnology Equity Research)

Great. Thanks for the cover and congrats on this update. Thank you.

Operator (participant)

Thanks, Yanan.

The next question we have comes from Biren Amin of Piper Sandler. Please go ahead.

Yeah. Hi, guys. Thanks for taking my questions. And congrats on all the progress with 102. Sean, maybe for the part B portion of the trial, given it's an amendment on IND, how seamless is it going to be to go to the part B with the current sites that are in the part A? Or will you need to start with IRB approval for each site, including the part A sites?

The second question is, given there's a significant number of patients in Europe, what are your plans to engage with EMA on requirements there? Thanks.

Sean Nolan (CEO)

Yeah. In terms of what's nice about the IND amendment, we will leverage existing sites, right, because we've already been through the contract process. They've already cleared the initial INDs within their institution. We've already prioritized how we want to triage and go through site activation. Definitely having multiple sites up and running and dosing patients is going to be to our advantage. We might add additional sites beyond that to help make sure that as we open up enrollment for part B, which we can do in parallel, we'd like to have the most expeditious enrollment possible.

The fact that we've got multiple sites that are trained on the product, that already have a lot of the activities done in the past, we think will facilitate it and allow us to move very, very quickly. Suku?

Sukumar Nagendran (President and Head of R&d)

Yeah. Also, Biren, some of these sites have multiple patients who are basically lining up. We could run multiple patients in parallel as long as they can handle the capacity.

Sean Nolan (CEO)

Exactly. Biren, as it relates to EMA, you're right. I mean, there's a nice opportunity over in Europe. When you look at Europe plus U.K., it's about the size of the U.S. It is a very significant patient population. We've got the U.K. activated. We've got the open CTA there. We've worked to, I would say, enable the EMA. We've got that going.

Again, with additional capital potentially down the road, that's where we could expand our footprint. We have been very disciplined with the resources that we've had. We focus primarily on the U.S. In the background, although we haven't said a lot about it, the regulatory team's done a great job of working in Europe to put us in a position where we can move forward at the appropriate time.

Operator (participant)

Thank you. The next question we have comes from Whitney Ijem of Canaccord Genuity. Please go ahead.

Whitney Ijem (Managing Director and Senior Biotechnology Analyst)

Hey, guys. I'll add my congrats on all the progress. Just wanted to follow up on the interactions with Astellas. I know you'd previously talked about having kind of the amount of data or the type of data that you'd need to start the clock on a potential opt-in this summer.

I guess, is that still on track, or has that been accelerated at all, I guess, given the regulatory outcome here? And then have you been having conversations with them in the meantime, or is it that you'll deliver kind of a final package to them whenever you have it?

Kamran Alam (CFO)

Yeah. Kamran, jump in here. Basically, the agreement is very specific in terms of when things get triggered. You're correct. There's a data package on pediatric patients that needs to be submitted to them, which is forthcoming now based on the data that we have. I really can't comment on any discussions that we may or may not have had with Astellas. I would just simply say that we'll execute the agreement as it's written. That's part of the process that we're stepping through at this particular point in time.

Whitney Ijem (Managing Director and Senior Biotechnology Analyst)

Great. Thanks.

Kamran Alam (CFO)

Thank you.

Whitney Ijem (Managing Director and Senior Biotechnology Analyst)

Thank you.

Operator (participant)

The next question we have comes from Jack Allen of Baird. Please go ahead.

Jack Allen (Biotech Senior Research Analyst and VP)

Great. Thanks for taking the questions and congratulations on all the progress made over the course of the quarter. I just wanted to ask about some of the recent FDA interactions. You had mentioned that you had spoken with the administration in the preceding Dr. Marks' departure. I'd love to hear any color you maybe have as it relates to discussions post-Peter Marks' departure, how consistent the people you've been talking to have been at the FDA, and if you plan to have any even informal interactions given the recent addition of Vignan Prasad to Seaber.

Sukumar Nagendran (President and Head of R&d)

Yeah. Suku, help me out here. From the beginning, our team has been very consistent with FDA since we submitted the IND in terms of the review team and things of that nature.

Because we have RMAT, Nicole Verdon has certainly been at the official meetings. She's been there in her capacity. We've had, again, consistent senior leadership review. I can say, because we've gotten a question particularly during when Peter departed, but Peter was never in any of the meetings. That's not his role. He leaves that up to Nicole and the teams beneath her. That part's been very consistent. There really has been no departure, no deviation from the conversations that we had going back to, call it, April of last year. Everything's been consistent in what we wanted to do, the strategy that we outlined. Again, all they've ever asked for is to see additional data and the natural history analysis, which we've provided. I would say through the process, things have been very, very consistent.

In the interactions that we've had after the departure of Peter, you would not have known that Peter had left. The team was still very focused on what we were working towards. There was no pause. The meetings that we had were on schedule. The team was fulsome that showed up. Everyone was very engaged, highly professional. We continued down the path. We haven't seen any impacts with these changes at FDA. I think in terms of additional interactions, the next interaction would be when we submit the protocol and the SAP to the IND. There may or may not be back and forth. If they have some questions and we need to jump on the phone and work things through, we'll do that. It's also possible that they're comfortable with everything and we just proceed.

That's a little difficult to answer that question. I would just say, as it relates to Vignan Prasad, I think as time has gone on, and he said more publicly, his comments seem to dovetail in with what Dr. Makari has said and that there's a high degree of understanding that rare disease is different than large chronic markets. They understand that not all programs need a placebo control. It's not appropriate, particularly for some of the rare disease programs. What's really important is context and a robust clinical trial design. We think context is important. That makes a lot of sense to us. That's why I think the natural history data will make a lot of sense to people in terms of its importance on how we ultimately have gotten to this point and hopefully beyond with the agency.

We feel right now we're in a really good spot. The agency and all these new players continue to talk about the importance of innovation. They specifically mentioned gene therapy. They talk about the fact that they want to move therapies forward as quickly as possible. We don't see that there's going to be any impediments based on our interactions today. I'd ask Suku to give some color as well because he's the one in the meetings.

Yeah. Sean, what I would say is that when it comes to the FDA and SIBA, the team that has been reviewing the Rett program for gene therapy has stayed consistent. It's the clinical team or the biostats team. No concern there when it comes to any variability in evaluations over time. When it comes to Dr.

Prasad, I think he's a very bright young individual who's done a lot of good research. The focus here is one disease at a time, give me appropriate data, and then it will obviously proceed rapidly through the FDA review process. Even though there was a lot of noise, I think when he was initially chosen, it's very clear recently that he is going to really make a difference when it comes to the whole rare disease review process.

Jack Allen (Biotech Senior Research Analyst and VP)

Got it. Thanks so much for the color. Congratulations again on all the progress.

Sean Nolan (CEO)

Thanks, Jack.

Operator (participant)

Thank you. Ladies and gentlemen, just a reminder, if you would like to ask a question today, please press star and then one now. The next question we have comes from Joon Lee of Truist Securities. Please go ahead.

Joon Lee (Managing Director and Senior Biotech Analyst)

Hey, thanks for the updates and for taking our questions.

Aside from clinical data, do you have any biomarker data from CSF or others that inform you that your construct is autoregulating MECP2 as designed? Are you able to indirectly at least approximate the level of MECP2 being produced in this patient's corresponding to the doses being administered and relative to the wild-type individuals? As a quick follow-up, what will be the timelines for part B enrollment and study completion after you amend the IND this quarter? Thank you.

Sean Nolan (CEO)

Yeah. On the second part, we will give more guidance on that once we hear back from FDA or we do not, once we get through the 30-day period. I would say if that is the case, June, then we would be initiating sites right away and potentially getting into dosing the fourth quarter of this year, first quarter of next year.

It's a very short timeline to make that happen. As it relates to the MECP2, I'll turn it over to Suku.

Sukumar Nagendran (President and Head of R&d)

Yeah. June, I mean, that's a good question. It's asked all the time. At the present time, there's no way to measure MECP2 levels in the CSF, bloodstream, or cell. And in the cell, I'm talking about the neuron or the astrocytes. It's an intranuclear protein that is there and then, I think, gets turned over very quickly. Thankfully, when it comes to our product, given how quickly these patients respond to our gene therapy given intrathecally and because our construct is also self-complementary, clinically, as you probably know, we help restore sleep abnormalities, autonomic dysfunction, fine and gross motor abnormalities usually within the first four to six weeks post-dosing.

The clinical measures, I think, are going to be the biomarker at this point in time.

Joon Lee (Managing Director and Senior Biotech Analyst)

Thank you.

Operator (participant)

Thank you. The next question we have comes from Silvan Tükcan of Citizens. Please go ahead.

Silvan Türkcan (Managing Director)

Thank you very much. And congrats on the update. And thanks for taking my question. Maybe a follow-up on Maury's earlier question. I just want to see if there's any more color you can give us on the FDA feedback on the endpoints before you actually reveal the endpoint. Did they specifically agree that it's not effort-based and not objective? Thank you.

Sean Nolan (CEO)

It's not effort-based. It is objective. And it's very clinically meaningful. Again, we've highlighted, Silvan, I think over the last year plus that gains of function or restoration of lost function is really something that's critically important to these patients. It's meaningful to the doctors.

It's also something when you start to think about even the payers, if you're able to demonstrate that people are functionally improving, that is going to be meaningful to that particular stakeholder group as well. We will outline specifically what this means and also how we would collect this data. We've been doing it in a very analogous way in part A. We will step through that when we present the data. I think our view will be it should give a good lens. The part A data should give a good lens of what you can predict part B to look like. We're excited to do that. Again, we're pleased with FDA's alignment with this. They've never been misaligned. It's only been, "Get us a little bit more data." Really, it was they hadn't seen the natural history data until this year.

Again, onwards for us. Great question.

Silvan Türkcan (Managing Director)

Great. Thank you. Thanks so much. Congrats. Sounds like a great update. Thanks.

Operator (participant)

Thank you. The final question we have comes from Evan Seigerman of BMO Capital Markets. Please go ahead.

Malcolm Hoffman (Biopharma Senior Equity Research Associate)

Hi. Malcolm Hoffman on for Evan. Thanks for taking our question. Can you characterize your level of confidence in Taysha 102's safety at this time? With no DLTs or serious AEs to date, it feels like we are getting to a point where there is less risk, but just wanted to get your thoughts there. Just a follow-up to that, can you indicate when the most recently dosed patient was dosed again? Appreciate it.

Sean Nolan (CEO)

Yeah. On the safety piece, Suku, maybe you can take this question.

I would just say that keep in mind we've now dosed more high-dose patients than low-dose patients, which is also comforting. But Suku, perhaps you can give more color from given all your experience.

Sukumar Nagendran (President and Head of R&d)

Yeah. I mean, based on our data set as of April, there is no treatment-emergent adverse events or dose-limiting toxicity. So we have no concern given that the intrathecal approach is pretty benign and the efficacy is pretty obvious based on the data that we've already revealed for the low dose, the benefits far outweighs the risk.

Operator (participant)

Thank you. Thank you. Ladies and gentlemen, we have reached the end of our question and answer session. Now I would like to turn the call back over to Sean Nolan for closing remarks. Please go ahead, sir.

Sean Nolan (CEO)

Thank you very much, operator. And thanks for everyone taking the time this morning.

Again, I just want to say how pleased we are with the alignment we've obtained with the FDA. We look forward to the next steps. The team is working hard right now to finalize the protocol and the SAP. We are on track to make that submission this quarter, again, which can enable us to begin to start site activation as early as summertime. Look forward to the updates at IRSF. Again, thanks for all your time. Take care.

Thank you. Ladies and gentlemen, that then concludes today's conference. Thank you for joining us. You may now disconnect your lines.