Taysha Gene Therapies Q2 2024 Earnings Report

Taysha Gene Therapies EPS Results

• Actual EPS: -$0.09
• Consensus EPS: -$0.10
• Beat/Miss: Beat by +$0.01
• One Year Ago EPS: -$0.38

Taysha Gene Therapies Revenue Results

• Actual Revenue: $1.11 million
• Expected Revenue: $3.62 million
• Beat/Miss: Missed by -$2.51 million
• YoY Revenue Growth: N/A

Taysha Gene Therapies Announcement Details

• Quarter: Q2 2024
• Date: 8/12/2024
• Time: Before Market Opens
• Conference Call Date: Monday, August 12, 2024
• Conference Call Time: 8:30AM ET

Taysha Gene Therapies (NASDAQ:TSHA) (NASDAQ: TSHA) is a clinical-stage biotechnology company focused on developing gene therapies for rare monogenic diseases of the central nervous system. Using a proprietary adeno-associated viral (AAV) vector platform, the company engineers novel capsids and regulatory elements to optimize delivery and expression of therapeutic genes. Its pipeline features lead programs such as TSHA-102 for GM2 gangliosidoses (Tay–Sachs and Sandhoff diseases), TSHA-101 for GM1 gangliosidosis and TSHA-103 for aromatic l-amino acid decarboxylase (AADC) deficiency, alongside earlier-stage candidates targeting other life-threatening pediatric CNS disorders.

Founded in 2019 and headquartered in Dallas, Texas, Taysha Gene Therapies completed its initial public offering in May 2021. The company has secured orphan drug designations from the U.S. Food and Drug Administration for its lead programs and established partnerships to support manufacturing and supply chain needs. With an integrated model that combines in-house research, process development and clinical operations, Taysha aims to accelerate the transition of its candidates from preclinical studies into human trials.

Through collaborations with academic institutions, patient advocacy groups and regulatory agencies, Taysha serves both domestic and international patient populations facing devastating genetic disorders. Its clinical trials are conducted across multiple trial sites in North America and Europe, with a focus on leveraging real-world insights to optimize study design and endpoint selection.

Led by a management team with deep expertise in gene therapy, translational research and rare disease development, Taysha Gene Therapies is committed to building a broad platform capable of delivering potentially transformative treatments for central nervous system disorders. The company continues to expand its scientific and clinical capabilities to bring durable, one-time gene therapies to patients worldwide.

Taysha Gene Therapies Q2 2024 Earnings Call Transcript

Key Takeaways

• Tayshia has completed low-dose cohorts in both adult/adolescent and pediatric Phase 1/2 REVEAL trials and initiated high-dose dosing for its lead gene therapy candidate, TASIA-102, in Rett syndrome patients.
• Preliminary data from the low-dose cohorts showed a well-tolerated safety profile with no serious drug-related adverse events and early signs of durable clinical improvements across key domains such as autonomic function, seizures, motor skills, hand function, and communication.
• The first high-dose adult patient has been dosed with TASIA-102 and the Independent Data Monitoring Committee cleared dosing of the second adult and first pediatric high-dose patients ahead of schedule, with further dosing planned for Q3 2024.
• A recent public follow-on offering generated $76.8 million net proceeds, extending Tayshia’s cash runway into Q4 2026 to support ongoing development of TASIA-102.
• Tayshia plans to report more mature safety and efficacy data from both low and high-dose cohorts in the first half of 2025 and will engage with the FDA under its RMAT designation via an upcoming Type B meeting to align on pivotal trial design.

Presentation

[Operator]

Greetings, and welcome to the Taysha Gene Therapies' Second Quarter 2024 Earnings Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star 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 and Head of Corporate Communications and Investor Relations. Thank you. You may begin.

[Hayleigh Collins, Director of Corporate Communications and Investor Relations at Taysha Gene Therapies Inc]

Thank you. Good morning, and welcome to Taysha's Second Quarter 2024 Financial Results and Corporate Update conference call. Earlier today, Taysha issued a press release announcing financial results for the second quarter ended June 30, 2024. A copy of this press release is available on the company's website and through our SEC filing. Joining me on today's call are Sean Nolan, Taysha's CEO, 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.

[Hayleigh Collins, Director of Corporate Communications and Investor Relations at Taysha Gene Therapies Inc]

Please note that on today's call, we will be making forward-looking statements, including statements relating to the therapeutic and commercial potential of TSHA-102, including the reproducibility and durability of any favorable results initially seen in the patients dosed to date in clinical trials to positively impact the 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 timelines for our clinical trials and reporting results therefrom, and our current cash resources supporting our planned operating expenses and capital requirements into the fourth quarter of 2026. These statements may include, but are not limited to, the expected timing and results of clinical trials for our product candidates and other clinical and regulatory plans, and the market opportunities for those programs.

[Hayleigh Collins, Director of Corporate Communications and Investor Relations at Taysha Gene Therapies Inc]

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. These risks include uncertainties related to the timing and results of clinical trials of, and regulatory interactions for our product candidates, our dependence upon strategic alliances and other third-party relationships, our ability to obtain patent protection for our discoveries, limitations imposed by patents owned or controlled by third parties, and the requirements of substantial funding to conduct our research and development activities.

[Hayleigh Collins, Director of Corporate Communications and Investor Relations at Taysha Gene Therapies Inc]

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, 2023, and our quarterly report on Form 10-Q for the quarter ended June 30th, 2024, that we filed today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 12th, 2024. 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 at Taysha Gene Therapies Inc]

Thank you, Hayleigh, and welcome everyone to our second quarter 2024 financial results and corporate update conference call. Today, I will begin with a brief update on our recent activities, and then Suku, our President and Head of R&D, will provide an update on our lead TSHA-102 program and clinical evaluation for Rett syndrome. Kamran Alam, our Chief Financial Officer, will follow up with a financial update, and I will provide closing remarks and open the call up for questions. In the second quarter of 2024, we made strong progress across the TSHA-102 program in clinical evaluation for pediatric, adolescent, and adult patients with Rett syndrome.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

This included reporting encouraging safety and efficacy data from the low-dose cohort in both our REVEAL Phase 1/2 trials, initiating the high-dose cohort, expanding our pediatric trial into Canada, and strengthening our balance sheet. With this progress, we believe we are well positioned to execute across key value-creating milestones in our TSHA-102 program. Our goal is to develop potentially transformative therapy option for for all patients suffering from Rett syndrome. We remain steadfast and focused on clinical trial execution and data collection across a broad range of ages and stages of patients with Rett syndrome, which will further inform our discussions with regulatory authorities on the development plan for the next phase of our studies. As a reminder, Rett syndrome is a rare neurodevelopmental disorder that afflicts an estimated 15,000-20,000 patients in the United States, European Union, and United Kingdom.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease, and there are significant unmet need. Rett syndrome is caused by mutations in the X-linked MECP2 gene, which results in the neural network dysfunction and leads to multisystem complications. It's characterized by loss of communication and hand function, slowing and/or regression of development, motor and respiratory impairment, seizures, intellectual disabilities, and shortened life expectancy. Individuals with Rett syndrome typically require 24/7 care and lifelong assistance with daily activities, resulting in high caregiver burden and significant impact on quality of life. Our TSHA-102 gene therapy candidate is a one-time intrathecal, intrathecally delivered treatment designed to address the underlying cause of the disease.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Rett syndrome is challenging to treat with traditional small molecule and gene therapy approaches due to the random X inactivation and subsequent mosaic expression pattern of MECP2 that results in a mixture of cells that are either deficient in MECP2 or express MECP2 normally. We believe TSHA-102, equipped with the novel miRARE technology, has the potential to appropriately address this challenge by mediating MECP2 expression in the central nervous system on a cell-by-cell basis to overcome the risks associated with both under and overexpression of MECP2. Recall, we have two ongoing Phase 1/2 REVEAL trials evaluating TSHA-102. An adolescent and adult trial taking place in Canada and the US for patients 12 and older with stage four Rett syndrome, which is the most advanced stage of the disease.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

A pediatric trial taking place in the U.S. and U.K., with recent clearance in Canada for patients five to eight years of age with stage three Rett syndrome. We are currently enrolling patients in Part A, the dose escalation portion of both trials, which is evaluating two dose levels of TSHA-102. Part B of the pediatric trial, the dose expansion portion, will evaluate TSHA-102 in two age cohorts: an expanded five to eight years of age cohort and a three to five years of age cohort. Two patients have been dosed in cohort one, which is evaluating the low dose of TSHA-102, 5.7E14 total vector genomes in each trial.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

At the 2024 Rett Syndrome Foundation, Rett Syndrome Scientific Meeting in June, we reported encouraging preliminary data from cohort one in our pediatric trial and longer-term data from cohort one in our adolescent and adult trial, which demonstrated a well-tolerated safety profile and improvements across consistent clinical domains impacting daily activities in the adult and the pediatric patients treated with the low dose of TSHA-102. We are pleased by the consistent clinical response demonstrated across multiple areas of disease, including autonomic function, seizures, gross motor skills, fine motor skills and hand function, and communication and socialization in both adult and pediatric patients with different genetic mutation severity. We look forward to continuing to evaluate the clinical impact of the low dose of TSHA-102 over time.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Following review of these data, the Independent Data Monitoring Committee, or IDMC, approved our request to dose escalate early in both REVEAL trials. Therefore, dosing in cohort one of both trials is complete. Expediting dose escalation is an important step in our development plan, as advancing earlier to the high dose accelerates our ability to further inform our clinical development and regulatory strategy for the next phase of our studies. With cohort one complete, we turned our focus to dosing patients in the high-dose cohort across both our REVEAL trials and building on our promising preliminary low-dose data set from both adult and pediatric populations. We dosed the first patient in cohort two of our adolescent and adult trial, which is evaluating the high dose of TSHA-102, which is 1x10^15 total vector genomes.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

We are pleased to share that the high dose of TSHA-102 was generally well-tolerated, with no serious adverse events or dose-limiting toxicities as of the patient's initial six weeks assessment. Following review of these data, the IDMC provided clearance to proceed with dosing the second patient in cohort two of the adolescent and adult trial, and the first patient in cohort two of the pediatric trial earlier than planned. Subsequently, we enrolled the second adolescent adult patient and the first pediatric patient in cohort two across both trials. Dosing of both patients is scheduled to occur in the third quarter of 2024. Lastly, we strengthened our balance sheet with the recent completion of a public follow-on offering that resulted in total net proceeds of $76.8 million.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

We expect the net proceeds to extend our anticipated cash runway into the fourth quarter of 2026 to support the continued development of our TSHA-102 program. Importantly, this capital infusion allows us to build on our preliminary TSHA-102 clinical data set in the adult and pediatric patients and enables us to focus on execution as we endeavor to deliver on key value-creating milestones. We are moving forward reporting cohort-based updates with more mature data sets in order to provide more fulsome updates on our clinical data. In line with this decision, we plan to report safety and efficacy data from the high-dose cohorts and an update on the safety and efficacy from the low-dose cohorts in both our adolescent and adult trial and our pediatric trial in the first half of 2025.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

With our balance sheet strengthened and cash runway extended, we believe we are in excellent position to execute on our key upcoming milestones. I will now turn the call over to Suku to provide a more in-depth discussion of our TSHA-102 program. Suku?

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Thank you, Sean, and good morning, everyone. I'm pleased to provide an update on our TSHA-102 gene therapy program in clinical evaluation for Rett syndrome. We will start with our REVEAL Phase 1/2 adolescent and adult trial. As Sean mentioned, we've completed dosing in cohort one, which included two adult patients who received low dose of TSHA-102. TSHA-102 demonstrated an encouraging safety profile, with no serious adverse events related to TSHA-102 or dose-limiting toxicities as of the week 52 assessment for the first patient and the week 36 assessment for the second patient. Additionally, long-term efficacy data showed a continued durable response with sustained and new improvement across multiple clinical domains and efficacy measures at week 52, following the completion of the steroid and sirolimus taper for the first patient, and at week 25, following the completion of the steroid taper for the second patient.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Both adult patients demonstrated partial restoration of functional improvement in areas of disease that were lost in early childhood, which is not typically observed in the natural history of Rett syndrome. While the disease severity differed between the two adult patients, the improvements were demonstrated in consistent clinical domain as early as four weeks post-treatment in both patients, which was sustained through longer-term assessments. This included improvements in autonomic function, seizures, gross motor skill, fine motor skill, and hand function, and communication and socialization, which can translate to beneficial impacts on quality of life and daily activities for patients and caregivers. We look forward to continuing to evaluate the patients over time for potential further improvements. These improvements are supported by clinical observations reported by the principal investigator, video evidence, and multiple clinical and caregiver-reported efficacy measures.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

The well-tolerated safety profile and durable response in both adult patients with the most advanced stage of disease is encouraging and supports the transformative potential of TSHA-102 across multiple genotypes of patients with stage four Rett syndrome. Now, let's turn to our ongoing REVEAL Phase 1/2 pediatric trial, evaluating the safety and preliminary efficacy of TSHA-102 in females five to eight years of age with stage three Rett syndrome. While this trial captures an earlier stage of disease, it is important to understand that most of these patients require lifelong caregiver dependence, and they present with hallmark symptoms and many advanced manifestations. Enrollment criteria require patients to be post-regression and have entered a stage of stabilization, meaning there have not been any identified loss of skill as in the last six months prior to treatment.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Cohort one, evaluating the low dose of TSHA-102 to complete. TSHA-102 demonstrated an encouraging safety profile with no serious adverse events related to TSHA-102 or dose-limiting toxicities as of the week 22 assessment for the first pediatric patient and week 11 assessment for the second pediatric patient. Similar to the adult patients, the pediatric patients possess different disease severity and genetic backgrounds. Importantly, both pediatric patients demonstrated initial improvements across the same clinical domains we observed in the adult patients, with early evidence of developmental gains following treatment at weeks 12 and eight, respectively. This included improvements in autonomic function, seizures, gross motor skills, fine motor skills, and hand function, and communication and socialization, which can translate to beneficial impacts on quality of life and daily activities for patients and caregivers. We look forward to continuing to evaluate the patients over time for potential further improvements.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

These improvements are supported by clinical observations reported by the principal investigator, video evidence, and multiple clinical and caregiver-reported efficacy measures. Rett syndrome is a highly complex syndromic disease. The critical takeaway is that we believe these early improvements and signs of developmental gain observed across consistent areas of disease in the adult and pediatric patients are very encouraging and support the potential of TSHA-102 to bring meaningful benefit to patients and caregivers. We look forward to collecting longer-term data on the low dose and moving to the high dose cohort across both REVEAL trials, where the totality of the data, will, we collect will further inform our developmental plan for the next phase of the study. I will now turn the call over to Kamran to discuss our financial results. Kamran?

[Kamran Alam, CFO at Taysha Gene Therapies Inc]

Thank you, Suku. Research and development expenses were $15.1 million for the three months ended June 30th, 2024, compared to $19.8 million for the three months ending June 30th, 2023. The $4.7 million decrease was primarily due to a milestone fee payable to Abeona Therapeutics during the three months ended June 30th, 2023, following the dosing of the first patient in the REVEAL Phase 1/2 adolescent and adult trial. General and administrative expenses were $7.3 million for the three months ended June 30th, 2024, compared to $6 million for the three months ended June 30th, 2023.

[Kamran Alam, CFO at Taysha Gene Therapies Inc]

The increase of $1.3 million was primarily due to $0.9 million of higher non-cash stock-based compensation expenses and $0.4 million of higher consulting, professional fees, and other expenses. Net loss for the three months ended June 30th, 2024, was $20.9 million, or $0.09 per share, compared to a net loss of $24.6 million, or $0.38 per share, for the three months ended June 30th, 2023. As of June 30th, 2024, Taysha had $172.7 million in cash and cash equivalents. The company expects that its 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 at Taysha Gene Therapies Inc]

Thank you, Kamran. Overall, we are encouraged by the well-tolerated safety profile in patients who received the low dose of TSHA-102, and the clinical effect being demonstrated across consistent clinical domains in the pediatric and adult patients with stage three and four disease treated with the low dose of TSHA-102. We believe these Cohort One data validate our novel construct and support the potential of TSHA-102 to address the significant unmet medical need in Rett syndrome for a broad range of ages and stages of patients. We are pleased the high dose of TSHA-102 was generally well tolerated as of the initial six-week assessment in the first patient treated in Cohort Two of the adolescent and adult trial.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

IDMC approval to proceed with dosing the second adolescent, adult, and the first pediatric patient earlier than planned in the high-dose cohort of our REVEAL trials enables us to build on the promising preliminary low-dose data that demonstrated relevant clinical effect across key clinical domains impacting activities of daily living in the adult and pediatric patients treated with TSHA-102. As we move to the high dose, we continue to look for a similar pattern of consistent improvement across adult, adolescent, and pediatric patient populations. Looking ahead, we remain focused on clinical trial execution and data collection. The totality of the data we collect from the low and high dose in Part A will inform further our discussions with regulatory authorities on our development plan for the next phase of the trials.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

We look forward to reporting safety and efficacy data from the low-dose and high-dose cohorts in both adolescent and adult trials and the pediatric trial in the first half of 2025. With that, I will now ask the operator to begin our Q&A session. Operator?

[Operator]

Thank you. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. To allow for as many questions as possible, we ask that you each keep to one question and one follow-up. Thank you. Our first question comes from the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your question.

[Kristen Kluska, Managing Director and Biotechnology Equity Research Analyst at Cantor Fitzgerald]

Hi, good morning, everyone. Thanks for taking my questions. So when you report the high-dose data next year, what, in your opinion, is going to be the best way to determine if there is a dose response? We already did see some profound changes from the low dose, and the definition of improvement really differs from patient to patient, given the heterogeneity in different domains impacted sometimes. But is there a clear way that you're looking to try to measure this?

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Thanks, Kristen. I'll, I'll take that initially, and Suku, feel free to, to jump in on this.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Sure.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

But I would say, you know, first of all, you know, when you take a look at the preclinical data at the high dose, there was an increase in survival. There was an improvement in gait abnormalities, you know, which is kind of a surrogate for overall health. And obviously, when you go into the high dose, you're going to be pushing more volume, should have greater biodistribution, greater transduction. And, you know, we would expect, you know, first and foremost, that we see consistent effect across all the clinical domains that we've talked about. I think at this point, the low dose is established. Frankly, it's established a high hurdle bar. I think we're in a good place with the high dose, and we expect that this would effectively build on that.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

I would say, you know, based on the preclinical data and the translation, the always difficult translation of, you know, exactly what's that going to look like in an adult, you know, it's difficult to predict both, I would say, the overall magnitude and the temporal aspect of things. So, you know, we expect that there should be an observed improvement. And the question is really, do we see it early on or does it take more time to manifest? You know, ultimately, we're gonna have to run the experiment, you know, to really fully answer your questions. Again, I would say that from a comparative perspective, we're utilizing the same endpoints, the same clinical observation mechanisms, the same ways to capture the data.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

So we're trying to keep all that as consistent as possible. And, you know, once we have enough data in patients over a longer course of time, you know, we feel confident we'll be able to make the determination, you know, of if there is a drug effect. But with that, I'll turn things over to Suku just to see if there's anything else he would add.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Yeah. Yeah, thanks, Kristen and Sean. So, you know, that you've raised a very interesting question. Usually in drug development, right, you do look for the highest dose that gives you the greatest efficacy and safety, and that seems to apply for gene therapy and in Rett syndrome. I guess the question is, there is a drug on the market. It's a small molecule, but still significant unmet medical need. And as you point out, Kristen, with such a heterogeneous disease, a lower dose is actually showing consistent response, I think that parents and patients will appreciate.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

But at the same time, though, if you look at some of our preclinical data, if you look at some of the work Sir Adrian Bird and others have done, there is justification to go to the higher dose and see if the higher dose will also give us a consistent and further better response than the lower dose. And I'll, I'll leave it open-ended like that because it's only the data that will eventually drive us to eventually the endpoints, the ideal dose that we're gonna get approved by the regulator, and a dose that will truly make a difference in this very complex disease and patient population.

[Kristen Kluska, Managing Director and Biotechnology Equity Research Analyst at Cantor Fitzgerald]

Thank you.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Thanks, Kristen.

[Operator]

Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question.

[Elizabeth Webster, Biotech Equity Research Associate at Goldman Sachs Research]

Hey, good morning, and thank you for taking our question. This is Elizabeth on for Salveen. Wondering on the regulatory front, if you could comment on how the dialogue is going with the regulatory authorities, and if there's any additional color you can share about the nature of those conversations to date? Thank you.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Thanks, Elizabeth. What I would say on the regulatory front is that we do have an upcoming Type B meeting as a result of the RMAT designation. So I would say there would be subsequent updates on that in the future. Our goal at this meeting, there are several goals, but I would say, you know, one of them is to basically align around the cadence of how we're gonna interface with the agency. You know, focus on some of the priorities that we're gonna wanna continue, the dialogue that we've had historically. So that would be the data that we have as it comes in. You know, we wanna make sure that they're seeing the data in an appropriate batching, but they're seeing it as real-time as possible.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

And that, plus the additional work that we're doing on natural history, it will be information that we share with them that ultimately will inform, you know, more thinking on both sides and our alignment around trial design and endpoints for Part B. So the next step in that journey is actually coming up in the relatively near future, and we will certainly provide updates on that, you know, in the coming quarter. Thank you.

[Elizabeth Webster, Biotech Equity Research Associate at Goldman Sachs Research]

Thank you.

[Operator]

Thank you. Our next question comes from line of Chris Raymond with Piper Sandler. Please proceed with your question.

[Chris Raymond, Senior Research Analyst at Piper Sandler]

Hey, thank you. Just a question on what you're gonna present, I guess, in the first half of next year in terms of time on therapy. Just looking back at the last update, I think the low-dose pediatric update, you know, you had some variability. I think one patient was 12 weeks post-dose, another one was eight weeks. Are you looking to standardize that follow-up, and what is that time point, if you can tell us? Thanks.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Yeah, Chris, I would say this: the number one, I think the fact that even at those early time points, you know, we were seeing signs of preliminary efficacy is super encouraging to us. And we felt the right thing to do to really provide more line of sight and clarity is, you know, generate more data over the course of time so that we can give you guys a more fulsome update. So I think the easiest way to answer that sitting here today would be that we would like, you know, so the way things are right now for the high dose, right? We would have three patients in each cohort, right?

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

So the pediatric cohort and the adolescent/adult cohort, and that for the majority of those patients, there's a minimum of six months, would be the way that I would think of it. I think that would be the minimum data set that we would plan to go out with. And I think that hopefully would give everyone you know, better line of sight, more consistency, et cetera. So that's how we're thinking of it right now. You know, we'll we can certainly work to refine our thinking as time moves on, but that's the minimum bar that we see right now. Hopefully, that's helpful.

[Chris Raymond, Senior Research Analyst at Piper Sandler]

Yep, very much. Thank you very much.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

You bet.

[Operator]

Thank you. Our next question comes from the line of Gil Blum with Needham and Company. Please proceed with your question.

[Gil Blum, Senior Analyst at Needham & Company]

Good morning, and thanks for taking our question. So, as it relates to the discussions that you are gonna have with the FDA over time, is there a situation in which, you know, a potential endpoint may depend on what the patients have at baseline? For example, if patients have a significant seizure burden, could they be assessed on that? Just trying to understand how to view a heterogeneous disease like that. Thanks.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Gil, great question. I would say a couple things and certainly turn it over to Suku for his thinking. You know, it's an evolving situation, is probably the best way to say it. I think when you do have a disease that's heterogeneous, you are always trying to think of a way that how do you best standardize what you're capturing? So, you know, while I really do believe that the point you're making is something that we, I can just tell you, we are taking into our calculus, and I can see a world where if you're able to restore or partially restore a lost function, like we've seen in the low-dose data, right?

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

If we've seen an adult who was, there was no expectation of having an effect, sit unassisted after not being able to do that for 10 years. We clearly saw in those video, at least in our opinion, that there was much greater, you know, communication and socialization in that same patient, or as you point out, reduction in seizures, you know, the ability to grasp in the pediatric patients, the improvements in the breathing. Those clinical effects are there. I think what we're working to refine is, you know, there may be a situation where a primary or a co-primary endpoint is more standardized. You know, you might focus more on really, you know, consistently measuring improvements, let's say, in fine motor function, looking at the hands or, you know, gross motor function.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

But I do think also capturing the data on the, what I call the, the restoration of, of function or, or, you know, regaining of a milestone. I think that would be, at a minimum, you know, very supportive data, that I think would be highly impactful, to, to the agency, the payers, et cetera. So, you know, we've been pretty consistent, I, I would say, in how we're, you know, trying to think about ultimate endpoint selection. And what I stepped through right now is, is, you know, just a high-level view of, like, strategically how we're thinking of it. And, you know, we're working as we collect the data, both in terms of our patient data at the high dose, also in terms of natural history data that we've been analyzing.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

I think that should help, you know, further put a fine point on, you know, what would be, you know, the best primary or potentially co-primary, and also allowing us to, you know, include, you know, potentially as a secondary or supportive, you know, these ideas of capturing the restoration of effect. So, Suku, would you add anything to that?

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Yeah, what I would add, Sean, is that, as we all know, it's a complex, heterogeneous disease. But we've shown so far, over a time frame in the patients treated with the low dose in the pediatric study and the adult study, there are consistent positive clinical impact of our gene therapy. So, but then the question that I think Gil brought up is a really important one, because as we get our natural history data from our databases back, and there are certain clinical features that actually could be good comparisons for us, regardless of clinical trial design, when we have our Part B Meeting, those variabilities within a clinical feature that our gene therapy is consistently, consistently helping to treat, is I think, also going to be important.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Because in our studies so far, we've shown that these patients have seizures, right? 80% to 90% of patients, I think, have seizures, but there is a range of seizures. I mean, some patients may have three seizures a day, others may have one seizure a quarter. So the question becomes: how do you assess the clinical impact of a seizure based on frequency and medication dose, versus, let's say, hand function, which is consistently lost to the extreme? So I think these are things that we have to continue to gather data on, and hopefully our clinical trial design in for the Part B component will allow us to assess them, hopefully over a shorter period of time, to show that we can actually have a positive clinical impact for this patient population.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

I guess what I'm really saying, Sean, is we are gathering the data, and hopefully we can put it all together for a very complex disease, where I think we have a pretty good gene therapy.

[Operator]

Thank you. Our next question comes from the line of Joon Lee with Truist Securities. Please proceed with your question.

[Joon Lee, Truist Securities at Managing Director and Senior Biotech Analyst]

Thanks for taking our question. So can you help us understand your 180-degree on the data disclosure strategy? You know, efficacy from your first patient, the patient with the best efficacy so far, was shared at week six. Yet the data from the second, the high dose cohort, passed the six-week mark, but you're reserving that for later. Anything you can share on that would be helpful there. And, you know, also, help us understand what you mean by fulsome. Like, how many patients worth of data you think is sufficient to get a clear picture, and how much data would you have by 1Q that passes that definition of fulsome data? Thank you so much.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

So Joon, just to be clear, you're talking about the fact that the very first patient we reported on was at six weeks, and now we're saying we're going to longer-term data set. So just, I just want to make sure.

[Joon Lee, Truist Securities at Managing Director and Senior Biotech Analyst]

Exactly.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

That's what you're considering.

[Joon Lee, Truist Securities at Managing Director and Senior Biotech Analyst]

Yes, yes. My understanding is that the first patient, that person's, that patient's efficacy was shared around that six-week mark. And just curious, you know, I understand the, the need to hold off until you have some fulsome data, but, you know, and you're changing data strategy, data disclosure strategy, but, anything you can share on behind those cohorts?

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Yeah, sure. I would say a couple things. First of all, one major change is the status and the fortune of the company in terms of balance sheet, right? I mean, when we reported the first patient out, to be totally frank, I think you all know this, the company was in an existential, you know, situation. And we were fortunate, frankly, that the first patient responded as quickly and as pronounced as they did, and that allowed us to go ahead and, you know, finance the company and put us in a much different, you know, situation. And then over the course of time, I think you can see that there's been an evolution of more, you know, more patient data being presented.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

And we ultimately, you know, got to the point where we just felt that, you know, in a more traditional fashion, you know, the easiest thing to do and the more robust way to present the data would be to present, you know, information on a cohort-by-cohort basis. And, you know, I felt an obligation to the investors that came in on the one patient worth of data. They supported us. You know, many of you, you know, supported us with that data because it was so, you know, transformational for that patient. And so I personally felt an obligation to, for a period of time, you know, show data earlier than I normally, you know, would have.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

You know, fortunately, from my perspective, you know, the data that we've continued to share has shown early, just like that first patient, onset of action and consistent effects. I mean, even in the data that we just showed at IRSF and the pediatric patients at eight weeks and 12 weeks, you know, I'll put that data up against anything, you know, that, that, that people have probably seen, right? I mean, where, where have you seen video of people getting restoration of function? And we can argue on the margins, you know, the standardization of the videos and things of that, and I, I acknowledge that, and that's what we're trying to work to standardize, you know, as we move forward. And, and in particular, we must have it all standardized for Part B.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

The point is, you know, there was clearly, clearly an effect, you know, in, in both patients that, I think anyone can, can see. So as we continued to think about it as a management team, we just felt, okay, you know, now we're stepping in, you know, we've, we've demonstrated, I would say, you know, very significant effect with the low dose. We got the okay from the IDMC to step to the high dose. So now we have an opportunity to present more data over time.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

And I think, you know, people looking at something, you know, I would say for us, a minimum threshold would be if we have three patients in the high-dose cohort, in the pediatric patient, and we would have three patients in the pediatric population, that at least the majority of those patients are over six months of time elapsed. In our view, we felt that that's a fulsome update, right? I mean, that's, that's, you're starting to see if, if, if you're getting consistency, durability, et cetera. And we think that is a, you know, a better way for everybody to be able to evaluate, you know, what we're seeing as we step into the high dose.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

So we felt it was a clean break, you know, going from the low dose to the high dose. We felt it was an evolution in how we've been reporting, and, you know, that's why we think ultimately this is the, you know, the best thing for all involved, you know, to see the data in a, in a more, you know, cohort batch basis. So hopefully that, that gets to, to what you're asking, Joon.

[Joon Lee, Truist Securities at Managing Director and Senior Biotech Analyst]

Yes, actually, that makes a lot more sense, and I really appreciate your responses. Thank you so much, and we look forward to the data in 1Q.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Of course. Thank you.

[Operator]

Thank you. Our next question comes from the line of Maury Raycroft with Jefferies. Please proceed with your question.

[Maury Raycroft, Equity Research Analyst at Jefferies]

Hi, thanks for taking my question. Does the timeline change to data impact your timeline for an end of Phase 1 meeting with FDA for the randomized pivotal? I guess, could that still happen in first half 2025 or, or more likely the second half of the year? And do you anticipate the, the first half 2025 data would still be sufficient to bring to FDA for alignment on a randomized Phase 2 pivotal, or would you need additional follow-up?

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Yeah, so Maury, great question. I mean, the way we're thinking about it is that, you know, for us to sit down with the FDA, and have a fulsome discussion around, you know, what Part B design looks like, I would say, number one, we want to complete cohort two dosing, right? So we wanna have that data. We wanna complete our natural history analysis.... And those are, I would say those are key data points that we need. Now, how much data do you need? I would say it's early to say. You know, is it three months of data, six months of data? You know, I think that's why we're guiding to more, in our own mind, you know, can we sit down with the FDA in the first half?

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

You know, that's what, that's what we'd intend to do. But in terms of precisely what's the right level of data to bring them, I'd say it's a little bit early on that. And really, what's gonna help facilitate, you know, getting better line of sight to that is going to be leveraging the RMAT process. So as I said, that starts this quarter, with our clinical Type B Meeting that we have. And we'll actually be talking about things more broadly than just clinical. But the point is, you know, we will inform them with information as we have it.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

So as I said earlier, you know, as we have the natural history data completed, you know, we'll share that with the FDA, and what we think that does to our clinical development plans and potential endpoints. As we generate data from the high dose and longer term data from the low dose, you know, we'll certainly share that with the FDA in a more real-time basis, leveraging the RMAT designation. So, you know, all that is leading and culminating to hopefully, you know, more detailed formal discussion in the first half. But again, I just wanna caveat that exactly how much data we need and exactly when that happens, you know, I think it's a little early to tell, but we should have more line of sight, you know, as in the next quarter or so.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Hopefully, that gives you a little perspective.

[Maury Raycroft, Equity Research Analyst at Jefferies]

Yep. Yeah, very helpful. Thank you.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Thanks.

[Operator]

Thank you. Our next question comes from the line of Yanan Zhu with Wells Fargo. Please proceed with your question.

[Yanan Zhu, Equity Analyst at Wells Fargo Securities]

Great. Thanks for taking our questions. So, based on what you just articulated about the maturity of the data, it feels like it's more, the first half 2025 guidance is probably going to be more second quarter than first quarter. Is that the right takeaway? And also, given that you have dosed just one of the six patients today, one of the six across the two high dose cohorts today, do you think you could have a timely enrollment and dosing to ensure the data could be available in first half 2025?

[Yanan Zhu, Equity Analyst at Wells Fargo Securities]

And if you can comment on the safety waiting period, is that 42-day period true for across all six patients in those two, dose, cohorts? Thanks.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Sure thing, Yanan. You know, so again, we're guiding to the first half to give ourselves, you know, flexibility. Your point on the stagger is a good one, and I would say this, I mean, per the protocol, at this time, the stagger is 42 days between patients. I would just simply say at this point in time that we have this topic very much in mind, and, you know, I would say the guidance that we've come up with, we feel very comfortable with. And so it is possible that you could see some changes down the road to the frequency in which we might be able to dose patients. But that is a future-looking comment.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

So again, first half is the way we're thinking about it right now, and, you know, we're confident in stating that, given everything we know today.

[Yanan Zhu, Equity Analyst at Wells Fargo Securities]

Got it. Thank you.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Thank you.

[Operator]

Thank you. Our next question comes from the line of Jack Allen with Baird. Please proceed with your question.

[Jack Allen, Senior Research Analyst at Baird]

All right, thanks for taking the questions, and congratulations on the progress. My first one was on the high dose patients that have been enrolled in the study to date. It seems like there are about three patients that have been enrolled. In the low dose cohorts, we noticed a difference in the severity of patients depending on their deletions. I was wondering if you could comment as it relates to the baseline characteristics of these high dose patients to some extent. And then, my second question is around the low dose data we expect in the first half of next year. I'd just love to hear the team's thoughts on any comments around how we think that data set should evolve over time.

[Jack Allen, Senior Research Analyst at Baird]

I think there had previously been some talk of, I guess, restoring MECP2 and, regaining of skills over time and a, kind of a teaching bias over time. But I'd love to hear of any thoughts you have around the long-term low dose data as well.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Sure. You know, Suku, I, I would ask you to to take those two questions. You know, I think the first was, you know, are there any baseline characteristics that we can talk about in the high dose patients that have been enrolled? We probably have to just stick to what CGI-Ss are. I think that's all we've guided to, but you can talk about that. And then the second one is just expectations potentially on progress of low dose patients over time.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Yes. So, Sean, I mean, to answer the first question, so if you think about consistency, though, yes, the CGI-S, right? I mean, these patients, for protocol, depending on which study they are, they tend to fall into a range of four to six. And as we all know, in Rett syndrome, the severity may sometimes drive the response, and there could be limitations to that as well. But what is more important is that there are clinical features, though, in the low-dose patients, which I think are consistent. So, autonomic dysfunction, I mean, for example, many of these patients have vascular abnormalities of the upper and lower extremities. Many of these patients did have respiratory abnormalities, the apneic spells and the hyperventilation. Seizures were pretty common.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Loss of hand function, as you know, is very common in the sense of loss of fine hand motor function and gross motor function and the repetitive movements, et cetera. I guess my point is there are certain clinical features that will always be there, and I think when you talk to the experts, they do confirm this. But what we are doing is we have natural history databases that we're looking at, which hopefully will also further support what we need to do for the future if this consistency is proven. So all I can say is that, you know, you have to stay tuned. And having said that, if you look at the high dose patients, I would anticipate you would see very similar commonalities in the clinical presentations that exist in Rett syndrome patients.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

The hand function, I guess you could say social withdrawal, maybe seizures, et cetera, et cetera. So, so this will all be there. And then the, then the other piece of the puzzle is, you know, when you have, whatever the mutation is, missense mutation, a nonsense mutation, or a massive deletion, which then results in a horrible or severe clinical presentation, then the question becomes, you know, any gene therapy, due to the mosaicism of the disease, what is the greatest impact it will have, and on which clinical features? So these are things that you're still collecting, and, and I would say that again, I would assume in gene therapy, if you have a product that has, significant clinical impact, you know, the commonalities of the features will only be seen in a few patients, right?

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Because you're dosing five, six, seven patients to move into part, from Part A into Part B, and then Part B into other studies, if that's what needs to be done. Sean, I mean, I don't know whether that helps answer the question, but the answer to the question for me is not, it's complex. And, and then the second question was, you know what? I, I lost my train there, Sean. Can the person ask?

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Well, I think you answered the question, you answered the question on the baseline characteristics, right? I mean, it is.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Right.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Going to be CGI-S between four and six. That, that's really all the.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Right.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Detail that we've provided thus far. There are going to be.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Right.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Genetic differences in all these patients. And in terms of low dose expectations, you know, I think just at a high level, to build on, you know, what you're saying is that, you know, over the course of time, at least, you know.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Mm-hmm.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

The older initial patients that we reported on, over time, you know, she did gain improvements, you know, further improvements in different aspects, whether it's getting stronger.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Sure.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

From a gross motor perspective, you know, improvement in hand function over the course of time, you know.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Mm.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Improvements in ability to communicate. So, I think, Jack, you know, as you think about the low dose patients in the pediatric, you know, that we just gave preliminary data on, you know, our hope would be that we would see, you know, progress like that. And hopefully, you know, potentially, you know, a little bit better, just given the fact that, you know, they're younger in age. So, you know, we'll have to. Again, we're running the experiment, and we'll look forward to reporting that data out, in the first half of next year. So, hopefully that gets at what you're asking, Jack.

[Jack Allen, Senior Research Analyst at Baird]

Yeah, definitely. Thanks so much for the call.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Thank you.

[Operator]

Thank you. Our final question this morning comes from the line of Silvan Türkcan with Citizens JMP. Please proceed with your question.

[Silvan Türkcan, Equity Research Analyst at Citizens JMP]

Hey, good morning, and thanks for taking my question. Are there any more details on the SAE that you observed in the pediatric patient that was related to the immunosuppressive regimen, that we haven't been or haven't heard before? And then on the safety committee, obviously, they accelerated your ability to dose into a higher dose. At what point could they accelerate or get rid of the stagger, the 45-day waiting period between patients? Thank you so much.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Suku, maybe you can take the first one. The second one, relative to the stagger is really, you know, I think it's a discussion between the company and the IDMC, you know, to talk about when they're comfortable, you know, making that type of a recommendation. So, you know, we have a view in our mind about what would be a sufficient and appropriate amount of data to potentially have that type of discussion. And it's predicated, of course, on having continued good safety results. So, you know, hopefully more to come on that in the future. And Suku, you know, relative to the SAE that was not treatment related.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Right.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

I don't know if there's more to add. I think the disclosure was pretty clear, and we haven't reported anything more, I think, because there has been a declared resolution of that from the PI. But just make sure I'm correct on that, please.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

Yeah, Sean, if I can add, though, the whole issue of a stagger, I wanted to clarify, though, because remember, our approach, I mean, is intrathecal. I mean, there are other approaches that IDMCs and the FDA have been quite flexible on really shortening the stagger. For example, systemic gene therapy, where they are willing to consider it as long as the benefit risk is appropriate, right? So I just wanted to throw that out there because it's important. Because, and that's what, you know, Dr. Peter Marks even wrote about last year.

[Sukumar Nagendran, President and Head of Research and Development at Taysha Gene Therapies Inc]

I think it was in Nature Magazine, because he was talking about why would you waste time on a first low dose, in the sense, as long as it's safe, you don't necessarily have to do all the patients as the protocol had defined. Then the second question around stagger the safety, though. I think, Sean, I mean, as you said, we have given a fair amount of detail, and as it was not related to our product, I don't think there was any issue with the IDMC doing what it needed to do to move the program forward.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Yeah. So there, there's been no additional disclosure on the SAE. I think it resolved and, you know, obviously we've moved ahead, as Suku said, from a dosing perspective. Is that good for you, Silvan?

[Silvan Türkcan, Equity Research Analyst at Citizens JMP]

Perfect. Thank you.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Thank you.

[Operator]

Thank you. Ladies and gentlemen, that concludes our question and answer session. I'll turn the floor back to Mr. Nolan for any final comments.

[Sean Nolan, CEO at Taysha Gene Therapies Inc]

Just appreciate everyone calling in, and always happy to follow up with any additional questions offline. Thank you all, and have a good day.

[Operator]

Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.

Participants

Executives

• Hayleigh Collins, Director of Corporate Communications and Investor Relations
• Kamran Alam, CFO
• Sean Nolan, CEO
• Sukumar Nagendran, President and Head of Research and Development

Analysts

• Chris Raymond, Senior Research Analyst at Piper Sandler
• Elizabeth Webster, Biotech Equity Research Associate at Goldman Sachs Research
• Gil Blum, Senior Analyst at Needham & Company
• Jack Allen, Senior Research Analyst at Baird
• Joon Lee, Truist Securities at Managing Director and Senior Biotech Analyst
• Kristen Kluska, Managing Director and Biotechnology Equity Research Analyst at Cantor Fitzgerald
• Maury Raycroft, Equity Research Analyst at Jefferies
• Silvan Türkcan, Equity Research Analyst at Citizens JMP
• Yanan Zhu, Equity Analyst at Wells Fargo Securities