Q2 2024 Taysha Gene Therapies Inc Earnings Call

August 12, 2024

Operator: Greetings, and welcome to Taysha Gene Therapy's 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.

Operator: Greetings and welcome to Taysha Gene Therapy's second quarter 2024 earnings call. At this time, all participants are in a listen-only mode.

Greetings and welcome to the Acacia gene therapies in 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.

Operator: 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.

As a reminder, this conference is being recorded.

I'd now like to turn the conference over to your host Hailey Collins director and head of corporate Communications and Investor Relations. Thank you you may begin.

Hayleigh Collins: 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.

Speaker Change: Thank you good morning, and welcome to <unk> second quarter, 2024 financial results and corporate update conference call.

Speaker Change: Earlier today <unk> issued a press release announcing financial results for the second quarter ended June 30th 2020 for.

Speaker Change: 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 patients CEO. Good morning, Catherine President and head of R&D, and Kamran Alam Chief Financial Officer.

Hayleigh Collins: 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. Please note that on today's call, we will be making forward-looking statements, including statements relating to the therapeutic and commercial potential of Taysha 102, including the reproducibility and durability of any favorable results initially seen in the patient's dose 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.

Speaker Change: We will hold a question and answer session following our prepared remarks.

Hayleigh Collins: Please note that on today's call, we will be making forward-looking statements, including statements relating to the therapeutic and commercial potential of Taysha 102, including the reproducibility and durability of any favorable results initially seen at the patient's dose to date in clinical trials to positively impact the quality of life and also the course of disease in the patients we seek to treat, our research, development, and regulatory plans for our product candidates, including timelines for our clinical trials 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: 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. 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.

Speaker Change: Please note that on today's call, we will be making forward looking statements, including statements relating to the therapeutic and commercial potential of T cell why don't you, 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 also of course of disease and the patients we seek to.

Treat our research development and regulatory plans for our product candidates, including timelines for our clinical trial and reporting results there from 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 Russell clinical trials for our product candidates and other clinical and regulatory plan and the market opportunity for those programs. This call may also contain forward looking statements relating to patient growth forecasted cash runway in future operating results discovery and development of product candidates strategic alliances and intellectual property.

Hayleigh Collins: 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. However, 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 for our product candidates 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.

Speaker Change: As well as matters that are not historical facts or information.

Speaker Change: Various risks may cause T shirts actual results to differ materially from those stated or implied in such forward. Looking statements. These risks include uncertainties related to the timing and Russell clinical trials up in regulatory interactions for our product candidates our dependence upon strategic alliances and other third party relationships our ability to obtain.

Speaker Change: Patent protection for our discoveries limitations imposed by patents owned or controlled by third parties and the requirements of substantial funding for research and development activity.

Hayleigh Collins: 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 10Q for the full year ended December 31, 2023, and in our quarterly report on Form 10Q for the quarter ended June 30, 2024, which we filed today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 12, 2024.

Hayleigh Collins: These risks include uncertainties related to the timing and results of clinical trials for our product candidates 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. 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 10Q for the full year ended December 31, 2023, and in our quarterly report on Form 10Q for the quarter ended June 30, 2024, which we filed today.

Speaker Change: For lifting 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 the Form 10-K for year ended December 31, two.

Speaker Change: <unk> 23 in our quarterly report on Form 10-Q for the quarter ended June 32024, we filed today. This conference call contains time sensitive information that is accurate only as of the date of this live broadcast August 12 2024.

Hayleigh Collins: This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 12, 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 security laws.

Hayleigh Collins: 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 security laws. With that said, I would now like to turn the call over to our CEO, Sean Nolan.

Speaker Change: So you should 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 maybe required by applicable securities laws with that I would now like to turn the call over to our CEO Sean Mullen.

Sean Nolan: 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 Taysha 102 program in 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 openly call out questions.

Sean Nolan: With that, I would now like to turn the call over to our CEO, Sean Nolan. 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 Taysha 102 Program in 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 to questions.

Sean Mullen: Thank you Haley and welcome everyone to our second quarter 2024 financial results and corporate update conference call.

Sean Nolan: In the second quarter of 2024, we made strong progress across the Taysha 102 program in clinical evaluation for pediatric, adolescent, and adult patients with Rett syndrome. 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 Taysha 102 program.

Sean Nolan: Our goal is to develop a potentially transformative therapy option 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 study. As a reminder, Rett syndrome is a rare neurodevelopmental disorder that afflicts an estimated 15 to 20,000 patients in the United States, the European Union, and the United Kingdom.

Today I will begin with a brief update on our recent activities and then sue our president and head of R&D, who will provide an update on our lead tissue one or two program clinical evaluation for Ret syndrome.

Sean Nolan: In the second quarter of 2024, we made strong progress across the Taysha 102 program in clinical evaluation for pediatric, adolescent, and adult patients with Rett syndrome. 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. With this progress, we believe we are well-positioned to execute across key value-creating milestones in our Taysha 102 program.

Kamran Alam, our Chief Financial Officer will follow with a financial update and I will provide closing remarks and open the call up for questions.

Kamran Alam: In the second quarter of 2024, we made strong progress across the <unk> program clinical evaluation for pediatric adolescent and adult patients with Ret syndrome.

Kamran Alam: This included reporting encouraging safety and efficacy data from the low dose cohort and both our reveal phase one two trials initiating the high dose cohort expanding our pediatric trial in Canada, and strengthening our balance sheet.

With this progress we believe we are well positioned to execute across key value, creating milestones in our case you why don't you program.

Kamran Alam: Our goal is to develop potentially transformative therapy option for.

Sean Nolan: Our goal is to develop potentially transformative therapy options 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 study. As a reminder, Rett syndrome is a rare neurodevelopmental disorder that afflicts an estimated 15 to 20,000 patients in the United States, the European Union, and the United Kingdom.

Kamran Alam: For all patients suffering from <unk> syndrome.

Kamran Alam: We remain steadfast and focused on clinical trial execution and data collection across a broad range of ages and stages of patients with ret syndrome.

Kamran Alam: Which will further inform our discussions with regulatory regulatory authorities on the development plan for the next phase of our studies.

Sean Nolan: Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease, and there are significant unmet needs. Rett syndrome is caused by mutations in the X-linked MECP2 gene, which results in neural network dysfunction and leads to multi-system 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

Kamran Alam: As a reminder, ret syndrome is a rare neuro developmental disorder that afflicts, an estimated 15 to 20000 patients in the United States European Union and the United Kingdom.

Kamran Alam: Currently there are no approved disease modifying therapies to treat the genetic root cause of the disease.

Kamran Alam: And there is significant unmet need.

Kamran Alam: <unk> syndrome is caused by mutations in the excellent <unk>, which results in the neural network dysfunction and leads the multi system complications.

Kamran Alam: Characterized by loss of communication the hand function.

Sean Nolan: 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 a high caregiver burden and significant impact on quality of life. Our Taysha-102 gene therapy candidate is a one-time, intrathecally-delivered treatment designed to address the underlying cause of the disease. 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.

Kamran Alam: <unk> <unk> regression of development motor and respiratory impairment seizures intellectual disabilities and shortened life expectancy.

Sean Nolan: Individuals with Rett syndrome typically require 24-7 care and lifelong assistance with daily activities, resulting in a high caregiver burden and a significant impact on quality of life. Our Taysha-102 gene therapy candidate is a one-time, intrathecally-delivered treatment designed to address the underlying cause of the disease. 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.

Kamran Alam: Individuals with Ret syndrome, typically require 24, southern care and lifelong assistance with daily activities, resulting in high caregiver burden and significant impact on quality of life.

Sean Nolan: We believe Taysha 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 I-II reveal trials evaluating Taysha-102. An adolescent and adult trial taking place in Canada and the U.S. for patients 12 and older with stage 4 Rett syndrome, which is the most advanced stage of the disease, and a pediatric trial taking place in the U.S. and U.K. with recent clearance in Canada for patients five to eight years old with stage 3 RETS.

Speaker Change: Our teacher, one or two gene therapy candidate is a one time interesting interests equally delivered treatment designed to address the underlying causes of disease Ret syndrome is challenging to treat with traditional small molecule and gene therapy approaches due to the random acts and activation and.

Speaker Change: Mosaiq expression pattern of <unk> that results in a mixture of cells that are either deficient in <unk> or express <unk> normally.

Speaker Change: We believe <unk> 102 equipped with the novel <unk> technology has the potential to appropriately address this challenge by mediating <unk> two expression in the central nervous system on a cell by cell basis to overcome the risks associated with both under and over expression of <unk>.

<unk>.

Sean Nolan: We are currently enrolling patients in Part A, the dose escalation portion of both trials, which is evaluating two dose levels of Taysha-102. Part B of the pediatric trial, the dose expansion portion, will evaluate Taysha 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 1, which is evaluating the low dose of Taysha 102 5.7 e to the 14 total vector genomes in each trial.

Speaker Change: Recall, we have two ongoing phase once you reveal trials evaluating tissue 102.

Speaker Change: In adolescent and adult trial, taking place in Canada, and the U S for patients 12, and older with stage for Ret syndrome, which is the most advanced stage of the disease and a pediatric trial, taking place in the U S and UK with recent clearance in Canada for patients five to eight years.

Sean Nolan: And a pediatric trial taking place in the US and UK with recent clearance in Canada for patients five to eight years of age with stage 3 Rett syndrome. We are currently enrolling patients in Part A, the dose escalation portion of both trials, which is evaluating two dose levels of Taysha-102. Part B of the pediatric trial, the dose expansion portion, will evaluate Taysha 102 in two age cohorts, an expanded five to eight years of age cohort and a three to five years of age cohort.

Speaker Change: Age with stage three ret syndrome.

Speaker Change: We are currently enrolling patients in part a the dose escalation portion of both trials, which is evaluating two dose levels of tissue 102.

Speaker Change: Part B of the pediatric trial, the dose expansion portion will evaluate tissue one or two in two age cohorts and expanded five to eight years of age cohort in a three to five years of age cohort.

Speaker Change: Two patients have been dosed in cohort one.

Sean Nolan: Two patients have been dosed in Cohort 1, which is evaluating the low dose of Taysha 102 5.7 e to the 14 total vector genomes in each trial. At the 2024 Rett Syndrome Foundation Rett Syndrome Scientific Meeting in June, we reported encouraging preliminary data from Cohort 1 in our pediatric trial and longer-term data from Cohort 1 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 pediatric patients treated with the low dose of Theta-102.

Which is evaluating the low dose of <unk> 100, 257, each of the 14 total vector genomes in each trial.

Sean Nolan: At the 2024 Rett Syndrome Foundation Rett Syndrome Scientific Meeting in June, we reported encouraging preliminary data from Cohort 1 in our pediatric trial and longer-term data from Cohort 1 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 pediatric patients treated with the low dose of Taysha 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, hand function, and communication and socialization, in both adult and pediatric patients with different genetic mutation severity.

Speaker Change: At the 'twenty 'twenty four Ret syndrome Foundation Ret syndrome scientific meeting in June we reported encouraging preliminary data from cohort, one and our pediatric trial and longer term data from cohort, one and our adolescent and adult trial, which demonstrated a well tolerated safety.

Speaker Change: I'll file and improvements across consistent clinical domains impacting daily activities and the adult and pediatric patients treated with the low dose of <unk> 102.

Speaker Change: 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.

Speaker Change: Patients with different genetic mutation severity.

Sean Nolan: We look forward to continuing to evaluate the clinical impact of the low dose of Taysha 102 over time. 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.

Speaker Change: We look forward to continuing to evaluate the clinical impact of the low dose of <unk>, one or two over time.

Speaker Change: Following a review of these data the independent data monitoring committee or <unk> approved our request to dose escalate early in both reveal trials therefore dosing in cohort one of both trials is complete.

Sean Nolan: 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 1 complete, we've 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 Taysha 102, which is 1E of the 15 total vector genomes.

Sean Nolan: 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 study. With cohort one complete, we've 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 2 of our adolescent and adult trial, which is evaluating the high dose of Taysha 102, which is 1E of the 15 total vector genomes. We are pleased to share that the high dose of Taysha 102 was generally well-tolerated with no serious adverse events or dose-limiting toxicities as of the patient's initial six-week assessment.

Speaker Change: Expediting dose escalation is an important step in our development plan is advancing early or to the high dose accelerates our ability to further inform our clinical development and regulatory strategy for the next phase of our studies.

Speaker Change: Cohort one complete we've 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.

Speaker Change: We dosed the first patient in cohort two of our adolescent and adult trial, which is the value were in the high dose of tissue want them too which is one is the 15 totaled total vector genomes we.

Sean Nolan: We are pleased to share that the high dose of Taysha 102 was generally well-tolerated, with no serious adverse events or dose-limiting toxicities as of the patient's initial six-week assessment. Following review of these data, the IDMC provided clearance to proceed with the dosing of the second patient in Cohort 2 of the adolescent and adult trial and the first patient in Cohort 2 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.

Speaker Change: We are pleased to share that the high dose of <unk> 102 was generally well tolerated with no serious adverse events or dose limiting toxicities as the patient's initial six weeks assessment.

Sean Nolan: Following review of these data, the IDMC provided clearance to proceed with dosing the second patient in Cohort 2 of the adolescent and adult trial and the first patient in Cohort 2 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 strengthen our balance sheet with the recent completion of a public follow-on offering that resulted in total net proceeds of $76.8 million.

Following review of these data the IBM see provided clearance to proceed with the 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 and adult patients in the first pediatric patient in cohort two across both trials dosing of both patients are scheduled to occur in the third quarter of 2024.

Sean Nolan: 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. We expect the net proceeds to extend our anticipated cash runway into the fourth quarter of 2026 to support the continued development of our Taysha 102 program. Importantly, this capital infusion allows us to build on our preliminary Taysha 102 clinical data set in adult and pediatric patients and enables us to focus on execution as we endeavor to deliver on key value-creating milestones.

Speaker Change: 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. We expect the net proceeds to extend our anticipated cash runway into the fourth quarter of 2026 to support the continued development of <unk>.

Sukumar Nagendran: We expect the net proceeds to extend our anticipated cash runway into the fourth quarter of 2026 to support the continued development of our Taysha 102 program. Importantly, this capital infusion allows us to build on our preliminary Taysha 102 clinical data set in 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 with reporting cohort-based updates with more mature datasets in order to provide more fulsome updates on our clinical data.

Speaker Change: 102 program.

Fortunately this capital infusion allows us to build on our preliminary tissue, one or two clinical dataset and the adult and pediatric patients and enables us to focus on execution as we endeavor to deliver on key value creating milestones.

Sean Nolan: We are moving forward with reporting cohort-based updates with more mature datasets 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. With our balance sheets strengthened and cash runway extended, we believe we are in an 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 Taysha 102 program. Circu

Speaker Change: We are moving forward reporting cohort based updates with more mature data sets in order to provide more fulsome updates on our clinical data and.

Speaker Change: In line with this decision we.

Speaker Change: 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 and the first half of 2025 with.

Sukumar Nagendran: 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. With our balance sheet strengthened and cash runway extended, we believe we are in an 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 Taysha 102 program.

Speaker Change: With our balance sheet strengthened and cash runway extended we believe we are in excellent position to execute on our key upcoming milestones.

Speaker Change: I will now turn the call over to <unk> to provide a more in depth discussion of our case, you're one or two programs <unk>.

Speaker Change: <unk>.

Sukumar Nagendran: Thank you, Sean, and good morning, everyone. I'm pleased to provide an update on our Taysha 102 gene therapy program in clinical evaluation for REC syndrome. We will start with our Reveal Phase 1-2 Adolescent and Adult Trial. As Sean mentioned, we have completed dosing in Cohort 1, which included two adult patients who received a low dose of Taysha 102. Taysha 102 demonstrated an encouraging safety profile with no serious adverse events related to Taysha 102 or dose-limiting toxicities as of the Week 52 assessment for the first patient and the Week 36 assessment for the second patient.

Sukumar Nagendran: Thank you, Sean, and good morning, everyone. I'm pleased to provide an update on our Taysha 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 have completed dosing in Cohort 1, which included two adult patients who received a low dose of Taysha 102. Taysha 102 demonstrated an encouraging safety profile with no serious adverse events related to Taysha 102 or dose-limiting toxicities as of the Week 52 assessment for the first patient and the Week 36 assessment for the second patient.

<unk>: Thank you, Sean and good morning, everyone.

Sukumar Nagendran: 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. Both adult patients demonstrated partial restoration of function or improvement in areas of disease that had been lost in early childhood, which is not typically observed in the natural history of Rett syndrome.

Speaker Change: Claims still provide an update on our passion to gene therapy program in clinical evaluation for Ret syndrome.

Sukumar Nagendran: 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. Both adult patients demonstrated partial restoration of function or improvement in areas of disease that had been 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, improvements were demonstrated in consistent clinical domains as early as four weeks post-treatment in both patients. It was sustained through longer-term assessment.

Maybe I'll start with our reveal one last two adolescent and adult trial.

Sukumar Nagendran: This included improvements in autonomic function, seizures, gross motor skills, fine motor skills, and hand function, as well as 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 observation reported by the principal investigator, video evidence, and multiple clinical and caregiver-reported efficacy measures.

Sukumar Nagendran: While the disease severity differed between the two adult patients, improvements were demonstrated in consistent clinical domains as early as four weeks post-treatment in both patients, to sustain through longer-term assessment. 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.

Speaker Change: John mentioned, we have completed dosing in cohort one which included two adult patients will receive low dose of <unk>.

Speaker Change: Shall I know too there's no we're not.

Sukumar Nagendran: 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 Taysha 102 across multiple genotypes of patients with stage 4 Rett syndrome. Now we turn to our ongoing Reveal Phase 1, 2 pediatric trial evaluating the safety and preliminary efficacy of Taysha 102 in females 5 to 8 years of age with stage 3 RETSIN. While this trial captures an earlier stage of disease, it is important to understand that most of these patients require lifelong caregiver support, and they present with hallmark symptoms and many advanced manifestations.

Speaker Change: Ooh amongst peers and encouraging safety profile with no serious adverse events led to protests or one or two or dose limiting toxicity as of the week 52 assessment.

Sukumar Nagendran: Enrollment criteria require patients to be post-regression and have entered a stage of stabilization, meaning there has not been any identified loss of skills as in the last six months prior to treatment. Both One evaluated the low dose of Taysha 102 to complete. Taysha 102 demonstrated an encouraging safety profile with no serious adverse events related to Taysha 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.

Sukumar Nagendran: Similar to the adult patients, the pediatric patients...possess different disease severity and genetic background. Importantly, both pediatric patients demonstrated initial improvements across the same clinical domains you observe in the adult patient, 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, as well as communication and socialization, which can translate to beneficial impacts on quality of life and daily activities for patients and caregivers.

Speaker Change: The first patient in the week 36 assessment for the second patient.

Speaker Change: Additionally, long term efficacy data showed a continued durable response.

Speaker Change: Then the new improvement.

Speaker Change: Multiple clinical domains and efficacy measured at week 52, following the completion of the theory that there are only about Tampa.

Suspension and at week 25, following the completion of the Fidelis Tampa for the second person.

Speaker Change: Both adult patients amongst standard partial restoration of functional improvement in areas of disease.

Speaker Change: The loss of an early childhood, which is not typically observed in the natural history of redfin.

Speaker Change: While the business, but it did differ between the two adult patients improvements with demand rather than 10 clinical demand.

Speaker Change: He is fully exposed to treatment in both patients.

Send through longer term assessments.

Speaker Change: The improvements in autonomic function.

Speaker Change: Gross motor skills, fine motor skills, and hand function and communication and socialization.

Speaker Change: Which can transmit the beneficial impact on quality of life and daily activities for patients and caregivers.

Speaker Change: We look forward to continually evaluate the payer since all the time.

Speaker Change: Potential further improvement.

Kamran Alam: The critical takeaway is that we believe these early improvements and signs of developmental gains observed across consistent areas of disease in adult and pediatric patients are very encouraging and support the potential of Taysha 102 to bring meaningful benefits to patients and caregivers. We look forward to sharing more. We're collecting longer-term data on the low-dose cohort and moving to the high-dose cohort across both revealed trials, where the totality of the data we collect will further inform our development plan for the next phase of the study. I will now turn the call over to Kamran to discuss our financial results. Kamran

Speaker Change: These improvements are supported by clinical observations.

Sukumar Nagendran: These improvements are supported by clinical observation reported by the principal investigator, video evidence, and multiple clinical and caregiver-reported efficacy measures. 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 Taysha 102 across multiple genotypes of patients with stage 4 Rett syndrome.

Speaker Change: Got it by the principal investigator video evidence in multiple clinical and calculate reported efficacy measure.

Speaker Change: The well tolerated safety profile and beautiful restaurant and bolt adult patients with the most advanced stage of disease is encouraging and supports.

Speaker Change: The transformative potential of peso, one or two across multiple genotypes of patients with stage all ret syndrome.

Sukumar Nagendran: Now let's turn to our ongoing Reveal Phase 1-2 Pediatric Trial, evaluating the safety and preliminary efficacy of Taysha 102 in females 5 to 8 years of age with Stage 3 retinitis. While this trial captures an earlier stage of disease, it is important to understand that most of these patients require lifelong caregivers, 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 has not been any identified loss of skills in the last six months prior to treatment.

Speaker Change: Now lets them well.

Sean Nolan: Thank you, Suku. Research and development expenses were $15.1 million for the three months ended June 30, 2024, compared to $19.8 million for the three months ended June 30, 2023. The $4.7 million decrease was primarily due to a milestone fee payable to Abiona Therapeutics during the three months ended June 30, 2023, following the dosing of the first patient and the announcement of Phase I-II adolescent and adult trials. General and administrative expenses were $7.3 million for the three months ended June 30, 2024, compared to $6 million for the three months ended June 30, 2023.

Speaker Change: Well ongoing real fans want to pediatric trial evaluating the safety and preliminary efficacy of this or one or two in females five to eight years of age.

Speaker Change: <unk> three that syndrome.

Speaker Change: While this trial capture an earlier stage of disease. It is important to understand that most of these patients.

Speaker Change: Quite a lifelong caregiver.

Speaker Change: Yeah.

Speaker Change: Dependence and they present with hallmark symptom and many advanced manifestation.

Speaker Change: The enrollment criteria required patients to be post progression.

Speaker Change: And third the stage of stabilization.

Speaker Change: Meaning they have not been any identified last osceola.

Speaker Change: Last six months prior to treatment.

Sukumar Nagendran: Both one evaluated the low dose of Taysha 102 to complete. Taysha 102 demonstrated an encouraging safety profile with no serious adverse events related to Taysha 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, pediatric patients possess different disease severity and genetic background.

Speaker Change: Well look one evaluating the load or soft tissue or one or two.

Speaker Change: To complete.

Speaker Change: So.

Speaker Change: There's one or two demonstrated an encouraging safety profile with no serious adverse events and that's the piece that one or two or dose limiting toxicities.

Speaker Change: Turning to do assessment for the first media took patient and weak loan assessment for the second pediatric patient.

Speaker Change: Similar to the adult patients are pediatric patients.

Speaker Change: Well, there's different disease, but it didnt genetic backgrounds.

Sukumar Nagendran: Importantly, both pediatric patients demonstrated initial improvements across the same clinical domains we observe in the adult patients, with early evidence of developmental gains following treatment, at Weeks 12, and eight, respectively. These included improvements in autonomic function, seizures, gross motor skills, fine motor skills, 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 improvement. These improvements are supported by clinical observation reported by the principal investigator, video evidence, and multiple clinical and caregiver-reported efficacy measures. Rett syndrome is a highly complex syndromic disease.

Speaker Change: Importantly, both pediatric basin demand to stay at that initial improvement across the same clinical demand observed in adult patients with early evidence of developmental gains following treatment.

Speaker Change: Weeks 12.

Speaker Change: And eight respectively.

Speaker Change: This included improvements in autonomic functions. These are gross motor skills by an order of skills and hand function and communication and socialization, which can translate to beneficially impact on quality of life and daily activities for patients and caregivers.

Speaker Change: We look forward to continuing to elevate the patients over time.

Speaker Change: Potential further improvement.

Speaker Change: These improvements are supported by clinical observation reported by the principal investigator video evidence and multiple clinical and caregiver reported efficacy measure.

Speaker Change: <unk> syndrome is a highly complex syndromic diseases. The critical takeaway is that we.

Sukumar Nagendran: The critical takeaway is that we believe these early improvements and signs of developmental gain observed across consistent areas of disease in adult and pediatric patients are very encouraging and support the potential of Taysha 102 to bring meaningful benefits to patients and caregivers. We look forward to sharing more. So collecting longer-term data on the low-dose and moving to the high-dose cohort across both revealed trials, where the totality of the data we collect will further inform our development plan for the next phase of the study. I will now turn the call over to Kamran to discuss our financial results. Kamran?

Speaker Change: We believe these early improvements in signs up developmental again.

Speaker Change: The costs consistent it is a disease.

Speaker Change: In pediatric patients.

Speaker Change: Very encouraging and supports the potential official one or two.

Speaker Change: Any meaningful benefit to patients and caregivers.

Speaker Change: We look forward.

Speaker Change: So collecting longer term data on the low dose and move into the higher dose cohort across both the reveal trial.

The ability of the data.

Operator: Greetings and welcome to the Taysha Gene Therapy's 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.

Speaker Change: That will further inform our developmental plan for the next phase of the study.

Kamran Alam: Thank you, Suku. Research and development expenses were $15.1 million for the three months ended June 30, 2024, compared to $19.8 million for the three months ended June 30, 2023. The $4.7 million decrease was primarily due to a milestone fee payable to Abiona Therapeutics during the three months ended June 30, 2023, following the dosing of the first patient and the announcement of Phase I-II adolescent and adult trials. General and administrative expenses were $7.3 million for the 3 months ended June 30, 2024, compared to $6 million for the 3 months ended June 30, 2023.

Sean Nolan: 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. The net loss for the three months ended June 30, 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 30, 2023. As of June 30, 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. Okay, Sean?

Speaker Change: I will now turn the call over to Cameron to discuss our financial results Ameren.

Operator: 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.

Kamran Alam: 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. The net loss for the three months ended June 30, 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 30, 2023. As of June 30th, 2024, Taysha had $172.7 million in cash and cash equivalents.

Cameron: Thank you Sue 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 30 of 2023.

Hayleigh Collins: 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. Thank you.

Cameron: The $4 7 million dollar decrease was primarily due to a milestone fee payable to abbvie on a therapeutics. During the three months ended June 32023, following the dosing of the first patient in the reveal phase one two adolescent and adult trial.

Hayleigh Collins: 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 and at June 30, 2024. A copy of this press release is available on the company's website and through our SEC filing.

Cameron: 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 30 of 2023, the increase of $1.3 million was primarily due to your point $9 million of higher noncash stock based compensation expense.

Hayleigh Collins: Joining me on today's call are Sean Nolan, Taysha's CEO, Sukumar Nagendran, President and Head of R&D in Cameron 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 relating to the therapeutic and commercial potential of Taysha 102, including the reproducibility and durability of any favorable results initially seen in the patient's dose-to-date and clinical trials to positively impact the quality of life and also the course of disease and the patients we seek to treat.

Cameron: And zero point $4 million of higher consulting professional fees and other expenses.

Cameron: Net loss for the three months ended June 30 of 2024 was $29 million or nine cents per share compared to a net loss of $24 $6 million or <unk> 38 per share for the three months ended June 30 of 2023.

Hayleigh Collins: Our research development and regulatory plans for our product came to the candidates, including timelines for clinical trials and reporting results therefrom in our current cash resources, supporting our plans, 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.

Cameron: As of June 30 of 2024 case, you had $172 $7 million in cash and cash equivalents.

Sean Nolan: 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.

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.

Hayleigh Collins: 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 or dependence upon strategic alliances and other third-party relationships with 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 for Dr. Research and Development Activity.

Sean Nolan: Thank you, Kamran. Overall, we are encouraged by the well-tolerated safety profile in patients who receive the low dose of Taysha 102 and the clinical effect being demonstrated across consistent clinical domains in pediatric and adult patients with stage 3 and 4 disease treated with the low dose of Taysha 102. We believe these Cohort 1 data validate our novel construct and support the potential of Taysha 102 to address the significant unmet medical need for Rett syndrome across a broad range of ages and stages of patients.

Thank you Cameron overall.

Sean Nolan: Overall, we are encouraged by the well-tolerated safety profile in patients who receive the low dose of Taysha 102 and the clinical effect being demonstrated across consistent clinical domains in pediatric and adult patients with stage 3 and 4 disease treated with the low dose of Taysha 102. We believe these Cohort 1 data validate our novel construct and support the potential of Taysha 102 to address the significant unmet medical need for Rett syndrome across a broad range of ages and stages of patients.

Speaker Change: Overall, we are encouraged by the well tolerated safety profile in patients who received the low dose of tissue 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 <unk> 102.

Speaker Change: We believe these cohort one data validate our novel construct and support the potential location 102 to address the significant unmet medical need and ret syndrome for a broad range of ages and stages of patients.

Sean Nolan: We are pleased that the high dose of Taysha 102 was generally well tolerated as of the initial six weeks assessment in the first patient treating cohort two of the adolescent and adult trial. 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 effects across key clinical domains impacting activities of daily living in the adult and pediatric patients treated with Taysha 102.

Sean Nolan: We are pleased that the high dose of Taysha 102 was generally well-tolerated as of the initial six-week assessment in the first patient treatment cohort two of the adolescent and adult trial. 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 effects across key clinical domains impacting activities of daily living in the adult and pediatric patients treated with Taysha 102.

Speaker Change: We are pleased the high dose of <unk> 102 was generally well tolerated as of the initial six week assessment and the first patient treated in cohort two of the adolescent and adult trial.

Hayleigh Collins: For a list in the 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 the form 10, 15, full year and a December 31, 2023. In our quarterly report on form 10, Q for the quarter-ended June 30, 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 12, 2024.

Speaker Change: <unk> approval to proceed with dosing the second adolescent and adult in the first pediatric patient earlier than planned and 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.

Speaker Change: Impacting activities of daily living and the adult and pediatric patients treated with tissue one or two as.

Sean Nolan: 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 doses in Part A will inform further our discussions with regulatory authorities on our development plan for the next phase of the trial. 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.

Speaker Change: As we move to the high dose we continue to look for a similar pattern of consistent improvement across adult adults adolescents and pediatric patient populations looking.

Sean Nolan: With that, I would now like to turn the call over to our CEO, Sean Nolan. 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 recent activities, and then Sukum, our President and Head of R&D will provide an update on our lead Taysha 102 Programming Clinical Evaluation for RETS 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.

Speaker Change: Looking ahead, we remain focused on clinical trial execution and data collection.

Speaker Change: A totality of the data we collect from the low and high dose in part a.

Speaker Change: We will inform further our discussions with regulatory authorities on our development plan for the next phase of the trials.

Speaker Change: We look forward to reporting safety and efficacy data from the low dose and high dose cohorts and both adolescent and adult trials and the pediatric trial and the first half of 2025.

Operator: With that, I will now ask the operator to begin our Q&A session. Operator? Thank you. If you'd like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue.

Speaker Change: With that I will now ask the operator to begin our Q&A session operator.

Sean Nolan: In the second quarter of 2024, we make strong progress across the Taysha 102 Program in Clinical Evaluation for Pediatric, Adolescent, and Adult Patients with RETS Syndrome. This included reporting encouraging safety and efficacy data from the low-dose cohort in both our reveal phase 12 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 Taysha 102 Program.

Operator: Thank you. If you'd like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. 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.

Speaker Change: Thank you.

Speaker Change: 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.

Speaker Change: You May press star two if you'd like to remove your question from Nick here for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star keys.

Operator: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. 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.

Speaker Change: To allow for as many questions as possible, we ask that you each keep to one question and one follow up thank you.

Sean Nolan: Thanks, Kristen. I'll take that initially, and Sukum, feel free to jump in on this. But I would say, first of all, 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, 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, and greater transduction.

Kristen Kluska: 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 and different domains impacted sometimes. But is there a clear way that you're looking to try to measure this? Thanks, Kristen. I'll take that initially, and Sukum, feel free to jump in on this.

Kristen <unk>: Our first question comes from the line of Kristen <unk> with Cantor Fitzgerald. Please proceed with your question.

Kristen <unk>: Hi, good morning, everyone. Thanks for taking my questions. So when you have what 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.

Sean Nolan: Our goal is to develop potentially transformative therapy option for all patients suffering from RETS Syndrome. We remain steadfast and focused on clinical trial execution and data collection across a broad range of ages and stages of patients with RETS Syndrome, which will further inform our discussions with regular authorities on the development plan for the next phase of our studies. As a reminder, RETS Syndrome is a rare neurodevelopmental disorder that afflicts an estimated 15 to 20,000 patients in the United States, European Union, and United Kingdom.

Genuity in different domains impacted sometimes but is there a clear way that youre looking to try to measure this.

Speaker Change: Thanks, Kristen I'll take that initially and sue can feel free to.

Speaker Change: Jumping on this but I would say.

Sean Nolan: But I would say, first of all, 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, 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, and greater transduction. And, you know, we would expect, first and foremost, that we see consistent effects across all the clinical domains that we've talked about.

Speaker Change: First of all.

Speaker Change: When you take a look at the preclinical data at the high dose there was an increase in survival there was an improvement in abnormalities.

Sean Nolan: Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease, and there is significant unmet need. RETS Syndrome is caused by mutations in the X-linked MECP2 gene, which results in the neuro-network dysfunction and leads to multi-system complications. It's characterized by loss of communication in the hand function, slowing and or regression of development, motor and respiratory impairment, seizures, intellectual disabilities, and shortened life expectancy. Individuals with RETS Syndrome typically require 24-7 care and lifelong assistance with daily activities, resulting in high caregiver burden and significant impact on quality of life.

Speaker Change: Just kind of a surrogate for overall health and obviously when you go into the high dose youre going to be pushing more volume should have greater bio distribution greater transduction.

Sean Nolan: And, you know, we would expect, first and foremost, that we see consistent effects across all the clinical domains that we've talked about. And I think at this point, the low dose has established, frankly, it has 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. I would say, based on the preclinical data and the translation, the always difficult translation of it, exactly what that is going to look like in an adult, it's difficult to predict both the overall magnitude and the temporal aspect of things.

Speaker Change: And we would expect first and foremost that we see consistent effect across all of the clinical domains that we've talked about I think at this point the low doses established frankly has established a high hurdle bar I think we're in a good place with the high dose and we expect that this would would effectively build on that I would say.

Sean Nolan: And I think at this point, the low dose has established, frankly, 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. I would say, based on the preclinical data and the translation, the always difficult translation of it, exactly what that's going to look like in an adult, 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?

Speaker Change: Based on the preclinical data and the translation that always difficult translation of exactly what's that going to look like an adult.

Speaker Change: It's difficult to project to predict both I would say that the overall magnitude.

Sean Nolan: Artesian 102 gene therapy candidate is a one-time, interestingly-delivered treatment designed to address the underlying cause of the disease. RETS Syndrome is challenging the 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 Tasia 102, equipped with the novel MIRAIR 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 over-expression of MECP2.

Speaker Change: Yeah.

Speaker Change: The temporal aspect of things so.

Sean Nolan: 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?

Speaker Change: We expect that there should be an observed an improvement.

Speaker Change: And the question is really do we see it.

Speaker Change: Early on.

Speaker Change: Or does it take more time to manifest you know ultimately we're going to have to run the experiment.

Sean Nolan: You know, ultimately, we're going to have to run the experiment to really fully answer your questions. Again, I would say that from a comparator perspective, we're utilizing the same endpoints, the same clinical observation mechanisms, and the same ways to capture the data. So, we're trying to keep all that as consistent as possible. And, you know, once we have enough data and patients over a longer course of time, we feel confident we'll be able to make the determination of whether there is a drug effect.

Sean Nolan: You know, ultimately, we're going to have to run the experiment 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, and the same ways to capture the data. So we're trying to keep all that as consistent as possible. And, you know, once we have enough data and patients over a longer course of time, we feel confident we'll be able to make the determination of whether 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.

Speaker Change: 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 are the same ways to capture the data. So we're trying to keep all of that as consistent as possible and.

Speaker Change: Once we have enough data in patients over a longer course of time.

Speaker Change: We feel confident we'll be able to make that determination.

Sean Nolan: Recall, we have two ongoing phase one to reveal trials evaluating Taysha 102. And adolescent and adult trial taking place in Canada and the U.S, for patients 12 and older for stage 4 right syndrome, which is the most advanced stage of the disease. And 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 was stage 3 red syndrome. We are currently enrolling patients in part A, the dose escalation portion of both trials, which is evaluating two dose levels of Taysha 102.

Speaker Change: You know if there is a drug effect.

Sukumar Nagendran: But with that, I'll turn things over to Suku just to see if there's anything else he would add. Yeah. Yeah. Thanks, Crystal and Sean. So, you know, that's great.

stupid: With that I'll turn things over to stupid just to see if there's anything else you would add.

Sukumar Nagendran: Yeah, yeah, thanks Kristen and Sean. So, you know, you've raised a very interesting question because, 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 whether there is a drug on the market. Although it's a small molecule, there's still significant unmet medical need. And as you point out, Kristen, with such a heterogeneous disease, a low dose is actually showing a consistent response that I think that parents and patients will appreciate.

Sukumar Nagendran: Yeah, yeah, thanks, Christopher and Sean. So, you know, you've raised a very interesting question because, usually, in drug development, right, you do look for the highest dose that gives you the greatest efficacy and safety 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.

stupid: Thanks, Crystal and so on so.

stupid: You raised a very interesting question because.

stupid: Usually in drug development, you do look for the highest dose that gives you the greatest efficacy and safety and that.

Speaker Change: It seems to apply for gene therapy and in Ret syndrome, I guess the question is.

Kristen <unk>: There is a drug on the market. It's a small molecule. So it's still significant unmet medical need and as you point out Kristen with such a heterogeneous disease, a lower dose is actually showing consistent best funds.

Sukumar Nagendran: There is still significant unmet medical need, and as you point out, Kristen, with such a heterogeneous disease, a lower dose is actually showing a consistent response that I think that parents and patients will appreciate. But at the same time, though, if you look at some of our preclinical data, if you look at some of the work that Dr. 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.

Sean Nolan: Part B of the pediatric trial, the dose expansion portion will evaluate Taysha 102 in two age cohorts and expanded five to eight years of age cohort and the three to five years of age cohort. Two patients have been dose in cohort one, which is evaluating the low dose of Taysha 102, 5.7, e to the 14 total vector genomes in each trial. At the 2024 RET syndrome foundation, RET syndrome scientific meeting in June re-reported encouraging preliminary data from cohort one and our pediatric trial and longer term data from cohort one and 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 Taysha 102.

Speaker Change: I think that parents and patients will approve it but at the same time, though if you look at some of our preclinical data. If you look at some of the work.

Sukumar Nagendran: But at the same time, though, if you look at some of our preclinical data, if you look at some of the work that Dr. 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.

Speaker Change: In blood and others have done.

There is a justification to go to the higher dose.

Speaker Change: If the higher dose it also give us a consistent and further better that sponsor and Deloitte and.

Sukumar Nagendran: And I'll leave it open-ended like that because it's only the data that will eventually drive us to the endpoints, the ideal dose that we're going to get approved by the regulators, and a dose that will truly make a difference in this very complex disease and patient population. Thank you. Thanks, Chris.

Sukumar Nagendran: And I'll leave it open-ended like that because it's only the data that will eventually drive us to the endpoints, the ideal dose that we're going to get approved by the regulator, and a dose that will truly make a difference in this very complex disease and patient population. Thank you. Thank you. Thanks, Kristen.

Speaker Change: And I'll leave it open ended like that because it's only the data that will eventually drive it eventually the endpoint the idea of door, that's you're going to get approved by the regulator and let those federal coolly make a difference in this very complex disease and patient population.

Speaker Change: Thank you.

Kristen <unk>: Thanks Kristen.

Sean Nolan: Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question. Hey, good morning, and thank you for taking our question.

Salveen Richter: Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question. Hey, good morning, and thank you for taking our question. This is Elizabeth on behalf of Salveen.

Speaker Change: Thank you. Our next question comes from the line of Salvino Victor with Goldman Sachs. Please proceed with your question.

Hey, good morning, and thank you for taking our question. This is all at the back on <unk> wondering on the regulatory front. If you could comment on how the dialogue is going with the regulatory authorities and if theres any additional color you can share about the nature of the conversation to date. Thank you.

Sean Nolan: 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 Taysha 102 over time. Following your view of the independent data monitoring committee or IDMC, approved our request to dose-escalate early in bulk reveal trials.

Elizabeth Webster: 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: 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 will be subsequent updates on that in the future. Our goal at this meeting, there are several goals, but I would say one of them is to basically align around the cadence of how we're going to interface with the agency, and focus on some of the priorities that we're going to want to continue the dialogue that we've had historically.

Sean Nolan: 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 will be subsequent updates on that in the future. Our goal at this meeting, there are several goals, but I would say one of them is to basically align around the cadence of how we're going to interface with the agency, focus on some of the priorities that we're going to want to continue the dialogue that we've had historically. So that would be the data that we have as it comes in. We want to make sure that they're seeing the data in an appropriate fashion, but they're seeing it as real-time as possible.

Elizabeth: Thanks Elizabeth.

Speaker Change: I'd say on the regulatory front is that we do have an upcoming type b meeting.

Speaker Change: As a result of the Army's designation.

Speaker Change: So I would say there would be subsequent updates on that in the future.

Speaker Change: Our goal at this meeting there are several goals, but I thought I would say one of them is basically align around the cadence of how we're going to interface with the agency.

Speaker Change: Focus on some of the priorities that we're going to want to continue the dialogue that we've had historically.

Sean Nolan: 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've turned our focus to dosing patients and 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.

Sean Nolan: So that would be the data that we have as it comes in. You know, we want to make sure that they're seeing the data in an appropriate fashion, but they're seeing it as real-time as possible. And that plus the additional work that we're doing on natural history will be information that we share with them that ultimately will inform more thinking on both sides and our alignment around trial design and endpoints for Part B.

Speaker Change: So that would be the data that we have as it comes in we want to make sure that theyre seeing the data.

Speaker Change: In an appropriate bashing, but theyre seeing us as real time as possible.

Speaker Change: And that <unk>.

Sean Nolan: Plus the additional work that we're doing on natural history, it will be information that we share with them that ultimately will inform 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. Thank you. Thank you. Our next question comes from the line of Chris Raymond with Piper Sandler. Please proceed with your question.

Speaker Change: Plus the additional work that we're doing on natural history that will be.

Speaker Change: Information that we share with them that ultimately will inform.

You know more thinking on both sides and our alignment around trial design.

Speaker Change: The 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.

Sean Nolan: 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. Thank you. Thank you. Our next question comes from the line of Chris Raymond with Piper Sandler. Please proceed with your question. Hey, thank you.

Sean Nolan: We dose the first patient in cohort two of our adolescent and adult trial, which is evaluating the high dose of Taysha 102, which is one of these the 15 total vector genomes. We are pleased to share that the high dose Taysha 102 was generally well tolerated with no serious adverse events for dose limiting taxes to these. As of the patient's initial six weeks assessment.

Speaker Change: In the coming quarter.

Speaker Change: Thank you.

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

Chris Raymond: Just a question on what you're going to 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... Twelve 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? Yeah, Chris, I would say this.

Sean Nolan: Hey, thank you.

Chris Raymond: Hey, Thank you just a question on what Youre going to present I guess in the first half of next year in terms of.

Sean Nolan: Smith. Following review of these data, the IDMC provided clearance to proceed with the 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.

Speaker Change: Time on therapy, just looking back at the last update I think the low dose pediatric update you had some variability I think one patient was <unk>.

Speaker Change: Two weeks post dose and another one was eight weeks.

Speaker Change: Are you looking to standardize that follow up and what what is that time point. If you can as you can tell us.

Sean Nolan: Yeah, Chris, I would say this. Number one, I think the fact that even at those early time points, 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 was to generate more data over the course of time so that we could 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, we would have three patients in each cohort, right, so the pediatric cohort and the adolescent adult

Sean Nolan: 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 was, you know, generate more data over the course of time so that we could 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, the way things are right now for the high dose, right?

Speaker Change: Yes, Chris I would say this.

Speaker Change: Number one I think the.

Fact that even if those early time points, we were seeing signs of preliminary efficacy super encouraging to us and we felt the right thing to do to really provide more line of sight and clarity.

Sean Nolan: We expect the net proceeds to extend our anticipated cash runway into the fourth quarter of 2026 to support the continued development of our Taysha 102 program. Importantly, this capital infusion allows us to build on our preliminary Taysha 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.

Speaker Change: Is generate more data over the course of time. So that we can give you guys. Some more fulsome update so I think the easiest way to answer that sitting here today would be that we would like.

Speaker Change: So the way things are right now for the the high dose rate, we would have three patients in each cohort right. So pediatric cohort in the adolescent and adult cohort.

Sean Nolan: We would have three patients in each cohort, right? 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 a better line of sight, more consistency, et cetera

Speaker Change: And in that.

Sean Nolan: 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, a better line of sight, more consistency, et cetera. So that's how we're thinking of it right now. You know, we can certainly work to refine our thinking as time moves on, but that's the minimum bar that we see right now.

Speaker Change: 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 dataset that we would.

Sean Nolan: 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. With our balance sheet strengthened and cash runway extended, we believe we are an excellent position to execute on our key of coming milestones.

Speaker Change: Plan to go out with and I think that hopefully would.

Speaker Change: Would you give everyone better line of sight more consistency.

Speaker Change: Et cetera, So that's how we're thinking of it right now we can certainly work to refine our thinking assigned moves on but that's the minimum bar that we see right now hopefully that's helpful.

Sean Nolan: So that's how we're thinking of it right now. 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.

Speaker Change: Very much thank you very much.

Speaker Change: You bet.

Sean Nolan: Hopefully, that's helpful. Yep, very much. Thank you very much. Thank you. Our next question comes from the line of Gil Blum with Niederman Company. Please proceed with your question. Good morning, and thanks for taking our question.

Operator: Thank you. Our next question comes from the line of Gil Blum with Niederman Company. Please proceed with your question.

Speaker Change: Thank you. Our next question comes from the line of Gil Blum with Needham <unk> Company. Please proceed with your question.

Sean Nolan: Thank you. Our next question comes from the line of Gil Blum with Niederman Company. Please proceed with your question. Good morning, and thanks for taking our question.

Sukumar Nagendran: I will now turn the call over to Suku to provide a more in-depth discussion of our Taysha 102 program. Suku, thank you Sean and good morning everyone. I'm pleased to provide an update on our Taysha 102G therapy program in clinical evaluation for rec syndrome.

Gil Blum: Good morning, and thanks for taking my question so as it relates to discussions with you.

Gil Blum: So, as it relates to the discussions that you will 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. Gil, great question. I would say a couple things and certainly turn it over to Suku for his thinking.

Speaker Change: Gonna have with the FDA over time.

Each of <unk>, and which you know a potential endpoint may depend on what the patients have at baseline.

Sukumar Nagendran: We will start with a reveal phase one slash two adolescent and adult trial. As Sean mentioned, we have completed dosing in cohort one which included two adult patients who received low dose of Taysha 102. Taysha 102 demonstrated an encouraging safety profile with no serious adverse events related to Taysha 102 or dose limiting toxicities as of the week 52 assessment for the first patient and the week 36 assessment for the second patient.

Speaker Change: For example.

Speaker Change: Patients have been significant seizure burden could they be assessed on that just trying to understand.

Speaker Change: How to view a heterogeneous disease.

Speaker Change: Yeah.

Operator: Gil, great question. I would say a couple things and certainly turn it over to Suku for his thinking.

Joe: Joe Great question, I would say a couple of things and certainly turn it over to <unk> for his thinking.

Speaker Change: You you know.

Sean Nolan: 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 to 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 you're able to restore or partially restore a lost function, like we've seen in the low-dose data, right? I mean, we've seen an adult who was, there was no expectation of it having an effect.

Speaker Change: It's an evolving situation is probably the best way to say it I think when you do have a disease.

Heterogeneous you are always trying to think of a way that how do you best standardize what you're capturing so.

Sukumar Nagendran: 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 steroidment taper for the first patient and at week 25 following the completion of the steroid taper for the second patient. Both adult patients demonstrated partial restoration of functional improvement in areas of disease that for last in early childhood which is not typically observed in the natural history of red syndrome.

Speaker Change: While I really do believe that the.

Speaker Change: At the point, you're making is something that.

Speaker Change: I can just tell you we are taking into our into our calculus on it and I can see a world where if you are able to restore.

Speaker Change: Or partially restore lost function like we've seen in the low dose data.

Speaker Change: We've seen an adult.

Speaker Change: There was no expectation of having an effect.

Sean Nolan: We clearly saw in those videos, at least in our opinion, that there was much greater communication and socialization in that same patient. Or, as you point out, reduction in seizures, the ability to grasp in the pediatric patients, the improvements in breathing, those clinical effects are there. I think what we're working to refine is there may be a situation where a primary or co-primary end point is more standardized. For example, you might focus more on really consistently measuring improvements, let's say, in fine motor function, looking at the hands or gross motor function.

Speaker Change: Sit on assisted after not being able to do that for 10 years. We clearly saw on those video at least in our opinion that there was much greater.

Sukumar Nagendran: While the disease severity deferred between the two adult patients, the improvements are demonstrated in consistent clinical domain as earlier four weeks for treatment in both patients, which was sustained through long-term assessments. This included improvements in autonomic function, the easier growth 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.

Speaker Change: Communication and socialization and that same patient or as you pointed out reduction in seizures of your ability to grasp in the pediatric patients the improvements in the in the breathing.

Speaker Change: Clinical effects are there I think what we're working to refine this and there may be a situation, where a primary or a co primary endpoint is more standardized.

Speaker Change: You might you might focus more on I'm really consistently measuring improvements, let's say and fine motor function looking at the hands or or gross motor function.

Sukumar Nagendran: We look forward to continuing to evaluate the patients over time for potential further improvement. These improvements are supported by clinical observation reported by the principal investigator, video evidence, and multiple clinical and caregiver reported efficacy measures. 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 Taysha 102 across multiple genotypes of patients with stage 4 red syndrome.

Speaker Change: But I do think also capturing the data on the what I call. The restoration of function or regaining of a milestone I think that would be at a minimum.

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

Sean Nolan: But I do think also capturing the data on what I call the restoration of function or regaining of a milestone would be, at a minimum, very supportive data that I think would be highly impactful to the agency, the payers, et cetera. So we've been pretty consistent, I would say, in how we're trying to think about Ultimate Endpoint Selection. And what I stepped through right now is just a high-level view of how we're thinking about it strategically.

Speaker Change: They're very supportive data.

Speaker Change: I think would be highly impactful.

Speaker Change: Two to the agency to payers et cetera. So.

Speaker Change: We've been pretty consistent I would say and how we're trying to think about ultimate endpoint selection and when I stepped through right. Now is just a high level view of like strategically how we're thinking of it and we're working as we collect the data both in terms of our patient data at the high dose.

Sukumar Nagendran: Now, let's turn to our ongoing reveal phase 12 pediatric trial, evaluating the safety and preliminary efficacy of Taysha 102 in females 5 to 8 years of age with stage 3 red syndrome. While this trial captures an earlier stage of disease, it is important to understand that most of 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 the stage of stabilization, meaning they have not been any identified loss of skills as in the last six months prior to treatment.

Sean Nolan: And we're working as we collect the data, both in terms of our patient data at high doses, and also in terms of natural history data that we've been analyzing. I think that should help further put a fine point on what would be the best primary or potentially co-primary, and also allow us to include, potentially, as a secondary or supportive these ideas of capturing the restoration of effect. So, Suku, would you add anything to that?

Speaker Change: Also in terms of natural history data that we've been analyzing I think that should help.

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

Speaker Change: <unk> put a fine point on what would be the best primary or potentially co primary and also allowing us to <unk>.

Speaker Change: <unk>.

Speaker Change: Potentially as the secondary are supportive.

Speaker Change: These ideas of capturing the restoration of effect.

Would you add anything to that.

Speaker Change: Yeah, what I would add Sean is that.

Sukumar Nagendran: 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 is a 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 the clinical trial design when we have our Part B meeting.

Sukumar Nagendran: 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 is a consistent positive clinical impact of our gene therapy. 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 the clinical trial design when we have our Part B meeting.

Speaker Change: As we all know it.

Speaker Change: Complex heterogeneous disease.

But we've shown so far.

Sukumar Nagendran: Both 1 evaluate in the low dose of Taysha 102 to complete Taysha 102 demonstrated and encouraging safety profile with no serious adverse events raised to Taysha 102 or those 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 patient, the pediatric patient possess different disease severity and genetic backgrounds. Importantly, both pediatric patient demonstrated initial improvement across the same clinical domain to observe in the adult patient with early evidence of developmental gains following treatment at week 12 and 8 respectively. This included improvements in autonomic functions, 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.

Speaker Change: Over that timeframe in the Ah patients treated with the lower dose in the pediatric study in the adult study.

Speaker Change: Our consistent positive clinical impact of our gene therapy. So well then the question that I think you brought up is a really important one because as you get that natural history data from a database that's back and there are sudden clinical features that actually could be good.

Comparisons for us regardless of clinical trial design when you have a part of the meeting.

Sukumar Nagendran: Those variability within a clinical seizure that our gene therapy is consistently helping to treat is, I think, also going to be important because, in our studies so far, we've shown that these patients have seizures, right? 80 to 90 percent of patients, I think, have seizures, but there is a range of seizures. I mean, some patients may have three seizures a day, and 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?

Speaker Change: Those the variability is within our clinical feature that.

Speaker Change: Gene therapy consistently didn't play helping to treat I think also going to be important because not studied so far we've shown that these patients have seasons, 80% to 90% of patients I think you'll see it.

Sukumar Nagendran: 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?

Speaker Change: But there is a range of T shirts, I mean, some patients may have.

Speaker Change: Seizures, a day I'll just add one seizure quarter. So the question becomes how do you assess the political impact of a seizure.

Speaker Change: Based on frequency and mitigation dose.

Speaker Change: Penn function, which is consistently lost.

Sukumar Nagendran: So, I think these are things that we have to continue to gather data on, and hopefully, our clinical trial design 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 on this patient population. So 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.

Speaker Change: So I think these are.

Sukumar Nagendran: We look forward to continue to evaluate the patients over time for potential further improvement. These improvements are supported by clinical observation reported by the principal investigator, video evidence and multiple clinical and caregiver reported efficacy measures.

Speaker Change: I think that we have to continue to gather data on that hopefully.

Speaker Change: Nickel trial design for the <unk>.

Speaker Change: B component will allow us to assist them hopefully over a shorter period of time.

It will show that we can actually have a positive clinical impact for this patient population.

Ronny B: I guess, what I'm really thanks, Ronny B, a gathering the data and hopefully we can put it altogether for a very complex disease, where I think we have a pretty good gene therapy.

Sukumar Nagendran: Red 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 Taysha 102 to bring meaningful benefit to patients and caregivers.

Speaker Change: Thank you. Our next question comes from the line of Joon Lee with true Securities. Please proceed with your question.

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

Joon Lee: Please proceed with your question. Thanks for taking our questions. 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 high dose cohorts passed the six week mark, but you're reserving that for later. Any sort of, anything you can share on efficacy would be helpful there.

Joon Lee: Hey, Thanks for taking our question.

Joon Lee: And, you know, also help us understand what you mean by fulsome data, 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. So June, 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 a longer-term data set. I just wanna make sure that's what you're confirming. Yes, yes.

Sean Nolan: Thanks for taking our questions. So, can you help us understand your 180 degree on the data disclosure strategy? You know, efficacy from the first patient, the patient with the best efficacy so far, was shared at week six. Yet, the data from the high-dose cohort passed the six-week mark, but you're reserving that for later. Anything you can share on that seems to be helpful there, and 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.

Sukumar Nagendran: 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 be collected will further inform our developmental plan for the next phase of the study.

Speaker Change: Can you help us understand your 180 degree on the data disclosure strategy efficacy from the first patient dosing patients with the best efficacy. So far was shared at <unk>.

Speaker Change: Yes.

Speaker Change: The second high dose cohort passed the six month, mark but the ore.

Kamran Alam: I will now turn the call over to Kamran to discuss our financial results. Kamran. Thank you, Sukum.

Speaker Change: Reserving that for later on any any sort of anything you can share there.

Speaker Change: Also.

Kamran Alam: Research and development expenses were $15.1 million for the three-month-ended June 30th, 2024, compared to $19.8 million for the three-month-end June 30th, 2023. The $4.7 million decrease was primarily due to a milestone fee payable to Abiona Therapeutics during the three-month-ended June 30th, 2023, following the dosing of the first patient and the reveal phase 1, 2 adolescent and adult trial.

Speaker Change: Can you help us understand what you mean by full like how many patients worth of data you think is sufficient to get a clear picture and how.

Speaker Change: How much data would you have by one chew that that passes that definition.

Speaker Change: Thank you so much.

Sean Nolan: So June, 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 a longer-term data set. I just want to make sure that's what you meant.

Speaker Change: So June just to be clear you're talking about.

June: The fact that the very first patient we reported on.

Speaker Change: Was it six weeks in and now we're saying we're going to longer term dataset just I.

Kamran Alam: General and administrative expenses were $7.3 million for the three-month-ended June 30th, 2024, compared to $6 million for the three-month-ended June 30th, 2023. The increase of $1.3 million was primarily due to $0.9 million of higher non-cast stock-based compensation expenses and $0.4 million of higher consulting, professional fees, and other expenses.

June: Just want to make sure exactly that's what Youre, yes, yes, my understanding is that the first patient.

Sean Nolan: Yes, yes. My understanding is that the first patient, that person, that patient's efficacy was shared around that six-week mark. And just curious, you know, I understand the need to hold off until you have some cool, some data, but you know, and your change in data strategy, data disclosure strategy, but anything you can share with the high-dose cohort. Yeah, sure. I would say a couple things.

Sean Nolan: My understanding is that the first patient, that person, that patient at 50, was shared around that six-week mark. And just curious, you know, I understand the need to hold off until you have some cool, some data, but, you know, and your change in data strategy, data disclosure strategy, but anything you can share on the high-dose cohort. Yeah, sure. I would say a couple things.

Speaker Change: But that person that patients efficacy was shared around that six week mark.

Speaker Change: And just curious.

Speaker Change: I understand that need to hold off until you have some custom beta.

Speaker Change: Yeah.

Speaker Change #100: And your change in data strategy.

Speaker Change #100: Clothing strategy, but any.

Kamran Alam: Net loss for the three-month-ended June 30th, 2024, was $20.9 million, or $9 per share, compared to a net loss of $24.6 million, or $38 per share, for the three-month-ended June 30th, 2023.

Speaker Change #101: We will share in the high dose cohort.

Sean Nolan: First of all, one major change is the status and the fortune of the company in terms of its 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 strongly as they did, and that allowed us to go ahead and finance the company and put us in a much different situation, and then, over the course of time, I think you can see that there's been an evolution of more and more patient data being presented, and we ultimately got to the point where we just felt that, in a more traditional fashion, the easiest thing to do, and the And I felt an obligation to the investors that came in on the one patient's worth of data. They supported us financially.

Speaker Change #101: Yes, sure I would say a couple of things first of all of <unk>.

Sean Nolan: First of all, One major change is the status and the fortune of the company in terms of the 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.

Speaker Change #101: One major change is the status and the fortunate.

Speaker Change #102: The company in terms of balance sheet.

Speaker Change #102: I mean, when we reported the first patient out to be totally Frank I think you. All know this the company was in an extra essential situation and.

Kamran Alam: As of June 30th, 2024, Tasia had $172.7 million in cash and cash equivalent. The company expects that its current cash resources will support planned operating expenses and capital requirements into the fourth quarter of 2026.

Speaker Change #102: We were fortunate.

Sean Nolan: The first patient responded as quickly and as loudly as they did, and that allowed us to go ahead and finance the company and put us in a much different situation. And then, over the course of time, I think you can see that there's been an evolution of more patient data being presented. And we ultimately got to the point where we just felt that, in a more traditional fashion, the easiest thing to do and the more robust way to present the data would be to present information on a cohort-by-cohort basis. And I felt an obligation to the investors that came in on the one patient's worth of data. They supported us financially.

Speaker Change #102: Frankly, the first patient responded.

Speaker Change #102: As quickly and as pronounced as they did in.

Sean Nolan: I will now turn the call back over to Sean for his closing remarks. Sean? Thank you, Cameron. Overall, we are encouraged by the well-tolerated safety profile and patients who received the low dose of Tasia 102, and the clinical effect being demonstrated across consistent clinical domains in the pediatric and adult patients with SAGE 3 and 4 disease treated with the low dose of Tasia 102. We believe these cohort-1 data validate our novel construct and support the potential of Tasia 102 to address the significant unmet medical need and ret syndrome for a broad range of ages and stages of patients.

Speaker Change #102: That allowed us to go ahead and.

Speaker Change #102: Finance the company and put us in a much different situation and then over the course of time I think you can see that there's been an evolution of more patient data being presented.

Speaker Change #102: And we ultimately got to the point, where we just felt that.

Speaker Change #102: In a more traditional fashion.

Speaker Change #102: The easiest thing to do and the and the more robust way to present, the data would be to present.

Speaker Change #102: Information on a cohort by cohort basis.

Speaker Change #102: And I felt an obligation to the investors that came in.

Speaker Change #102: On the one patient worth of data they supported us.

Sean Nolan: Many of you supported us with that data because it was so transformational for that patient. And so I personally felt an obligation to, for a period of time, show data earlier than I normally would have. Fortunately, from my perspective, 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 that people have probably seen, right? I mean, where have you seen videos of people getting restoration of function?

Sean Nolan: Many of you supported us with that data because it was so transformational for that patient. And so I personally felt an obligation to, for a period of time, show data earlier than I normally would have. 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 that people have probably seen, right? I mean, where have you seen videos of people getting restoration of function?

Sean Nolan: We are pleased the high dose of Tasia 102 was generally well-tolerated as of the initial six-week assessment in the first patient-treason cohort of the adolescent and adult trial. High DMC approval to proceed with dosing the second adolescent adult and the first pediatric patient earlier than planned in the high dose cohort of our revealed 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 Taysha 102.

Speaker Change #102: Many of you supporting us with that data because it was so.

Speaker Change #102: Transformational for that for that patient and so I personally felt an obligation to for a period of time.

Speaker Change #102: Show data earlier than normally.

Speaker Change #103: Would have.

Speaker Change #103: Fortunately from my perspective, the data that we've continued to share has shown early just like that first patient.

Speaker Change #103: Onset of action and consistent effect I mean, even though the data that we just showed at IRS soften the pediatric patients at eight weeks and 12 weeks.

Sean Nolan: 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 totalities 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.

Speaker Change #103: I'll put that data up against anything.

Speaker Change #104: The people, who probably see right.

Speaker Change #105: Where have you seen video of people.

Sean Nolan: And we can argue on the margins, you know, about the standardization of videos and things of that. And I acknowledge that. And that's what we're trying to work to standardize, you know, as we move forward. And in particular, we must have it all standardized for Part B. But the point is, you know, there was clearly an effect in both patients that I think anyone can see. And so, as we continue to think about it as a management team, we just felt, okay, you know, now we're stuffing in, you know, we've demonstrated, I would say, you know, a very significant effect with the low dose.

Speaker Change #105: Getting restoration of function and we can argue on the margins 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.

Sean Nolan: And we can argue on the margins, you know, about the standardization of the videos and things of that, and I acknowledge that, and that's what we're trying to work to standardize as we move forward, and in particular, we must have it all standardized for Part B. But the point is, you know, there was clearly an effect in both patients that I think anyone can see, and so as we continue to think about it as a management team, we just felt, okay, you know, now we're stuffing in, you know, we've demonstrated, I would say, you know, a very significant effect with the low dose.

Speaker Change #105: We move forward and in particular, we must have it all standardized for part B, but the point is you know there was clearly clearly an effect.

Speaker Change #106: And both patients that I think any one.

Sean Nolan: 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.

Speaker Change #105: C.

Speaker Change #105: And so as we continue to think about it as a management team. We just felt okay. Now we're stuffing and we've demonstrated I would say very.

Sean Nolan: We got the okay from the IDMC to step up to a high dose. And so, now we have an opportunity to present more data over time. And I think, you know, people looking at something, you know, I would say for us, a minimum threshold would be if we had three patients in the high-dose cohort in the pediatric patient population, and we would have three patients in the pediatric population, that at least the majority of those patients were over six months of Time Elapsed, and in our view, we felt that that was a wholesome update. I mean, that's you're starting to see if you're getting consistency, durability, etc.

Operator: With that, I will now ask the operator to begin our Q&A session, 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 Q. You may press star two if you'd like to remove your question from the Q. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Speaker Change #105: Significant effect with the low dose we got the okay from the IMC just up to the high dose and so now we have an opportunity.

Sean Nolan: We got the okay from the IDMC to stuff them with the high dose, and so now we have an opportunity to present more data over time. And I think, you know, people looking at something, you know, I would say for us, a minimum threshold would be if we had three patients in the high-dose cohort in the pediatric population, and we would have three patients in the pediatric population, at least the majority of those patients were over six months of time elapsed.

Operator: To allow for as many questions as possible, we ask that you each keep to one question and one follow up. Thank you.

Speaker Change #105: To present more data over time and.

Speaker Change #105: And I think people looking at something I would say for us a minimum threshold would be if we have three patients in the high dose cohort in the pediatric patients and we would have three dose we would have three patients in the pediatric population.

Speaker Change #105: And at least the majority of those patients are over six months.

Kristen Kluska: Our first question comes from the line of Kristen Kliska with Cantor Fitzgerald. Please proceed with your question. Hi, good morning, everyone.

Speaker Change #105: Of time elapsed.

Sean Nolan: In our view, we felt that that was a fulsome update, right? I mean, you're starting to see if you're getting consistency, durability, et cetera. And we think that is, you know, a better way for everybody to be able to evaluate what we're seeing as we step into the high dose. 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.

Speaker Change #107: In our view, we felt that that's a fulsome update right I mean, that's that's.

Sean Nolan: Things started 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?

Speaker Change #107: You're starting to see if youre getting consistency durability et cetera.

Speaker Change #107: And we think that is.

Sean Nolan: And we think that is, you know, a better way for everybody to be able to evaluate what we're seeing as we step into the high dose. 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 that's why we think, ultimately, this is the best thing for all involved, you know, to see the data in a more cohort batch phase. So hopefully, that gets to what you're asking, Jim. Yes, actually, that makes a lot more sense. And I really appreciate your responses.

Speaker Change #107: A better way for for everybody to be able to evaluate.

Speaker Change #107: What we're seeing as we step into the high dose. So we felt it was a clean break going from the low dose for the high dose. We felt it was an evolution and how we've been reporting and <unk>.

Sean Nolan: Thanks, Kristen. I'll take that initially and Sukku feel free to jump in on this. 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 abnormalities, 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 mild distribution, greater transduction.

Sean Nolan: And, you know, that's why we think, ultimately, this is the best thing for all involved, you know, to see the data in a more cohort batch basis. So hopefully, that gets to what you're asking, Jim. Yes, actually, that makes a lot more sense.

That's why we think ultimately this is the.

Speaker Change #107: The best thing for all involved to see the data in a more.

Speaker Change #107: Cohort batch basis, so hopefully that gets to what you're asking.

Sean Nolan: Yes, actually, that makes a lot more sense, and I really appreciate your responses. Thank you so much, and we look forward to seeing you in Q1.

Speaker Change #107: Yes, actually that makes a lot more sense and I really appreciate your responses. Thank you. So much I mean, we look with data and one of the two.

Speaker Change #107: Of course, thank you.

Speaker Change #107: Thank you. Our next question comes from the line of Maury Raycroft with Jefferies. Please proceed with your question.

Joon Lee: Thank you so much. And we look forward to data in 1Q. Of course, thank you. Thank you. Our next question comes from the line of Maurice Raycroft with Jefferies.

Operator: Thank you. Our next question comes from the line of Maurice Raycroft with Jefferies. Please proceed with your question. Hi, thanks for taking my question.

Operator: Of course, thank you. Thank you. Our next question comes from the line of Maurice Raycroft with Jefferies. Please proceed with your question.

Sean Nolan: 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. And I think at this point, the low dose is established. Frankly, it's established a high hurdle mark. I think we're in a good place with the high dose. And we expected this would effectively build on that. I would say, you know, based on the preclinical data and the translation, that always difficult translation of it, you know, exactly what's that going to look like in an adult.

Maurice Raycroft: Please proceed with my question. Does the timeline change to data impact your timeline for an end of phase one meeting with FDA for the randomized pivotal? I guess, could that still happen in the first half of the year or more likely in the second half of the year?

Maury Raycroft: Hi, Thanks for taking my question.

Maury Raycroft: Does that timeline change to data impact your timeline for an end of phase one meeting with FDA for the randomized pivotal I guess could that still happen in first half 'twenty five or more likely the second half of the year and do you anticipate the first half 'twenty five data would still be would be sufficient to bring to FDA for alignment on a randomized phase II.

Sean Nolan: And do you anticipate the first half-25 data would be sufficient to bring to FDA for alignment on a randomized phase two pivotal, or would you need additional follow-up? Yeah, that's a 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 what Part B design looks like, I would say, number one, we want to complete cohort two doses. So we want to have that data, we want to complete our natural history analysis, and those are, I would say, key data points that we need. Now, how much data do you need?

Speaker Change #109: Or would you need additional follow up.

Sean Nolan: You know, it's difficult to predict, to predict both. I would say that 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 going to 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 end points, the same clinical observation mechanisms, the same ways to capture the data.

Sean Nolan: Yeah, that's a great question. 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 what Part B design looks like, I would say, number one, we want to complete Cohort 2 dosing, right? So, we want to have that data. We want to complete our natural history analysis.

Sean Nolan: I would say it's too early to say. You know, is it, you know, three months of data, six months of data. I think that's why we're guiding them more in our own minds. Can we sit down with the FDA in the first half? That's what we 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 getting better line of sight on that is going to be leveraging the RMAT process.

Speaker Change #109: Yes, Mark Great question, I mean, the way we're thinking about it is that for us to sit down with the FDA.

Speaker Change #109: And have a fulsome discussion around.

Speaker Change #110: What part B design looks like I would say number one we want to complete cohort two dosing.

Sean Nolan: And those are, I would say, those are the key data points that we need. Now, how much data do you need? I would say it's too early to say.

Speaker Change #110: So we want to have that data, we want to complete our natural history analysis and.

Speaker Change #110: 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.

Sean Nolan: You know, is it, you know, three months of data, six months of data? You know, I think that's why we're guiding them more in our own minds. You know, can we sit down with the FDA in the first half? You know, that's what we'd like 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 going to help facilitate, you know, getting better line of sight on that is going to be leveraging the RMAT process.

Is it.

Speaker Change #111: Three months of data six months of data.

Sean Nolan: So, we're trying to keep all that as consistent as possible. And, you know, once we have enough data and patience over a longer course of time, you know, we feel confident we'll be able to make the determination, you know, if there is a drug effect. With that, I'll turn things over to Sukum just to see if there's anything else he would add. Yeah, thanks, Chris and Sean. So, you know, that you've raised a very interesting question because usually in drug development, right?

Speaker Change #112: That's why we're guiding to more in our own mind.

Speaker Change #112: Can we sit down with the FDA in the first half.

That's what you would intend to do.

Speaker Change #113: But in terms of precisely what's the right level of data to bring down I'd say, it's a little bit early on that.

Speaker Change #114: And really what's going to help facilitate getting better line of sight to that is going to be leveraging the arm at process. So as I said that starts this quarter with the clinical type B meeting that we have.

Sean Nolan: 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. So, as I said earlier, you know, as we have the natural history data completed, we'll share that with the FDA and what we think that does to our clinical development plans and potential endpoints.

Sean Nolan: 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 red syndrome, I guess the question is, there is a drug on the market, it's a small molecule. So, I feel significant unmet medical need. And as you point out, Kristen, with such a heterogeneous disease, a low dose is actually showing consistent response. I think that parents and patients will appreciate, but at the same time, though, if you look at some of our pre clinical data, if you look at some of the work.

Speaker Change #113:

Speaker Change #113: And we'll actually be talking about things more broadly than just clinical but but the point is we will inform them with information as we have it so as I said earlier.

Speaker Change #113: As we have the natural history data completed we'll share that with the FDA.

Speaker Change #115: 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 we will certainly share that with the FDA in a more real time basis leveraging Dr. Matt <unk>.

Sean Nolan: 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 on a more real-time basis, leveraging the RMAT designation. So, you know, all that is leading and culminating to, hopefully, more detailed, formal discussion in the first half. But again, I just want to 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, in the next quarter or so. Hopefully, that gives you a little perspective.

Sean Nolan: So, Adrian, Bird and others have done. There is justification to go to the high dose and see if the high dose will also give us a consistent and further better response than the lower dose. And I'll leave it open ended like that because it's only the data that will eventually driver the end points, the ideal dose that we're going to get approved by the regulator. And that dose that will make a difference in this very complex disease and patient population. Thank you. Thanks, Kristen.

Operator: Thank you.

Speaker Change #116: <unk> nation, so all of that is leading and culminating to hopefully.

Speaker Change #116: More detailed formal discussion in the first half, but again I just want to caveat that is exactly how much data we need exactly when that happens I think it's a little early to tell but we should have more line of sight.

Speaker Change #116: And the next quarter or so hopefully that gives you a little perspective.

Sean Nolan: Yep, yeah, very helpful. Thank you. Thank you. Our next question comes from the line of Yanan Zhu with Wells Fargo. Please proceed with your question. Great.

Speaker Change #117: Yeah, Yeah very helpful. Thank you.

Thanks.

Speaker Change #117: Thank you. Our next question comes from the line of Yanan, Zhu with Wells Fargo. Please proceed with your question.

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

Elizabeth Webster: Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question. Hey, good morning, and thank you for taking our question.

Sean Nolan: 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 25 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 timely enrollment and dosing to ensure the data could be available in the first half of 25? And if you can comment on the safety waiting period, is that 42-day period true for across all six patients in those two cohorts?

Yanan Zhu: Thanks for taking our questions. So, based on what you just articulated about the maturity of the data, it feels like the first half 25 guidance is probably going to be more second quarter than first quarter. Is that the right takeaway?

Yanan Zhu: 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 in the first half 'twenty five guidance, it's probably going to be more second quarter.

Sean Nolan: This is Elizabeth on for Salveen. I'm wondering on the regulatory front if you could comment on how the dialogue is going. What's the regulatory authority? Is there any additional color you can share about the nature of those conversations to date? Thank you. 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 R-MAT designation. So, I would say there would be subsequent updates on that in the future.

Speaker Change #119: First quarter is that the right takeaway and also.

Yanan Zhu: 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 timely enrollment and dosing to ensure the data could be available in the first half of 25? And if you can comment on the safety waiting period, is that 42-day period true for across all six patients in those two cohorts? Thanks. True thing, Yanan. So again, we got into the first half to give ourselves flexibility. Your point on the stagger is a good one.

Speaker Change #120: Given that you haven't dosed Ah.

Speaker Change #121: Just one of the six patients today.

Speaker Change #121: Today.

Speaker Change #122: One of the six across the two.

Speaker Change #122: Hydro was cohorts today.

Speaker Change #122: Do you think you could.

Sean Nolan: Our goal at this meeting, there are several goals, but I would say one of them is to basically align around the cadence of how we're going to interface with the agency. You know, focus on some of the priorities that we're going to want to continue the dialogue that we've had historically. So, that would be the data that we have as it comes in. You know, we want to make sure that they're seeing the data in an appropriate batching, but they're seeing you just real time as possible.

Speaker Change #122: Have a timely enrollment and dosing to ensure.

Speaker Change #123: The data could be available in first half 'twenty five and if you can comment on the safety Wade from period at that.

Speaker Change #123: 42 day period true for <unk>.

Speaker Change #124: All six patients in those two dose cohort two cohort. Thanks.

Sean Nolan: True thing on it, you know, so again, we got into the first half to give ourselves, you know, flexibility. Your point on the stagger is good one, and I would say this: 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, and we feel very comfortable with the guidance that we've come up with. And so it is possible that you could see some changes down the road to the frequency with which we might be able to dose patients. But that is a future-looking comment. So, again, the 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.

Sure thing.

Sean Nolan: And that... That plus the additional work that we're doing on natural history will be information that we share with them that ultimately will inform more thinking on both sides and our alignment around trial design and end points for part B.

Sean Nolan: Thanks. True thing, Yanan. So again, we'll

Speaker Change #125: So again, we're guiding to the first half to give ourselves flexibility.

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

Speaker Change #126: Your point on the stagger is a good one and I would say this I mean per the protocol.

Sean Nolan: 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, and 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.

Speaker Change #127: At this time the stagger is 42 days between patients.

Operator: So the next step in that journey is actually coming up in the relatively near future, and we will certainly provide updates on that in the coming quarter. Thank you.

Speaker Change #128: I would just simply say at this point in time that.

Speaker Change #128: We we have this.

Speaker Change #128: Topics very much in mind and.

Speaker Change #128: 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.

Christopher Raymond: Our next question comes from Ryan of Chris Raymond with Piper Sandler. Please proceed with your question. Hey, thank you. Just a question on what you're going to 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.

Speaker Change #128: But that is a future looking comment.

Sean Nolan: So, again, the 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. Okay. Thank you. Thank you. Thank you. Our next question comes from the line of Jack Allen with Baird.

Speaker Change #128: So again first half is the way we're thinking about it right now and we're confident in stating that I've given everything we know today.

Speaker Change #129: Got it thank you.

Speaker Change #130: Thank you.

Sean Nolan: Are you looking to standardize that follow up and what is that time point if you can tell us. Thanks. 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 that to really provide more line of sight and clarity is generate more data over the course of time so that we can give you guys a more false some update.

Speaker Change #130: Thank you. Our next question comes from the line of Jack Allen with Baird. Please proceed with your question.

Speaker Change #131: Alright, thanks for taking the questions and congratulations on the progress.

Jack Allen: Please proceed with your question. 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 today. It seems like there are about three patients that have been enrolled.

Operator: All right, thanks for taking the questions and congratulations on the progress. My first question was on the high-dose patients that have been enrolled in the study today. 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. Can anybody, you can comment as it relates to the baseline characteristics of these high-dose patients to some extent?

Jack Allen: My first one was on the high dose patients had been enrolled in the study today. It seems like there are about three patients had been enrolled in the in the low dose cohorts, we noticed a difference in the severity of patients depending on their deletions.

Jack Allen: In the low-dose cohorts, we noticed a difference in the severity of patients depending on their deletions, something you can comment on 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.

Speaker Change #133: Somebody new to comment as it relates to the baseline characteristics.

Speaker Change #134: These high dose patients because that makes sense and then my.

Sean Nolan: So I think the easiest way to answer that sitting here today would be that 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, 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.

Operator: 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. I think there had previously been some talk of, I guess, restoring MeCP2 and regaining skills over time and kind of a teaching bias over time, but I'd love to hear any thoughts you have around the long-term low-dose data as well.

Speaker Change #135: Second question is around the low dose data we expected in the first half of next year.

Speaker Change #136: Just wanted to hear the teams thoughts on any comments around how we think that data set should evolve over time I think they had previously been some talk of.

Jack Allen: I think there had previously been some talk of, I guess, restoring MeCP2 and regaining skills over time, and kind of a teaching bias over time, but I'd love to hear any thoughts you have around the long-term low-dose data as well. Sure, Sukumar, I would ask you to answer those two questions. I think the first question was, 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-S is.

Speaker Change #137: Restoring Mexico, two and regaining of skills over time in a kind of a teaching bias overtime.

Speaker Change #138: Do you have any thoughts you have around that long term low dose data as well.

Sukumar Nagendran: Sure. You know, Sukumar, I would ask you to take those two questions. You know, I think the first question 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-S's are. I think that's all we've got to do, but you can talk about that. And then the second one is just expectations about the progress of low-dose patients over time.

Speaker Change #138: Sure.

Speaker Change #139: So I would ask you to take those two questions I think the first was.

Sean Nolan: 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. Yep, very much. Thank you very much. You bet.

Speaker Change #140: Are there any baseline characteristics that we can talk about in the high dose patients that have been enrolled we probably ought to just stick to what CG CGI S. Saar I think that's why we've guided to you can talk about that and then the second one is just expectations essentially on progress of low dose patients over.

Sukumar Nagendran: I think that's all we've got to do, but you can talk about that. And then the second one is just expectations, potentially about the progress of low-dose patients over time. Yes. So, Sean, to answer the first question, so if you think about consistency, though, yes, the CGI is.

Speaker Change #139: Time.

Speaker Change #139: Okay.

Sukumar Nagendran: Yes. So, Sean, I mean, to answer the first question. So if you think about consistency though, yes, the CGI-esque. I mean, these patients, for protocol, depending on which study they are in, they tend to fall into a range of four to six. As you all know, in Rett syndrome, 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 low-dose patients, which I think are consistent.

Speaker Change #139: Yes, so Sean I mean to answer the first question.

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

Sean Nolan: Good morning and thanks for taking your question. So as it relates to discussions with you, we're going to have with the FDA over time. There's a situation in which, you know, a potential endpoint may depend on what the patients have at baseline. For example, if patients have significant seizure burden, could they be assessed on that just trying to understand how to view a heterogeneous disease like that. Gil, great question. I would say a couple of things and certainly turn it over to just to prove for his thinking.

Speaker Change #141: So if you think about consistency though.

Speaker Change #141: Yes, the CGI.

Sukumar Nagendran: I mean, these patients, for protocol, depending on which study they are in, they tend to fall into a range of four to six. As you all know, in Rett syndrome, 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.

Speaker Change #142: Right I mean these patients well.

Speaker Change #143: Protocol, depending on which study there they tend to fall into a range of four to six and as you all know indirect syndrome.

Speaker Change #143: Severity, sometimes trade the restaurants, and there could be limitations to that as well but.

Speaker Change #143: But what is more important is.

Speaker Change #143: That they are all clinical features though the low dose patients.

Speaker Change #144: I think a consistent.

Sukumar Nagendran: 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, apneic spells, and hyperventilation, and seizures were pretty common. Lots of hand functions, as we know, are very common, in the sense lots of fine hand motor functions and gross motor functions and repetitive movements, etc.

Speaker Change #144: So autonomic dysfunction I mean for example.

Speaker Change #145: Any of these patients have.

Sean Nolan: 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 loss function, like we've seen in the load of data.

Speaker Change #145: That's still abnormalities.

Speaker Change #145: <unk> extremities.

Sukumar Nagendran: Many of these patients did have respiratory abnormalities, the apneic spells, and hyperventilation, and seizures were pretty common. Lots of hand function, as we know, is very common, in the sense lots of fine hand motor functions and gross motor functions and repetitive movements, etc.

Speaker Change #145: Any of these patients did have respiratory abnormalities that takes spells in the hyperventilation.

Speaker Change #146: Seizures are pretty common lots of hand function. As you know is very common in the defense lots of fine hand.

Speaker Change #146: Multifunction, then gross motor function and repetitive movements et cetera.

Sukumar Nagendran: 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.

Sukumar Nagendran: 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.

Speaker Change #146: I guess my point is that.

Speaker Change #146: Critical 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 the natural history database is that they're looking at which hopefully will also further support what we need to do for the future is this consistency is proven so all I can say that you have to stay tune.

Sean Nolan: If we've seen an adult, there was no expectation of having an effect sit on assisted after it, not being able to do that for 10 years. We clearly saw in those videos, at least in our opinion, that there was much greater communication and socialization than that same patient. Or as you point out, reduction in seizures, the ability to grasp and the pediatric patients, the improvements in the breathing. Those little effects are there.

Sukumar Nagendran: And having said that, then if you look at the high-dose patients, I would anticipate that you would see very similar commonalities in the clinical presentations that exist in Rett syndrome patients, the hand function, I guess you could say social withdrawal, maybe seizures, et cetera, et cetera. So, these will all be there. And then the other piece of the puzzle is, whatever the mutation is, a micense mutation, horrible or severe clinical presentation, then the question becomes, you know, any gene therapy due to the mosaic is another disease. What is the greatest impact it will have, and on which clinical features? So these are things that I am still collecting.

Sukumar Nagendran: And having said that, then 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, the hand function, I guess you could say social withdrawal, maybe seizures, et cetera, et cetera. So these will all be there.

Speaker Change #146: And having said that if you look at the higher dose patients.

Speaker Change #146: I would anticipate you would see very similar.

Speaker Change #147: Common commonalities in the clinical presentation that existing ret syndrome patients the hand function.

Speaker Change #148: Yes, you could say social withdrawal, maybe seizure et cetera et cetera.

Sean Nolan: I think what we're working to refine is there may be a situation where a primary or a co-primary endpoint is more standardized. You might focus more on really consistently measuring improvements, let's say in fine motor function, looking at the hands or gross motor function. But I do think also capturing the data on what I call the restoration of function or re-gaining of a milestone. I think that would be at a minimum, very supportive data that I think would be highly impactful to the agency, to payers, et cetera.

Speaker Change #149: Is it all be there and then.

Sukumar Nagendran: And then the other piece of the puzzle is... when you have whatever the mutation is, a horrible or severe clinical presentation, then the question becomes, you know, any gene therapy due to the mosaic is another disease. What is the greatest impact it will have, and on which clinical features? So these are things that you're still collecting.

Speaker Change #149: The other piece of the puzzle is the.

Speaker Change #149: You know when you have.

Speaker Change #149: Whatever the mutation is my sense mutation, a nonsense mutation or a massive deletion, which then results in a.

Speaker Change #149: Horrible severe clinical presentation.

Speaker Change #149: Question becomes you know any gene therapy.

Speaker Change #149: Due to the mosaic is that all of the disease.

Speaker Change #149: What is the greatest impact it will have on and on which clinical features. So these are things that just still collecting and and I would say that again.

Sukumar Nagendran: And I would say that again, I would assume in gene therapy, if you have a product that has significant clinical impact, the commonalities of the features will only be seen in a few patients, right? Because you're dosing five, six, seven patients to move from part A to part B and then part B to other studies if that's what needs to be done. Sean, I mean, I don't know whether that helped answer the question, but the answer to the question for me is not, it's complex. And then the second question was, you know, I lost my train there.

Sukumar Nagendran: And I would say that again, I would assume in gene therapy, if you have a product that has significant clinical impact, the commonalities of the features will only be seen in a few patients, right? Because you're dosing five, six, seven patients to move from part A to part B and then part B to other studies if that's what needs to be done. John, I mean, I don't know whether that helped answer the question, but the answer to the question for me is not, it's complex. And then the second question was, you know, I lost my train there, Sean.

Speaker Change #149: A few in gene therapy, if you have a product that has.

Speaker Change #149: There's a.

Speaker Change #149: Significant clinical impact.

John: The commonality of the features you'll only see be seen in a few patients because you're dosing 26, seven patient move into pop from patent pardon me and then part B to other studies, if that's what needs to be done John I mean, I don't know whether that helps.

Sean Nolan: We've been pretty consistent, I would say, in how we're trying to think about ultimate endpoint selection. When I step through right now is just a high level view of strategically how we're thinking of it. And 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. I think that should help further put a fine point on what would be the best primary or potentially co-primary.

John: It helps to answer the question.

Then the question for me is not it's complex and and then the second question was.

Speaker Change #151: I lost my trend Sean.

Speaker Change #151: Okay.

Sean Nolan: You answered the question on the baseline characteristics, right? It is going to be CGI assets between four and six. That's really all the detail that we've provided thus far. There are going to be genetic differences between all these patients. And in terms of low-dose expectations, you know, I think just at a high level to build on what you're saying is that, you know, over the course of time, at least the older initial patient that we reported on, over time, she did gain improvements, further improvements in different aspects, whether it's getting stronger from a gross motor perspective, improvement in hand function over the course of time, improvements in ability to communicate.

Sean Nolan: You answered the question on the baseline characteristics, right? It is going to be CGI assays between four and six. That's really all the detail that we've provided thus far. There are going to be genetic differences between all these patients.

Speaker Change #152: I think you answered the question you answered the question on the.

Speaker Change #152: The baseline characteristics I try to do it it's not going to be.

Speaker Change #153: Gis is between four and six that's really all right. So that we have provided thus far there are going to be trying to like differences in all of these patients and in terms of low dose expectations.

Sean Nolan: And also allowing us to include potentially as a secondary or supportive of these ideas of capturing the restoration of effects. So Suku, would you add anything to that? Yeah, what I would have shown is that as we all know, it's a complex heterogeneous disease. But we've shown so far over a time frame in the patient treated with the low dose in the pediatric study and the adult study. There are consistent positive clinical impact of our gene therapy.

Sean Nolan: In terms of low-dose expectations, I think just at a high level to build on what you're saying is that over the course of time, at least the older initial patient that we reported on, over time, she did gain improvements, further improvements in different aspects, whether it's getting stronger from a gross motor perspective, improvement in hand function over the course of time, and improvements in ability to communicate. So I think, Jack, as you think about the low-dose patients in the pediatric population that we just gave preliminary data on, our hope would be that we would see progress like that and, hopefully, potentially, look a little bit better, just given the fact that they're younger in age. So we'll have to, again, run the experiment, and we look forward to reporting that data out in the first half of next year. So hopefully, that gets at what you're asking, Jack. Yeah, definitely.

Speaker Change #154: I think just at a high level to build on what you are saying is that over the course of time at least.

The older finish.

Speaker Change #154: Initial patients that we reported on over time, she she did gain.

Movements, you know further improvements in different aspects, whether it is getting stronger from a gross motor perspective.

Speaker Change #154: <unk> and hand function over the course of time.

Sean Nolan: So but then the question that I think you brought up is a really important one because as you get a 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 be meeting those variability is within a clinical feature that our gene therapy is consistently helping to treat is I think also going to be important because in our studies so far we've shown that where these patients have seizures.

Speaker Change #154: Improvements in ability to communicate.

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

Speaker Change #154: So I think Jack you know as you think about the low dose patients in the pediatric.

Jack Allen: A preliminary data on our hope would be that we would see progress like that.

Jack Allen: And hopefully you know potentially.

Speaker Change #155: Well, a little bit better just just given the fact that.

Speaker Change #156: They're younger in age so we'll have to again, we're running the experiment and we look forward to reporting that data out.

Sean Nolan: Right, 80 to 90 percent of patients I think can see here. But there is a range of seizures. I mean some patients may have these seizures a day others may have one seizure 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 for the part be 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. So 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.

Speaker Change #156: In the first half of next year, so hopefully that gets at what Youre asking Jacques.

Sukumar Nagendran: Thank you.

Jack Allen: Thanks so much for the call. Thank you. Thank you. Our final question this morning comes from the line of Silvan Tuerkcan with Citizens J&P. Please proceed with your question. 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 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. Could they, at what point could they accelerate or get rid of the stagger, the 45 day waiting period?

Speaker Change #157: Yeah definitely thanks, so much for the color.

Jacques: Thank you.

Sean Nolan: Yeah, definitely. Thanks so much to my colleagues. Thank you. Thank you. Our final question this morning comes from the line of Silvan Tuerkcan with Citizens J&P. Please proceed with your question. Good morning, and thanks for taking my question.

Operator: Thank you. Our final question this morning comes from the line of Silvan Tuerkcan with Citizens J&P. Please proceed with your question.

Speaker Change #159: Thank you. Our final question. This morning comes from the line of Sylvan token with citizens JMP. Please proceed with your question.

Speaker Change #160: Hey, good morning, and thanks for taking my question.

Operator: Are there any more...

Speaker Change #161: Are there any more details on the SAE that you observed in the pediatric patient that was related to the immunosuppressive regimens.

Speaker Change #162: We haven't been haven't heard before and then on the safety Committee, obviously, you've accelerated your ability to dosing to a higher dose could be at what point could they accelerate or get rid of a stagger. The 45 day waiting period between patients. Thank you so much.

Speaker Change #161: Yeah.

Silvan Tuerkcan: Thank you so much. Sukumar, maybe you can take the first one out. The second one related to the SAGIR is really, you know, I think it's a discussion between the company and the IDMC about when they're comfortable making that type of recommendation. So, you know, we have a view in our minds 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, you know, 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, I don't know if there's more to add.

Sean Nolan: Sukumar, maybe you can take the first one out. The second one relative to the SAGIR is really, you know, I think it's a discussion between the company and the IDMC to talk about when they're comfortable making that type of recommendation. So, you know, we have a view in our minds 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, you know, continued good safety results.

Speaker Change #163: <unk>, maybe you can take the first one the second one relative to the CAGR is really.

Speaker Change #164: I think it's a discussion between the company and the <unk>.

Operator: Our next question comes from the line of Joon Lee with true securities. Please proceed with your question. Thanks for taking our questions. So can you help us understand your 180 degree on the data disclosure strategy? The first patient with the best efficacy so far was shared that we've seen. The high dose cohort passed the six weeks mark, but you're reserving that for later. Any sort of anything you can share enough to see helpful there.

Speaker Change #164: To talk about when they are comfortable making that type of a recommendation so.

Speaker Change #165: 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.

Sean Nolan: 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, 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 had been a declared resolution of that from the PI. But just make sure I'm correct on that. Yes, John.

Speaker Change #165: <unk> good good safety results so.

Speaker Change #165: Hopefully more to come on that in the future and Sukru realm.

Speaker Change #165: Relative to the SAE that was not treatment related.

Speaker Change #165: But I don't know if theres more to add I think the disclosure was pretty clear.

Operator: And, you know, also, help us understand what you mean by full sum. Like how many patients worth of data you think is sufficient to get a clear picture and how much data would you have by one two that passes that definition of full sum data. Thank you so much. 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.

Sukumar Nagendran: I think the disclosure was pretty clear, and we haven't reported anything more, I think, because there had been a declared resolution of that from the PI. But just make sure I'm correct on that. Yes, 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. There are other approaches that IDMC and the FDA have been quite flexible on really shortening the stagger, for example, sustaining gene therapy, where they are willing to consider it as long as the benefit risk is appropriate, right?

Speaker Change #166: We haven't reported any anything more because there had been declared resolution of that from the pie, but just to make sure I'm correct on that please yeah, sorry, if I can add though.

Sukumar Nagendran: Yes, Sean, if I can add, though, the whole issue of a staggered... I wanted to clarify, though, because remember, our approach is, I mean, inter-ethical. I mean, there are other approaches that IDMC and the FDA have been quite flexible in 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.

Speaker Change #166: Oh sure.

Operator: Yes, yes, my understanding is that the first patient that person that patients at 50 was shared around that six week mark. And just curious, you know, I understand that that need to hold off until you have some full sum data. And you're changing data strategy data disclosure strategy, but anything can share in the high dose cohort. Yes, 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.

Speaker Change #167: I wanted to clarify, though because limbaugh.

Speaker Change #167: I mean is it.

Speaker Change #168: I mean, there are other approaches.

Speaker Change #168: The <unk> and the FDA.

Speaker Change #168: Have been quite flexible on.

Speaker Change #168: Really shocked me that stacking up for example, systemic gene therapy.

Speaker Change #168: They are willing to consider it as long as.

Speaker Change #168: The benefit.

Sukumar Nagendran: 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. I think it was in Nature magazine, because he was talking about why would you waste time on a first loader, in the sense, as long as it's safe, you don't necessarily have to do all the patients as the protocol has defined. Then the second question around safety, Sean. I think, 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. Yeah, so there's been no additional disclosure on the SAE, it's resolved, and, you know, obviously, we've moved ahead, as Suku said, Is that good for you, Silvan?

Speaker Change #168: Risks as appropriate right. So I just wanted to throw that out there, but that's important because that's what I'm asking a lot about last year.

Sukumar Nagendran: Because, and that's what Dr. Peter Marks even wrote about last year. 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 that, as long as it's safe, you don't necessarily have to do all the patients as the protocol defined. Then the second question around Stagger and safety, Sean. I think, 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. Yeah, so there's been no addition.

Speaker Change #169: It goes in nature magazine, because he was talking about <unk>.

Speaker Change #170: Nine months.

Speaker Change #170: On our first defense as long as it fit.

Speaker Change #170: They have to do all of the patients is affordable and have declined.

Speaker Change #170: Then the second question around.

Speaker Change #170: That is the safety, though I think so I mean as you said, we have given a fair amount of detail.

Operator: 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 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 finance the company and put us in a much different situation. And then over the course of time, I think you can see that there's been an evolution of more patient data being presented.

Speaker Change #171: It was not in there.

Operator: 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 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 supported us with that data because it was so, you know, transformational for that patient.

Speaker Change #172: Who are product I don't think that was an issue.

Speaker Change #172: But the idea of doing what they needed to do to move the program forward.

Sean Nolan: Yeah, so there's been no additional disclosure on the SAE. It resolved, and, you know, obviously, we've moved ahead, as Suku said, from a dosing perspective. Is that good for you, Silvan?

Speaker Change #172: Yeah. So there has been no additional disclosure on the <unk>.

Speaker Change #172: Resolved and.

Speaker Change #172: Obviously, we had a super said from a dosing perspective.

Speaker Change #172: Good for you Silvan.

Speaker Change #172: Perfect. Thank you.

Speaker Change #173: Thank you.

Silvan Tuerkcan: Perfect. Thank you. Thank you. 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: 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.

Speaker Change #174: 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: I just appreciate everyone calling in and am always happy to follow up with any additional questions offline. Thank you all and have a good day.

Sean Nolan: I just appreciate everyone calling in and am always happy to follow up with any additional questions offline. Thank you all and have a good day. Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.

Mr. Nolan: 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.

Speaker Change #176: Thank you. This concludes today's conference call you may disconnect. Your lines at this time. Thank you for your participation.

Operator: And so I personally felt an obligation to, for a period of time, you know, show data earlier than I normally would have. 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 the people have probably seen.

Operator: I mean, 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 acknowledge that. And that's what we're trying to work to standardize, you know, as we move forward. And in particular, we must have it all standardized for part B. But the point is, you know, there was clearly clearly an effect, you know, in both patients that I think anyone can see.

Operator: And so, as we continue to think about it as a management team, we just felt, okay, you know, now we're stuffing in, you know, we've demonstrated, I would say, you know, very significant effect with the low dose. We got the okay from the IDMC to stuff to the high dose. And so now we have an opportunity, to present more data over time. 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 kind of last.

Operator: In our view, we felt that's a wholesome update, right? I mean, that's your starting to see if you're getting consistency, durability, et cetera. And we think that is a better way for everybody to be able to evaluate, you know, what we're seeing as we step into the high-dose. 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 and how we've been reporting.

Operator: 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, you know, in a more, you know, cohort-batch basis. So hopefully that gets to what you're asking, June. 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 one two. Of course, thank you. Thank you.

Maurice Raycroft: Our next question comes from the line of Mori Raycroft with Jeffrey. Please proceed with your question. Hi, thanks for taking my question. Does the timeline change to data impact your timeline for an end-of-phase one meeting with FDA for the randomized pivotal? I guess could that still happen in first half 25 or more likely the second half of the year? And do you anticipate the first half 25 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: Yeah, that's a, Mori, 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, what part B design looks like. I would say, number one, we want to complete cohort two dosing, right? So we want to have that data. We want to complete our natural history analysis. And those are, I would say those are key data points that we need.

Sean Nolan: Now, how much data do you need? I would say it's early to say. You know, is it, you know, three months of data, six months of data, you know, I think that's why we're, we're guiding them more in our own mind, you know, can we sit down with the FDA in the first half? You know, that's what we 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.

Sean Nolan: And really, what's going to help facilitate, you know, getting better line of sight to that is going to be leveraging the R-MAT process. So as I said, that starts this quarter with the clinical type B meeting that we have. And we'll actually be talking about things more broadly than just clinical. But, but the point is, you know, we will inform them with information as we have it. 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, 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.

Sean Nolan: You know, we'll certainly share that with the FDA in a more real-time base, this leveraging B-R-MAT designation. So, you know, all that is leading and culminating to, hopefully, you know, more detailed formals, this discussion in the first half. But again, I just want to 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 sighted, you know, in the next quarter or so. Hopefully, that gives you a little perspective.

Operator: Thank you.

Yanan Zhu: Our next question comes from the line of Yanan Zhu with Wells Fargo. Please proceed with your question. Great. Thanks for taking our questions.

Sean Nolan: So based on what you just articulated about the maturity of the data, it feels like it's more, it's the first half than first quarter is that the right takeaway. And also given that you have those just one of the six patients today, one of the six across the two high-dose cohorts today, do you think you could have timely enrollment and dosing to ensure the data could be available in first half 25.

Sean Nolan: And if you can comment on the safety waiting period, in that 42-day period, true for across all six patients in those two cohorts. Thanks. True thing, Allen. So again, we're gotten to the first half to give ourselves 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.

Sean Nolan: And 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. So again, first half is the way we're thinking about it right now. And you know, we're confident in stating that and I've given everything we know today. Got it.

Sean Nolan: Thank you.

Jack Allen: Our next question comes from the line of Jack Allen with Bear. Please proceed with your question. All right.

Sukumar Nagendran: 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 today. It seems like there are about three patients that have been enrolled. In the in the low dose cohorts, we noticed a difference in the severity of patients depending on their deletions. So I'm going to give you a comment as it relates to the baseline characteristics of these high dose patients, to some extent.

Sukumar Nagendran: And then my second question is around the low dose data we expect in the first half next year. I just want to hear the team stop on any comments around the how we think that data such evolve over time. I think there have previously been some talk of I guess restoring mech feet too and regaining of skills over time and kind of a teaching bias over time. But if I'm to hear any thoughts, you have around the long-term low dose data as well.

Sukumar Nagendran: Sure. Yeah, Sukumar, I would ask you 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-S's are. I think that's all we've guided to. You can talk about that. And then the second one is just expectations potentially on progress of low-dose patients over time.

Sukumar Nagendran: Yes, so Sean, I mean, that's the first question. So if you think about consistency though, yes, the CGI-S, right, I mean, these patients are protocol depending on which study they are, they tend to fall into a range of 4 to 6. As you all know, in red 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.

Sukumar Nagendran: So autonomic dysfunction, I mean, for example, many of these patients have vestular abnormalities of the up-and-low extremities. Many of these patients did have respiratory abnormalities. They actually expelled, and the hyperventilation. Features were pretty common. Lots of hand function, as you know, is very common in the sense lots of fine hand multifunction, then growth multifunction, and the repetitive movement, 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.

Sukumar Nagendran: But what we are doing is we have naturalistic 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, then if you look at the high-dose patients, I would anticipate you would see very similar commonalities in the clinical presentations that exist in red syndrome patients, the hand function, I guess you could say social withdrawal, maybe seizures, et cetera, et cetera.

Sukumar Nagendran: So these will all be there. And then the other piece of the puzzle is, you know, when you have whatever the mutation is, my sense 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 mosaic disease, what is the greatest impact it will have, and on which clinical features. So these are things that are still collecting, 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, you will only see, we see in a few patients, right, because you're dosing 5, 6, 7 patients to move from part into part B, and then part B to other studies, if that's what needs to be done.

Sukumar Nagendran: 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 then the second question was, you know, I love my trend there, Sean. You answered the question on the baseline characteristics. It is going to be CGI assets between four and six. That's really all that we've felt that we've provided thus far. There are going to be different in all these patients and in terms of low dose expectations, I think just said at a high level, the build on what you're saying is that over the course of time, the older initial patients that we reported on over time, she did gain improvements.

Sukumar Nagendran: Further improvements in different aspects, whether it's getting stronger from a gross motor perspective, improvement in hand function over the course of time, improvements in ability to communicate. I think Jack, as you think about the low dose patients in the pediatric, that we just gave preliminary data on our hope, would be that we would see progress like that, and hopefully potentially a little bit better just given the fact that they're younger and aged. We'll have to, again, we're running the experiment and we'll be looking forward to reporting that data out in the first half of next year. So hopefully that gets to what you're asking, Jack.

Sean Nolan: Yeah, definitely.

Operator: Thanks so much for the call. Thank you.

Silvan Tuerkcan: Our final question this morning comes from the line of Sylvan Turkin with citizens JMP. Please proceed with your question. Good morning, and thanks for taking my question.

Sean Nolan: 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. Could they, at what point could they accelerate or get rid of the stagger the 45 day waiting period between patients? Thank you so much. Sue, who maybe you can take the first one out, 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.

Sean Nolan: So, you know, we have a view in our mind about what would be a sufficient and appropriate amount of data that potentially have that type of discussion and it's predicated, of course, on having, you know, continued good, good safety results. So, you know, hopefully more to come on that in the future. And, and Suku, you know, relative to the SAE that was not treatment related. I don't know if there's more to add.

Sean Nolan: I think the disclosure was pretty clear and there, we haven't reported anything more. I think because there had been declared resolution of that from the PI. But just make sure I'm frank with that, please. 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 inter-thinkable. I mean, there are other approaches that the IDMC and the FDA have been quite flexible on really shortening the sector.

Sean Nolan: I have, for example, receiving 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 Marx even wrote about last year. I think it was a nature magazine because you're talking about why would you waste time on a, on a, on a, on a, on a first.

Sean Nolan: Then the second question around Stagger, the safety, though. I think Sean, I mean, as we said, we have given a firm out the detail. And it was not related to our product. I don't think there was any issue with the idea of doing what it needed to do to move the program forward. Yeah, so there's been no additional disclosure on the essay. It resolved and, you know, obviously we've moved ahead as simply said from a dosing perspective. Is that good for you, Silvan? Perfect. Thank you.

Sean Nolan: Ladies and gentlemen, that concludes our question and answer session. I'll turn the floor back to Mr. Nolan for any final comments. Just appreciate everyone calling in and always happy to follow up within the additional questions offline. Thank you all and have a good day. Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.

Q2 2024 Taysha Gene Therapies Inc Earnings Call

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