Q2 2026 Taysha Gene Therapies Inc Earnings Call

August 11, 2026

Speaker #1: Hello, and welcome to the Taysha Gene Therapies Q2, 2026 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session.

Operator: Hello, and welcome to the Taysha Gene Therapies second quarter 2026 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand has been raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. It is now my pleasure to introduce Vice President of Corporate Communications and Investor Relations, Hayleigh Collins.

Speaker #1: To ask a question during the session, you will need to press *11 on your telephone. You will then hear an automated message advising your hand has been raised.

Speaker #1: To withdraw your question, please press *11 again. Please be advised that today's conference is being recorded. It is now my pleasure to introduce Vice President of Corporate Communications and Investor Relations, Hayleigh Collins.

Speaker #2: Thank you. Good afternoon, and welcome to Taysha's second quarter 2026 financial results and corporate update conference call. Earlier today, Taysha issued a press release announcing financial results for the quarter ended June 30, 2026.

Hayleigh Collins: Thank you. Good afternoon, and welcome to Taysha's second quarter 2026 financial results and corporate update conference call. Earlier today, Taysha issued a press release announcing financial results for the quarter ended 30 June 2026. A copy of this press release is available on the company's website and through our SEC filings. Joining me on today's call are Sean Nolan, Taysha's Chief Executive Officer, Sukumar Nagendran, President and Head of R&D, and Kamran Alam, Chief Financial Officer. We will hold a question and answer session following our prepared remarks. On today's call, we will be making forward-looking statements, including statements concerning the potential of TSHA-102, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials, including with respect to functional milestones to positively impact quality of life and alter the course of disease in the patients we seek to treat.

Speaker #2: A copy of this press release is available on the company's website and through our SEC filings. Joining me on today's call are Sean Nolan, Taysha's Chief Executive Officer; Sukumar Nagendran, President and Head of R&D; and Kamran Alam, Chief Financial Officer.

Speaker #2: We will hold a question-and-answer session following our prepared remarks. On today's call, we will be making forward-looking statements including statements concerning the potential of Taysha 102, including the reproducibility and durability of any favorable results initially seen in patients' dose-to-date and clinical trials, including with respect to functional milestones.

Speaker #2: To positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development, and regulatory plans for our product candidates include the timing of initiating additional trials, reporting data from our clinical trials, and making regulatory submissions; the timing or outcomes of communications with the FDA on the regulatory pathway for Taysha 102; the potential for product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies; our ability to realize the benefits of breakthrough therapy designation for Taysha 102; our ability to drive long-term value for stockholders; and the market opportunity for our programs.

Hayleigh Collins: Our research, development, and regulatory plans for a product candidate, including the timing of initiating additional trials, reporting data from our clinical trials, and making regulatory submissions, timing or outcomes of communications with the FDA on the regulatory pathway for TSHA-102, the potential for product candidate to receive regulatory approval from the FDA or equivalent foreign regulatory agencies. Our ability to realize the benefits of breakthrough therapy designations for TSHA-102, our ability to drive long-term value for stockholders, and the market opportunity for our programs. This call may also contain forward-looking statements relating to Taysha's growth, forecasted cash runway, and future operating results, discovery and development of product candidates, 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 #2: 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.

Speaker #2: Various risks may cause Taysha's actual results to differ materially from those stated or implied in such forward-looking statements. For a list and description of the risks and uncertainties that we face, please see the reports we've filed with the SEC, including our annual report on Form 10-K for the year ended December 31, 2025, which we filed on March 19, 2026.

Hayleigh Collins: For a list and description of the risks and uncertainties that we face, please see the reports we filed with the SEC, including our annual report on Form 10-K for the full year ended 31 December 2025, that we filed on 19 March 2026. This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast, 11 August 2026. Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of the conference call, except as may be required by applicable securities laws. With that, I would now like to turn the call over to our CEO, Sean Nolan.

Speaker #2: This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast, August 11, 2026. Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities laws.

Speaker #2: With that, I would now like to turn the call over to our CEO, Sean Nolan.

Speaker #3: Thank you, Hayleigh. And welcome, everyone, to our Q2 2026 financial results and corporate update conference call. On today’s call, I will begin with an update on our recent clinical, manufacturing, and commercial readiness activities.

Sean Nolan: Thank you, Hayleigh, and welcome everyone to our Q2 2026 financial results and corporate update conference call. On today's call, I will begin with an update on our recent clinical manufacturing and commercial readiness activities. Dr. Sukumar Nagendran, President and Head of R&D, will then discuss data presented at the recent IRSF Rett Syndrome scientific meeting, which strengthens the clinical and scientific foundation of the TSHA-102 program. Kamran Alam, our Chief Financial Officer, will follow up with a financial update, and I will then provide closing remarks before opening the call up for questions. The Q2 of 2026 was a highly productive period for Taysha. We continue to execute against our clinical development strategy while advancing key manufacturing and commercial readiness initiatives as we move toward a potential BLA submission for TSHA-102.

Speaker #3: Dr. Sukumar Nagendran, President and Head of R&D, will then discuss data presented at the recent IRSF Rett Syndrome Scientific Meeting, which strengthens the clinical and scientific foundation of the Taysha 102 program.

Speaker #3: Kamran Alam, our Chief Financial Officer, will follow up with the financial update and I will then provide closing remarks before opening the call up for questions.

Speaker #3: The Q2 of 2026 was a highly productive period for Taysha; we continue to execute against our clinical development strategy while advancing key manufacturing and commercial readiness initiatives as we move toward a potential BLA submission for Taysha 102.

Speaker #3: We achieved several important milestones, including the completion of dosing in both the REVEAL pivotal and ASPIRE trials, as well as the presentation of compelling longer-term Part A data from the REVEAL Phase 1/2 trials.

Sean Nolan: We achieved several important milestones, including the completion of dosing in both the REVEAL pivotal and ASPIRE trials, as well as the presentation of compelling longer-term Part A data from the REVEAL phase I/II trials. Beyond the clinical development, we expanded our partnership with Catalent to include future commercial manufacturing support for TSHA-102, completed payer research to inform further market access planning initiatives, continue to build our leadership team, and strengthen our balance sheet through a successful follow-on financing that is expected to support our planned activities into the H2 of 2028 and through potential BLA approval. Collectively, we believe these accomplishments place us in a position of strength as we approach the planned six-month interim analysis from the REVEAL pivotal trial, continue our engagement with the FDA and advance commercial readiness activities. I will begin with a clinical update.

Speaker #3: Beyond the clinical development, we expanded our partnership with Catalent to include future commercial manufacturing support for Taysha 102. We completed payer research to inform further market access planning initiatives, continued to build our leadership team, and strengthened our balance sheet through a successful follow-on financing that is expected to support our planned activities into the second half of 2028 and through potential BLA approval.

Speaker #3: Collectively, we believe these accomplishments place us in a position of strength as we approach the planned 6-month interim analysis from the Reveal Pivotal trial, continue our engagement with the FDA, and advance commercial readiness activities.

Speaker #3: I will begin with a clinical update. We continue to execute with discipline across our Reveal Pivotal and Aspire trials, and are pleased with the significant progress made to date.

Sean Nolan: We continue to execute with discipline across our REVEAL pivotal and ASPIRE trials and are pleased with the significant progress made to date. In June, we announced the successful completion of dosing in the over-enrolled REVEAL pivotal trial with a total of 17 patients dosed with TSHA-102. Importantly, similar to our REVEAL Part A trials, we enrolled a well-balanced distribution of ages across pediatric, adolescent, and adult patients that is reflective of the broader Rett syndrome population. We believe this allows us to generate a comprehensive data set that may support a broad label for TSHA-102. Once all 17 patients in the pivotal trial complete six months of follow-up, we will conduct a six-month interim analysis, which may serve as the basis for our planned BLA submission and potentially accelerate our submission timeline by at least two full quarters relative to filing on the 12-month data.

Speaker #3: In June, we announced the successful completion of dosing in the over-enrolled REVEAL pivotal trial, with a total of 17 patients dosed with Taysha 102.

Speaker #3: Importantly, similar to our REVEAL Part A trials, we enrolled a well-balanced distribution of ages across pediatric, adolescent, and adult patients, as reflected by the broader Rett syndrome population.

Speaker #3: We believe this allows us to generate a comprehensive dataset that may support a broad label for Taysha 102. Once all 17 patients in the pivotal trial complete six months of follow-up, we will conduct a six-month interim analysis, which may serve as the basis for our planned BLA submission and potentially accelerate our submission timeline by at least two full quarters relative to filing on the 12-month label.

Speaker #3: Given our longer-term Part A data substantially exceeded the FDA-aligned 33% minimum efficacy threshold established for the Pivotal trial, we believe this further strengthens the potential for regulation submission based on local trial analysis.

Sean Nolan: Given our longer-term Part A data substantially exceeded the FDA-aligned 33% minimum efficacy threshold established for the pivotal trial, we believe this further strengthens the potential for an accelerated submission based on the trial interim analysis. I am also pleased to share that as such, we have begun dosing in our ASPIRE trial, where we treated four patients aged 2 to less than 4 years old with TSHA-102. ASPIRE is primarily a safety-focused trial intended to support a broad label for patients aged 2 years and older with Rett syndrome as part of our planned BLA package. In addition to generating supportive safety data, ASPIRE is designed to provide insight into the impact of early interventions, including the potential to reverse disease manifestations and restore function, while also preventing further disease progression in younger patients.

Speaker #3: I must also share that, as such, we have been dosing our Aspire trial, where we treated four patients, aged 8 months to less than 4 years old, with Taysha 102.

Speaker #3: Aspire is primarily a safety-focused treatment intended to support a broad label for patients aged 2 years and older with Rett Syndrome as part of our planned BLA package.

Speaker #3: In addition to generating supportive safety data, Aspire is designed to provide insight into the impact of early interventions, including the potential to reverse disease manifestations and restore function while also preventing further disease progression in younger patients.

Speaker #3: With dosing now complete in both trials, we are laser-focused on preparing for the Pivotal trial interim analysis and subsequent discussions with the FDA to inform next steps toward a BLA submission.

Sean Nolan: With dosing now complete in both trials, we are laser-focused on preparing for the pivotal trial interim analysis and subsequent discussions with the FDA to inform next steps toward a BLA submission. We expect to provide an update on both fronts in H1 2027. We continue to believe the increasingly robust body of evidence generated across the program strengthens the rationale for this potentially expedited submission plan. Turning to safety, both high and low-dose TSHA-102 continue to be generally well-tolerated. There have been no severe treatment-related SAEs or DLTs observed since the clinical trial began over three years ago across the 33 patients treated in the REVEAL phase I/II pivotal and ASPIRE trials as of the August 2026 data cutoff, supporting a favorable and consistent safety profile.

Speaker #3: We expect to provide an update on both fronts in the first half of 2027. We continue to believe the increasingly robust body of evidence generated across the program strengthens the rationale for this potentially expedited submission plan.

Speaker #3: Turning to safety: both high- and low-dose Taysha 102 continue to be generally well tolerated. There have been no severe treatment-related serious adverse events or dose-limiting toxicities observed since the clinical trial began over three years ago, across the 33 patients treated in the REVEAL Phase 1/2, Pivotal, and ASPIRE trials as of the August 2026 data cutoff.

Speaker #3: Supporting a favorable and consistent safety profile. In early July 2026, over the holiday weekend, one patient in the Reveal Pivotal trial experienced a single moderate Grade 2 treatment-related adverse event of peripheral sensory neuropathy.

Sean Nolan: In early July 2026, over the holiday weekend, one patient in the REVEAL pivotal trial experienced a single moderate Grade 2 treatment-related adverse event of peripheral sensory neuropathy, an expected AAV-associated risk approximately six weeks after treatment. Consistent with the treating institute's policy, the patient was admitted overnight for management and observation, thus resulting in a technical classification of the Grade 2 event as serious adverse event. The patient was discharged the following day, and importantly, rapidly demonstrating substantial recovery. Clinical trial dosing is now complete, and we have surpassed three years since the first patient received TSHA-102. To date, 33 patients spanning a broad range of ages, genotypes, and disease severities have been treated, with no severe treatment-related SAEs or DLTs reported. The safety profile of TSHA-102 has remained encouraging, with a consistent benefit-to-risk profile throughout the program.

Speaker #3: And expected AAV-associated risk. Approximately six weeks after treatment, consistent with the treating institute's policy, the patient was admitted overnight for management and observation, thus resulting in a technical classification of the Grade 2 event as a serious adverse event.

Speaker #3: The patient was discharged the following day and, importantly, rapidly demonstrating substantial recovery. Clinical trial dosing is now complete, and we have surpassed 3 years since the first patient received Taysha 102.

Speaker #3: To date, 33 patients spanning a broad range of ages, genotypes, and disease severities have been treated, with no severe treatment-related serious adverse events or dose-limiting toxicities reported.

Speaker #3: The safety profile of Taysha 102 has remained encouraging, with a consistent benefit-to-risk profile throughout the program. I would like to recognize the expertise and vigilance of our participating principal investigators, the rigorous training and oversight provided by our clinical development and clinical operation teams, as well as our CRO partner.

Sean Nolan: I would like to recognize the expertise and vigilance of our participating principal investigators, the rigorous training and oversight provided by our clinical development and clinical operations teams, as well as our CRO partner, and importantly, the commitment of the patients and caregivers whose participation in the trials and dedication to help ensure the best possible outcomes for the Rett syndrome community. Based on the totality of the data generated to date, including the favorable safety profile and compelling efficacy data from the longer-term follow-up from the REVEAL Part A, we continue to believe TSHA-102 has the potential to be a differentiated and transformative therapy for a broad population of patients with Rett syndrome, who continue to face high unmet medical need.

Speaker #3: And importantly, the commitment of the patients and caregivers, whose participation in the trials and dedication help ensure the best possible outcomes for the Rett syndrome community.

Speaker #3: Based on the totality of the data generated to date, including the favorable safety profile and compelling efficacy data from the longer-term follow-up from the REVEAL Part A, we continue to believe TSHA-102 has the potential to be a differentiated and transformative therapy for a broad population of patients with Rett syndrome, who continue to face high unmet medical needs.

Speaker #3: The strengthened body of evidence supporting Taysha 102 was highlighted at this year's IRSF Rett Syndrome Scientific Meeting, where we presented data that collectively reinforced the clinical and scientific foundation of our development program and registrational strategy.

Sean Nolan: The strengthened body of evidence supporting TSHA-102 was highlighted at this year's IRSF Rett Syndrome Scientific Meeting, where we presented data that collectively reinforced the clinical and scientific foundation of our development program and registrational strategy. Suku will discuss the data in greater detail shortly. Before I turn the call over, I wanted to touch on our ongoing commercial readiness efforts. We have continued to make meaningful progress in preparation for a potential launch. This past quarter, we completed payer market research, which demonstrated strong support for TSHA-102's value proposition and reimbursement potential. Specifically, the research demonstrated that TSHA-102 was viewed as a high-value therapy due to its transformative disease-modifying potential in a population with significant unmet need, coupled with the convenience of a one-time intrathecal administration that is less invasive than other direct-to-CNS approaches and can be administered in a broadly accessible outpatient setting.

Speaker #3: Suka will discuss the data in greater detail shortly, but before I turn the call over, I wanted to touch on our ongoing commercial readiness efforts.

Speaker #3: We have continued to make meaningful progress in preparation for a potential launch. This past quarter, we completed payer market research, which demonstrated strong support for Taysha 102’s value proposition and reimbursement potential.

Speaker #3: Specifically, the research demonstrated that Taysha 102 was viewed as a high-value therapy due to its transformative, disease-modifying potential in a population with significant unmet need.

Speaker #3: Coupled with the convenience of a one-time intrathecal administration that is less invasive than other direct-to-CNS approaches, and can be administered in a broadly accessible outpatient setting.

Sean Nolan: Importantly, payer willingness to provide coverage was primarily driven by the potential for TSHA-102 to deliver durable, clinically meaningful benefits. Payers consistently emphasized the importance of demonstrating durable functional gains and improvements that translate into real-world benefit for patients and caregivers, areas where we believe the growing body of clinical evidence supporting TSHA-102 is particularly compelling and differentiating. Finally, the research demonstrated that strong efficacy, safety, and durability are expected to be the primary drivers of coverage and support reimbursement, with durable functional improvements serving as the most important determinant of value. These findings reinforce our confidence in TSHA-102's commercial potential and reimbursement outlook. We are leveraging these insights to further refine our market access strategy and support a successful potential commercial launch.

Speaker #3: Importantly, payer willingness to provide coverage was primarily driven by the potential for Taysha 102 to deliver durable, clinically meaningful benefits. Payers consistently emphasized the importance of demonstrating durable functional gains and improvements that translate into real-world benefit for patients and caregivers.

Speaker #3: Areas where we believe the growing body of clinical evidence supporting Taysha 102 is particularly compelling and differentiating. Finally, the research demonstrated that strong efficacy, safety, and durability are expected to be the primary drivers of coverage and support reimbursement, with durable functional improvements serving as the most important determinant of value.

Speaker #3: These findings reinforce our confidence in the Taysha 102's commercial potential and reimbursement outlook. We are leveraging these insights to further refine our market access strategy and support a successful, potential commercial launch.

Speaker #3: In tandem with our market access strategy, we have also expanded our longstanding partnership with Catalent, the leading global contract development and manufacturing organization. Catalent will serve as our primary commercial manufacturing partner following potential FDA approval of Taysha 102.

Sean Nolan: In tandem with our market access strategy, we have also expanded our longstanding partnership with Catalent, the leading global contract development and manufacturing organization. Catalent will serve as our primary commercial manufacturing partner following potential FDA approval of TSHA-102. This expanded agreement secures a long-term commercial manufacturing capacity and establishes a scalable supply framework intended to support TSHA-102's potential launch and future demand. Under the agreement, manufacturing will be conducted at Catalent's FDA-licensed gene therapy campus in Harmans, Maryland, which is an established AAV manufacturing facility with significant commercial expertise. Catalent will leverage its experience across more than 90 gene therapy programs, including multiple commercial products. With BLA-enabling process performance qualification activities underway, we believe we have established a strong manufacturing foundation necessary to support the anticipated significant demand for TSHA-102 following its potential launch and commercialization.

Speaker #3: This expanded agreement secures the long-term commercial manufacturing capacity and establishes a scalable supply framework intended to support Taysha 102's potential launch and future demand.

Speaker #3: Under the agreement, manufacturing will be conducted at Catalin's FDA-licensed gene therapy campus in Harmans, Maryland. Which is an established AAV manufacturing facility with significant commercial expertise.

Speaker #3: Catalent will leverage its experience across more than 90 gene therapy programs, including multiple commercial products. With BLA-enabling process performance qualification activities underway, we believe we have established a strong manufacturing foundation necessary to support the anticipated significant demand for TSHA-102 following its potential launch and commercialization.

Speaker #3: Finally, we continue to strengthen our organization through key leadership hires that position us for the next phase of growth. This includes the recent appointment of Mike Johannessen as Chief Legal Officer.

Sean Nolan: Finally, we continue to strengthen our organization through the key leadership hires that position us for the next phase of growth. This includes the recent appointment of Mike Johannesen as Chief Legal Officer. Mike brings more than three decades of experience across corporate law, governance, compliance, and strategic transactions, including extensive leadership experience in the gene therapy space. His tenure at Advanced Medicine Partners, Jaguar Gene Therapy, and AveXis will be instrumental as we execute on our strategic priorities and continue to evolve the organization. I would now like to turn the call over to Suku to dive deeper into our recent data presentations at the IRSF Scientific Meeting.

Speaker #3: Mike brings more than three decades of experience across corporate law, governance, compliance, and strategic transactions, including extensive leadership experience in the gene therapy space.

Speaker #3: His tenure at Advanced Medicine Partners Jaguar Gene Therapy and Evexis will be instrumental as we execute on our strategic priorities and continue to evolve the organization.

Speaker #3: I would now like to turn the call over to Suka to dive deeper into our recent data presentations at the IRSF Scientific Meeting.

Speaker #2: Thank you. As Sean highlighted, we've achieved several important milestones supporting the advancement of Taysha 102 towards potential registration. Including the successful completion of dosing, in both the Reveal and Aspire trials, as well as multiple data presentations at the IRSF Scientific Meeting supporting Taysha 102.

Sukumar Nagendran: Thank you. As Sean highlighted, we have achieved several important milestones supporting the advancement of TSHA-102 to its potential registration, including the successful completion of dosing in both the REVEAL and ASPIRE trials, as well as multiple data presentations at the IRSF Scientific Meeting supporting TSHA-102. Importantly, these data sets reinforce our confidence in the program and collectively support the transformational potential of TSHA-102 to deliver durable real-world benefits to patients. We presented longer-term REVEAL Part A data, where all 12 patients treated had at least 12 months of follow-up data as of the May 2026 data cut-off, enabling a more comprehensive assessment of the durability, depth, and consistency of treatment effect over time. The data continue to demonstrate broad multi-domain functional impact that deepened over time through greater than 12 months post TSHA-102. We are particularly encouraged by the durability and deepening of the treatment effect.

Speaker #2: Importantly, these datasets reinforce our confidence in the program and collectively support the transformational potential of Taysha 102 to deliver durable, real-world benefits to patients.

Speaker #2: We presented longer-term Reveal Part A data where all 12 patients treated had at least 12 months of follow-up data as of the May 2026 data cutoff, enabling a more comprehensive assessment of the durability, depth, and consistency of treatment effect over time.

Speaker #2: The data continue to demonstrate broad, multi-domain functional impact that deepened over time through greater than 12 months post-Taysha 102. We particularly encouraged by the durability and deepening of the treatment effect.

Speaker #2: Notably, we have not observed evidence of a plateau effect, with data continuing to trend upwards over time. Using the FDA-aligned developmental milestone assessment criteria that serve as the primary endpoint in the REVEAL pivotal trials, results from Part A far exceeded our FDA-aligned pivotal response rate threshold of 33%, with a 75% response rate seen as early as 3 months and increasing to 83% at 6 months.

Sukumar Nagendran: Notably, we have not observed evidence of plateau effect. The data continue to trend upwards over time. Using the FDA-aligned developmental milestone assessment criteria that serves as the primary endpoint in the REVEAL pivotal trial, results from Part A far exceeded our FDA-aligned pivotal response rate threshold of 33% with a 75% response rate seen as early as three months and increasing to 83% at six months. By 12 months, 100% of the 12 patients were responders. These results further bolster our confidence going into the upcoming six-month interim analysis of the REVEAL pivotal trial. We have observed a consistent and clinically meaningful treatment effect across the pediatric, adolescent, and adult patients treated. Across the six pediatric patients evaluated, 16 total developmental milestones were achieved. Among the six adolescent and adult patients, 15 developmental milestones were achieved. Together, patients achieved a total of 31 developmental milestones.

Speaker #2: By 12 months, 100% of the 12 patients were responders. These results further bolster our confidence going into the upcoming 6-month interim analysis of the Reveal pivotal trial.

Speaker #2: We've observed a consistent and clinically meaningful treatment effect across the pediatric, adolescent, and adult patients treated. Across the six pediatric patients evaluated, 16 total developmental milestones were achieved, and among the six adolescent and adult patients, 15 developmental milestones were achieved.

Speaker #2: Together, patients achieved a total of 31 developmental milestones. Given that over 85% of the prevalent Rett syndrome population is older than 10 years of age, we are particularly encouraged by the consistency observed regardless of age or disease severity, which supports the commercial opportunity for Taysha 102.

Sukumar Nagendran: Given that over 85% of the prevalent Rett syndrome population is older than 10 years of age, we are particularly encouraged by the consistency observed regardless of age or disease severity that supports the commercial opportunity for TSHA-102. In addition to the consistent treatment effect across age groups, we have observed broad functional impact across core disease domains of Rett syndrome. At 12 months and beyond, patients demonstrated a total of 310 functional gains across communication, fine motor, gross motor, and autonomic domain, averaging 26 gains per patient. These gains included both natural history-defined developmental milestones as well as additional skills and improvements that meaningfully impact daily life, such as enhanced motor skills and hand use, the ability to respond to questions, reduced seizure activity, and decreased hand stereotypies, to name just a few.

Speaker #2: In addition to the consistent treatment effect across the age groups, we've observed a broad functional impact across core disease domains of Rett syndrome. At 12 months and beyond, patients demonstrated a total of 310 functional gains across communication, fine motor, gross motor, and autonomic domains, averaging 26 gains per patient.

Speaker #2: These gains included both natural history-defined developmental milestones as well as additional skills and improvements that meaningfully impact daily life, such as enhanced motor skills and hand use, the ability to respond to questions, reduced seizure activity, and decreased hand stereotypies to name just a few.

Speaker #2: Collectively, these findings reinforce our belief that Taysha 102 has the potential to provide meaningful therapeutic benefit across a broad Rett syndrome population, and deliver tangible gains in independence and quality of life for patients and caregivers.

Sukumar Nagendran: Collectively, these findings reinforce our belief that TSHA-102 has the potential to provide meaningful therapeutic benefit across a broad Rett syndrome population and deliver tangible gains in independence and quality of life for patients and caregivers. We continue to be encouraged by the favorable safety profile of TSHA-102, with no severe treatment-related SAEs or DLTs across the 33 patients treated as of the August 2026 data cut-off. The safety profile of TSHA-102 has remained encouraging, a consistent benefit to risk profile throughout the program. To that end, I would like to recognize our participating principal investigators for their clinical expertise and diligence in patient care, and thank our clinical development and clinical operations teams and CRO partner for their exceptional training, proactive monitoring, and commitment to maintain the highest standards of patient safety and trial execution throughout the study.

Speaker #2: We continue to be encouraged by the favorable safety profile of Taysha 102, with no severe treatment-related SAEs or DLTs across the 33 patients treated as of the August 2026 data cutoff.

Speaker #2: The safety profile of Taysha 102 has remained encouraging, with a consistent benefit-to-risk profile throughout the program. To that end, I would like to recognize our participating principal investigators for their clinical expertise and diligence in patient care, and thank our clinical development and clinical operations teams and CRO partners for the exceptional training, proactive monitoring, and commitment to maintaining the highest standards of patient safety and trial execution throughout the study.

Speaker #2: In addition to the clinical data, we also presented analysis from the Rett Syndrome Natural History Study, supporting the design of the REVEAL pivotal trial.

Sukumar Nagendran: In addition to the clinical data, we also presented analysis from the Rett Syndrome Natural History Study supporting the design of the REVEAL pivotal trial. The data demonstrated a clear developmental plateau after six years of age, with the likelihood of gaining or regaining a developmental milestone that was lost after defined number of years declining sharply to less than 6.7%. These results support the minimum inclusion age of six years in our well-controlled, single-arm interventional trial evaluating gain and regain of developmental milestones. We also further strengthen our confidence that the developmental gains observed in REVEAL are meaningful and distinguishable from the expected natural history of the disease in patients six years and older. We also presented methods evaluation study data supporting the developmental milestone assessment, DMA for short, as a psychometrically valid and FDA-supported primary endpoint for single-arm interventional studies.

Speaker #2: The data demonstrated a clear developmental plateau after 6 years of age, with the likelihood of gaining or regaining a developmental milestone that was lost after defined number of years declining sharply to less than 6.7%.

Speaker #2: These results support the minimum inclusion age of 6 years in a well-controlled, single-arm interventional trial, evaluating gain and regain of developmental milestones. We also further strengthen our confidence that the developmental gains observed in REVEAL are meaningful and distinguishable from the expected natural history of the disease in patients 6 years and older.

Speaker #2: We also presented methods evaluation study data supporting the Developmental Milestone Assessment, or DMA for short, as the psychometrically valid and FDA-supported primary endpoint for single-arm interventional studies.

Speaker #2: Prior to initiating Reveal, the DMA was evaluated in a multi-site, non-interventional study to assess its applicability as a clinical outcome measurement in a registrational study.

Sukumar Nagendran: Prior to initiating REVEAL, the DMA was evaluated in a multi-site non-interventional study to assess its applicability as a clinical outcome measurement in a registrational study. These findings were shared with and reviewed by the FDA as part of the trial protocol developmental discussions and strengthen our confidence in the integrity and interpretability of the data set we expect to generate from the REVEAL pivotal trial. Finally, we presented previously reported preclinical data supporting the design of the TSHA-102 construct. The data demonstrated that Taysha's mini MeCP2 is functionally comparable to full-length MeCP2 across molecular and biochemical functions. In addition, Taysha's self-complementary AAV9 vector enables superior MeCP2 expression compared to a single-stranded AAV9. This supports our construct design and ability to achieve broad effective delivery to the central nervous system through the minimally invasive intracerebral administration approach, which as Sean referenced earlier, is of particular importance to care.

Speaker #2: These findings were shared with and reviewed by the FDA as part of the trial protocol development discussions, and they strengthen our confidence in the integrity and interpretability of the data set we expect to generate from the REVEAL pivotal trial.

Speaker #2: Finally, we presented previously reported preclinical data supporting the design of the Taysha 102 construct. The data demonstrated that Taysha's mini MECP2 is functionally comparable to full-length MECP2 across molecular and biochemical functions.

Speaker #2: In addition, Taysha's self-complementary AV9 vector enables superior MECP2 expression compared to a single-stranded AV9. This supports our construct design and ability to achieve broad effective delivery to the central nervous system through the minimally invasive intrathecal administration approach, which has Sean referenced earlier, is of particular importance to pairs.

Speaker #2: Taken together, the durability and breadth of the clinical responses observed to date consistency in response across patient populations, supportive natural history analysis, and psychometric validation of the DMA pivotal trial endpoint, together with the favorable safety profile, continue to position Taysha 102 as a potentially transformative therapy.

Sukumar Nagendran: Taken together, the durability and breadth of the clinical responses observed to date, consistency in response across patient populations, supportive natural history analysis and psychometric validation of the DMA pivotal trial endpoint, together with a favorable safety profile, continue to position TSHA-102 as a potential transformative therapy. I'll now turn the call over to Kamran to review our financial results.

Speaker #2: I'll now turn the call over to Kamran to review our financial results.

Speaker #1: Thank you, Suku. Research and development expenses were $38.6 million for the 3-month ended June 30, 2026, compared to $20.1 million for the 3-month ended June 30, 2025.

Kamran Alam: Thank you, Suku. Research and development expenses were $38.6 million for the three months ended 30 June 2026, compared to $20.1 million for the three months ended 30 June 2025. The $18.5 million increase was primarily driven by BLA-enabling PPQ manufacturing initiatives performed during the three months ended 30 June 2026, and higher clinical expenses from the REVEAL and ASPIRE trials. Compensation expenses, including non-cash stock-based compensation, also increased as a result of additional research and development headcount. General and administrative expenses were $12.1 million for the three months ended 30 June 2026, compared to $8.6 million for the three months ended 30 June 2025. The increase of $3.5 million was primarily due to higher compensation expenses, including non-cash stock-based compensation expense and increases in consulting and professional fees, including commercial launch readiness initiatives.

Speaker #1: The $18.5 million increase was primarily driven by BLA-enabling PPQ manufacturing initiatives performed during the 3-month ended June 30, 2026, and higher clinical expenses from the Reveal and Aspire trials.

Speaker #1: Compensation expenses, including non-cash stock-based compensation, also increased as a result of additional research and development headcount. General and administrative expenses were $12.1 million for the three months ended June 30, 2026, compared to $8.6 million for the three months ended June 30, 2025.

Speaker #1: The increase of $3.5 million was primarily due to higher compensation expenses, including non-cash stock-based compensation expense, and increases in consulting and professional fees, including commercial launch readiness initiatives.

Speaker #1: Net loss for the 3-month ended June 30, 2026 was $46.6 million, or $0.13 per share, compared to a net loss of $26.9 million, or $0.09 per share, for the 3-month ended June 30, 2025.

Kamran Alam: Net loss for the three months ended 30 June 2026, was $46.6 million or $0.13 per share, compared to a net loss of $26.9 million or $0.09 per share for the three months ended 30 June 2025. As of 30 June 2026, Taysha had $455.4 million in cash and cash equivalents. This reflects the gross proceeds of $230 million from the June 2026 follow-on financing, including full exercise of the underwriter's option to purchase additional shares. We expect that our current cash resources will support planned operating expenses and capital requirements into the H2 2028. I will now turn the call over to Sean for his closing remarks. Sean?

Speaker #1: As of June 30, 2026, Taysha had $455.4 million in cash and cash equivalents. This reflects the gross proceeds of $230 million from the June 2026 follow-on financing, including the full exercise of the underwriter's option to purchase additional shares.

Speaker #1: We expect that our current cash resources will support planned operating expenses and capital requirements into the second half of 2028. I will now turn the call over to Sean for his closing remarks.

Speaker #1: Sean?

Speaker #3: Thank you, Kamran. We believe the growing body of evidence supporting Taysha 102 further strengthens its path toward potential registration and our commitment to bringing this potentially transformative therapy to a broad population of patients with Rett syndrome.

Sean Nolan: Thank you, Kamran. We believe the growing body of evidence supporting TSHA-102 further strengthens its path toward potential registration and our commitment to bringing this potentially transformative therapy to a broad population of patients with Rett syndrome. We believe the continued progress across our clinical, manufacturing, and commercial readiness initiatives, combined with our strengthened balance sheet, positions us well as we approach the REVEAL pivotal 6-month interim analysis, continue our engagement with the FDA, and prepare for the potential BLA submission and commercialization. We remain on track to complete the BLA-enabling PPQ campaign in Q4 2026, and we anticipate reporting top-line data from the REVEAL pivotal trial 6-month interim analysis and FDA feedback on the BLA submission pathway in H1 2027. I will now ask the operator to begin our Q&A session. Operator?

Speaker #3: We believe the continued progress across our clinical, manufacturing, and commercial readiness initiatives, combined with our strengthened balance sheet, positions us well as we approach the Reveal pivotal 6-month interim analysis.

Speaker #3: Continue our engagement with the FDA and prepare for the potential BLA submission and commercialization. We remain on track to complete the BLA-enabling PPQ campaign in the fourth quarter of 2026, and we anticipate reporting top-line data from the Reveal pivotal trial 6-month interim analysis and FDA feedback on the BLA submission pathway in the first half of 2027.

Speaker #3: I will now ask the operator to begin our Q&A session. Operator?

Speaker #4: Certainly. As a reminder, to ask a question, please press star one-one on your telephone and wait for your name to be announced. To withdraw your question, please press star one-one again.

Operator: Certainly. As a reminder, to ask a question, please press *11 on your telephone and wait for your name to be announced. To withdraw your question, please press *11 again. We ask participants to limit themselves to one question. One moment, please. Our first question comes from the line of Kristen Kluska with Cantor Fitzgerald.

Speaker #4: And you asked participants to limit themselves to one question. One moment, please. And our first question comes from the line of Kristen Kluska with Cantor Fitzgerald.

Speaker #5: Hi, everyone. Thanks so much for taking the question. The one I wanted to ask was on your payer research. Obviously, they see the potential of this therapy in the unmet need, but you made some comments around the one-time IT administration procedure in particular.

Kristen Kluska: Hi, everyone. Thanks so much for taking the question. The one I wanted to ask was on your payer research. Obviously, they see the potential of this therapy and the unmet need, but you made some comments around the one-time IT administration procedure in particular. Curious if there was anything specific they said about that kind of procedure and the outpatient that was important in the payer discussions, and yeah, how we should be thinking about the specifics behind that. Thank you.

Speaker #5: Curious if there was anything specific they said about that kind of procedure and the outpatient aspect that was important in the payer discussions, and, yeah, how we should be thinking about the specifics behind that.

Speaker #5: Thank you.

Speaker #3: Yeah, Kristen, thanks for the question. And there will be more to come on this. And I would say this is the second step in our payer discussions, more to come later this fall, and hopefully we can provide more updates as time goes on.

Sean Nolan: Yeah, Kristen, thanks for the question. There will be more to come on this. I would say this is the second step in our payer discussions. More to come later this fall, and hopefully we can provide more updates as time goes on. Number one, in terms of high value, as you would expect, the focus was primarily on the potentially transformative data set that we have. They really like this idea of the milestones and being able to demonstrate functional gains and improvements that have never been demonstrated before. This also highlighted the strength and the robustness of the natural history analysis that we did, because it really contextualized for the payers what they were getting for the money that would be spent on the therapy.

Speaker #3: But the number one, in terms of high value—as you’d expect—the focus was primarily on the potentially transformative dataset that we have. They really liked this idea of milestones and being able to demonstrate functional gains and improvements that have never been demonstrated before.

Speaker #3: So, this also highlighted the strength and robustness of the natural history analysis that we did, because it really contextualized for the payers what they were getting for the money that would be spent on the therapy.

Speaker #3: The second thing was around the durability, and the fact that at this point, we could share with them that we have at least three years' worth of data in our patients.

Sean Nolan: The second thing was around the durability and the fact that, at this point, we could share with them that we have at least 3 years' worth of data in our patients. By the time we get to market, that is going to be closer to 4-plus, 5 years, things of that nature. That obviously meant a lot to them. The safety aspect was another one, too. They like the fact that we have continued to demonstrate that overall, this is a well-tolerated gene therapy. That combination of the product offering really resonated in the context of a high unmet need, rare disease with nothing that has been demonstrated to truly transform outcomes in patients. The IT piece was something they definitely anchored to because of the fact that they realized that this is a much less invasive route of administration versus other ways to go direct to the CNS.

Speaker #3: By the time we get to market, that's going to be closer to four-plus, five years—things of that nature. And obviously, that meant a lot to them.

Speaker #3: And the safety aspect was another one, too. I mean, they like the fact that we've continued to demonstrate that, overall, this is a well-tolerated gene therapy.

Speaker #3: So that combination of the product offering really resonated in the context of a high unmet need, rare disease, with nothing that's been demonstrated to truly transform outcomes in patients.

Speaker #3: The IT piece was something they definitely anchored to because they realized that this is a much less invasive route of administration versus other ways to go direct to the CNS.

Speaker #3: They know that, because of this administration aspect, the reimbursement is going to be on the outpatient side. And so, those are going to be attractive margins.

Sean Nolan: They know that because of this administration aspect, that the reimbursement is going to be on the outpatient side, and so those are going to be attractive margins for those folks. They also realized that when you start thinking about the scalability of it, you can get some more patients with this. As they thought about the economics, they could see how the outpatient reimbursement could be quite attractive to them, relative to other potential administrations with other gene therapies that are out there. Hope that helps.

Speaker #3: For the folks, and they also realized that, as—when you start thinking about the scalability of it, you can get to more patients with this.

Speaker #3: So, as they thought about the economics, they could see how the outpatient reimbursement could be quite attractive to them relative to other potential administrations with other gene therapies that are out there.

Speaker #3: Hope that helps.

Speaker #5: Thank you.

Kristen Kluska: Thank you.

Speaker #4: Thank you. And our next question comes from the line of Salvine Richter with Goldman Sachs.

Operator: Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs.

Speaker #5: Good afternoon. Thanks for taking my question. Can you help us further understand the grade 2 SA you noted that this is an expected AV-associated risk, but how do you mitigate this risk on the forward, and how frequent are these type of events for gene therapies that leverage AV9?

Salveen Richter: Good afternoon. Thanks for taking my question. Can you help us further understand the Grade 2 SAE? You noted that this is an expected AAV associated risk, but how do you mitigate this risk going forward, and how frequent are these type of events for gene therapies that leverage AAV9? Thank you.

Speaker #5: Thank you.

Speaker #3: Yeah, Salvine, great question. I think a few things for context here. Number one, the Rett population in general—there's data on this—over 50% of Rett patients have peripheral neuropathies as part of the disease course.

Sean Nolan: Yeah. Salveen, great question. I think a few things for context here. Number one, the Rett population in general, there is data on this, over 50% of Rett patients have peripheral neuropathies as part of the disease course. Number two, as you stated, AAV9, it is a known effect of AAV9 that you can see peripheral neuropathies. And there are multiple product labels where that is indicated. It is not unexpected here. In this particular case, it was a Grade 2, which is a moderate event. I would say that in terms of the management of this, I would ask Suku to comment on that. But from what we see from the product profile, the balance between risk and benefit really tilts heavily on the benefit side here, without question. We were hoping to get through the whole clinical trial program without any type of situation like this.

Speaker #3: Number two, as you stated, AAV9 does have—it's a known effect of AAV9 that you can see peripheral neuropathies, and there are multiple product labels where that's indicated.

Speaker #3: It's not unexpected here. In this particular case, it was a grade 2, which is a moderate event. I would say that, in terms of the management of this, I would ask Suku to comment on that.

Speaker #3: But from what we see from the product profile, the balance between risk and benefit really tilts heavily on the benefit side here without question.

Speaker #3: We were hoping to get through the whole clinical trial program without any type of situation like this, but the fact that it's a Grade 2 is certainly encouraging.

Sean Nolan: But the fact that it is a Grade 2 is certainly encouraging. It was not severe. I will turn it to Suku, but I just want to highlight that this team really worked hard with the PIs in terms of monitoring and then managing. This will get at your question, is how do you mitigate these type of things? Because they are expected to occur. Suku?

Speaker #3: It was not severe. And I'll turn it to Suku, but I just want to highlight that his team really worked hard with the PIs in terms of monitoring and then managing. And this will get at your question of how do you mitigate these types of things, because they are expected to occur.

Speaker #3: Suku?

Speaker #6: Yes, Sean. And Salvine, thanks for the question. So, as Sean highlighted, with the AAV9 programs, you do see sensory neuropathies, so it's not uncommon.

Sukumar Nagendran: Yes, Sean and Salveen, thanks for the question. As Sean highlighted, with AAV9 programs, you do see sensory neuropathy, so it is not uncommon. And it is usually easily managed with immunomodulatory agents if the clinical consequences need that kind of intervention. As Sean highlighted, in our program, we have looked at this carefully, and the benefit is significantly more than any risk to this patient population. And there is very good data that in Rett syndrome patients that you do get peripheral neuropathy. So at times, the peripheral neuropathy and the clinical features of the disease itself can sometimes mask or be the main reason that you have the sensory neuropathy. In this specific case, we worked very closely with the investigator and followed the institutional treatment protocols to work with them and to have appropriate immunomodulatory agents to treat the clinical presentation.

Speaker #6: And it is usually easily managed with immunomodulatory agents if the clinical consequences need that kind of intervention. And as Sean highlighted, in our program, we've looked at this carefully, and the benefit significantly continues.

Speaker #6: The benefit is significantly more than any risk to this patient population. And there is very good data that in Rett syndrome patients, you do get peripheral neuropathies.

Speaker #6: So, at times, the peripheral neuropathy and the clinical features of the disease itself can sometimes mask or be the main reason that you have the sensory neuropathy.

Speaker #6: And in this specific case, we worked very closely with the investigator and followed the institutional treatment protocols to work with them and to have appropriate immunomodulatory agents to treat the clinical presentation.

Speaker #6: And this patient recovered pretty quickly to a substantial recovery post-discharge. On the hospital within 24 hours. So overall, we are quite pleased with the outcome for this patient.

Sukumar Nagendran: This patient recovered pretty quickly, substantially recovered and was discharged from the hospital within 24 hours. Overall, we are quite pleased with the outcome for this patient.

Speaker #4: Thank you. And our next question comes from the line of Taysheen Ahmad with Bank of America.

Operator: Thank you. Our next question comes from the line of Tazeen Ahmad with Bank of America.

Speaker #5: Hi. Good afternoon. Thanks for taking my question. Maybe just to follow up, have you discussed these events with the FDA? Have they provided any kind of feedback on any changes to monitoring requirements or changes in general to outpatient administration?

Tazeen Ahmad: Hi, good afternoon. Thanks for taking my question. Maybe just to follow up, have you discussed these events with FDA? Have they provided any kind of feedback on any kind of change to monitoring requirements, or changes just in general to outpatient administration? Have you seen any similar neurological symptoms in other treated patients? Thanks.

Speaker #5: And have you seen any similar neurological symptoms in other treated patients? Thanks.

Speaker #3: Yeah. Taysheen, thanks for the question. Let me give you a little bit of context on this one too, because I think it really does matter.

Sean Nolan: Yeah. Tazeen, thanks for the question. Let me give a little bit of context on this one too, because I think it really does matter. Every situation is a little bit unique. In this particular instance, again, keep in mind, this is a Grade 2 moderate. Grade 4 is considered life-threatening. Grade 5 obviously is the worst outcome possible. So this is a mild to moderate type of a finding. It happened on the 4 July holiday. So the PI's out of town, sub PI is managing things. A patient has a presentation, and we very much supported this. They did exactly what Suku and his team had trained them to do, which is monitor closely and then treat very quickly.

Speaker #3: Every situation is a little bit unique, and in this particular instance—again, keep in mind, this is a grade 2, moderate. Grade 4 is considered life-threatening.

Speaker #3: Grade 5, obviously, is the worst outcome possible. So, this is a mild to moderate type of finding. It happened on the July 4th holiday.

Speaker #3: So the PIs out of town, sub-PIs managing things, patient has a presentation, and we rightly we very much supported this. They did exactly what Suku and his team have trained them to do, which is monitor closely, and then treat very, very quickly.

Speaker #3: As a result of that, the policy at the hospital was overnight administration and monitoring, and that's what led to this being deemed a serious adverse event.

Sean Nolan: As a result of that, the policy at the hospital was an overnight administration and monitoring, and that's what led to this being deemed a serious adverse event. Suku, you want to comment on that?

Speaker #3: Suku, you want to comment on that?

Speaker #6: Yes, I was also going to address Taysheen's question about the FDA. We did send this case report into the FDA, so it has been disclosed to them.

Sukumar Nagendran: Yes. I was also going to address Tazeen's question about the FDA.

Sean Nolan: Yep.

Sukumar Nagendran: We did send this case reporting to the FDA, so it has been disclosed to them, and at this point they have not had any questions. We've also disclosed this to the IDMC, and they felt it was part of the usual process for the AAV9 therapy, and they raised no concerns either, and did not suggest anything different from what we've done up to now.

Speaker #6: And at this point, they have not had any questions. We've also disclosed this to the IDMC, and they felt it was part of the usual process of AAV9 therapy, and there are no concerns either.

Speaker #6: And did not suggest anything different from what we've done up to now.

Speaker #3: Right. So the reason I was giving you the background, Taysheen, is to give you the context that I think Heather and I have been some of these circumstances that I mentioned very likely we wouldn't even be talking about this.

Sean Nolan: Right. The reason I was giving you the background, Tazeen, is to give you the context that I think had there not been some of these circumstances that I mentioned, very likely we wouldn't even be talking about this. It was a unique set of circumstances that contributed, which is why, as Suku mentioned, we feel very comfortable in our ability to manage this going forward. It's not unexpected in the disease or with AAV9, and obviously the IDMC felt that way. It's been several weeks since we've corresponded with the FDA, and again, nothing from them, which we frankly wouldn't expect anyway. Hope that helps.

Speaker #3: So it was a unique set of circumstances that contributed, which is why as Suku mentioned, we feel very comfortable in our ability to manage this going forward.

Speaker #3: It's not unexpected in the disease or with AAV9. And obviously, the IDMC felt that way, and it's been several weeks since we've corresponded with the FDA, and again, nothing from them—which we frankly wouldn't expect anyway.

Speaker #3: Hope that helps.

Speaker #5: Yep. Thank you.

Tazeen Ahmad: Yeah. Thank you.

Speaker #4: Thank you. And our next question comes from the line of Maury Raycroft with Jefferies.

Operator: Thank you. Our next question comes from the line of Maury Raycroft with Jefferies.

Maury Raycroft: Hi. Thanks for taking my questions. I was going to focus on just the seizure data that you are collecting. For Part A, wondering if EEG data were collected. If so, are you seeing any objective changes in EEG activity that correspond with the higher level improvements in seizures that were reported at IRSF? How will seizure activity be assessed more rigorously in the pivotal versus Part A? Are you going to have enough patients and baseline data to evaluate benefit on seizures and potentially include that in the label?

Speaker #7: Hi. Thanks for taking my questions. I was going to focus on just the seizure data that you're collecting for Part A, wondering if EG data were collected.

Speaker #7: And if so, are you seeing any objective changes in EG activity that correspond with the higher-level improvements in seizures that were reported at IRSF?

Speaker #7: And how will seizure activity be assessed more rigorously in the pivotal versus Part A? Are you going to have enough patients and baseline data to evaluate benefit on seizures, and potentially include that in the label?

Speaker #6: So Maury, that's a very interesting and important question. So as you probably know, when it comes to Rett syndrome, 80% to 90% of Rett syndrome patients do have a history of seizures, especially around three to four years of age.

Sukumar Nagendran: So Maury, that is a very interesting and important question. As you probably know, when it comes to Rett syndrome, 80% to 90% of Rett syndrome patients do have a history of seizures, especially once they are 3 to 4 years of age. That is when they first start showing features of different types of seizures, whether it is generalized tonic-clonic or partial complex absence, et cetera. We do have seizure data from the Part A data set that we are evaluating. Overall, as Dr. Elsa Robledo also disclosed in her presentation, there appears to be an overall decrease in seizure frequency and severity, and maybe even in the combination of meds dose. We are evaluating that data further in depth, and we may disclose some of that data at a major medical meeting, hopefully either late this year or maybe early next year.

Speaker #6: That's when they first start showing features of different types of seizures, whether it's generalized tonic-clonic or partial complex absence, etc. We do have seizure data from the Part A dataset that we are evaluating.

Speaker #6: And overall, as Dr. Ilsa Rosignol also disclosed in her presentation, there appears to be an overall decrease in seizure frequency and severity, and maybe even in the combination of meds or dose.

Speaker #6: We are evaluating that data further in depth. And we may disclose some of that data at a major medical meeting. Hopefully, at a late this year or maybe early next year.

Speaker #6: In the Part B dataset, there are EEG data at baseline that are the patient's medical history, the medication history, etc., which includes anticonvulsant medications that are used.

Sukumar Nagendran: In the Part B data set, there are EEG data at baseline that occur. The patient's medical history, the medication history, et cetera, that includes anticonvulsant medications that are used. There are EEGs being done as a part of the protocol, but it's not a primary or secondary endpoint. It's probably more going to be exploratory. So at this point, it will give us a signal potentially on hopefully the beneficial effects of TSHA-102 when it comes to seizure control as well. All I can say at this point is stay tuned, and we will update you further as we get that information. One thing that's reassuring at this point in time, as of today, is we don't see worsening of seizures, which is important as well. Thanks, Maury.

Speaker #6: And we will there are EGs being done as a part of the protocol, but it's not a primary or secondary endpoint. It's probably more going to be exploratory.

Speaker #6: So at this point, it will give us a signal potentially on the hopefully, the beneficial effects of patient one or two when it comes to seizure control as well.

Speaker #6: But all I can say at this point is, stay tuned, and we will update you further as we get that information. One thing that's reassuring at this point in time, as of today, is that we don't see worsening of seizures, which is important as well.

Speaker #6: Thanks.

Speaker #4: Thank you.

Maury Raycroft: Got it. Thank you.

Speaker #7: Got it. Thank you.

Speaker #4: And our next question comes from the line of Chris Raymond with Raymond James.

Operator: Our next question comes from the line of Chris Raymond with Raymond James.

Speaker #8: Hey, this is Stanley Chom for Chris Raymond. Thank you for taking our question. Maybe just one more follow-up on the safety events. I know that this is related to, A, the exposure, but do you think that this also could have been related to the intrathecal administration?

Stan Chong: Hey, this is Stan Chong for Chris Raymond. Thank you for taking our question. Maybe just one more follow-up on the safety event. I know that this is related to AAV exposure, but do you think that there also could have been related to the intrathecal administration? Was there anything about the patient, such as age, dose exposure, or any other risk factors that might have predisposed them to the event?

Stanley Chong: Hey, this is Stan Chong for Chris Raymond. Thank you for taking our question. Maybe just one more follow-up on the safety event. I know that this is related to AAV exposure, but do you think that there also could have been related to the intrathecal administration? Was there anything about the patient, such as age, dose exposure, or any other risk factors that might have predisposed them to the event?

Speaker #8: And was there anything about the patient, such as age, dose exposure, or any other risk factors, that might have predisposed them to the event?

Sean Nolan: I'll turn this over to Suku, but I can say at a high level, there was nothing relative to the administration that was noted by the PI. As you know, this is done very commonly. The age of the patient really had no bearing on this circumstance, and things essentially can happen. I think that's what we had here. I don't believe there's any read-through, but Suku, you should certainly comment on this.

Speaker #6: I'll turn this over

Speaker #3: To Suku, but I can say at a high level, there was nothing related to the administration that was noted by the PI. As you know, this is done very, very commonly.

Speaker #3: Again, the age of the patient really had no bearing on this circumstance. Things essentially can happen, and I think that's what we have here.

Speaker #3: So I don't believe there's any read-through, but Suku, you should certainly comment on this.

Speaker #6: Yeah. Sean, I agree that I don't think the lumbar puncture procedure itself puts the patient at high risk for this kind of incident. With AV9, as we said earlier, you do sometimes do see peripheral sensory neuropathies develop.

Sukumar Nagendran: Yeah, Sean, I agree that I don't think the lumbar puncture procedure itself puts the patient at high risk for this kind of incident. With AAV9, as we said earlier, you do sometimes see peripheral sensory neuropathies develop, and that could be one of the reasons that this occurred. Also, an important point we made earlier was that Rett syndrome patients do have their own features of peripheral and polyneuropathy, and that also develops over time. Sometimes could they have both occurred at the same time? Maybe, but we won't know at this point in time. The most important thing is the patient responded and is doing much better now and that obviously reassures us as well on the overall safety profile for the product.

Speaker #6: And that could be one of the reasons that this occurred. But also, an important point we made earlier was that Rett syndrome patients do have their own features of peripheral and polyneuropathy.

Speaker #6: And that also develops over time. So sometimes could they have both conquered at the same time? Maybe, but we won't know at this point in time.

Speaker #6: But the most important thing is the patient responded, and he's doing much better now. That obviously reassures us as well on the overall safety profile for the product.

Speaker #4: Thank you. And our next question comes from the line of Jack Allen with Baird.

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

Speaker #7: Great, thanks for taking the questions, and congrats on the progress made over the course of the quarter. Two quick ones from our end. I was hoping you could provide some more color on when the dosing of the SPiRE completed.

Jack Allen: Great. Thanks for taking the questions and congrats on the progress made over the course of the quarter. Two quick ones from our end. I was hoping you could add some more color on when the dosing of ASPIRE completed. I think you guys were targeting July, and I'm just curious if you have any more precision about when in July that may have completed. As it relates to the more recent disclosure around the sensory neuropathy, it's great to hear the patient is on the mend. Any more color you can provide on the immunomodulatory agents that were given to that patient and the time course to recovery would be very helpful as well.

Speaker #7: I think you guys were targeting July, and I'm just curious if you have any more precision about when in July that may have completed.

Speaker #7: And then, as it relates to the more recent disclosure around the sensory neuropathy, it's great to hear the patient is on the mend. Any more color you can provide on the metered modulatory agents that were given to that patient and the time course to recovery would be very helpful as well.

Sean Nolan: Yeah, Jack, thanks for the questions. I think we haven't been super precise in terms of dates on the dosing just historically. I would say it's been several weeks since the last ASPIRE patient was dosed. This event that we're talking about here happened six weeks post-dosing. All the people in the pivotal trial are beyond that, obviously. That's probably the most clarity that we can provide on that. I don't know, Suku, if there's anything more to add.

Speaker #3: Yeah, Jack, thanks for the questions. I think we haven't been super precise in terms of dates. On the dosing, just historically, I would say it's been several weeks since the last ASPIRE patient was dosed.

Speaker #3: This event that we're talking about here happened six weeks post-dosing for all. So, all the people in the pivotal trial are beyond that, obviously.

Speaker #3: So that's probably the most clarity that we can provide on that. I don't know, Suku, if there's anything more to add.

Speaker #6: Well, what I would add, Sean, is that the patient started recovering pretty quickly after the treatment was given. And we haven't gotten into details around what the specific therapies were or what the details were behind the patient, because that could disclose potential protected health information for the patient as well.

Sukumar Nagendran: Well, what I would add, Sean, is that the patient started recovering pretty quickly after the treatment was given.

Sukumar Nagendran: We haven't got into details around what the specific therapies were or what the details were behind the patient, because that could be disclosing the patient's potential protected health information as well. We are not going to get into that at this point in time.

Speaker #6: So you're not going to get into that at this point, Jack.

Speaker #3: But you did mention, Suku, that the way to manage these types of things is with immunosuppression or immunomodulatory agents.

Sean Nolan: But you did mention, Suku.

Sukumar Nagendran: Yes

Sean Nolan: The way to manage these types of things is with immunosuppression or immunomodulatory agents.

Sukumar Nagendran: That's what's-

Speaker #6: And that's what's pretty straightforward.

Sukumar Nagendran: That's what's-

Sean Nolan: It's relatively straightforward.

Speaker #3: Yeah. Very standard. Hope that helps, Jack.

Sukumar Nagendran: Very standard.

Sean Nolan: Yeah. Very standard.

Sukumar Nagendran: Yeah.

Sean Nolan: Hope that helps, Jack.

Speaker #7: Yeah. Very helpful. Thanks so much for the color.

Jack Allen: Yeah, very helpful. Thanks so much for the call.

Speaker #3: You got it.

Sean Nolan: You got it.

Speaker #4: Thank you. And our next question comes from the line of Yan and Zhou with Wells Fargo.

Sukumar Nagendran: Yes.

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

Speaker #8: Oh, great. Thanks for taking our questions. Just on the safety event, I was wondering, is it the expectation that patients who might have peripheral neuropathy could have full recovery upon immunomodulatory treatment?

Yanan Zhu: Oh, great. Thanks for taking our questions. Just on the safety event, was wondering, is it the expectation that patients who might have peripheral neuropathy could have a full recovery upon immunomodulatory treatment? Also was wondering the role of prophylactic immunosuppression, how that could have impacted on this kind of event. I believe patients do have prophylactic steroid. Although I wasn't sure whether sirolimus was also used prophylactically. Thanks.

Speaker #8: And then also, I was wondering about the role of prophylactic immunosuppression and how that might have an impact, or could have impacted, on this kind of event.

Speaker #8: I believe patients do have prophylactic steroids, although I wasn't sure whether surveillance was also used prophylactically. Thanks.

Speaker #6: You had multiple questions in your question there, so let me try to answer all of them in a very simple manner. The prophylactic immunomodulation given per protocol overall, I think, does have a very positive impact on the occurrence of these peripheral neuropathies post-AAV9 gene therapy.

Sukumar Nagendran: Yanan Zhu, you had multiple questions in your question there, so let me try to answer all of them in a very simple manner. The prophylactic immunomodulation given for protocol, overall, I think does have very positive impact on the occurrence of these peripheral neuropathies for AAV9 gene therapy. That is why they're not overwhelmingly seen, but they are seen common. If you see what I mean. Second is the peripheral neuropathies that may or may not be related to AAV9 gene therapy, regardless of route of administration. If the recovery to the immunomodulatory intervention is rapid, we observe that the patient is going to get much better quicker over time. That is a positive signal clinically. Hopefully that's what we see eventually with these patients. There was another question. You had three questions. Did I answer your question, Yanan?

Speaker #6: So that is why they're not overwhelmingly seen, but they are seen commonly. Okay? So if you know what I mean. Second is the peripheral neuropathies that may be related to AV9 gene therapy, regardless of what the administration, if the recovery to the immunomodulatory intervention is rapid, the odds are that the patient is going to get much better quicker over time.

Speaker #6: So that is a positive signal clinically. So hopefully, that's what we see eventually with this patient. And there was another question. You had three questions.

Speaker #6: Did I answer your question, Jenna?

Speaker #8: Would sorry, I didn't quite hear whether prophylactic treatment could play a role in preventing this or.

Yanan Zhu: Sorry, I didn't quite hear whether prophylactic treatment could play a role in preventing this or-

Sukumar Nagendran: Yes. Prophylactic treatment will play a role not in preventing, but in reducing the incidence. Does that make sense?

Speaker #6: Yeah, prophylactic treatment will play a role—not in preventing, but in reducing the incidence. Does that make sense?

Speaker #8: Okay. Yeah.

Yanan Zhu: Okay. Yeah.

Speaker #6: Yeah. So what I'm saying is if you didn't give any prophylactic treatment, you might see a few more cases. But it won't be overwhelming, though.

Sukumar Nagendran: Yeah. What I am saying is if you did not give any prophylactic treatment, you might see a few more cases, but it will not be overwhelming. But prophylactic treatment reduces the incidence.

Speaker #6: But prophylactic treatment reduces the incidence, though.

Speaker #8: Okay. Great. Great. Thanks. For the additional color.

Yanan Zhu: Okay, great. Thanks for the additional input.

Speaker #4: Thank you. And our next question comes from the line of Gil Blum with Needham.

Operator: Thank you. Our next question comes from the line of Gil Blum with Needham.

Speaker #8: Hey, guys. This is Jonathan on for Gil. I just had a quick question if you guys could provide any color around the over-enrollment, it looks like, for your Aspire and pivotal trials.

[Analyst] (Evercore ISI): Hey, guys. This is Jonathan on for Gil. I just had a quick question, if you guys could provide any color around the over-enrollment it looks like for your ASPIRE and pivotal trials. It seems like you guys got an extra patient in the ASPIRE and two in the pivotal.

[Analyst] (Needham): Hey, guys. This is Jonathan on for Gil. I just had a quick question, if you guys could provide any color around the over-enrollment it looks like for your ASPIRE and pivotal trials. It seems like you guys got an extra patient in the ASPIRE and two in the pivotal.

Speaker #8: It seems like you guys got an extra patient in the Aspire and two in the pivotal.

Speaker #3: Yeah, Jonathan. The rationale behind that was because we didn't want to we didn't want to leave any patient behind. So we made a commitment that if you went into screening, and you screened into the study, that we would treat you.

Sean Nolan: Yeah, Jonathan, the rationale behind that was because we did not want to leave any patient behind. So we made a commitment that if you went into screening and you screened into the study, that we would treat you. One of the reasons that you have to consider doing that is that if you do get a screen fail, and you do not have more patients than you are planning for in the process of being screened, you could end up delaying your enrollment. So we made a conscious decision to work that way as a clinical operations organization, and we work very closely with the PIs and the potential caregivers so that they understood that and they understood the commitment that we made. So that is why there is a few more patients in the REVEAL pivotal and one additional patient in the ASPIRE trial.

Speaker #3: And so, one of the reasons that you have to consider doing that is that if you do get a screen fail, and you don't have more patients than you're planning for in the process of being screened, you could end up delaying your enrollment.

Speaker #3: So we made a conscious decision to work that way as a clinical operations organization. And we work very closely with the PIs and the potential caregivers so that they understood that, and they understood the commitment that we made.

Speaker #3: So that's why there are a few more patients in the REVEAL pivotal, and one additional patient in the ASPIRE trial.

Speaker #8: Great. Thanks so much.

[Analyst] (Evercore ISI): Great. Thanks so much.

[Analyst] (Needham): Great. Thanks so much.

Speaker #3: You got it.

Sean Nolan: You got it.

Speaker #4: Thank you. And our next question comes from the line of Angela Keelin with Cannock Originality.

Operator: Thank you. Our next question comes from the line of Angela Kewin with Canaccord Genuity.

Speaker #5: Hey guys, this is Angela on for Whitney. Thank you for taking our questions. First question is on the safety—you guys mentioned that patients typically get peripheral neuropathy.

Angela Kewin: Hey, guys. This is Angela on for Whitney. Thank you for taking our questions. First question is on the safety. You guys mentioned that patients typically get peripheral neuropathy. Does that present normally more like acute events, or is that more chronic when it happens in the population? Separately, have you guys talked about potential sales size for us and what the commercial organization would need to look like to support a launch?

Speaker #5: Does that present normally more like acute events, or is that more chronic when it happens in the population? And then separately, have you guys talked about potential sale size force and what the commercial organization would need to look like to support a launch?

Speaker #3: Just on that last question, did you ask about the size of the commercial organization?

Sean Nolan: Just on that last question, did you ask about the size of the commercial organization?

Speaker #5: Yeah. Have you said anything about how many salespeople you might need to support the launch?

Angela Kewin: Yeah, just have you said anything about how many salespeople you might need to support the launch?

Speaker #6: How many salespeople?

Sukumar Nagendran: How many sales details.

Sean Nolan: No, you know what, I'll take that part first. I would say more to come on that, Angela. It's a relatively discreet SG&A, and I think what you're going to see is a combination of a relatively small amount of "sales representatives." You're going to have a group of people that are very focused on working to secure reimbursement for the families, and that's going to be a big part of what we do. Patient services is going to be another group that's instrumental in working with the families to make sure that everything gets navigated from the time the prescri gets written to them getting to the institution and treated, to them working with the insurance companies to make sure that reimbursement occurs.

Speaker #3: Oh, no. You know what? I'll take that part first. I would say more to come on that, Angela. It's a relatively discrete SG&A, and I think what you're going to see is a combination of a relatively small amount of, quote-unquote, "sales representatives."

Speaker #3: You're going to have a group of people that are very focused on working to secure reimbursement for the families. And that's going to be a big part of what we do.

Speaker #3: Patient services is going to be another group that's instrumental in working with the families to make sure that everything gets navigated, from the time the prescription gets written, to them getting to the institution and treated, to them working with the insurance companies to make sure that reimbursement occurs.

Speaker #3: So we're going to put the resources in play to make sure that it's the most optimal situation and journey for the families going through this.

Sean Nolan: We're going to put the resources in play to make sure that it's the most optimal situation and journey for the families going through this. So there'll definitely be more to come later this year, beginning of next year, as we further refine our details around the go-to-market strategy and what that organization looks like. We've done a lot of work thus far, and at this point, it's again doing more market research and work to make sure we really understand the patient journey and flow. And we have a good idea right now. I think we have 80% line of sight of what this is going to look like, but I think before we give more detail, I'd like to get additional information, and then we can give you a very fulsome report on that.

Speaker #3: So, there will definitely be more to come later this year and at the beginning of next year as we further refine our details around the go-to-market strategy and what that organization looks like.

Speaker #3: We've done a lot of work thus far and at this point, it's again, doing more market research and work to make sure we really understand the patient journey and flow.

Speaker #3: And we have a good idea right now. I'd say we're 80% of what we I think we have 80% line of sight to what this is going to look like, but I think before we get more detail, I'd like to get additional information, and then we can give you a very fulsome report on that.

Speaker #6: And you had another question on the neuropathy. Patients with Rett syndrome do develop peripheral sensory, and at times a mixed, neuropathy, and it becomes chronic over time.

Sukumar Nagendran: Patients with Rett syndrome do develop peripheral sensitive at times, a mixed neuropathy, and it becomes chronic over time. If your question is it sudden acute, and does it resolve on its own? Usually not. It is more of a chronic process.

Speaker #6: So if your question is, is it sudden, acute, and does it resolve on its own? Usually not. It's more of a chronic process.

Speaker #4: Thank you. And our next question comes from the line of Evan Seegerman with BMO Capital Markets.

Operator: Thank you. Our next question comes from the line of Evan Seigerman with BMO Capital Markets.

Speaker #7: Hi, guys. Thank you so much for taking my question and providing the updates. I wanted to touch on some of the manufacturing and CMC work that you're working on.

Evan Seigerman: Hi, guys. Thank you so much for taking my question and providing the updates. I wanted to touch on some of the manufacturing and CMC work that you are working on. Beyond the completion of the PPQ runs, what CMC activities remain on the critical path to the BLA? Are we talking assay validation, process validation reports, shipping hold time validation, or other kind of components of that? Just as a follow-up, when you say the FDA has agreed with the comparability approach, can you just drill into what that actually means in terms of the process in getting to commercial product? Thank you so much.

Speaker #7: Beyond the completion of the PPQ runs, what CMC activities remain on the critical path to the BLA? Are we talking about assay validation, process validation reports, shipping hold time validation, or other components of that?

Speaker #7: And just as a follow-up, when you say the FDA has agreed with the comparability approach, can you just drill into what that actually means in terms of the process and getting to commercial products?

Speaker #7: Thank you so much.

Speaker #3: Yeah, great question. I would say, in terms of—if we start with the comparability, the first time we hit a line with the FDA on comparability was when we compared the clinical lot.

Sean Nolan: Yeah, great question. I would say if we start with the comparability, the first time we had a line with the FDA on comparability was when we compared the clinical lot, so that was the lot in Part A, with our first commercial lot, which is the part in Part B. Right? It was a one-to-one comparison. We went through all the different analytics and product characterization parameters with the FDA, analytically comparable. Subsequent to that, we have run more batches of the commercial process, and they have continued, and I think we disclosed this a few quarters ago, that they continue to deem us analytically comparable to the clinical lot.

Speaker #3: So that was the lot in part A with our first commercial lot, which is the part in part B. Right? And so it was kind of a one-to-one comparison.

Speaker #3: And we went through all the different analytics and product characterization parameters with the FDA analytically comparable. Subsequent to that, we've run more batches. Of the commercial process.

Speaker #3: And they've continued, and I think we disclosed this a few quarters ago, that they continue to deem us analytically comparable to the clinical lot.

Speaker #3: So, the next step is that when we complete the PPQ runs, if those two are comparable from an analytical perspective—which we fully expect—that then allows us to utilize the Part A data, both in terms of efficacy and safety, to support the regulatory submission.

Sean Nolan: The next step is that when we complete the PPQ runs, if those two are comparable from an analytical perspective, which we fully expect, that then allows us to utilize the Part A data, both in terms of efficacy and safety, to support the regulatory submission. We are in a really good spot there. You asked about assay validations and things of that nature. We are in a really good spot there with the FDA. What is on the critical path is us completing the PPQ runs and then having that discussion with the FDA after we submit all the data around what the comparability looks like. I would say in a nutshell, we are very pleased where we are on the CMC side. At this point in time, CMC is not a critical path item for us.

Speaker #3: So we're in a really good spot there. You asked about assay validations and things of that nature. We're in a really good spot there.

Speaker #3: With the FDA. So really, what's on the critical path is us completing the PPQ runs and then having that discussion with the FDA after we submit all the data around what the comparability looks like.

Speaker #3: So I would say in a nutshell, we're very pleased where we are. On the CMC side, and at this point in time, CMC is not a critical path item for us.

Speaker #4: Thank you. And our next question comes from the line of Joshua Werman with Citizens.

Operator: Thank you. Our next question comes from the line of Joshua Woodman with Citizens.

Speaker #8: Hey, thanks for taking my question. And congrats on the update. Maybe just going back to IRSF, you presented a really great poster outlining the establishment of the RSDMA, the Development Milestone Assessment.

Joshua Woodman: Hey, thanks for taking my question, and congrats on the update. Maybe just going back to IRSF, you presented a really great poster outlining the establishment of the RFDMA, the Development Milestone Assessment. I was hoping you guys could just reiterate the key points there and highlight how this provides confidence in the reliability of the potential raters and confidence in the validity and interpretability of the data from a regulator's perspective. Thank you.

Speaker #8: I was hoping you could just reiterate the key points there, and highlight how this provides confidence in the reliability of the central raters, as well as confidence in the validity and interpretability of the data from a regulator's perspective.

Speaker #8: Thank you.

Speaker #3: We can tag team this, but I think it starts with the fact that we're creating the milestone strategy a novel pathway for approval in Rett syndrome, right?

Sean Nolan: We can tag team this, but I think it starts with the fact that we are creating, via the milestone strategy, a novel pathway for approval in Rett syndrome, right? To date, the only thing that has been approved has been approved based on CGI and RSBQ. We knew that for a gene therapy, that was not going to be sufficient to garner capturing the value we think would be commensurate with the product. The payers would not have paid with that as your two endpoints, essentially. We struck out on an endeavor to figure out what would be a clinically meaningful, very robust endpoint that is unequivocal that demonstrated the value of the product. Fortunately for us, we found the milestone plateau and then began to work on what is the construct of the actual tool that we will use with the instrument to capture this data.

Speaker #3: I mean, today, the only thing that's been approved has been approved based on CGI and RSVQ. And we knew that for a gene therapy, that was not going to be sufficient to garner capturing the value we think would be commensurate with the product.

Speaker #3: The payers would not have paid with that as a year-two endpoint, essentially. So we struck out on an endeavor to figure out what would be a clinically meaningful, very robust endpoint that's unequivocal, that demonstrated the value of the product.

Speaker #3: And fortunately for us, we found the milestone plateau and then began to work on what’s the construct of the actual tool that will use the instrument to capture this data.

Speaker #3: And so what we were able to do with the DMA is do exactly that. And so it's a very systematized way to go through the assessment of the milestone.

Sean Nolan: And so what we were able to do with the DMA is do exactly that. So it is a very systematized way to go through the assessment of the milestones. So keep in mind, there is 28 milestones. So you are going to want to put in place a process that is very systematic and very rigorous. So as an example, the sequence of the milestones is tested the same way every time. Any implements used in the study are consistent from baseline throughout the study. So it is very easy to, again, measure what you are seeing there. The angles of the cameras, as an example, is something that was tested. The manuals for the training. All of this took a lot of time. So it took 18 months from the concept to us being able to lock it down with the FDA. And fortunately for us, we ran a pilot in the background.

Speaker #3: So keep in mind, there are 28 milestones, so you're going to want to put in place a process that's very systematic and very rigorous. As an example, the sequence of the milestones is tested the same way every time.

Speaker #3: Any implements used in the study are consistent from baseline throughout the study, so it's very easy to, again, measure what you're seeing there. The angles of the cameras, as an example, is something that was tested. The manuals for the training—all of this took a lot of time.

Sean Nolan: Any implements used in the study are consistent from baseline throughout the study. So it is very easy to, again, measure what you are seeing there. The angles of the cameras, as an example, is something that was tested. The manuals for the training. All of this took a lot of time. So it took 18 months from the concept to us being able to lock it down with the FDA. And fortunately for us, we ran a pilot in the background.

Speaker #3: So it took 18 months from the concept to us being able to lock it down with the FDA, and fortunately for us, we ran a pilot in the background.

Sean Nolan: We have not talked too much about it, but we call it the REVEAL Trial. So we were able to do the DMA in a non-treated population that was also, for the most part, sites in the clinical trial. So you knew that was going to be a good index against then the ultimate final version of this. And that was also part of the submission that we made to the FDA. And that is how when we say that it is psychometrically validated, that pilot helped us validate that. We shared all that with the FDA, and that is what got them comfortable around taking this approach in an open label study, was how rigorous you are going to be able to collect that data and ensure that you had a clear baseline. So we can go chapter and verse deeper on that, but at a very high level, that is what happened.

Speaker #3: We haven't talked too much about it, but we call it the RESCUE trial. And so, we were able to do the DMA in a non-treated population that was also, for the most part, sites in the clinical trial.

Speaker #3: So you knew that was going to be a good index against then the ultimate final version of this. And that was also part of the submission that we made to the FDA.

Speaker #3: And that's how, when we say that it's psychometrically validated, that pilot helped us validate that. We shared all that with the FDA, and that's what got them comfortable around taking this approach in an open-label study—how rigorous you're going to be able to collect that data and ensure that you had a clear baseline.

Sean Nolan: We shared all that with the FDA, and that is what got them comfortable around taking this approach in an open label study, was how rigorous you are going to be able to collect that data and ensure that you had a clear baseline. So we can go chapter and verse deeper on that, but at a very high level, that is what happened.

Speaker #3: So, I mean, we can go chapter and verse deeper on that, but at a very high level, that's what happened. It took a lot of hard work from the team, and it took a lot of time.

Sean Nolan: And it took a lot of hard work from the team, and it took a lot of time. It was not something you could just jump into, and it was something the FDA was very concerned around, was the rigor and the systemization of that data collection. I do not know, Suku, if there is any more you might want to-

Speaker #3: It wasn't something you could just jump into, and it was something the FDA was very concerned about—the rigor and the systemization of that data collection.

Speaker #3: I don't know, Sukumar, if there's any more you might want to add.

Sukumar Nagendran: No. All I would add, Sean, is the process and rigor of the collection and validation of the data set for the DMA was what was done in that study, and that was what was disclosed in the poster. And interestingly, there was an FDA representative at the IRSF meeting who actually presented to the audience and talked about the need for this kind of rigor, and also made a point that just because the patient population being studied is potentially highly variable, that cannot be used as an excuse for a poorly designed trial or approval of a product. It was a very interesting discussion that was raised. And this is a review of what also may be involved in the registration of currently approved products as well. So it was pretty timely that this data disclosure, as well as the other presentations that occurred at IRS.

Speaker #2: All I would add, Sean, is that the process and rigor of the collection and validation of the data set for the DMA was what was coming with the study.

Speaker #2: And that was what was disclosed in the poster. And interestingly, there was an FDA representative at the IRSF meeting who actually presented to the audience and talked about the need for this kind of rigor.

Speaker #2: And also made a point that just because a patient population being studied is potentially highly variable, that doesn't cannot be used as an excuse for a poorly designed trial for approval of a product.

Speaker #2: It was a very interesting discussion that was raised. And this is a review of what had also been involved in the red space with the currently approved product as well.

Speaker #2: So it was pretty timely that our data disclosure, as well as the other presentations, occurred at IRSF.

Sean Nolan: Thank you.

Speaker #4: Thank you.

Joshua Woodman: Great. Thanks again.

Speaker #8: Thanks again.

Speaker #4: And I'm showing no further questions. So with that, I'll hand the call back over to Chairman and CEO, Sean Nolan, for any closing remarks.

Operator: I am showing no further questions. So with that, I will hand the call back over to Chairman and CEO, Sean Nolan, for any closing remarks.

Speaker #3: We appreciate everyone taking the time to hear our update. And we look forward to speaking with everyone in the future. Have a good night.

Sean Nolan: We appreciate everyone taking the time to hear our update, and we look forward to speaking with everyone in the future. Have a good night. Take care.

Speaker #3: Take care.

Operator: Ladies and gentlemen, thank you for participating. This does conclude today's program, and you may now disconnect.