Taysha Gene Therapies, Inc. (TSHA) Q2 2026 Earnings Report, Transcript and Summary

Hello, and welcome to the Taysha Gene Therapies Second Quarter 2026 Financial Results Conference Call. [Operator Instructions] 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.

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. 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. Our research, development, and regulatory plans for our product candidates, including the timing of initiating additional trials, reporting data from our clinical trials, and making regulatory submissions, timing or outcomes of communications with the FDA on the regulatory pathway for 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. 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 December 31, 2025, that we filed on March 19, 2026. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, 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. With that, I would now like to turn the call over to our CEO, Sean Nolan.

Thank you, Hayleigh, and welcome everyone to our second quarter 2026 financial results and corporate update conference call. On today's call, I will begin with an update on our recent clinical, manufacturing, and commercial readiness activities. Dr. Suku Nagendran, President and Head of R&D, will then 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 second quarter of 2026 was a highly productive period for Taysha. We continued 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. 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, 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. 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. 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. 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's 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 6 months of follow-up, we will conduct a 6-month interim analysis, which may serve as the basis for our planned BLA submission and potentially accelerate our submission time line by at least 2 full quarters relative to filing on the 12-month data. 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 based on the most current trial analysis. I also want to share that as of July, we have completed dosing in our ASPIRE trial, where we treated 4 patients aged 2 to less than 4 years old with TSHA-102. ASPIRE is primarily a safety-focused and 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 intervention, including the potential to reverse disease manifestations and restore function while also preventing further disease progression in younger patients. 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 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. Turning to safety, both high and low dose TSHA-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 3 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. In early July 2026, over the holiday weekend, 1 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 6 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 3 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 serious adverse events or dose-limiting toxicities reported. The safety profile of TSHA-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, 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. 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, but 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 onetime intrathecal administration that is less invasive than other direct-to-CNS approaches and can be administered in a broadly accessible outpatient setting. 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. 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. 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 3 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.

Thank you. As Sean highlighted, we've achieved several important milestones supporting the advancement of TSHA-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 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 cutoff, 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're particularly encouraged by the durability and deepening of the treatment effect. Notably, we have not observed evidence of plateau effect with 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 3 months and increasing to 83% at 6 months. 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. We have observed a consistent and clinically meaningful treatment effect across the pediatric, adolescent, and adult patients treated. Across the 6 pediatric patients evaluated, 16 total developmental milestones were achieved. And among the 6 adolescent and adult patients, 15 developmental milestones were achieved. 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 that supports the commercial opportunity for TSHA-102. In addition to the consistent treatment effect across age groups, we've 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 domains, averaging 26 gains per patient. These gains included both naturally 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. Collectively, these findings reinforce our belief that TSHA-102 has the potential to provide meaningful therapeutic benefit across the 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 cutoff. The safety profile of TSHA-102 has remained encouraging, the 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. 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 6 years of age, with the likelihood of gaining or regaining a developmental milestone that was lost after a defined number of years declining sharply to less than 6.7%. These results support the minimum inclusion age of 6 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 6 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. Prior to initiating REVEAL, the DMA was evaluated in a multi-site, noninterventional 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 discussion 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 miniMeCP2 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 intrathecal administration approach, which as Sean Nolan referenced earlier, is of particular importance to care. 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 potentially transformative therapy. I'll now turn the call over to Kamran Alam to review our financial results.

Thank you, Suku. Research and development expenses were $38.6 million for the 3 months ended June 30, 2026, compared to $20.1 million for the 3 months ended June 30, 2025. The $18.5 million increase was primarily driven by BLA-enabling PPQ manufacturing initiatives performed during the 3 months ended June 30, 2026, and higher clinical expenses from the REVEAL and ASPIRE trials. Compensation expenses, including noncash stock-based compensation, also increased as a result of additional research and development headcount. General and administrative expenses were $12.1 million for the 3 months ended June 30, 2026, compared to $8.6 million for the 3 months ended June 30, 2025. The increase of $3.5 million was primarily due to higher compensation expenses, including noncash stock-based compensation expense, and increases in consulting and professional fees, including commercial launch readiness initiatives. Net loss for the 3 months 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 months ended June 30, 2025. 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 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 second half of 2028. I will now turn the call over to Sean for his closing remarks. Sean?

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

[Operator Instructions] Our first question comes from the line of Kristen Kluska with Cantor Fitzgerald.

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 onetime 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 yes, how we should be thinking about the specifics behind that?

Yes, 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. But the number one in terms of high value, as you would expect, the focus was primarily on the potentially transformative data set that we have. And they really like this idea of the milestones and being able to demonstrate functional gains and improvements that have never been demonstrated before. So 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. 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's going to be closer to 4-plus, 5 years, things of that nature. And obviously, that meant a lot to them. And the safety aspect was another one, too. And they liked the fact that we've continued to demonstrate that overall, this is a well-tolerated gene therapy. So 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. 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. And they also realize that when you start thinking about the scalability of it, you can get to more patients with this. So as they thought about the economics, they can 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.

Our next question comes from the line of Salveen Richter with Goldman Sachs.

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?

Yes, Salveen, 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. Number two, as you stated that AAV9 does have a -- it's a known effect of AAV9 that you can see peripheral neuropathies, and there's multiple product labels where that's indicated. 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. 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, but the fact that it's a Grade 2 is certainly encouraging. It was not severe. And I'll 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. And this will get at your question, is how do you mitigate these type of things because they are expected to occur. Suku?

Yes, Sean and Salveen, thanks for the question. So as Sean highlighted, with AAV9 programs, you do see sensory neuropathy, so it's not uncommon. 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 to -- 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 neuropathies. 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. 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, and this patient recovered pretty quickly. There was substantial recovery post discharge from the hospital within 24 hours. So overall, we are quite pleased with the outcome for this patient.

Your next question comes from the line of Tazeen Ahmad with Bank of America.

Maybe just a 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?

Yes. 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 and in this particular instance, again, keep in mind, this is a Grade 2 moderate [Audio Gap] 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 July 4 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 have trained them to do, which is monitor closely and then treat very quickly. And so, 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?

Yes. I was also going to address Tazeen's question about the FDA. So we did send this case report into the FDA, and so it has been disclosed to them. 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 they raised no concerns either, and did not suggest anything different from what we have done up to now.

Right. So 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 would not even be talking about this. 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. 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 have corresponded with the FDA and again, nothing from them, which we frankly wouldn't expect anyway. Hope that helps.

Our next question comes from the line of Maury Raycroft with Jefferies.

I was going to focus on just the seizure data that you are collecting. For Part A, wondering if EEG data were collected, and 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? 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?

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 once they are 3 to 4 years of age. That's when they first start showing features of different types of seizures, whether it's 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 Rossignol 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. 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. 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, we don't see worsening of seizures, which is important as well.

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

This is Stanley on for Chris Raymond. 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? 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?

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. Again, the age of the patient really had no bearing on this circumstance. And things essentially can happen, and I think that's what we have here. So I don't believe there's any read-through, but Suku, you should certainly comment on this.

Yes, 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. But also, an important point we made earlier was that Rett syndrome patients do have their own features of peripheral and polyneuropathies, and that also develops over time. So sometimes could they have both concurred at the same time? Maybe, but we will not know at this point in time. But the most important thing is the patient responded and is doing much better now, and that obviously assures us as well on the overall safety profile for the product.

Our next question comes from the line of Jack Allen with Baird.

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. 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 immunomodulatory agents that were given to that patient and the time course to recovery would be very helpful as well.

Yes, 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 6 weeks post dosing. So all the people in the pivotal trial are beyond that, obviously. 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?

Well, what I would add, Sean, is that, the patient started recovering pretty quickly after the treatment was given. And 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. So we are not going to get into that at this point in time.

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

Correct. Because that's what's relatively standard.

Yes, it's pretty forward. Very standard. Hope that helps, Jack.

Our next question comes from the line of Yanan Zhu with Wells Fargo.

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? And then also, I was wondering the role of prophylactic immunosuppression and how that might have -- could have impacted on this kind of event. I believe patients do have prophylactic steroid, although whether they had -- I wasn't sure whether steroid was also used prophylactically.

So, Yanan, you had multiple questions in your question there, so let me try to answer all of them in a very simple manner. So the prophylactic immunomodulation given for protocol, overall, I think, does have very positive impact on the occurrence of these peripheral neuropathies post-AAV9 gene therapy. So that is why they're not overwhelmingly seen, but they are seen common. Okay? So if you know what I mean. Second is the peripheral neuropathies that may or may 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. So that is a positive signal clinically. So hopefully that's what we see eventually with this patient. And what was the other -- there was another question. You had 3 questions. Did I answer your question, Yanan?

Sorry, I didn't quite hear whether prophylactic treatment could play a role in preventing this or...

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

Okay. Yes.

Yes. 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. But prophylactic treatment reduces the incidence.

Our next question comes from the line of Gil Blum with Needham.

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 2 in the pivotal.

Yes, Jonathan. The rationale behind that was because 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. 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. 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's why there is a few more patients in the REVEAL pivotal and one additional patient in the ASPIRE trial.

Our next question comes from the line of Angela Qian with Canaccord Genuity.

This is Angela on for Whitney. First question is on the safety. You guys mentioned that Rett patients typically get peripheral neuropathy. 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 sales size for us and what the commercial organization would need to look like to support a launch?

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

Yes, just like have you said anything about how many salespeople you might need to support the launch?

How many salespeople?

Oh, 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 kind of 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 prescription gets written to them, getting to the institution and treated to them working with the insurance companies to make sure that reimbursement occurs. 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. 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 would say we're 80% of what we -- 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.

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

Our next question comes from the line of Evan Seigerman with BMO Capital Markets.

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

Yes, 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, 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 1-to-1 comparison. And we went through all the different analytics and product characterization parameters with the FDA [Audio Gap] analytically comparable. Subsequent to that, we've run more batches of the commercial process, 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. So the next step is that, when we complete the PPQ runs, if those 2 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. 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 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. 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.

Our next question comes from the line of [ Joshua Woodman ] with Citizens.

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. I was hoping you guys could just reiterate the key points there and highlight how this provides confidence in the reliability of essential raters and confidence in the validity and interpretability of the data from a regulator's perspective.

We can tag team this, but I think it starts with the fact that we're creating, via the milestone strategy, a novel pathway for approval in Rett syndrome, right? I mean, to date, the only thing that has been approved has been approved based on CGI and RSBQ. 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. The payers would not have paid with that as your 2 endpoints, 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. And fortunately for us, we found the milestone plateau and then began to work on what's the construct of the actual tool that we'll use as the instrument to capture this data. 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. So keep in mind, there's 28 milestones, so you're going to want to put in place a process that's 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'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. 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. We haven't talked too much about it, but we call it the [indiscernible] trial. And so, we were able to do the DMA in an nontreated population that was also, for the most part, sites in the clinical trial. So you knew like 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's how when we say that it is 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, was how rigorous you're going to be able to collect that data and ensure that you had a clear baseline. So, I mean, we can go chapter and verse deeper on that, but at a very high level, that's what happened, and it took a lot of hard work from the team, and it took a lot of time. It wasn't 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 don't know, Suku, if there is any more you might want to add?

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 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. It was a very interesting discussion that was raised. So this is a review of what also may be more relevant space with a currently approved product as well. So it was pretty timely, our data disclosure as well as the other presentations that occurred at IRSF.

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.

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.

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