Q3 2024 Taysha Gene Therapies Inc Earnings Call
Banch,
Speaker Change: Greetings and welcome to the Teja Gene Therapy's 3rd Quarter 2024 earnings call. At this time all participants are in listen-only mode. A question-and-answer session will follow the formal presentation.
As a reminder, this conference is being recorded.
Speaker Change: If anyone should require operator assistance during the call, please signal for an operator by pressing star and then zero. It is now my pleasure to introduce Hayleigh Collins, the Director and Head of Investor Relations. Thank you, and you may proceed, Hayleigh.
Hayleigh Collins: Thank you. Good afternoon and welcome to TASHA's third quarter 2024 Financial Results and Corporate Update conference call.
Hayleigh Collins: Earlier today, FACIA issued a press release announcing financial results for the 3rd quarter ended September 30, 2024. A copy of this press release is available on the company's website and through our SEC filing.
Hayleigh Collins: Joining me on today's call are Sean Nolan, SACES CEO, Suzumar Nagendran, President and Head of R&D, and Kamran Alam, Chief Financial Officer. We will hold a question and answer session following our prepared remarks.
Hayleigh Collins: initially seeing a patient's dose-to-date in clinical trials to positively impact Ollie's life.
Hayleigh Collins: and also the course of disease in the patients we seek to treat.
Our research, development, and regulatory plans for our product candidates.
Hayleigh Collins: including the timing of initiating additional trials and reporting data from our clinical trials.
Hayleigh Collins: The potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies. The clinical potential of interest-equal administration and our current cash resources supporting our planned operating expenses and capital requirements into the fourth quarter of 2026.
Hayleigh Collins: These statements may include the expected timing and results of clinical trials for our product candidates and other clinical regulatory plans, and the market opportunity for those programs.
Hayleigh Collins: This call may also contain forward-looking statements relating to TASIA'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.
Hayleigh Collins: Various risks may cause cases' actual results to differ materially from those stated or implied in such forward-looking statements.
Hayleigh Collins: These risks include uncertainties related to the timing and results of clinical trials of and regulatory interactions for our product candidates.
Hayleigh Collins: our dependence upon strategic alliances and other third-party relationships, our ability to obtain patent protection for discoveries, limitations imposed by patents owned or controlled by third parties, and the requirements of substantial funding to conduct our research and development activities.
Hayleigh Collins: For a list and description of the risks and uncertainties that we face, please see the reports we have filed with the Securities and Exchange Commission, including in our annual report on Form 10-K for the full year ended December 31, 2023, and our quarterly report on Form 10-Q for the quarter ended September 30, 2024, that we filed today.
Hayleigh Collins: This conference call contains sensitive information that is accurate only as of the date of this live broadcast, November 13, 2024.
Speaker Change: The patient undertakes no obligation to revise or update any solar building statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable security laws. With that, I would now like to turn the call over to our CEO, Sean Nolan.
Sean Nolan: Thank you, Hayleigh, and welcome, everyone, to our third quarter 2024 Financial Results and Corporate Update conference call.
Sean Nolan: I will begin with a brief update on our recent activities and then Sukriti Nagendran, President and Head of R&D of Tayshia, will provide an update on our lead Tayshia 102 program and clinical evaluation for Rett syndrome.
Sean Nolan: Kamran Alam, our Chief Financial Officer, will follow up with a financial update. I will then provide closing remarks and open up the call for questions.
Thank you. Thank you. Thank you.
Speaker Change: In the third quarter, we continued to drive progress across our TATIA 102 program in clinical evaluation for pediatric, adolescent, and adult patients with Rett syndrome.
Our accomplishments included achieving important clinical and CMC regulatory progress.
collecting additional clinical data.
Speaker Change: Further supporting the safety profile of Tayshia 102 across different ages and stages of disease and enrolling additional patients in the high-dose cohort across both our adolescent-adult and our pediatric-reveal Phase I-II trials.
Speaker Change: which support our expeditious development of Tayshia 102 for patients and families suffering from Rett syndrome.
Speaker Change: We recently completed our initial Type B multidisciplinary meeting with the FDA that was granted as a benefit of receiving Regenerative Medicine Advanced Therapy, or RMAT designation, for Tayshia 102.
We are pleased with the progress made with the FDA.
on further elucidating the potential regulatory pathway for patient 102.
as we advance discussions on trial design.
Speaker Change: Endpoints, and the Potential Use of an Established Natural History Dataset for Part B of our Revealed Trials.
Speaker Change: Additionally, we aligned on a meeting cadence with the FDA to expedite the development plan for CAESA-102.
Speaker Change: We recently completed a Type D CMC meeting, which was well attended by the FDA, including senior officials.
Speaker Change: We obtained FDA approval to use the pivotal Tayshia-102 product in our reveal trials based on a successful demonstration of analytical comparability between the clinical product and the product derived from the final commercial manufacturing process.
Speaker Change: Subsequently, we released the Pivotal product, which we intend to use in Part B of our trials. With this progress, we believe we are in a strong position with our CMC activities for Tayshia 102. Suku will discuss this in more detail.
Speaker Change: We also received approval from the Independent Data Monitoring Committee, or IDMC.
to proceed with continued enrollment in Cohort 2.
for both reveal phase 1-2 trials.
Speaker Change: Following the IDMC's review of available clinical data from the three patients treated with the high dose.
Speaker Change: I am pleased to share that the high dose of KHA-102 continues to demonstrate an encouraging safety profile.
Speaker Change: Patient 102 was generally well-tolerated with no serious adverse events or dose limiting toxicities in the first two adolescent adult patients as of 20 weeks and nine weeks post-treatment, respectively, and in the first pediatric patient at six weeks post-treatment.
Speaker Change: Subsequently, we dosed the third patient in the high-dose cohort of the adolescent adult trial and enrolled the second patient in the high-dose cohort of the pediatric trial with dosing scheduled for the current quarter.
Speaker Change: As a reminder, Rett syndrome is a rare neurodevelopmental disorder that afflicts an estimated 15 to 20,000 patients in the United States, Europe, and the United Kingdom.
Speaker Change: Currently there are no approved disease modifying therapies to treat the genetic root cause of the disease and there is significant unmet need.
Speaker Change: Rett syndrome is caused by mutations in the X-linked MECP2 gene which inhibits neuronal development and leads to multi-system complications.
It's characterized by loss of communication and hand functions.
slowing or regression of development, motor and respiratory impairment,
Autonomic Dysfunction, Seizures, Intellectual Disabilities, and Shortened Life Expectancy.
Speaker Change: Individuals with Rett syndrome typically require 24-7 care and lifelong assistance with daily activities, resulting in high caregiver burden and significant impact on quality of life.
We remain confident in our differentiated gene therapy candidate.
Speaker Change: which we believe has potential to provide meaningful therapeutic benefit to a broad population of patients with Rett syndrome using a minimally invasive delivery approach that has the potential to be administered in the outpatient setting for both children and adults.
Speaker Change: Patient 102 is a one-time intrinsically delivered gene therapy that was strategically designed to enable optimal and controlled transgene expression across the central nervous system.
Thank you.
Speaker Change: Rett syndrome is challenging to treat with traditional small molecules and gene therapy approaches due to the random inactivation and subsequent mosaic expression pattern of MECP2 that results in a mixture of cells that are either deficient in MECP2 or expressive normally.
Speaker Change: We believe Tayshin-102, equipped with the novel miRARE technology, has the potential to appropriately address this challenge by mediating MECP2 expression in the central nervous system on a cell-by-cell basis.
Speaker Change: By silencing the transgene in healthy cells expressing MECP2 and enabling protein production in deficient cells, MI-RARE is designed to overcome the risks associated with both under and overexpression of MECP2.
Speaker Change: Importantly, R-Capsid is paired with a self-complementary viral genome to enhance the effectiveness of gene transduction.
Speaker Change: We made the decision to utilize the mini MECP2 gene, which is a smaller version of the MECP2 gene that contains the essential functional domains necessary for therapeutic benefit, so that we were able to package our construct with a self-complementary technique.
Speaker Change: Self-complementary vectors have a smaller packaging capacity than traditional single-stranded vectors, but they offer the important advantage of faster, more efficient transduction.
Speaker Change: because they're able to entirely bypass the step of converting the vector genome into a double-stranded DNA prior to gene expression. As a result, a self-complementary vector can speed up the onset of transgene expression and potentially improve the efficacy of the gene therapy.
Speaker Change: We believe these strategic attributes of our construct enable the early and consistent clinical improvements that persisted and strengthened over time, as we've seen in the adult and pediatric patients treated with the low-dose of Tissue 102.
Speaker Change: Since Rett Syndrome is a progressive disease, we believe early clinical response increases the likelihood of reversing the disease trajectory and may be predictive of long-term clinical outcomes.
Speaker Change: Rett Syndrome requires an increased MECP2 protein to activate the neural circuits necessary for regaining function.
Speaker Change: And it also requires time for patients to strengthen these reactivated circuits to enable deeper learning of the skills affected by the disease.
Speaker Change: We believe the sooner positive clinical impact is observed following treatment, the greater the trajectory of potential improvement and longer-term outcomes.
Speaker Change: Therefore, early clinical benefit is a strong indicator that MECP2 protein has reached therapeutic levels that, in turn, create the opportunity for patients to further strengthen and gain new skills that can positively impact their activities of daily living.
Importantly...
Speaker Change: The clinical data presented from the adult patients with the most advanced stage of the disease
treated with the low dose of Tayshia 102.
Speaker Change: indicate a pattern of early clinical improvements and functional gains across multiple domains within four weeks post-treatment that persisted and strengthened over time.
Speaker Change: Specifically, improvements in autonomic function, including breathing and sleep, were demonstrated as early as two weeks post-treatment.
Speaker Change: At four weeks, clinical improvements and functional gains were reported across multiple domains impacting daily activities, including time-engrossed motor skills, socialization and communication, and seizure events.
Speaker Change: This includes beginning to use eating utensils, sitting without support, saying mama or daddy.
Speaker Change: petting a dog, improved attentiveness and social interactions with family members, and improved use of an eye-based driven communication device.
Speaker Change: as documented by video evidence, efficacy measures, and or clinical observations reported by the principal investigator.
As the pediatric data mature...
Speaker Change: We anticipate that the early clinical improvements and functional gains observed should also persist and strengthen over time in the pediatric patients treated with Tayshia 102 as the neural network matures and patients develop the strength to gain more complex skills.
Speaker Change: We look forward to further evaluating the pediatric patients over time.
Speaker Change: As clinical evaluation of Tayshia 102 further progresses, it is important to note that our program leverages a routine, minimally invasive delivery approach.
Speaker Change: that has the potential to be administered in the outpatient setting. Preclinical findings support the clinical potential of intrathecal administration as an effective delivery method for AAV-based gene therapies that are designed to treat the genetic root cause of CNS diseases.
Speaker Change: as it enables widespread and consistent bio-distribution across the brain and spinal cord.
Speaker Change: We believe this widespread distribution has been demonstrated throughout the clinical data.
Speaker Change: Through the clinical data, we reported that showed broad improvements across key clinical domains important in disease pathology, including fine and gross motor skills, communication and socialization, autonomic and seizure events.
Speaker Change: Importantly, we saw this consistently in the two adult and two pediatric patients treated with the low dose of Tayshia 102, despite differences in baseline disease severity. This was translationally reinforced with data from the analysis of
Speaker Change: five non-human primate studies that we recently presented at the ESGTC Annual Congress.
Speaker Change: which demonstrated that intrathecal delivery of gene therapies reaches key areas of the brain and spinal cord. Suku will discuss this in more depth.
Speaker Change: Collectively, we believe the strategic design of our construct has contributed to the encouraging safety and efficacy data we have reported today in both reveal trials.
Speaker Change: We believe there is potential to see continued improvements as the data mature and we look forward to reporting longer-term data from the low-dose cohort and data from the high-dose cohort in both reveal trials in the first half of 2025.
Speaker Change: We plan to continue working closely with the FDA through the RMAP mechanism.
Speaker Change: to solidify the regulatory pathway for TATIUM-102 based on the totality of data and we remain focused on the execution as we prepare for what we expect to be an impactful year ahead.
Speaker Change: I will now turn the call over to Suku to provide a more in-depth discussion of TASER 102. Suku?
Suku: Thank you, Sean, and good afternoon, everyone. I'm pleased to provide an update on our KESA 102 gene therapy program in clinical evaluation for Rett syndrome.
Speaker Change: As Sean mentioned, we believe we have achieved important regulatory progress for TESLA-102 over the last quarter. As a reminder, our approach is to use Part A of the trials to generate data that will inform our development plan for Part B of the trials.
Speaker Change: Therefore, Part A is Hypothesis Generating, not Hypothesis Testing, and was intentionally designed to collect data across a multitude of endpoints to help inform the final key elements for the next phase of our studies.
Speaker Change: We recently completed an ARMA Type B multidisciplinary meeting with the FDA regarding our ongoing TESHA 102 development plan.
Speaker Change: I'm pleased to share the meeting was very productive and we continue to find alignment in the potential regulatory pathway forward for PHRSA 102.
Speaker Change: We advanced discussions with the agency on the trial design, endpoints, and potential use of an established natural history dataset for Part B of our revealed trials.
Speaker Change: Based on FDA feedback from our ongoing discussions, we intend to focus on objective measures that clinically capture functional gains.
Speaker Change: In line with this focus, the caregiver-reported Rett Syndrome Behavior Questionnaire, or RSVQ, will not be included as a primary or secondary endpoint in Part B of our review trials, as discussed with the FDA.
Speaker Change: We will no longer be reporting RSVQ scores as part of future data readouts in our ongoing Revital Phase I-II trials.
Speaker Change: The FDA confirmed our existing non-clinical data package is adequate to support BLA submission, and we aligned on a meeting cadence with the FDA to expedite the development plan for TESLA-102.
Speaker Change: We recently completed a Type D CMC meeting with the FDA, and I'm pleased to share, the FDA approved the use.
Speaker Change: of pivotal TESA-102 product in our reveal trials based on the successful demonstration of analytical comparability between the clinical product and the product derived from the final commercial manufacturing process.
Speaker Change: Subsequently, we released the pivotal product, which we intend to use in Part B. The FDA also endorsed the proposed analytical methods and corresponding qualification and validation plans, including mechanism of action potency release assays.
Speaker Change: We believe this feedback provides further evidence of our meaningful progress towards Part B of the Reveal Trials.
It also demonstrates our CMC readiness for BLA submission.
Speaker Change: in the completed development of our final commercial scale process and pivotal product release for use in Part B. Importantly, this progress provides a path forward to potentially utilize the clinical data from Part A of our trials in our future BLA submission.
Speaker Change: Collectively, we believe our discussions with the FDA have been encouraging. We plan to continue working closely with the FDA through the ARGMENT mechanism to solidify the regulatory pathway for Pesha 102 based on the totality of data.
Speaker Change: Now let's turn to our clinical progress. As a reminder, we have two ongoing phase 1, 2 review trials evaluating patient 1 or 2. An adolescent and adult trial taking place in Canada and the U.S. for patients 12 and older with Strange 4-H Syndrome and a pediatric trial
Speaker Change: taking tests in the U.S., the U.K., and Canada for patients 5 to 8 years of age with stage 3 Rett syndrome.
Speaker Change: We are currently enrolling patients in Part A, the dose escalation portion of both trials, which is evaluating two dose levels of Trisha 102.
Speaker Change: With cohort 1 complete across both reveal trials, which is evaluating the low dose of 5.7E14 total vector genomes, we have made substantial progress in the enrollment of cohort 2, evaluating the high dose of TESHA-102 at 1E15 total vector genomes.
Speaker Change: The high dose of TESHA-102 continues to be generally well-tolerated with no serious adverse events or dose-limiting toxicities as of 20 and 9 weeks for the first two adolescent adult patients and as of six weeks for the first pediatric patient treated.
Speaker Change: Following the IDMC review of this data, we received approval to continue with enrollment in the high-dose cohort.
Speaker Change: Subsequently, we dose the third patient in the high-dose cohort of the adolescent adult trial and we enroll the second patient in the high-dose cohort of the pediatric trial with dosing scheduled for the current quarter.
Speaker Change: We also activated additional clinical trial sites across both reveal trials to further support Part B readiness.
in collaboration of our intrathecal delivery approach to KSR-102.
Speaker Change: The clinical potential for intrathecal delivery as an effective, safe, and minimally invasive delivery approach for broad targeting of the central nervous system at the annual ESGCT Congress.
Speaker Change: Data from the analysis of 28 human primates across five studies.
Evaluating AAV-9 Gene Therapy Delivery, Sean.
Speaker Change: that both lumber, intrathecal and intrasystemal magnet administration led to comparable, consistent, and wide-
Speaker Change: spread by distribution of AV9 vector throughout the brain and spinal cord regions.
Speaker Change: Importantly, these findings provide translational support for the clinical data we reported across both review trials that demonstrated broad clinical improvements seen across key areas of disease pathology that are known to impact different regions of the brain.
Speaker Change: We believe our continued clinical trial execution and data collection, supporting a continued, well-tolerated safety profile of Tesla 102, at the low and the high dose.
Speaker Change: combined with the encouraging regulatory discussions that we have, that have further shaped our developmental plan, strongly position us for success as we work to solidify our developmental plan for Part B of our studies.
Speaker Change: I will now turn the call over to Kamran to discuss our financial results. Kamran?
Kamran Alam: Thank you, Suku. Research and development expenses were $14.9 million for the three-month-ended September 30, 2024, compared to $11.8 million for the three-month-ending September 30, 2023.
Kamran Alam: The $3.1 million increase was driven by a $0.8 million increase in GMP batch activities during the three months ended September 30, 2024, which is representative of the intended commercial manufacturing process for Tayshia-102 and Rett syndrome.
Kamran Alam: Additionally, compensation for R&D employees increases as a result of higher headcount and this is partially offset by lower consultant and contractor expenses.
Kamran Alam: General and administrative expenses were 7.9 million dollars for the three months ended September 30th, 2024, compared to 8.6 million dollars for the three months ended September 30th, 2023.
Kamran Alam: The reduction of $0.7 million was primarily due to the decrease in issuance costs allocated to liability classified 2023 pre-funded warrants associated with the August 2023 financing.
Kamran Alam: Net loss for the three months ended September 30, 2024 was $25.5 million, or $0.10 per share.
Kamran Alam: compared to a net loss of $117.1 million, or $0.93 per share, for the three months ended September 30, 2023.
Kamran Alam: The reduction in net loss in 2024 was primarily due to a non-cash loss of $100.5 million reported in 2023 from a change in fair value of warrant liability from the 2023 pre-funded warrants associated with the August 2023 financing.
Kamran Alam: As of September 30, 2024, Tayshia had $157.7 million in cash and cash equivalents.
Speaker Change: Haysha expects that its current cash resources will support planned operating expenses and capital requirements into the fourth quarter of 2026.
Sean Nolan: I will now turn the call back over to Sean for his closing remarks. Sean? Thank you, Kamran.
Sean Nolan: We are pleased with the continued progress made across our CAESA 102 clinical development program and we remain confident in the potential of CAESA 102 to provide therapeutic benefit to adult, adolescent, and pediatric patients with Rett syndrome across different genetic mutation severity.
Sean Nolan: We remain steadfast and focused on execution as we prepare for what we expect to be an impactful year ahead, which is planned to include reporting longer-term data from the low-dose cohort and data from the high-dose cohort in both reveal trials.
Sean Nolan: and solidifying the development plan for Part B of our trials.
Sean Nolan: We look forward to continued discussions with regulatory authorities as we work to bring a new treatment option to patients with Rett syndrome as expeditiously and safely as possible. With that, I will now ask the operator to begin our Q&A session. Operator?
Speaker Change: Thank you very much. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star and then 1 on your telephone keypad. You may press star and then 2 if you would like to remove your question from the queue.
Speaker Change: Please may I ask that you limit your questions to one question and one follow-up question.
Speaker Change: For participants using speaker equipment, it may be necessary for you to pick up your handset before pressing the star keys. One moment please while we poll for questions.
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Speaker Change: The first question comes from Kristen Kuska from Canter Fitzgerald. Please proceed with your questions, Kristen.
Speaker Change: Everyone, thanks for taking the questions. It sounds like it was a very productive quarter for you. I wanted to ask one on the regulatory side. Considering that the endpoint could focus on objective measures, how are you broadly thinking about this in the context that this is a largely heterogeneous disorder? Will it be more personalized, or could it focus on something perhaps that's broad that covers a few areas and specific measures?
Thanks for the question, Chris, isn't it?
Speaker Change: You know, I would say it's, you definitely have to take the heterogeneity into considerations you're thinking through this. And so, as an example of that, we're looking at different types of potential trial designs.
Speaker Change: You know, possibly thinking about the patient as their own control could be a consideration.
Speaker Change: And I think to do that, you need to have good natural history, and we've completed our analysis of natural history and look forward to our next discussion with the FDA about
Speaker Change: And specific to Endpoints, I think at this point, you know, I put it into a couple of buckets.
Speaker Change: One would be, you know, looking at milestones and functional gains, right? I mean, to your point,
Speaker Change: Every patient is going to have loss or never having gained certain functions or milestones, and if you can potentially restore those, you can have different milestones for different patients.
Speaker Change: But yet, it may be something that's very consistent across all patients is that you would never expect them to have these types of gains.
Speaker Change: And, you know, I think we've seen some preliminary evidence of, you know, supporting this kind of thinking actually, you know, communicated to the market earlier this week.
I also think, if you think broadly about the disease,
Speaker Change: in a standardized approach that would lead to high data integrity and demonstration potentially of a very exciting, clinically meaningful effect for patients. Hopefully that gives you a little bit of color.
[inaudible]
Speaker Change: Yes, it does, thanks. And then just for the follow-up on that, I was hoping to get a little bit more context around the natural history completed analysis and then thinking about using it as a potential comparator here. Are there any stratifications to expect to compare this or will it kind of just be broadly based on many of these patients couldn't achieve milestone X and we're seeing Y in our trial?
Speaker Change: Yeah again I just want to I want to keep it at a high level you know I think there is a distinction between you know using it as a comparator to the extent like in SMA you can say type 1 patients all followed a similar progression.
Speaker Change: That's not what the natural history would indicate here. However, you know, there are aspects of the disease, including, you know, when people lose or never gain certain functions seems to be very consistent as well. So, you know, again, we have to think about this, you know, carefully, but when you think there's a path forward here, we've had preliminary discussions with the FDA and look forward to next steps in that discussion, hopefully later on here in the quarter.
and many more. Thank you. Thank you.
Speaker Change: And one thing I would also add is also the totality of clinical evidence will also play an important role in this disease. As you pointed out, it's heterogeneous and these patients have many clinical features.
Speaker Change: Thank you very much. The next question comes from Chris Raymond from Piper Zander. Please proceed with your question, Chris.
Speaker Change: Thanks. A couple of questions. Maybe just on the safety update you guys had today from the two adults and pediatric patients.
Speaker Change: It seems at least from NeuroGene's language and the way they were talking with that SAE they saw that showed up, was it a patient that just had been very recently been dosed?
Speaker Change: I'm just it looks like you guys are 29 and 6 weeks out with your high dose just thinking about maybe the window for an AED related SAE is there a range when you think a patient might be in the clear?
And I have a follow-up
Speaker Change: Yeah, and Chris, just to be clear, and I'll turn it over to Suku, we've now hosted four
Speaker Change: high-dose patients. We reported safety and free because the fourth patient was very recently dosed, so they didn't get that cut off yet. But to answer your question specifically, I'll turn it over to Suku.
Suku: What I'm going to kind of walk you through is based on my experience with both systemic gene therapies as well as other alternative routes, which include in Topeka. So keeping
Suku: in mind that in tropical ICV, the doses given could become eventually an important factor in some of these...
Suku: clinical reactions that you might see in this patient population. So again, I have no idea what exactly happened with the NeuroGene program, but what I can tell you is the following, right?
Thank you very much.
Speaker Change: Is there an immune response T-cell or sometimes a mixed antibody and T-cell response that can result in elevated liver enzymes and so forth?
and sometimes the
Speaker Change: The product itself, I guess the purity of the product can also play a role in the immune response, so that's something else to keep in mind.
The second is that...
Speaker Change: When you do an ICV procedure, and I'm sure Neon Gene knows this better than we do, when they do an ICV procedure, from a surgical standpoint, the needle itself, if it impacts the brain and causes some damage or there's spillage of the product,
Speaker Change: that can also sometimes cause an immune response, even though the patient may be on tricoliminal modulation. And that can cause inflammation in that part of the brain, and that could obviously cause symptomatic concern within the trial. The other component to keep in mind is as...
Speaker Change: product gets into the systemic circulation you can get something called TMA, thrombotic microangiopathy, which I've seen many times in the past with DMD
Speaker Change: But I think it's pretty unusual when you do an intrathecal ICV approach so
So if that is something that's going on...
Speaker Change: Here, obviously, you've got to wait to see what they share with us, but it also tends to be an immune response. There's complement activation, and then there's the entire cascade of the immune system can get activated, which results in TMA that can then result in a systemic inflammatory response that affects the liver, the kidney, etc., etc. So, and there might be something else that you're not aware of, and this all circles back.
Speaker Change: to the purity of the product. So that's about all I can tell you based on my past experience. But again, with the NeuroGene program, I cannot speculate at all.
For more information visit www.FEMA.gov
Speaker Change: Okay, cool. Thanks. And then just on, I know you gave a lot of detail on RSVQ and not using that in FDA, your discussion with FDA, just, but it was a co-primary endpoint for trifenatide, maybe, but it is also highly variable as you guys have been pointing out.
Just any sort of reaction from KOLs?
Speaker Change: In terms of their reliance on that, do docs use that, any sort of reaction to actually or paying attention to RSVQ as an end point?
Speaker Change: Suku and I can tag-team this. I would say in our discussions with KOLs that they are very, I would say, universal in their view that RSVQ is a
tool to measure clinical
Speaker Change: intervention with a therapeutic is not a good idea at all. And the first thing they go to is the fact that it was never designed for that purpose. It's highly variable. It's given by caregivers. And if you're gonna use it, you're gonna have to use a placebo.
Speaker Change: to try to control for it, which is what Tripp Venati didn't.
Speaker Change: So, in our discussions with KOLs, they're supportive and they're actually pleased, you know, with the discussions we've had with the FDA, and instead of looking at that, focusing more on some of these, you know, very clinically meaningful, objective type endpoints.
Sean Nolan: Sean, what I would add to that is that RSVQ, as you said, is very subjective.
Sean Nolan and Kamran Alam
Thank you very much.
Speaker Change: who designed clinical trials, and I think some of the KOs already know the scores, RSVQL, are relieved that you're not using it.
Speaker Change: Yeah, and I guess the last point, Chris, is just keep in mind that the RSPQ measures behavior rather than function, and I think we've given multiple examples where function has improved and the RSPQ gets worse.
Speaker Change: because the behaviors that like certain aspects of behavior that people couldn't have done in the past because they didn't have the functions looks to be a negative when the function itself is a positive. So just just another reason to not use that scale in this type of a setting.
Very helpful. Thank you.
Sure.
Speaker Change: Thank you. The next question comes from Whitney Igem from Kennacord community. Please proceed with your questions Whitney.
Whitney Igem: Hey, you guys. Congrats on all the progress for me as well. Just curious, enrollment in the high-dose cohorts is obviously going really well, but wondering if you can characterize the level of demand or interest in the study, I guess, in the adults in particular, with an eye towards thinking through kind of the ultimate market opportunity and kind of demand from older patients that you might be hearing or seeing.
Speaker Change: Yeah, I mean, we've had significant demand. I mean, we've had, you know, there's multiple...
patients wanting to get into the slots in both protocols.
And, yeah, I think that...
Speaker Change: We've gotten feedback from the community that it's that they're very pleased that we've cast such a wide net I mean oftentimes you start with
Speaker Change: you know, a younger population and then expand over time possibly. Um, you know, I think they've appreciated the approach and the consideration of the fact that we're trying to take care and offer a potential treatment for all patients suffering from from breath.
Speaker Change: Got it. That's helpful. And then just lastly, on the point of the route of administration, which is a clear point of differentiation between you guys and NeuroGene, can you walk us through what happens from a patient perspective as it relates to treatment? Remind us what's the immunomodulatory regimen, when does that start, and what does the day look like from a patient perspective logistically and timeline-wise around treatment?
Speaker Change: You're talking about the immune therapy that we're immunosuppression regimen that we're using in our protocol?
Speaker Change: Yeah, that and then just kind of like, what does treatment day look like for these patients?
I'll treat you in a day, okay?
and many more. Thank you. Thank you.
Oh, okay, okay, I get it.
Speaker Change: Yeah, so right now, Whitney, our protocol is such that, if you recall, when we originally started our studies, we were using prednisone.
Speaker Change: and still all the rest, but they were for a much longer duration.
Speaker Change: And that was done for many different reasons, but as you got more experience with the gene therapy, the procedure and how patients are responding, we've been shortening the immunomodulatory duration because we feel that the patients don't really need it. So right now,
Speaker Change: The visa loan is started on day minus seven, so roughly one week before the day of administration, at one milligram per kilogram per body weight, and then it's given for six weeks, and then it's tapered off over six weeks. So it's a total of 12 weeks.
Speaker Change: And then sirolimus, which was at one point running for almost 37-40 weeks, has now been reduced to 24 weeks, or 25 weeks, and it's 0.8 milligrams per kilogram. And obviously...
Speaker Change: Ideally, I would like to see that duration shortened further and keep it as simple as possible for this patient population. So, obviously, before a patient is brought in for actual treatment and engagement within the study, they have to go through multiple screening procedures to make sure they actually qualify for the trial.
Speaker Change: And there's a time range that can run somewhere from, say, 20 days, let's say, to 50 days. I mean, there's a duration. So I'm not being exact here, but I'm just going to give you a feel. So once they qualify through screening, then they're given immunosuppressant module, modulatory agents at day minus seven, and then they come in on that day, and they have to be prepped for the procedure. Now, the caveat here is, remember, R is a simple number puncture, which can be done inpatient or outpatient, and this has significant impact.
Speaker Change: on who is actually doing the lumbar puncture because eventually, a lumbar puncture that can be done in an outpatient setting by not necessarily a neurologist but can be done by an internist or a physician who.
for the press conference.
Speaker Change: So that's kind of the big picture at the present time, so the ease of use, a lot of administration and obviously the immunosuppressive regimen, keeping it simple and
Speaker Change: I'm not being too aggressive with it, all of those could make it much...
Speaker Change: More palatable gene therapy for this case. It's a broad range in application So yeah, and the only thing I would add to that just come up just so you have a sense of time You know once once the you know, the patient is brought in for the procedure the administration itself You know, we're talking 10 to 20 minutes. So it's very very short and You know, we like to make it as easy as we can on the patients and their families
Very helpful. Thank you.
Sure.
Speaker Change: Thank you. The next question comes from Salveen Rathdale from Goldman Sachs. Please proceed with your question, Salveen.
Speaker Change: Good afternoon. Thanks for taking my question. Can you elaborate on the exact objective measures you're looking at in Part B of the REVEAL study based on the FDA feedback and the specific milestones and or functional gains you'll be monitoring? Thank you.
Speaker Change: I really don't want to get into the details of that at this point in time. I think it's better to keep it high level in terms of...
The areas that we're looking at, which would be milestones.
Speaker Change: , we're going to do is we're going to focus on gross motor function. The actual means that we're going to do that and what we're going to follow, I can tell you we've got a very specific set. It's all been identified and validated
Madrigs
So there's nothing new that we're introducing here.
Speaker Change: And I'd prefer to wait until, you know, we have everything, you know, fully and finally flushed out with the FDA. We've got another meeting with them coming up here, hopefully before the end of the year is the next step. You know, we've talked about locking it all in.
Speaker Change: In a meeting likely in the first half of next year, we're continuing to make good progress, but I'd hesitate from getting into the details until we're fully aligned.
and many more. Thank you. Thank you.
Speaker Change: Thank you for watching. Please subscribe to my channel. See you in the next video.
Speaker Change: Dalvin, may I just check if you have any further questions?
Thank you so much.
Speaker Change: Thank you. The next question comes from Gil Blum from Needham and Co. Please proceed with your questions.
Hi everyone and thanks for taking our questions.
Speaker Change: Maybe a more general question as it relates to your type D meeting. So were there some garnered synergies from prior experience with Zolgensamma that kind of helped you?
Speaker Change: Get the equivalents through here, or is this just the new product, checking all the boxes, and I have a follow-up.
Speaker Change: You're talking about the comparability between the clinical lot and then the product made from the final commercial process?
Yep.
Speaker Change: Yeah, well, I would just keep it at a high level, Gil, and say...
Speaker Change: You know, we really didn't do much to the upstream, they're very, very similar.
Speaker Change: You know, between the two processes, what we wanted to do was, was just to continue, like, one of the things that we brought over from the Sol Gensma experience is that, you know, we always want to make.
Speaker Change: the most pure product that we can. I mean, then you're minimizing the dose exposure that you're giving a patient. So
You know, while we've never had any...
Speaker Change: direction from the FDA or anything like that. I mean, the FDA has generally been looking at, you know, keep empty capsids from, you know, going above 30.
Speaker Change: percent or so, and we want to be way, way less than that. And so we focused a little bit more on the downstream.
Speaker Change: and you know that's where we that's where we did our work and so when you look at the actual attributes of the product
Speaker Change: The data were very, very consistent and the improvements that we made were clear and we identified those and obviously where we landed with the FDA was in a very positive fashion.
Speaker Change: So, we're pleased with where we are and look forward to, I guess I'd make the point that we're at scale. We've got our final process and we've got product in the freezer that we're planning to use in Part B.
Speaker Change: and we're looking forward to that. So having CMC lined up at this point in time is a big step for the program because generally it turns out that CMC gets on the critical path and that's not the case for us.
[inaudible]
Speaker Change: Okay, and that's very helpful and another follow-on as it relates to potential designs for you know pivotal studies here
Speaker Change: It sounds like we're looking more at natural history here, but would you guys still consider a randomized study in adult patients, for example, or does the disease heterogeneity make that very complicated? Thank you.
I mean, the heterogeneity is...
Speaker Change: really they're in all patient ages and stages. So, you know, that's one of the reasons that we're thinking about, you know, multiple trial designs, but ultimately if you can come up with a construct
Speaker Change: where it's defendable to use the patient as their own control, you know, regardless of age, would be an optimal setting.
because
Speaker Change: The patients are so heterogeneous that, you know, using a delayed treatment group.
Speaker Change: That really isn't taking care of the issue either. I can tell you we've given a great deal of time and effort around this.
Speaker Change: We've had discussions with the FDA on multiple occasions, and we've basically said we'll continue to bring forward both clinical data as well as the final assessment of our
Speaker Change: the work we did in natural history to make our case, you know, for, you know, why we think a certain approach makes the most sense. And I can just say the agency has been very open to that. There's been no pushback. There's, I would say, a very...
Speaker Change: Good understanding by the agency of the disease and the inherent challenges
that you would have.
And so that's where we've been thinking a lot about.
Speaker Change: The combination of the trial design and the endpoints to, you know, allow us to facilitate, you know, getting this drug approved in the most expedited fashion.
Speaker Change: possible with the greatest scientific rigor. And, you know, it's our view that the natural history work that we've done will be helpful in facilitating that. And look, you know, we have to certainly get there in final form with the FDA, but that's where we're thinking at this point in time, and we're encouraged by previous discussion.
[inaudible]
Speaker Change: Thank you very much. The next question comes from Morrie Raycroft from Jeffries. Please proceed with your questions.
Speaker Change: Hi, congrats on the progress and thanks for taking my questions. Just clarifying, it sounds like you could have that alignment on a registrational study design and endpoints ahead of the data update first half of 2025. So would that be part of your first half 2025 disclosure?
Speaker Change: In a perfect world, yes. We would like to basically come out with the feedback from the FDA and do the data update.
simultaneously would be fantastic.
Speaker Change: Just to be clear, what I was pointing at, we are going to have another meeting with the FDA.
and Kamran Alam, Hayleigh Collins.
Speaker Change: goal, our preference to align it. So we'd love to come out and tell you guys, here's where we landed with the FDA. Here's the data update. And here's the next steps in the program. It's how we've drawn it up. And hopefully we're able to execute and make that happen.
Got it. Okay, let's all pull in.
Speaker Change: Maybe just a quick one. Wondering if you discussed with FDA the potential to dose a younger cohort of patients at 3 to 5 year olds in Part B, or is this part of longer-term plans? I guess just based on the safety and profile that you have so far, could you potentially get into those younger patients in Part B?
Speaker Change: Yeah, I mean right now Part B does include three to five-year-olds, and I would just say, Maury, that
Speaker Change: We would, our intent is ultimately to make sure that this is available, you know, for patients newly diagnosed.
you know, throughout.
We've played to all sorts.
So, we are contemplating all of that in our full...
put it below where it should be.
program.
Speaker Change: and we'll step through it accordingly. We've got the plan in place and we're in concert in discussion with the FDA about that and how to best step through that.
Got it. Okay. Thanks for taking my questions.
Speaker Change: Thank you. The next question comes from Yanan Zhu from Wells Fargo. Please proceed with your questions, Yanan.
Speaker Change: Hi, this is Jeff Hahn for Yannan. Thanks for taking our questions. Can you just give us your overall thoughts on the neurogene data and how you see comparing to Tayshia 102? And then secondly, is dosing above the high dose of 1 times 10 to the 15 vector genomes with Tayshia 102 possible? Do you think there's a safety room to dose higher? Thanks.
Speaker Change: Yeah, I mean, I can say that in our non-human primate talks...
We were clean at 2E to the 15th.
Speaker Change: So, we could potentially go higher if we wanted to. Based on the preclinical data, it looks like 1 in 15 is the right choice at the higher dose.
Thank you.
Speaker Change: But it's something that we could certainly contemplate. We have the ability...
Speaker Change: to go higher. So I think that's a key point. You know, I think as it relates to the neurogene data, you know, I think number one, I would just say that it's a positive for the Rett community that
The merging data was, you know, demonstrating benefit.
Speaker Change: to patients. And I think what it highlights is that utilizing gene therapy to target MECP2 is a good target and that there's a benefit that's been derived now from two different constructs.
Speaker Change: And I think we have to look at, you know, over, over time, you know, how, how things elapse. I don't think it's appropriate to get into the details of how one may be better than the other at this particular point in time. But I think that the win, if you will.
Speaker Change: is for the community and that you know hopefully there's there's options available for the families suffering from Rett.
and many more. Thank you. Thank you.
Okay, thanks very much.
Thank you.
Speaker Change: Thank you. Ladies and gentlemen, if I may just ask, could you please limit, if you could please just limit your questions to just one question per end list. The next question comes from Jack Allen from Baird. Please proceed with your question.
Thank you.
Speaker Change: Great, thanks so much for taking the questions and congratulations on the progress made over the course of the quarter. I wanted to ask about the four patients that have been dosed with a high dose. How should we think about those patients and the centers at which they've been dosed? I'm trying to understand if there's a broadening footprint here and if additional physicians are getting hands-on experience with Tayshia 102.
Thanks for any contacts you provide.
Speaker Change: Yes, Suku, don't make sure I get this right, but we have seven total sites available, five sites available right now to dose in the two protocols, and so of the four
at least two different
Slides.
Speaker Change: So right now we've had a total, when you look at the total, the both reveal programs.
There's at least three sites that have endorsed patients.
and hopefully that makes sense. Three different sites.
Thank you.
Speaker Change: Got it. And then three sites, I guess, just to clarify across both the low and the high dose, is the way to think about it.
Yes.
Okay, thanks so much for the call.
and many more. Thank you. Thank you.
Speaker Change: Thank you. The next question comes from June Lee from Tourist Securities. Please proceed with your questions.
Speaker Change: Okay, thanks for taking our questions. As we look forward to Part A data in the first half of next year, will you be providing updates on RSB-Q or are you no longer sharing RSB-Q as part of the assessment? And for the endpoint you are considering for Part B, can you at least share if that's something that you're already tracking in Part A? Thank you.
Speaker Change: Yeah, June, we are not going to give updates on RSVQ anymore, given the fact that in our discussions with the FDA.
Speaker Change: It's very clear that they didn't see it as a viable option as a primary endpoint, or a secondary endpoint for that matter, and we completely are on board with that. We see no value to continue to show up.
Speaker Change: Yeah, and so, you know, for those reasons, we're focused more on, you know,
Speaker Change: Most importantly to us are really what are the functional gains and clinical observations that are being demonstrated. We still think CGI is something that's that's relevant to look at but again that's not a primary endpoint in our in our view and discussions with the FDA.
Speaker Change: So, we will consistently give updates on the other aspects of the program that we have, but we just felt RSPQ, given that it's been completely ruled out, and given the focus that people have put on it.
Speaker Change: makes no sense. We're trying to be very clear that it is no effect on the program going forward from a regulatory perspective and it's not a good assessment of clinical effectiveness.
Speaker Change: As it relates to your question about Part A, yes, I mean, we are collecting milestone data. We've reported on a lot of
milestones over the course of time.
Speaker Change: You know that'll certainly go into the discussion that we're having with the FDA in terms of endpoints we've already had.
Speaker Change: several discussions about that, as well as hand function and gross motor function. So, you know, when we give our update in the first half of next year, you know, we're hopefully it can be very comprehensive for everyone in terms of where we landed from trial design and end points.
Speaker Change: How does that correlate to what we've seen in Part A, and then what does your high-dose data look like?
So we're excited. I think we're exiting the year.
Speaker Change: with a ton of momentum. We're in a good place, and what we have to do as a team is execute across the board, generate clinical data, and continue our dialogue with regulators to put us in a great position that we plan to share in the first half of 2025.
Thank you. Have a good day. Thank you.
All right. Thank you.
Good luck.
Speaker Change: Thank you. The next question comes from Sylvan Turkin from Citizens JMP. Please proceed with your questions.
Sylvan Turkin: Good evening and thanks for taking my question. I just want to ask about the doses and how you view the equivalency between your dosing exposure and that of Neogen, given you've also recently presented data at EHCT on biodistribution.
Thank you.
Speaker Change: So can you can you kind of restate that question? I want to make sure I understand it and act and can be accurate in giving the answer.
Speaker Change: Basically, you know, like, your low dose is a little bit below what Neurogen is administering and now you escalated at the higher dose to approximate the same dose. Obviously, the route of administration is different, so I just wanted to get an idea of, you know, if you have any sense of what the exposure around the critical part of the brain is.
Speaker Change: in terms of the two gene therapies and what that means for the efficacy we've seen so far with the two products.
and many more. Thank you. Thank you.
hopefully giving good context to the question of
Speaker Change: What's the bioavailability look like when you go direct to brain versus intrathecally?
across all the ADB-9 programs that we have.
Speaker Change: And when we looked at the biodistribution data, there really wasn't a difference between intrathecal levels of transduction versus what happens with ICM or direct-to-brain. So I think the first point is the biodistribution appears to be equal.
Speaker Change: And number two, when you look at the clinical data, that makes sense.
because, you know, when we reported our data initially...
Speaker Change: We were seeing effects occur across clinical domains, and so as you know, autonomic function, socialization communication, gross and fine motor function, seizures, all those happen in different parts of the brain.
Speaker Change: Asleep, you know, so it that lines up well with with the bio distribution data that I talked about that you have to be getting to all parts
Speaker Change: And then, when you look at the data that was announced later this week, you know,
Thank you. Bye.
Speaker Change: There seems to be similar effects, you know, one or two point improvements in CGI, you know, so
Speaker Change: It looks like the roots of administration are, you know, relatively, you know, equal in terms of delivering, you know, the effect across clinical domains, and I would just point to the fact that, you know, our dose is about 50% less.
then what was used at 1E to the 15th.
Speaker Change: and you know part part of that can also be the construct design and so we've talked about the fact that having a double strand and self-complementary generally leads to greater levels of transduction efficiency than versus using a single strand.
Speaker Change: So, I think all the data kind of line up with, you know, what we've been saying for the last couple of years. And so, you know, we're encouraged by what we've seen at the low dose.
Speaker Change: Even in the pediatrics at early time points, you know, within four weeks we were seeing effects across, you know, breathing, sleep. We were seeing impacts on fine motor skills, gross motor skills.
Speaker Change: Seizure activity and you know that was in as little as four to twelve weeks.
Speaker Change: So from our perspective, that's super exciting. And we think that sets the trajectory for how these patients are going to do over time. So, you know, it's, it's our anticipation that as longer term data unfolds at the low dose, and we believe hopefully even a better magnitude at the high dose, we're going to be able to do a lot more. So we're going to be able to do a lot more.
and Kamran Alam.
The proof-of-concept now has been proven.
Speaker Change: So that is number one. Number two is, yes, the urogen does use a high dose.
Speaker Change: and the only thing is, you know, from an overall safety standpoint
Speaker Change: It's pretty well known in gene therapy to hire the dose, even small changes from a logarithmic standard sometimes can impact certain types of safety treatments. So this is the recent safety issue. I think there's a lot of curiosity as to what is going on. The third is about distribution, as you pointed out. There was a lot of...
Thank you very much.
Speaker Change: We are creating a neural network quite effectively and we work...
quite rapidly when it comes to clinical efficacy.
Speaker Change: much quicker than a single-stranded construct. That is very clear. And then if you don't use the right dosage from a single-stranded construct, your efficacy is slow, it takes a while, and it may not even persist. So those are some of the questions I think that have to be answered between the two constructs over time.
Thank you so much.
Thanks all.
Speaker Change: Thank you. The next question comes from Keith Tapper from BMO Capital Markets. Please proceed with your question.
and many more. Thank you. Thank you.
Speaker Change: Hey guys, thanks for taking my questions and appreciate the execution across the program.
Speaker Change: I'm just trying to frame for investors the motivation for the high-dose co-work given the potential safety trade-off and really an absence of mature low-dose data in pediatric patients.
Speaker Change: Maybe could you remind us of expectations for the higher dose? Are we looking for upside to efficacy, durability, bio-distribution, or a broad use of the patient population with two doses?
Speaker Change: possibly moving to approval and then from where we are today, I guess, could you characterize the higher dose as experimental, exploratory or necessary for competitiveness? Thanks.
Speaker Change: Yeah, I mean, Keith, we decided to, when we picked the doses,
Speaker Change: We see in preclinical data that there should be benefit to go to the 1D to the 15.
Speaker Change: based on all the preclinical work that we've done. And given the fact that we have, you know,
Speaker Change: double that, 2x that safety margin. In our tox studies, you know, we feel, you know, we feel encouraged about the benefit risk.
Speaker Change: And I think that utilizing the intrathecal approach, assuming that you have equal biodistribution, in our view, the data that we've put out pre-clinically and more importantly clinically support the biodistribution, intrathecal is, you know.
Speaker Change: It's not the safest one of the safest ways to administer therapy to target the benefit and minimize the risk
Speaker Change: So, you know, we're very pleased with what we've seen at the low dose.
Speaker Change: And it's our view that at the high dose, there is a relatively very low likelihood of any type of safety issue, and there is a better than, you know,
Speaker Change: there's a good chance that we're going to see incremental benefit that the patients are going to get derived by going to that dose. So for us
Speaker Change: it's a it's a very easy calculus to say let's go to the high dose and I can tell you you know in the IDMC meetings you know we continue to show high versus low dose looking at all of the different
Speaker Change: You know parameters that are collected whether it's liver function platelets all that kind of stuff
And, you know, we've seen essentially no difference.
Speaker Change: and the two. So again, that's why we feel good about things and have decided to, you know, to move the high dose even, you know, earlier than we were supposed to based on the protocol. And of course, the IDMC supported that recommendation.
Speaker Change: Okay, great. That's helpful. And just one follow-up, if I could.
Speaker Change: How should we think about the more mature adult clinical data that we have in terms of translatability to the pediatric cohort?
Speaker Change: Just maybe in context of baseline characteristics and the original goals of the adult trial and then considering differences in brain development and disease stage for the adults. Another way, you know, do you have different expectations for pediatric versus adult responses to treatment? Thanks.
Well, I think...
Speaker Change: Keep in mind when we started the adult trial, I think that the consensus view was we wouldn't see any efficacy. That was kind of what the KOL community felt. And, you know, within four, actually within two weeks, uh, you know, sleep normalized. Seven days was okay. Seven days. And, and, uh, you know,
Speaker Change: Within six weeks, gross motor function improving were milestones being achieved that, you know, hadn't occurred in over eight years, essentially.
Speaker Change: and you know what we've seen when we look at the high-dose data is that the patients do seem to strengthen over the course of time.
Speaker Change: And so sometimes, like the CGI eyes, sometimes the scale will get better and the adults sometimes it might stay the same. But what's happening to the patient, the activities of daily living, the functional gains.
Speaker Change: Those are improving over over time seizure reduction that's improving over the course of time And so you know what the way we've described it is is that in the adult population you see early
Speaker Change: benefits, early, you know, clinical improvements and functional gain, and then over time, those are either sustained or they get better.
And so it's our expectation in the pediatric group
that that should also
Speaker Change: be the case. It should follow a similar pattern. And so we were very encouraged with the early data that we put out in June. You know, in eight weeks we had, you know, a patient with a two-point improvement in CGII. You know, that's that's fantastic.
Speaker Change: And then we were seeing changes occur in terms of function, right? I mean, one of the girls got her ability to use her thumb and pincer grasp back.
Speaker Change: after having not had it for five years. Like that's, that's incredible. And so it's our view that those patients should get better over the course of time as they get stronger, they get used to having certain skills. The socialization aspect.
Speaker Change: Also, you know, with what we've seen in the adults and even in the early data of the pediatrics got better over the course of a few months, we would expect that to to do the same. So, you know, it's kind of like you think about.
Speaker Change: Two possibilities, you know, with the pediatric patients that I feel pretty good about is I would hope, and I'm hoping based on what I've seen in the adults, that the pediatric low-dose data looks even better over the long term.
Speaker Change: And then that the high dose looks even better, both in the short and the long term, than the low dose.
Speaker Change: So, again, that's why we're so excited about 2025, because I think the teams worked hard to put us in a position.
Speaker Change: with regulators, with opening, you know, multiple sites. I mean, we're not just getting our data from one site.
Speaker Change: We've now got five sites that are active and enrolling, and we've dosed patients at three of those five with the other two coming online here with our online. It's just getting to the dosing that we've got scheduled already. So we feel good about where we are and where the program's going.
Speaker Change: Thank you very much. Ladies and gentlemen, we have reached the end of the question and answer session. And I'd now like to hand the call back to Mr. Sean Nolan for closing remarks. Thank you sir.
Sean Nolan: I just want to thank everyone for taking the time this evening to hear the update and look forward to any follow-up questions. Take care and have a good night.