Taysha Gene Therapies Q2 2024 Earnings Call Transcript

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Provided by Quartr
August 12, 2024

There are 10 speakers on the call.

Operator

Greetings, and welcome to the Tayshia Gene Therapies Second Quarter 2024 Earnings Call. At this time, all participants are in a listen only mode. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Haley Collins, Director and Head of Corporate Communications and Investor Relations.

Operator

Thank you. You may begin.

Speaker 1

Thank you. Good morning, and welcome to Tayshia's Q2 2024 Financial Results and Corporate Update Conference Call. Earlier today, Tayshia issued a press release announcing financial results for the Q2 ended June 30, 2024. 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, Tayshia's CEO Sukumar Nagandran, President and Head of R&D and Cameron Alam, Chief Financial Officer.

Speaker 1

We will hold a question and answer session following our prepared remarks. Please note that on today's call, we will be making forward looking statements, including statements relating to the therapeutic and commercial potential of TASIA-one hundred and two, including the reproducibility and durability of any favorable results initially seen in the patient's dose to date in clinical trials to positively impact the quality of life and alter the course of disease in the patients we seek to treat our research, development and regulatory plans for our product candidates, including timelines for our clinical trials and reporting results therefrom and our current cash resources supporting our planned operating expenses and capital requirements into the Q4 of 2026. These statements may include, but are not limited to, the expected timing and results, of clinical trials for our product candidates and other clinical and regulatory plans and the market opportunities for those programs. This call may contain forward looking statements relating to Tasiast'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 Tayshia's actual results to differ materially from those stated or implied in such forward looking statements.

Speaker 1

These risks include uncertainties related to the timing and results of clinical trials of and regulatory interactions for our product candidates, our dependence upon strategic alliances and other third party relationships, our ability to obtain patent protection or discoveries, limitations imposed by patents owned or controlled by third parties, and the requirements of substantial funding to conduct our research and development activities. For a list and description of the risks and uncertainties that we face, please see the reports we have filed with the SEC, including in our annual report on the Form 10 ks for the full year ended December 31, 2023, in our quarterly report on Form 10 Q for the quarter ended June 30, 2024 that we filed today. This conference call contains time sensitive information that is accurate only as of the date of this live broadcast, August 12, 2024. Satia 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.

Speaker 2

Thank you, Haley, and welcome, everyone, to our Q2 2024 financial results and corporate update conference call. Today, I will begin with a brief update on our recent activities and then Suku, our President and Head of R and D will provide an update on our lead TASIA-one hundred and two program in clinical evaluation for Rett syndrome. Cameron Olam, our Chief Financial Officer will follow-up with a financial update and I will provide closing remarks and open the call up for questions. In the Q2 of 2024, we made strong progress across the TATEO-one hundred and two program and clinical evaluation for pediatric, adolescent and adult patients with Rett syndrome. This included reporting encouraging safety and efficacy data from the low dose cohort in both our REVEAL Phase onetwo trials, initiating the high dose cohort, expanding our pediatric trial into Canada and strengthening our balance sheet.

Speaker 2

With this progress, we believe we are well positioned to execute across key value creating milestones in our and rare neurodevelopmental disorder that afflicts an estimated 15,000 to 20000 patients in the United States, European Union and United Kingdom. Currently, there are no approved disease modifying therapies that treat the genetic root cause of the disease and there is significant unmet need. Rett syndrome is caused by mutations in the X linked MECP2 gene, which results in the neural network dysfunction and leads to multisystem complications. It's characterized by loss of communication in the hand function, slowing and or regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy. Individuals with Rett syndrome typically require 20 fourseven care and lifelong assistance with daily activities, resulting in high caregiver burden and significant impact on quality of life.

Speaker 2

Our TASIA-one hundred and two gene therapy candidate is a one time intrathecally delivered treatment designed to address the underlying cause of the disease. Rett syndrome is challenging to treat with traditional small molecule and gene therapy approaches due to the random X inactivation and subsequent MOSAIC expression pattern of MECP2 that results in a mixture of cells that are either deficient in MECP2 or express MECP2 normally. We believe TASIA-one hundred and two equipped with the novel miRARE technology has the potential to appropriately address this challenge by mediating MECP2 expression in the central nervous system on a cell by cell basis to overcome the risks associated with both under and overexpression of MBCP2. Recall, we have 2 ongoing Phase IIIREVEAL trials evaluating TASIA-one hundred and two. An adolescent and adult trial taking place in Canada and the U.

Speaker 2

S. For patients 12 and older with Stage 4 Rett syndrome, which is the most advanced stage of the disease and a pediatric trial taking place in the U. S. And UK with recent clearance in Canada for patients 5 to 8 years of age with Stage 3 Rett Syndrome. We are currently enrolling patients in Part A, the dose escalation portion of both trials, which is evaluating 2 dose levels of TATIA-one hundred and two.

Speaker 2

Part B of the pediatric trial, the dose expansion portion will evaluate TASION-one hundred and two in 2 age cohorts, an expanded 5 to 8 years of age cohort and a 3 to 5 years of age cohort. 2 patients have been dosed in Cohort 1, which is evaluating the low dose of TASIA-one hundred and two, 5.7e14 total vector genomes in each trial. At the 2024 Rett Syndrome Foundation Rett Syndrome Scientific Meeting in June, we reported encouraging preliminary data from Cohort 1 in our pediatric trial and longer term data from cohort 1 in our adolescent and adult trial, which demonstrated a well tolerated safety profile and improvements across consistent clinical domains impacting daily activities in the adult and the pediatric patients treated with the low dose of TASIA-one hundred and two. We are pleased by the consistent clinical response demonstrated across multiple areas of disease, including autonomic function, seizures, gross motor skills, fine motor skills and hand function and communication and socialization in both adult and pediatric patients with different genetic mutation severity. We look forward to continuing to evaluate the clinical impact of the low dose of TASIA-one hundred and two over time.

Speaker 2

Following review of these data, the Independent Data Monitoring Committee or IDMC approved our request to dose escalate early in both REVEAL trials. Therefore, dosing in cohort 1 of both trials is complete. Expediting dose escalation is an important step in our development plan as advancing earlier to the high dose accelerates our ability to further inform our clinical development and regulatory strategy for the next phase of our studies. With Cohort 1 complete, we've turned our focus to dosing patients in the high dose cohort across both our REVEAL trials and building on our promising preliminary low dose data set from both adult and pediatric populations. We dosed the 1st patient in Cohort 2 of our adolescent and adult trial, which is evaluating the high dose of TASIA-one hundred and two, which is 1 of the 15 total vector genomes.

Speaker 2

We are pleased to share that the high dose of TASIA-one hundred and two was generally well tolerated with no serious adverse events or dose limiting toxicities as of the patient's initial 6 weeks assessment. Following review of these data, the IDMC provided clearance to proceed with the dosing the second patient in Cohort 2 of the adolescent and adult trial and the 1st patient in Cohort 2 of the pediatric trial earlier than planned. Subsequently, we enrolled the 2nd adolescent adult patient and the 1st pediatric patient in Cohort 2 across both trials. Dosing of both patients is scheduled to occur in the Q3 of 2024. Lastly, we strengthened our balance sheet with the recent completion of a public follow on offering that resulted in total net proceeds of $76,800,000 We expect the net proceeds to extend our anticipated cash runway into the Q4 of 2026 to support the continued development of our TASIA-one hundred and two program.

Speaker 2

Importantly, this capital infusion allows us to build on our preliminary TASIA-one 102 clinical data set in the adult and pediatric patients and enables us to focus on execution as we endeavor to deliver on key value creating milestones. We are moving forward reporting cohort based updates with more mature data sets in order to provide more fulsome updates on our clinical data. In line with this decision, we plan to report safety and efficacy data from the high dose cohorts and an update on the safety and efficacy from the low dose cohorts in both our adolescent and adult trial and our pediatric trial in the first half of twenty twenty five. With our balance sheet strengthened and cash runway extended, we believe we are in excellent position to execute on our key upcoming milestones. I will now turn the call over to Suku to provide a more in-depth discussion of our TACEY-one hundred and two program.

Speaker 2

Suku?

Speaker 3

Thank you, Sean, and good morning, everyone. I'm pleased to provide an update on our TASIA-one hundred and two gene therapy program in clinical evaluation for Rett syndrome. We will start with our REVEAL Phase II adolescent and adult trial. As Sean mentioned, we've completed dosing in Cohort 1, which included 2 adult patients who received low dose of TASHA-one hundred and two. TASHA-one hundred and two demonstrated an encouraging safety profile with no serious adverse events related to TASHA-one hundred and two or dose limiting toxicities as of the week 52 assessment for the 1st patient and the week 36 assessment for the 2nd patient.

Speaker 3

Additionally, long term efficacy data showed a continued durable response with sustained and new improvement across multiple clinical domains and efficacy measures at week 52 following the completion of the steroid and sirolimus taper for the first patient and at week 25 following the completion of the steroid taper for the second patient. Both adult patients demonstrated partial restoration of function or improvement in areas of disease that were lost in early childhood, which is not typically observed in the natural history of Rett syndrome. While the disease 780 differed between the 2 adult patients, the improvements were demonstrated in consistent clinical domain as early as 4 weeks post treatment in both patients, which was sustained through longer term assessments. This included improvements in autonomic function, seizures, gross motor skills, fine motor skills, and hand function and communication and socialization, which can translate to beneficial impacts on quality of life and daily activities for patients and caregivers. We look forward to continuing to evaluate the patients over time for potential further improvement.

Speaker 3

These improvements are supported by clinical observations reported by the principal investigator, video evidence and multiple clinical and caregiver reported efficacy measures. The well tolerated safety profile and durable response in both adult patients with the most advanced stage of disease is encouraging and supports the transformative potential of TACE-one hundred and two across multiple genotypes of patients with Stage 4 Rett Syndrome. Now let's turn to our ongoing REVEAL Phase onetwo pediatric trial evaluating the safety and preliminary efficacy of TASHA-one hundred and two in females 5 to 8 years of age with Stage 3 Rett Syndrome. While this trial captures an earlier stage of disease, it is important to understand that most of these patients require lifelong caregiver dependence and they're present with hallmark symptoms and many advanced manifestation. Enrollment criteria require patients to be post regression and have entered a stage of stabilization, meaning there have not been any identified loss of skills as in the last 6 months prior to treatment.

Speaker 3

HORT1, evaluating the low dose of TASHA-one hundred and two to complete TASHA-one hundred and two demonstrated an encouraging safety profile with no serious adverse events related to TASHA-one hundred and two or dose limiting toxicities as of the week 22 assessment for the 1st pediatric patient and week 11 assessment for the 2nd pediatric patient. Similar to the adult patients, the pediatric patients possess different disease severity and genetic backgrounds. Importantly, both pediatric patients demonstrated initial improvements across the same clinical domains we observed in the adult patients with early evidence of developmental gains following treatment at weeks 12 and 8 respectively. This included improvements in autonomic functions, seizures, gross motor skills, fine motor skills and hand function and communication and socialization, which can translate to beneficial impacts on quality of life and daily activities for patients and caregivers. We look forward to continue to evaluate the patients over time for potential further improvement.

Speaker 3

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

Speaker 3

Cameron?

Speaker 4

Thank you, Suku. Research and development expenses were $15,100,000 for the 3 months ended June 30, 2024, compared to $19,800,000 for the 3 months ending June 30, 2023. The $4,700,000 decrease was primarily due to a milestone fee payable to Abeona Therapeutics during the 3 months ended June 30, 2023 following the dosing of the first patient in the REVEAL Phase III adolescent and adult trial. General and administrative expenses were $7,300,000 for the 3 months ended June 30, 2024 compared to $6,000,000 for the 3 months ended June 30, 2023. The increase of $1,300,000 was primarily due to $900,000 of higher non cash stock based compensation expenses and $400,000 of higher consulting, professional fees and other expenses.

Speaker 4

Net loss for the 3 months ended June 30, 2024 was $20,900,000 or $0.09 per share compared to a net loss of $24,600,000 or 0 point for the 3 months ended June 30, 2023. As of June 30, 2024, Tayshia had $172,700,000 in cash and cash equivalents. The company expects that its current cash resources will support planned operating expenses and capital requirements into the Q4 of 2026. I will now turn the call back over to Sean for his closing remarks. Sean?

Speaker 2

Thank you, Cameron. Overall, we are encouraged by the well tolerated safety profile in patients who receive the low dose of TASIA-one hundred and two and the clinical effect being demonstrated across consistent clinical domains in the pediatric and adult patients with Stage 3 and 4 disease treated with the low dose of TASIA-one hundred and two. We believe these cohort 1 data validate our novel construct and support the potential of TASIA-one hundred and two to address the significant unmet medical need in Rett syndrome for a broad range of ages and stages of patients. We are pleased the high dose of TASION-one hundred and two was generally well tolerated as of the initial 6 week assessment in the first patient treated in Cohort 2 of the adolescent and adult trial. IDMC approval to proceed with dosing the 2nd adolescent adult and the 1st pediatric patient earlier than planned in the high dose cohort of our REVEAL trials enables us to build on the promising preliminary low dose data that demonstrated relevant clinical effect across key clinical domains impacting activities of daily living in the adult and pediatric patients treated with TASIA-one hundred and two.

Speaker 2

As we move to the high dose, we continue to look for a similar pattern of consistent improvement across adult, adolescent and pediatric patient populations. Looking ahead, we remain focused on clinical trial execution and data collection. The totality of the data we collect from the low and high dose in Part A will inform further our discussions with regulatory authorities on our development plan for the next phase of the trials. We look forward to reporting safety and efficacy data from the low dose and high dose cohorts in both adolescent and adult trials and the pediatric trial in the first half of twenty twenty five. With that, I will now ask the operator to begin our Q and A session.

Speaker 2

Operator? Thank

Operator

Our first question comes from the line of Kristin Kluska with Cantor Fitzgerald. Please proceed with your question. Hi, good morning everyone. Thanks for taking my questions. So when you report the high dose data next year, what in your opinion is going to be the best way to determine if there is a dose response?

Operator

We already did see some profound changes from the low dose and the definition of improvement really differs from patient to patient given the heterogeneity in different domains impacted sometimes. But is there a clear way that you're looking to try to measure this?

Speaker 2

Thanks, Kristen. I'll take that initially and Suku feel free to jump in on this. But I would say, 1st of all, when you take a look at the preclinical data at the high dose, there was an increase in survival, there was an an improvement in gait abnormalities, which is kind of a surrogate for overall health. And obviously, when you go into the high dose, you're going to be pushing more volume, should have greater biodistribution, greater transduction. And we would expect 1st and foremost that we see consistent effect across all the clinical domains that we've talked about.

Speaker 2

I think at this point, the low dose is established frankly, it's established a high hurdle bar. I think we're in a good place with the high dose and we expect that this would effectively build on that. I would say based on the preclinical data and the translation that always difficult translation of it, exactly what's that going to what's that going to look like in adult, it's difficult to predict both, I would say, the overall magnitude and the temporal aspect of things. So we expect that there should be an observed improvement. And the question is really do we see it early on or does it take more time to manifest?

Speaker 2

Ultimately, we're going to have to run the experiment to really fully answer your questions. Again, I would say that from a comparative perspective, we're utilizing the same endpoints, the same clinical observation mechanisms, the same ways to capture the data. So we're trying to keep all that as consistent as possible. And once we have enough data in patients over a longer course of time, we feel confident we'll be able to make the determination of if there is a drug effect. But with that, I'll turn things over to Suku Des to see if there's anything else he would add.

Speaker 3

Yes. Thanks, Kristen and Sean. You've raised a very interesting question. Usually in drug development, right, you do look for the highest dose that gives you the greatest efficacy and safety and that seems to apply for gene therapy. And in Rett syndrome, I guess the question is, there is a drug on the market, it's a small molecule, but still significant unmet medical need.

Speaker 3

And as you point out, Kristen, with such a heterogeneous disease, a low dose is actually showing consistent response that I think that parents and patients will appreciate. But at the same time though, if you look at some of our preclinical data, you look at some of the work, Adrian Bird and others have done, there is justification to go to the high dose and see if the higher dose will also give us a consistent and further better response than the lower dose. And I'll leave it open ended like that because it's only the data that will eventually drive us to eventually the endpoints, the ideal dose that we're going to get approved by the regulator and a dose that will truly make a difference in this very complex disease and patient population.

Operator

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

Speaker 5

Hey, good morning and thank you for taking our question. This is Elizabeth on for Salveen. Wondering on

Speaker 1

the regulatory front, if you could comment on how the dialogue

Speaker 5

is going with the regulatory authorities and if there's any additional color you can share about the nature of those conversations to date? Thank you.

Speaker 2

Thanks, Elizabeth. What I would say on the regulatory front is that we do have an upcoming Type B meeting as a result of the RMAT designation. So I would say there would be subsequent updates on that in the future. Our goal at this meeting, there are several goals, but I would say one of them is basically aligned around the cadence of how we're going to interface with the agency, focus on some of the priorities that we're going to want to continue, the dialogue that we've had historically. So that would be the data that we have as it comes in.

Speaker 2

We want to make sure that they're seeing the data in an appropriate batching, but they're seeing it as real time as possible. And that plus the additional work that we're doing on natural history, it will be information that we share with them that ultimately will inform more thinking on both sides and our alignment around trial design and endpoints for Part B. So the next step in that journey is actually coming up in the relatively near future and we will certainly provide updates on that in the coming quarter. Thank you.

Speaker 5

Thank you.

Operator

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

Speaker 6

Hey, thank you. Just a question on what you're going to present, I guess, in the first half of next year in terms of time on therapy. Just looking back at the last update, I think the low dose pediatric update, you had some variability. I think one patient was 12 weeks post dose, another one was 8 weeks. Are you looking to standardize that follow-up?

Speaker 6

And what is that time point, if you can tell us? Thanks.

Speaker 2

Yes, Chris. I would say this, the number 1, I think the fact that even at those early time points, we were seeing signs of preliminary efficacy is super encouraging to us. And we felt the right thing to do to really provide more line of sight and clarity is generate more data over the course of time so that we can give you guys a more fulsome update. So I think the easiest way to answer that sitting here today would be that we would like so the way things are right now for the high dose, right, we would have 3 patients in each cohort, right, so the pediatric cohort and the adolescent adult cohort. And that for the majority of those patients, there's a minimum of 6 months would be the way that I would think of it.

Speaker 2

I think that would be the minimum data set that we would plan to go out with. And I think that hopefully would give everyone better line of sight, more consistency, etcetera. So that's how we're thinking of it right now. We can certainly work to refine our You bet. And You bet.

Operator

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

Speaker 6

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

Speaker 2

Thanks. Phil, great question. I would say a couple of things and certainly turn it over to Suku for his thinking. It's an evolving situation is probably the best way to say it. I think when you do have a disease that's heterogeneous, you are always trying to think of a way that how do you best standardize what you're capturing.

Speaker 2

So, while I really do believe that the point you're making is something that we can just tell you, we are taking into our calculus and I can see a world where if you're able to restore or partially restore a loss function like we've seen in the low dose data, right? I mean, if we've seen an adult who was there was no expectation of having an effect sit unassisted after not being able to do that for 10 years. We clearly saw on those video, at least in our opinion, that there was much greater communication and socialization in that same patient. Or as you point out, reduction in seizures, the ability to grasp in the pediatric patients, the improvements in the breathing. Those clinical effects are there.

Speaker 2

I think what we're working to refine is there may be a situation where a primary or co primary endpoint is more standardized. You might focus more on really consistently measuring improvements, let's say, in fine motor function, looking at the hands or gross motor function. But I do think also capturing the data on the, what I call the restoration of function or regaining of a milestone, I think that would be at a minimum very supportive data that I think would be highly impactful to the agency, to payers, etcetera. So we've been pretty consistent, I would say, in how we're trying to think about ultimate endpoint selection. And when I step through right now is just a high level view of like strategically how we're thinking of it.

Speaker 2

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

Speaker 3

Yes. What I would add, Sean, is that, as we all know, it's a complex heterogeneous disease. But we've shown so far over a timeframe in the patients treated with the low dose in the pediatric study and the adult study, there are consistent positive clinical impact of our gene therapy. So, but then the question that I think Gil brought up is a really important one because as we get our natural history data from our databases back and there are certain clinical features that actually could be good comparisons for us regardless of clinical trial design when we have our Part B meeting. Those variability is within a clinical feature that our gene therapy is consistently helping to treat is I think also going to be important because in our studies so far we've shown that these patients have seizures, right, 80% to 90% of patients I think have seizures, but there is a range of seizures.

Speaker 3

I mean some patients may have 3 seizures a day, others may have 1 seizure a quarter. So the question becomes, how do you assess the clinical impact of a seizure based on frequency and medication dose versus let's say, hand function, which is consistently lost to the extreme. So I think these are things that we have to continue to gather data on and hopefully our clinical trial design for the Part B component will allow us to assess them hopefully over a shorter period of time to show that we can actually have a positive clinical impact for this patient population. So I guess what I'm really saying Sean is we are gathering the data and hopefully we can put it all together for a very complex disease where I think we have a pretty good gene

Speaker 2

therapy. Thank

Operator

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

Speaker 7

Hey, thanks for taking our question. So can you help us understand your 180 degree on the data disclosure strategy? You know, efficacy from your first patient, the patient with the best efficacy so far was shared at week 6. Yet the data from the 2nd the high dose cohorts passed the 6 week mark, but you're reserving that for later. Any sort of anything you can share on that could seem to be helpful there?

Speaker 7

And also help us understand what you mean by fulsome, like how many patients worth of data you think is sufficient to get a clear picture? And how much data would you have by 1Q that passes that definition of full film data? Thank you so much.

Speaker 2

So June, just to be clear, you're talking about the fact that the very first patient we reported on was at 6 weeks and now we're saying we're going to longer term data set. So just want to make sure

Speaker 3

that's

Speaker 2

what you're

Speaker 7

Yes, yes. My understanding is that the first patient that person that patient's efficacy was shared around that 6 week mark. And just curious, I understand that need to hold off until you have some fulsome data, but and your change in data strategy, data disclosure strategy, but anything can share on the high dose cohort?

Speaker 2

Yes, sure. I would say a couple of things. First of all, one major change is the status and the fortune of the company in terms of balance sheet, right? I mean, when we reported the first patient out, to be totally frank, I think you all know this, the company was in an existential situation. And we were fortunate, frankly, that the first patient responded as quickly and as pronounced as they did.

Speaker 2

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

Speaker 2

Many of you supported us with that data because it was so transformational for that patient. And so I personally felt an obligation to for a period of time show data earlier than I normally would have. Fortunately, from my perspective, the data that we've continued to share has shown early just like that first patient, onset of action and consistent effects. I mean even in the data that we just showed at IRSF and the pediatric patients at 8 weeks 12 weeks, I'll put that data up against anything that the people have probably seen, right? I mean, where have you seen video of people getting restoration of function?

Speaker 2

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

Speaker 2

We got the okay from the IDMC to step to the high dose. And so now we have an opportunity to present more data over time. And I think people looking at something, I would say for us a minimum threshold would be if we have 3 patients in the high dose cohort in the pediatric patient and we would have 3 dose we would have 3 patients in the pediatric population, that at least the majority of those patients are over months of time elapsed. In our view, we felt that that's a fulsome update, right? I mean, that's you're starting to see if you're getting consistency, durability, etcetera.

Speaker 2

And we think that is a better way for everybody to be able to evaluate what we're seeing as we step into the high dose. So we felt it was a clean break going from the low dose to the high dose. We felt it was an evolution how we've been reporting. And that's why we think ultimately this is the best thing for all involved to see the data in a more cohort batch basis. So hopefully that gets to what you're asking, Jim.

Speaker 7

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

Speaker 2

Of course. Thank you.

Operator

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

Speaker 8

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

Speaker 2

Yes. Maury, great question. I mean, the way we're thinking about it is that for us to sit down with the FDA and have a fulsome discussion around what Part B design looks like. I would say number 1, we want to complete Cohort 2 dosing, right. So we want to have that data.

Speaker 2

We want to complete our natural history analysis. And those are I would say those are key data points that we need. Now, how much data do you need? I would say it's early to say. Is it 3 months of data, 6 months of data?

Speaker 2

I think that's why we're guiding to more in our own mind, can we sit down with the FDA in the first half? That's what we'd intend to do. But in terms of precisely what's the right level of data to bring them, I'd say it's a little bit early on that. And really what's going to help facilitate getting better line of sight to that is going to be leveraging the RMAT process. So as I said, that starts this quarter with our clinical Type B meeting that we have.

Speaker 2

And we'll actually be talking about things more broadly than just clinical. But the point is, we will inform them with information as we have it. So as I said earlier, as we have the natural history data completed, we'll share that with the FDA and what we think that does to our clinical development plans and potential endpoints As we generate data from the high dose and longer term data from the low dose, we'll certainly share that with the FDA in a more real time basis leveraging the RMAT designation. So all that is leading and culminating to hopefully more detailed formals discussion in the first half. But again, I just want to caveat that exactly how much data we need and exactly when that happens.

Speaker 2

I exactly how much data we need and exactly when that happens. I think it's a little early to tell, but we should have more line of sight in the next quarter or so. Hopefully that gives you a little perspective.

Speaker 8

Yes. Very helpful. Thank you.

Speaker 2

Thanks.

Operator

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

Speaker 9

Great. Thanks for taking our questions. So based on what you just articulated about the maturity of the data, It feels like it's more the first half twenty twenty five guidance is probably going to be more second quarter than Q1. Is that the right takeaway? And also, given that you have dosed just one of the 6 patients today, one of the 6 across the 2 high dose cohorts today.

Speaker 9

Do you think you could have timely enrollment and dosing to ensure the data could be available in first half twenty twenty five? And if you can comment on the safety waiting period, is that 42 day period true for across all 6 patients in those 2 cohorts?

Speaker 5

Thanks.

Speaker 2

Sure thing, Anand. So again, we're guiding to the first half to give ourselves flexibility. Your point on the stagger is a good one. And I would say this, I mean, per the protocol, at this time, the stagger is 42 days between patients. I would just simply say at this point in time that we have this topic very much in mind.

Speaker 2

And I would say the guidance that we've come up with, we feel very comfortable with. And so it is possible that you could see some changes down the road to the frequency in which we might be able to dose patients. But that is a future looking comment. So again, first half is the way we're thinking about it right now and we're confident in stating that given everything we know today.

Speaker 9

Got it. Thank you.

Speaker 2

Thank you.

Operator

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

Speaker 8

All right. Thanks for taking the questions and congratulations on the progress. My first one was on the high dose patients that have been enrolled in the study today. It seems like there are about 3 patients that have been enrolled. In low dose cohorts, we noticed a difference in the severity of patients depending on their deletions.

Speaker 8

I was wondering

Speaker 6

if you could comment as

Speaker 8

it relates to the baseline characteristics of these high dose patients to some extent? And then my second question is around the low dose data we expect in the first half

Speaker 7

of next year. I just want to

Speaker 8

hear the team's thoughts on any comments around the how we think that data set should evolve over time. I think there had previously been some talk of, I guess, restoring MECP2 and regaining of skills over time and kind of a teaching bias over time. But I'd love to hear any thoughts you have around the long term low dose data as well.

Speaker 2

Sure. Yes, Sukhub, I would ask you to take those two questions. I think the first was, are there any baseline characteristics that we can talk about in the high dose patients that have been enrolled? We probably have to just stick to what CGISs are. I think that's all we've guided to, but you can talk about that.

Speaker 2

And then the second one is just expectations potentially on progress of low dose patients over time.

Speaker 3

Yes. So Sean, I mean to answer the first question, so if you think about consistency though, yes, the CGIS, right? I mean these patients for protocol depending on which study they are, they tend to fall into a range of 4 to 6. And as we all know, in Rett syndrome, the severity may sometimes drive the response and there could be limitations to that as well. But what is more important is that there are clinical features though in the low dose patients, which I think are consistent.

Speaker 3

So autonomic dysfunction, I mean, for example, many of these patients have vascular abnormalities of the upper and lower extremities. Many of these patients did have respiratory abnormalities, the apnea spells and the hyperventilation. Seizures were pretty common. Loss of hand function, as you know, is very common in the sense, lots of fine hand, motor function and gross motor function and the repetitive movements, etcetera. I guess my point is there are certain clinical features that will always be there.

Speaker 3

And I think when you talk to the experts, they do confirm this. But what we are doing is we have naturalistic databases that we're looking at, which hopefully will also further support what we need to do for the future if this consistency is proven. So all I can say is that you have to stay tuned. And having said that, then if you look at the high dose patients, I would anticipate you would see very similar commonalities in the clinical presentations that exist in Rett syndrome patients, the hand function, I guess you could say social withdrawal, maybe seizures, etcetera, etcetera. So this will all be there.

Speaker 3

And then the other piece of the puzzle is, when you have whatever the mutation is, Mison's mutation, a nonsense mutation or a massive deletion, which then results in a horrible or severe clinical presentation. Then the question becomes, any gene therapy due to the most is another disease, what is the greatest impact it will have and on which clinical features. So these are things that you're still collecting. And I would say that again, I would assume in gene therapy, if you have a product that has significant clinical impact, the commonalities of the features, we will only see be seen in a few patients, right, because you're dosing 5, 6, 7 patients to move into part from Part A into Part B and then Part B into other studies, if that's what needs to be done. John, I mean, I don't know whether that helps answer the question, but the answer to the question for me is not it's complex.

Speaker 3

And then the second question was, I lost my trend there, Sean. Can the person ask Well, I think

Speaker 2

you answered the question on the baseline characteristics, right? I mean, it is going to be CGIS between 46. That's really all the detail that we've provided thus far. There are going to be genetic differences in all these patients. And in terms of low dose expectations, I think just at a high level to build on what you're saying is that over the course of time, at least the older initial patients that we reported on, over time, she did gain improvements, further improvements in different aspects, whether it's getting stronger from a gross motor perspective, improvement in hand function over the course of time, improvements in ability to communicate.

Speaker 2

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

Speaker 8

Yes, definitely. Thanks so much for the color.

Speaker 2

Thank you.

Operator

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

Speaker 8

Hey, good morning and thanks for taking my question. Haven't been or haven't heard before? And then on the safety committee, obviously, they accelerated your ability to dose into a higher dose. Could they at what point could they accelerate or get rid of the stagger, the 45 day waiting period between patients? Thank you so much.

Speaker 2

Suku, maybe you can take the first one out. The second one relative to the stagger is really, I think it's a discussion between the company and the IDMC to talk about when they're comfortable making that type of a recommendation. So we have a view in our mind about what would be a sufficient and appropriate amount of data to potentially have that type of discussion. And it's of course, on having continued good safety results. So hopefully more to come on that in the future.

Speaker 2

And Suku, relative to the SAE that was not treatment related, I don't know if there's more to add. I think the disclosure was pretty clear and there's we haven't reported anything more I think because there had been a declared resolution of that from the PI. But just to make sure I'm

Speaker 3

correct on

Speaker 2

that, please.

Speaker 3

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

Speaker 3

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

Speaker 2

Yes. So there's been no additional disclosure on the SAE. It resolved and obviously we've moved ahead as Suku said from a dosing perspective. Is that good for you Sylvan?

Speaker 8

Perfect. Thank you.

Speaker 2

Thank you.

Operator

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

Speaker 2

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

Operator

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

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Earnings Conference Call
Taysha Gene Therapies Q2 2024
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