Taysha Gene Therapies Q1 2023 Earnings Call Transcript

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Provided by Quartr
May 11, 2023

There are 10 speakers on the call.

Operator

You for standing by. This is the conference operator. Welcome to the Tayshia Gene Therapies First Quarter 2023 Earnings Conference Call. As a reminder, all participants are in listen only mode and the conference is being recorded. After the presentation, there will be an opportunity to ask I would now like to turn the conference over to Haley Collins, Director, Head of Corporate Communications.

Operator

Please go ahead.

Speaker 1

Thank you. Good afternoon, and welcome to Tayshia's Q1 2023 financial results and corporate update conference call. Earlier today, Tayshia issued a press release announcing financial results for the Q1 2023. 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 Suppumar Mandandran, President and Head of Research and Development Chairman Alam, Chief Financial Officer and Salman Bai, Assistant Professor of Neurology at UT Southwestern.

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 existing clinical data for TASIA-one hundred and twenty, the therapeutic and commercial potential of TASIA-one hundred and twenty and TASIA-one hundred and two. These statements may include expected timing and results of clinical trials for our product candidates and other clinical and regulatory plans and the market opportunity for those programs. This call may also 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 for our discoveries, limitations imposed by patents owned or controlled by third parties and the requirements of substantial funding to conduct our research and development activities. For a list and description of these risks and uncertainties that we face, Please see the reports we have filed with the Securities and Exchange Commission, including our annual report on Form 10 ks for the year ended December 31, 2022. The conference call contains time sensitive information that is accurate only as of the date of this live broadcast, May 11, 2023. Tayshia undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances after the date of this conference 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 2023 Q1 financial results and corporate update conference call. Today, I will begin with a brief corporate update. Then Doctor. Sukun Nagandran, President and Head of R and D of Tayshia, We'll provide an update on our clinical development programs along with our collaborator, Doctor. Sawman Bai, Assistant Professor of Neurology At UT Southwestern, Cameron Allam, our Chief Financial Officer, will then follow-up with a financial update before I provide closing remarks and open the call up for questions.

Speaker 2

We've made significant progress across 2 lead programs in Rett syndrome and giant axonal neuropathy this year and remain on track to deliver on multiple key milestones, including the generation of 1st in human clinical data for TASIA-one hundred and two in adult patients with Rett syndrome, The submission of a CTA to the MHRA to initiate expansion of TASIA-one hundred and two in pediatric patients, The submission of an IND application to the FDA for TASIA-one hundred and two and obtaining further clarity from the FDA on the regulatory path forward for TASIA-one hundred and twenty in GaN. Screening is completed and the dosing of our first potential patient with TASIA-one hundred and two In the Phase IIIREVEAL trial in adult Rett syndrome is scheduled for the Q2 of this year. For our GaN program, the new comprehensive analyses of the totality of the data for TASIA-one hundred and twenty continues to be encouraging and includes compelling findings that offer potential to further support our regulatory path forward. I want to highlight that much of the data presentation planned for the FDA will be new to the agency, and we will work to contextualize the data in a manner that clearly elucidates the potential for meaningful benefit to patients.

Speaker 2

We plan to submit the meeting request this quarter and expect the formal meeting to occur in the Q3 of this year. In the near term, we look forward to hosting an R and D Day in June, where we will provide an overview of the GaN disease state and share these new clinical data analyses. Additionally, we plan to provide an update on our RET program. Suku and Solomon will discuss this in more detail shortly. At the upcoming ASGTC conference, new preclinical data supporting TASIA-one hundred and two and the MI rare technology in Rett syndrome will be presented as part of a poster presentation.

Speaker 2

We remain focused on achieving the anticipated near term milestones for our Rett syndrome and I will now turn the call over to Suku to provide a more in-depth discussion of our clinical programs in Rett syndrome and GaN. Suku?

Speaker 3

Thank you, Sean, and good afternoon, everyone. First, I will start with an update on TASIA-one hundred and two, Our gene therapy program in development for the treatment of Rett syndrome. As a reminder, TAYSHA-one hundred and two utilizes An innovative miRNA responsive autoregulatory element or miRear platform to regulate the cellular expression of MECP2. At the upcoming ASGCT conference, we are excited to present new preclinical data that we believe supports the potential for TAYSHA-one hundred and two and the MRI technology as part of a poster presentation on May 19. For our Phase IIIREVEAL study In adult patients with Rett syndrome, we have completed screening and scheduled the dosing for the 1st potential patient.

Speaker 3

We expect the dosing to take place in the Q2 of 2023. We plan to report initial available clinical data, We shall be primarily on safety in the Q2 of the year at our upcoming R and D Day. In the second half of the year, We plan to continue dosing adult patients with Rett syndrome in our REVEAL trial and provide quarterly updates on available clinical data thereafter. We received feedback from Health Canada on our protocol amendment to expand enrollment eligibility to subject 15 years or older in the REVEAL trial, which suggests that Health Canada supports the expansion following initial efficacy and safety data from adult patients. We plan to submit a CTA to the UK MHRA for TAYSHA-one hundred and two in mid-twenty 23 to enable the initiation of a pediatric Rett syndrome study.

Speaker 3

We also have an IND application submission to the U. S. FDA plan in the second half of the year to further expand our clinical study footprint with TESHA-one hundred and two. Now let's turn to TESHA-one hundred and twenty for the treatment of GaN, An ultrarare neurodegenerative indication with no approved treatments or established regulatory pathway. As Sean mentioned, we are currently completing a comprehensive review of data from the ongoing natural history and interventional trial that includes functional, biological and electrophysiological assessments.

Speaker 3

We plan to seek a formal meeting with the FDA to discuss the new analysis that FDA has not seen and regulatory path forward for TAYSHA-one hundred and twenty. As a reminder, early analysis based on MFM32, the primary efficacy scale discussed At the FDA Type B end of Phase 2 meeting, demonstrated clinically meaningful slowing of disease, progression in patients with GaN following treatment with TAYSHA-one hundred and twenty Across the therapeutic dose cohorts. Importantly, long term analysis points to sustained durability and the ability of TASIA-one hundred and twenty to prevent nerve degeneration, generate nerve fibers and preserve visual acuity, which are significant findings for patients affected by neurodegeneration. Importantly, over 6 point years of long term clinical safety data It supports a well tolerated safety profile with no major drug related events. The FDA stated that MFM32 Can be a relevant primary endpoint in the setting of a randomized double blind controlled trial and acknowledge Tayshia's challenge in executing and enrolling such a study design due to the ultra rare nature of GaN.

Speaker 3

As such, the FDA indicated that it is open to regulatory flexibility in a controlled trial setting and is willing to consider alternative study designs utilizing objective measurements to demonstrate a relatively large An interventional trial, which will inform our plans for future interactions with the FDA, continues to be encouraging and includes compelling new findings with potential to further support our regulatory path forward. I will now turn the call over to our collaborator, Doctor. Salman Bai from UT Southwestern, We will provide a high level overview of some of our initial analysis of the data for TASIA-one hundred and twenty in GaN and the clinical relevance to the disease state. Salman?

Speaker 4

Thank you, Suku, and hello, everyone. My name is Doctor. Salman Pai, and I'm an Assistant Professor of Neurology at UT Southwestern. I earned my medical degree and completed my neurology clinical training at Harvard Medical School with sub specialization in neuromuscular disorders. As a practicing neuromuscular neurologist, I'm keenly aware of the devastation that GaN causes, not only to patients, but also to their families.

Speaker 4

I've been working closely with Tayshia on the development of the Tayshia 120 program for over a year and a half and then energized by the opportunity to help bring a potentially Transformational treatment to the GaN community. I've been heavily involved in the ongoing comprehensive analysis of the totality of data I've been working collaboratively with the team to identify new data findings. Based on the GaN clinical phenotype and pathophysiology, We are building a clinical narrative around the data to support our regulatory path forward for TASION-one hundred and twenty. I'm pleased to provide an update on the compelling findings from our ongoing data analysis. One goal of evaluating the totality of the data for TASIA-one hundred and twenty Just to determine whether we can identify potential objective measurements that demonstrate a clinically meaningful treatment effect.

Speaker 4

For context, I think it's important to understand that GaN clinically manifests with marked in coordination ataxia Due to both severe central and peripheral nervous system degeneration, we leached a significant disability and early mortality caused by respiratory failure. Database of GaN to date through the NIH. As a result of our analysis of these data, we have a clear understanding of how to measure meaningful Treatment effect for these patients. I'm a neurologist, so of course, let's start with the neuroanatomy. We know there's Central and peripheral nervous system degeneration with GaN.

Speaker 4

Specifically, this involves the cerebellum, long tracks and sensory motor nerves. Clinically, these anatomical localizations translate to severe incoordination, which is ataxia and weakness. Patients struggle with simple tasks like picking up objects and feeding themselves. How can we measure this? The integration of the We believe we have a comprehensive scale that we prospectively collected in the natural history and interventional patients, The modified Friedreich Ataxia Rating Scale or mFARS, which was recently used as the primary outcome measure for drug approval for Friedreich's ataxia.

Speaker 4

This scale is based on functional and objective measures within the neurologic exam focusing on ataxia, a key driver of disability in GaN patients. As a whole, we can prospectively measure the integration of the central and peripheral nervous systems using mFARS. We can then capture several objective peripheral nervous system data points, including nerve conduction studies, myometry and nerve pathology. We have scientific evidence of TASIA-one hundred and twenty leading to peripheral nerve regeneration in some patients, meaning nerves are growing back. Nerve conduction studies indicate sensory nerves recover responses that were absent prior to treatment, a key finding that was truly unexpected and to my knowledge has never been demonstrated previously in GaN patients.

Speaker 4

We also see an increase in regenerative clusters on nerve biopsy. This is direct electrophysiologic and biological evidence of nerve regeneration in a neurodegenerative disease. The peripheral nervous system data is key because recovery of sensory nerves directly impacts patients' performance on mFARS, providing links between objective biologic data and a clinical rating scale. Importantly, by is predictable, monotonic and homogeneous across patients. Thus, we can use this model to determine treatment effect.

Speaker 4

Preliminary determinations of treatment effect size relative to the disease progression model as measured by AMPARS and with multiple peripheral nervous system endpoints Show disease slowing. Let me repeat, we have direct central nervous system and peripheral nervous system outcome measures and clinical and biological objective data that show positive disease modification with TAYSHA-one hundred and twenty in an ultra rare fatal neurodegenerative disorder that has no approved treatment. The restoration of sensory nerve responses If treated at an earlier stage of disease with TASIA-one hundred and twenty. I believe these data have the potential to provide objective measurements that demonstrate We are truly, truly inspired by these patients and their caregivers. We are hopeful that we can bring a potentially transformational treatment to the GaN community and we look forward to working collaboratively with the FDA through our anticipated future discussions.

Speaker 4

With that, I'll now turn the call back to Suku.

Speaker 3

Thank you, Salman. As you can see, we have compelling findings that we expect to submit as a part of our formal meeting request to the FDA in the Q2 of this year. These data will inform our discussions with the FDA regarding alternative study designs, additional objective measures and ultimately a regulatory path forward. We anticipate a formal meeting to occur in the Q3 of 2023. Importantly, administration of TASIA-one hundred and twenty Also shows a translational correlation between preclinical and clinical studies.

Speaker 3

With TASIA-one hundred and twenty, GaN knockout mice show improved dorsal root ganglion pathology and motor function, both of which translate to our human studies with improved sensory nerve integrity and Sensory Nerve Action Potentials, better known as SNAP, as detected by nerve conduction studies and biopsy analysis and improvement of stabilization in strength. We saw similar clinical translational impact with spinal muscular atrophy and the SMN Delta-seven mouse model, which we developed Zolgensma at AveXis, which showed improvement of stabilization in motor function and strength after treatment with gene therapy that were congruously seen in human studies as well. In June, we are excited to host a virtual R and D Day, where we will detail these new analyses and review therapeutic potential in the context of the GaN disease state as well as provide an update on our Rett syndrome program, including new preclinical data for TAYSHA-one hundred and two In Rett syndrome being presented at the upcoming ASGCT Annual Meeting and available clinical data from Phase IIIREVEAL trial in adults. Lastly, with respect to manufacturing, we have completed the CMC Module 3 amendment submission detailing our commercial process, product And drug comparability analysis and are awaiting feedback from the FDA.

Speaker 3

We continue to believe in the transformative potential of TASIA-one hundred and twenty and look forward to having a collaborative dialogue with the FDA regarding the potential registrational path to bring TESHA-one hundred and twenty two patients with GaN, who to reiterate have no approved treatments. I will now turn the Call over to Cameron to discuss financials. Cameron? Thank you, Jisoo.

Speaker 5

Research and development expenses were $12,500,000 for the 3 months ended March 31, 2023 compared to $38,200,000 for the 3 months ended March 31, 2022. The $25,700,000 decrease was due to reduced research and development compensation as a result of lower headcount of $10,700,000 The decrease was also due to reduced manufacturing and other raw material purchases of $7,100,000 We also incurred $6,400,000 General and administrative expenses were $8,800,000 for the 3 months ended March 31, 2020 $2,700,000 was due to reduced general and administrative compensation as a result of lower headcount and reduced consulting and professional fees. Net loss for the 3 months ended March 31, 2023 was $17,600,000 or $0.28 per share as The net loss for the 3 months ended March 31, 2023 was partially offset by revenue of $4,700,000 recognized related to As of March 31, 2023, Tayshia had $63,400,000 in cash and cash equivalents. Asia continues to expect that its current cash resources will support planned operating expenses and capital requirements into the Q1 of 2024. I will now turn the call back over to Sean for his closing remarks.

Speaker 5

Sean?

Speaker 2

Thank you, Cameron. We believe that the clinical and the therapeutic potential for our innovative programs to address severe unmet needs in monogenic central nervous system disease. In the year ahead, we are focused on executing across our near term milestones in our Rett syndrome and GaN programs. In the Q2 of this year, we look forward to dosing the 1st potential adult patient with Rett syndrome and reporting initial clinical safety data for TASIA-one hundred and two. We are excited to host an R and D Day in June to review the analysis of the totality of the data for TASIA-one hundred and twenty that will inform our regulatory path forward for TASION-one hundred and twenty as well as provide an update on our Rett syndrome program.

Speaker 2

We look forward to providing further updates on our programs throughout the year. With that, I will now ask the operator to begin Q and A. Operator?

Operator

Thank you. We will now begin the question and answer session. The first question comes from Yianan Zhu with Wells Fargo Securities. Please go ahead.

Speaker 6

Hi. Thanks for taking our question. This is Kwan on for Yanan And congrats on the progress. So first, the GAN program. So I wonder thanks for the color on the new analysis.

Speaker 6

I wonder if the patient's data would be compared to their own control like pretreatment progression or be compared to the natural history. And I wonder if there is a bar a clear bar on what levels of change on those readout

Speaker 2

Thank you for the question. I would ask Suku to take that first And feel free to add in, Salman.

Speaker 3

Yes. So I will answer the question based on how I understood it. And if I do not please clarify your question. So the analysis that is still ongoing, we do plan to compare Each patient to their own pretreatment status as well based on the natural history that has been collected by the NIH. But we also have the option of looking at the broader data set in the National History database where there were 52 patients with a mix of All types of GaN, which include classic GaN and non classic GaN.

Speaker 3

And I would remind you that in these two types of GaN, the root cause of the disease is the same. Hence, the gene therapy and its findings, I think, will lead to hopefully a very productive discussion with the FDA if and when we get that meeting. I hope that answers the core of your question. Was there a second part of your question that I may have missed?

Speaker 6

Yes. Thank you For the color on that. The second part is, for those readout, is there a clear bar on what levels of change are clinical meaningful?

Speaker 4

Great question. It's important to understand clinically what's not only important for the patients, but also for the families. Right. A simple number on MFAR set changes doesn't necessarily mean it's important to the patient. And that's why we work closely with patients and have interview with families too to identify what's most important from them.

Speaker 4

As a clinician, it's important for me to understand that patients Enjoy independence. And we're looking at our data to correlate objective biologic data with functional clinical outcome measures to define how that link is there and what it means for patients. When we have that data in totality, we are seeing positive trends, but of course this is preliminary. We also use data from other diseases that have ataxia and peripheral nervous system disease to come up with correlates. As you know, this is an ultra rare disease.

Speaker 4

So to clearly identify clinical meaningfulness for this disease alone is difficult and perhaps impossible. However, if we correlate it to other diseases and other clinical syndromes related to this, we can come up with very good proxies that would give you a reasonable answer What patients think is important.

Speaker 6

Got it. Thank you so much.

Operator

The next question comes from Jack Allen with Baird. Please go ahead.

Speaker 7

Hi. This is Abby Gray on for Jack Allen. Thank you for taking our questions. Recently, we've seen the FDA leadership Make what appears to be a significant push to pursue the accelerated approval pathways for gene therapies, I guess, namely, Sarpeta's product in DMD. And we realized that you're still discussing the regulatory pathways for GaN, but we're hoping you could provide some color surrounding the correlations you're seeing for retinal vein thickness and neurobiopsy results.

Speaker 4

Excellent question. All right. When we take a look at functional clinical measures, of course, there's And issue with sometimes there's bias or effort dependence and that's where we turn to biology. And that's in the biology, that's where the question of accelerated approval can come in. So specifically, if we're looking at sensory nerve action potentials, for example, something that we're seeing recover that was not previously there, well, that feeds into the feedback Into your coordination for mfars and motor function as well, if you have deafferentation of your muscles, meaning you can't feel where your muscles are, Your strength will decrease.

Speaker 4

And so having these kinds of markers correlate to clinical measures is important. We take it a step further because Evaluate this data, we can also look for giant axons decreasing and that gets closer and closer to the biology. So we can then tie and correlate that biology from histology to clinical data to functional outcome measures and have a very clear trajectory of what's happening to the patient. Does that answer your question?

Speaker 3

Can I add a little bit also more information, which I think is relevant? As Doctor. Salman Bai walked you through, To step back and look at GaN, obviously, it's an ultra rare disease. There's no therapeutic option available. Obviously, you need an intervention where the benefit outweighs the risk.

Speaker 3

And in our assessment using the predefined efficacy endpoints for the protocol in the interventional study, looking at the model that we've generated, looking at the progression of the disease, Looking at post hoc analysis, what we are seeing collectively at this point in time is a trend when it comes to functional, physiological, Biological, electrophysiological and even potentially the radiologic impact of the intrathecal gene therapy that affects the broad spectrum Of the disease in the central nervous system and the peripheral nervous system in a clinically meaningful way. So hopefully, once we complete the analysis And we go to the FDA and receive that meeting, we can make our case for an appropriate regulatory path, which may hopefully result in approval sooner rather than later.

Speaker 1

Wonderful. Thank you so much.

Speaker 6

Thank you.

Operator

The next question comes from Kristen Kluska with Cantor Fitzgerald. Please go ahead.

Speaker 8

Hi, this is Rick on for Kristen. Thank you for taking our question. Just to ask about, maybe you could add a little bit more color on the preclinical Rett syndrome data guided for ASGCT this month. How can we kind of put this into context as it relates to other Data other preclinical data we've seen from the program and what should we be expecting there?

Speaker 3

No, that's a great question. So let me start by saying I'm very excited about the ASGCT data with the caveat that I can't speak about it in great detail because it's embargoed. So the date, I think, is in our press release, but it's on the Friday. Let's see, that's next Friday, which is the 19th, between 12 to 2 is when the information will be presented in front of the poster. So If someone is there, hopefully, you all will go review it.

Speaker 3

What is fascinating about gene therapy, and I've been in drug development for a very long time, But it's very rare, unusual where I see preclinical data translate directly into the clinic in the human. I saw this with the SMA program when I was CMO, Chief Medical Officer of Exys. I did comment that we are seeing this with GaN now where the preclinical data appears to translate into the human Based on the 14 patients we've dosed and what I would say is that the RET preclinical data that's being presented at ASGCT next week It's very interesting, but the details as you decipher them, I think will hopefully show that we have a very good construct with the Hopefully, it will be validated in this preclinical data set that will be presented next week. And to go beyond that, I'm also hoping that once we start dosing patients, Both adults and hopefully children that all this preclinical work that has been done in these different rodent models and other models will now translate almost 1 to 1 in the human Hopefully, create an SMA like situation in Zolgensma. So again, to tie this back together, I'm sincerely hoping that the preclinical data presented next week At Rett, which I think I hope you'll find impactful, will translate into the human and give us hope that we have something clinically meaningful in this gene therapy product.

Speaker 6

Thank

Operator

The next question comes from Joon Lee with Truist Securities. Please go ahead.

Speaker 9

Hi, good afternoon. This is Mehdi on for June. So Given the ultra rare situation for GaN, is it at all feasible to do Double blind placebo controlled trial or not? And also for Objective measures like Ampharas, is there the aim for getting A statistically significant change for this indication for this measure and if that again

Speaker 4

Excellent question. When we think about ultra rare diseases like this, first we come into a question of what's the practicality of doing an RCT in a blinded I think with this disease that's not possible. We simply don't have enough patients to power a study to find statistical significance And that's why we're using our data to look at patients' own control as well as natural history to serve as a control, right? With this disease, When we have natural history as a control, it serves as a powerful comparator arm. Now that we have several other patients within the natural history It's of course the neurologic exam, which I love.

Speaker 4

So that adds some objectivity to it and we're able to detect changes, especially when we use the disease progression model To show differences, the next step is to find clinical meaningfulness in that data and that's our hope with the biology, The histology, the electrophysiology to the clinical impact, right, it's quite widespread over the central and peripheral nervous system And we're able to detect those changes. Suku?

Speaker 3

Yes, Simon. And one more thing I have to emphasize is the Largest natural history database that exists in the world for GaN. That's point 1. Number 2 is the interventional data that we have is also the largest for a disease like GaN. The third thing that The night and we've discovered in the natural history study is that all these patients have ataxia and therefore makes them far as an appropriate clinical measure To see the efficacy of the product, right?

Speaker 9

Do you

Speaker 4

agree, Norman? Yes. The neuroanatomy fits perfectly what we're seeing in patients and 100% have ataxia. So why not measure that?

Speaker 2

And why not use biologic measures to show that correlation between biology to function? This is Sean. Maybe just to add one other point Is that the FDA asked for a double blind placebo controlled trial in the context of MFM being the primary Endpoint because they thought it was effort based. And when we asked them for clarification around that, they did come back and acknowledge that in this type of a disease state with an Orphan population, you could not feasibly conduct that study. But they also then went on to say and reinforce published guidance That a well controlled trial that has clinically meaningful endpoints that are objective would be considered.

Speaker 2

And hopefully, what you're getting a flavor For here and that Doctor. Bai is providing additional color on is that as we've interrogated the database and As Sukru said, it's the largest database in the world for GaN. We're seeing across multiple clinical domains that affect Both the CNS and the PNS, what we think is clinically meaningful impact on objective endpoints that are unequivocally Objective. And so that's why we're so confident or I should say encouraged by the data that we're generating thus far. And we look forward to Showing it in much more detail at the upcoming R and D Day.

Speaker 2

Can I add a point

Speaker 4

to that too? With the natural history data, What's crucial for this model, which we've shown is that it's homogeneous, it's predictable. And Based off those reasons, we can now use that model to compare to our intervention patients.

Speaker 9

Awesome. So if I may, like I reformulate the question and ask it different way. If Ampharas was the primary objective From the beginning, would that trial data so far make it convincing for FDA to have to approve the drug?

Speaker 4

Awesome question, Right. In hindsight, when we take a look at this data, right, it's clear. We look at the neuroanatomy, it's quite clear. But with an ultra rare disease like this, It's always a struggle, right? What's the initial hypothesis and what are we getting?

Speaker 4

So if we were to go back and make that the primary, of course, Right. This is a disease that has ataxia in 100% of patients, and those are the findings that we're seeing that we believe to be clinically meaningful.

Speaker 3

And I would add one more thing to what Doctor. Bai just said is that these patients who were treated were 6 years and older. So the disease had already progressed somewhat Given it was neurodegenerative and given that we saw 6 or more patients having restoration of SNAP or sensory nerve action potential and other measures of electrophysiology That could potentially translate into a clinically meaningful effect that could be far greater if these children were treated much earlier Given that the neurodegeneration may have not progressed as much, obviously, I have to caveat it by saying we haven't studied children younger than 6 years of age, and we have great interest to see If you can have that kind of significant impact in younger patients as well. So collectively, we are very encouraged with the data that we are seeing and looking forward to meeting with the FDA and talking to them.

Speaker 9

Thank you very much for taking our questions. Thank

Operator

The next question comes from Gil Blum with Needham and Co. Please go ahead.

Speaker 6

Good afternoon, everyone. This is Gil on for Gil. Maybe a good place to start is just to help me understand the order of events. So you're having your R and D event ahead of an FDA meeting in the Q3. Why not the other way around?

Speaker 9

You want to

Speaker 3

take that, Sukit? Sure. So that's a good question. So keep in mind though that we are putting the meeting request in, in the Q2 and there is going to be a certain time lag before we actually get the meeting hopefully. But at the same time, we are generating significant amounts of data from prespecified endpoints post hoc analysis and the model that Doctor.

Speaker 3

Bai was talking about That we think are truly clinically relevant and there is significant interest from many who would like to understand not only the impact of our intrathecal gene therapy on this specific Ultradare disease to understand benefit over risk, but there's also significant interest in trying to understand the typical platform. What kind of impact would it have across a broad aspect of neurodegenerative and neurodevelopmental disorders? And I would again remind you that if you look at the SMA program with Zolgensma, The IV formulation had significant impact in SMA Type 1 and some other subtypes as well. Recently Novartis released more data with the intrathecal approach where there was significant clinical impact in SMA Type 2, Type 3 and Type 4 as well. So this platform, I think, being proven over time will give us hopefully a simple route of administration, which is through lumbar puncture that could address many complex disorders of the central nervous system.

Speaker 3

So due to the significant interest, we think it's appropriate to have this R and D meeting Towards the end of June, so that we can talk about some of our findings that I think will be hopefully significantly relevant to the patients in question.

Speaker 2

I think the other thing to add to that is that in a perfect world, there would be a Scientific conference that lines up with this and that would have been the preferable way to disclose things. But in all candor, we stepped Through this analysis, not knowing exactly what's the outcomes we're going to be. And at this point, we're very encouraged by what we're seeing. And you hopefully can tell from The way we're coming across on the call that we feel this is very compelling. And so we felt that was the best way to disclose it, explain how we were going to Move things forward with the agency and highlight our rationale and provide the data That in our view justifies our conviction with the program.

Speaker 6

Okay. That's fair. And bear with me here for a second because this is a little complicated. So Sarepta is on top of mind of everyone. And I'll venture to say that the reason the FDA was okay with Sarepta submitting on an external control for a functional measure Because they have a randomized study right behind it.

Speaker 6

And that's basically the key difficulty, right? And if you're doing an open label Study for functional endpoint, the training aspect of it, right? That's what the FDA does not like. And that gets me to my actual question.

Speaker 4

As a neurologist, of course, I would Say that it is. So for example, if you hold your arms out in front of you, if you happen to have a headset on and you take your right pointer finger and touch your nose, there's a little bit of jitter there. Now to most people that might not be much, but to me I can pick that up. Now if you have even more jitter, I can pick that up further and start to objectify exam there that I can point towards and say this has intra and inter rater reliability, but there's also objective measures that then back that up. So if I was a bad neurologist and not diagnosing correctly, right, I have objective measures there to help support that.

Speaker 4

But Ampharas, I would argue, has objective measures within that.

Speaker 6

Okay. Because In my opinion, I think that might go to the heart of the matter because it's really obvious that the FDA doesn't like

Speaker 2

And also like The Rietta product that was approved with mPARS, right?

Speaker 3

Yes. So there is a

Speaker 2

For example.

Speaker 3

Exactly. But there is a history on the regulatory side You know that sometimes it's just impractical to ask for randomized placebo controlled trials and perfection when it comes to clinical trial design. But when there is no therapeutic option available and these kind of studies, especially in ultra rare disease, show clinical benefit, I think that it becomes a negotiation between the regulatory agencies

Speaker 9

and the sponsor in

Speaker 3

making sure the product is appropriately made available to the And the sponsor in making sure the product is appropriately made available to the patient community in question. And I would go even further to state Peter Marks and colleagues have been out there, obviously, encouraging a serious discussion between the agency, CEVA, and the sponsor of this kind of ultra rare disease programs In having some flexibility, if the benefit outweighs the risk and there's no other therapeutic option available to the patient community such as in gang, which is frankly a terrible disease, If you meet these patients and families and see what happens to them, I think that Staphway is now open for us to appropriately position our data, talk to the FDA and show them that we ourselves are convinced and hopefully we can convince them that this is an appropriate product for approval such that patients can use the gene therapy product.

Speaker 2

And I think one other thing to add to it would simply be that in addition to mFARs, What we're trying to do is also demonstrate multiple endpoints that are objective. I mean, we want to talk about SNAP or EIMs, CMAPS, CMAPS and MRIs, right? So to show that no matter where you're kind of cutting The bread, you're getting an effect in all these domains that can only be attributable to the drug. And I think with the model that we've got put together, we have a very scientifically driven, data driven Control that we can point to and this highlights the effectiveness across all these different domains. So Put very simply, we're not hanging our hat on any one thing.

Speaker 2

It is the totality of the data.

Speaker 6

Okay. Thank you for taking our questions and again congrats on the progress. Thank you.

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Earnings Conference Call
Taysha Gene Therapies Q1 2023
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