Q1 2025 Taysha Gene Therapies Inc Earnings Call
Okay.
Speaker Change: Greetings and welcome to the T shirt, Jean therapies first quarter 'twenty 25 earnings call.
Speaker Change: At this time, all participants are in listen only mode.
Speaker Change: A question and answer session will follow the formal presentation.
Speaker Change: Anyone should require operator assistance during the conference. Please press Star then zero on your telephone keypad.
Speaker Change: As a reminder, this conference is being recorded.
Speaker Change: I would now like to turn the conference over to your host Hailey Collins Director head of corporate Communications. Please go ahead.
Speaker Change: Thank you good morning, and welcome to <unk> first quarter 2025 financial results and corporate update conference call earlier today <unk> issued a press release announcing financial results for the first quarter ended March 31, 2025, a copy of this press release is available on the company's website and through our SEC filings.
Speaker Change: Joining me on today's call are Sean Nolan <unk>, Chief Executive officer, because aren't a gantry president and head of R&D and Kamran Alam Chief Financial Officer, We will hold a question and answer session. Following our prepared remarks.
Speaker Change: Please note that on today's call, we won't be making forward looking statements, including statements concerning the potential Acacia why don't you.
Speaker Change: The reproducibility and durability of any favorable Russell initially seen in the patients don't stay in clinical trials to positively impact quality of life and alter the course of disease and the patients we seek to treat our research development and regulatory plans for our product candidates, including the timing of additional trials and reporting data from our clinical trials.
Speaker Change: Advice from the FDA on the regulatory pathway for tissue, one or two the potential for the product candidate for regulatory approval from the FDA or equivalent foreign regulatory agencies.
Speaker Change: Opportunities for our programs and our current cash resources supporting our planned operating expenses and capital requirements into the fourth quarter of 2026.
Speaker Change: Call May also contain forward looking statements relating to patient growth forecasted cash run way in 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 <unk> actual results to differ materially from those treated or.
Speaker Change: Or implied in such forward looking statements.
Speaker Change: For a list and description of the risks and uncertainties that we face. Please see the reports we have filed with Securities and Exchange Commission, including in our annual report on Form 10-K for the full year ended December 31, 2024 that we filed on February 26, 2025, and our quarterly report on Form 10-Q for the quarter ended.
Speaker Change: 31, 2025, we filed today. This conference call contains time sensitive information that is accurate only as of the date of his wife Broadcom may 15th 2025.
Speaker Change: Hey, she 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 maybe required by applicable securities laws.
Sean Nolan: I would now like to turn the call over to our CEO Sean Nolan.
Sean Nolan: Thank you Haley and welcome everyone to our first quarter 2025 financial results and corporate update conference call.
I'll begin with a brief update on our recent activities, then sukkah mcandrew, President and head of R&D of tissue will provide an update on our lead takes you went on to gene therapy programs in clinical development for Ret syndrome chair.
Speaker Change: Chairman alarm, our Chief Financial Officer will follow up with a financial update.
Speaker Change: And I will provide closing remarks and open up the call for questions.
Speaker Change: This year has been marked by strong execution across our Tisha 102 program in clinical evaluation for pediatric adolescent and adult patients suffering from ret syndrome.
Speaker Change: We are pleased with the significant regulatory and clinical progress that we believe continue to support a clear path to registration.
Speaker Change: Importantly, our analysis of the natural history data, coupled with the longer term clinical data from our low dose cohort and interim high dose data that we have collected across a broad range of ages and stages of patients with ret syndrome and are to reveal phase one two trials have further informed a therapeutic.
Speaker Change: Retention rotation 102, and supported our alignment with the U S. F D. A on key elements of our development plan for part B the pivotal phase of our trials.
Speaker Change: In February we shared that we completed dosing of the 10 patients in part a the dose escalation portion of the reveal phase one two adolescent and adult trial and the reveal phase one two pediatric trial with six patients in cohort two evaluating the high dose of tissue I wanted to avoid.
Speaker Change: Needed the 15th total vector genomes and for patients in cohort one evaluating the low dose of tissue and 102 of $5 70 to 14 total vector genomes.
Speaker Change: Our data further mature we're pleased to take your one or two continues to be generally well tolerated across the high and low dose cohorts with no treatment related serious adverse events or dose limiting toxicities as of the April 10, 2025 data cutoff.
Speaker Change: Recall patients being evaluated in our room reveal phase one two trials or in the post regression period of the disease, where functional gains a restoration of loss function are not expected to occur in the untreated population.
Speaker Change: Previously we showed clinical data from the low dose cohort in our reveal trials, where pediatric and adult patients with advanced disease, not only showed clinical improvements, but also gained functional skills across the domains of fine motor gross motor and socialization and.
Speaker Change: Asian, which represent improvements in activities of daily living.
Speaker Change: This included beginning to use eating utensils sitting independently standing up from a chair independently and the ability to use an eye gaze communication device. Each of these functional gains reflect meaningful skills that can significantly improve a patient's quality of life by affording.
Speaker Change: Greater independence and autonomy.
Speaker Change: These functional gains which are not expected to occur in the untreated population of patients with ret syndrome based on natural history data and the additional clinical data we have collected.
Speaker Change: From our reveal trials have supported our interactions with the FDA regarding the optimal regulatory pathway for tissue 102.
Speaker Change: Over the past 18 months, we have maintained frequent ongoing discussions with a broad FDA review team, including including senior leadership.
Speaker Change: Regenerative medicine advanced therapy or arm at mechanism.
Speaker Change: These discussions which have been rooted in a robust data driven findings have been aimed at advancing tissue went out to toward a pivotal trial design in which clinically meaningful functional gains are assessed in a rigorous and bias mitigated manner across a broad patient population.
Speaker Change: To date, we believe our interactions with the FDA have consistently been productive and supportive of our development approach.
Speaker Change: As such I'm pleased to share that we have obtained written alignment from the F. D. A on key elements of our pivotal part B trial designed for Tisha 102, and next steps to enable the initiation of the pivotal trial.
Speaker Change: Importantly, the FDA advised us to proceed directly to submitting our pivotal trial protocol and associated Statistical analysis plan as an amendment to the investigational new drug or IND application, which we expect to submit in the current quarter.
Speaker Change: This approach eliminates the need for a formal end of phase meeting, which may expedite study initiation and registration.
Speaker Change: We truly appreciate the clear constructive and collaborative interactions with F. D. A to date and believe this progress on our Registrational pathway support the strength.
Speaker Change: Of our data driven approach and further enables our goal to bring tissue 102 to patients with this devastating disease as expeditiously as possible.
Speaker Change: We are focused on finalizing the details of our protocol and statistical analysis plan as we prepare to submit the I N D Amendment this quarter.
Speaker Change: In the coming weeks, we plan to provide a fulsome update on our pivotal part B trial design.
Speaker Change: <unk> syndrome natural history data analysis, and the clinical data from part a of our reveal trials as part of a Taishan 102 program update in conjunction with the international Ret syndrome foundations 20, twenty-five ret syndrome scientific meeting taking place June nine to the 11th.
Speaker Change: At the I R. S. Ash meeting, we will deliver three oral presentations related to tissue 102, including one focused on our clinical data.
Speaker Change: As we approach these critical milestones our confidence and our differentiated gene therapy candidates continues to strengthen based on the recent developments highlighted today, we believe taishan, one or two has the potential to provide meaningful benefit to a broad population of patients with ret syndrome, using a minimally invasive delivery.
Speaker Change: Approach with a clear path to registration based on the critical alignment reached with F. D. A.
Speaker Change: I will now turn the call over to Sue to provide more context on these the best advancements that further support a clearer path to registration Sue group.
Sue: Thank you Sean and good morning, everyone. As Shawn mentioned, we believe we have made significant progress on advancing our cash have an auto program towards registration.
Sue: Recall, we have two ongoing phase one to reveal trials you by the way.
Sue: I didn't catch that one or two and adolescent and adult trials, taking place in Canada and the U S for females age 12, and all of that.
Sue: Great.
Sue: <unk> syndrome, and the pediatric trial, taking place in the U S. The U K and Canada females five to eight years old with Tourette syndrome.
Sue: We are currently evaluating two dose levels of one or two in part in the dose escalation portion of book trials.
Sue: Although approach from the outset has been to utilize part a good January.
Sue: It's a data set that informs the key elements of a pivotal part B trial.
Sue: Yeah, So what I'll tee aspects are ret syndrome that have shaped our development approach for tests that one or two as we work to align with the FDA on key elements of a pivotal trial design.
Sue: <unk> syndrome is a devastating and progressive neuro developmental disease that leads to complications and fine and gross motor function socialization and communication autonomic function in seizures.
Sue: The functional impairments and disease features often necessitate 24, seven cap and lifelong assistance.
Sue: Going to a significant caregiver burden and severe impact on quality of life.
Sue: There is a significant unmet medical need.
Sue: Additionally, while <unk> syndrome is a heterogeneous condition with different levels of clinical severity based on each patient's distinct genetic background patients generally follow common trajectory regarding the achievement of functional developmental skills.
Sue: Following a period of regression affected individuals typically interrupt plateau period around the age of five or six during which they are highly unlikely to gain new functional skills are regained skills that have been lost to disease progression.
Sue: As you think about gene therapy for patients in the post regression population or ret syndrome.
Sue: Already develop the hallmark characteristics of the disease and the ultimate goal is restoration of function and improvement in activities of daily living.
Sue: Yes that one or two is designed as a onetime gene therapy that aims to address the underlying cause of ret syndrome <unk>.
Sue: And we see Peter protein expression on a cell by cell basis across the central nervous system.
Sue: Therefore, we believe queso on a cool may provide the opportunity for patients with advanced stage of ret syndrome to develop new functional skills.
Sue: <unk> syndrome requires an increase in M. C. P tau protein to activate the neural circuits necessary forgetting function.
Sue: As well as time for patients to strengthen these see activated circuits.
Sue: On skills that are affected by the disease. Therefore, we believe that early clinical benefit is a strong indicator that in Mississippi to protein has reached therapeutic levels that in turn cleared the opportunity for patients to straighten their neural network all the time and learn complex skills.
Sue: And both on reveal trials, we have consistently seen early clinical improvement and functional gains post treatment that persisted in sentiment over time.
Sue: That could be highly unlikely based on natural history data.
Sue: Has been highly encouraging since patients being evaluated in our reveal phase one two trials in the post progression period of the disease.
Sean Nolan: As Sean noted functional gains have explorations of lost function and not expected to occur in the untreated population.
As you prepare to report long term low dose data and preliminary idose data across our pediatric and adolescent and adult patients to reveal trial, we hope to see a consistent pattern of all of that sponsor deepens over time okay.
Sean Nolan: A broad population of patients it's very in genotype <unk>.
Sean Nolan: We believe this could further support the broad treatment potential upsell shawano too and move us closer to our goal of bringing a potentially transformative treatment to all patients with <unk> syndrome.
Sean Nolan: Overall these functional outcomes seen thus far in patients treated with one or two have supported our ability to reach alignment with the FDA on key elements of the pivotal trial design and potential one or two and next steps to enable study initiation.
Sean Nolan: So a lot of their country, one findings and I'm going to discussions with the FDA. We remain steadfast in our conviction that functional outcomes are the most relevant objective and clinically meaningful assessments of the treatment effect of takes out one or two in patients with tourette's syndrome.
Sean Nolan: I'll now turn the call over to Cameron to discuss well financed.
Speaker Change: Hey, Brian.
Sean Nolan: Okay.
Sean Nolan: Thank you Sue.
Speaker Change: Research and development expenses were $15 $6 million for the three months ended March 31, 2025 compared to $27 million for the three months ended March 31 2020 for.
Speaker Change: The $5 $1 million decrease was driven by good manufacturing practices or GMP batch activities with the intended commercial manufacturing process for Acacia <unk> performed during the three months ended March 31 2024.
Speaker Change: The decrease in expenses was partially offset by higher compensation expenses for R&D employees as a result of increased head count.
Speaker Change: General and administrative expenses were $8 $2 million for the three months ended March 31, 2025, compared to $7 $1 million for the three months ended March 31 2024.
Speaker Change: The increase of $1 $1 million was primarily due to higher compensation expenses and increases in legal and professional fees.
Speaker Change: Net loss for the three months ended March 31, 2025 was $21 $5 million or eight cents per share compared to a net loss of $24 $1 million or <unk> 10 per share for the three months ended March 31 2024.
Speaker Change: As of March 31, 2025, Asia had $116 $6 million in cash and cash equivalents. We continue to expect that our 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.
Sean Nolan: Thanks Kamran.
Sean Nolan: We are pleased with the significant regulatory and clinical progress made across our tissue 102, Ret syndrome program that continues to support a clear path to registration with written alignment from the FDA on key elements of our part B.
Sean Nolan: The pivotal trial design and next steps to enable study initiation. We believe we are strongly positioned for success as we work to rapidly advance our tisha went on to gene therapy program toward the pivotal trial and bring us closer to our mission of delivering on tissue one onto to the ret syndrome community as expeditiously as <unk>.
Sean Nolan: Hospital in the coming weeks, we look forward to providing a fulsome update on our pivotal part B trial design, our ret syndrome natural history data analysis, and the clinical data on both the high and low dose cohorts of our reveal trials during a program update in conjunction with the IRS up scientific meeting.
Sean Nolan: With that I will now ask the operator to begin our Q&A session operator.
Sean Nolan: Okay.
Speaker Change: Thank you Sir.
Speaker Change: At this time, we will be conducting a question and answer session.
Speaker Change: If you would like to ask a question. Please press Star then one on your telephone keypad.
Speaker Change: Formation tone will indicate your line is in the question queue.
Speaker Change: You May press Star and then two if you would like to move your question from the queue. Please.
Speaker Change: Please note participants are limited to one question and one follow up at a time.
The first question we have comes from Christian <unk> of Cantor. Please go ahead.
Christian <unk>: Good morning, and looking forward to IRS soft in a few short weeks here. So one question, we've been getting and what signals can potentially point to there being a dose response given this is a highly heterogeneous syndrome should we be thinking about the time stream answer are there any specific.
Christian <unk>: Vic endpoints or anecdotes, where the effects might be easier to measure to see if that dose responses there.
Speaker Change: Yes, Kristen good question and you can feel free to jump in on this but I think theres a couple of things. We can look at one is as you mentioned a temporal aspect.
Christian <unk>: As we think about.
Christian <unk>: Gains a function, we think about some of the improvements we see on a more qualitative level using metrics like our MBA.
C G I.
Christian <unk>: And what we've reported to date you see early improvements in strengthening over time, we think there could be no differentiation at the high dose in terms of you know the time period to see that and also the magnitude of the response that we're seeing and so again if it assuming the safety continues to look like.
Christian <unk>: We've seen thus far.
Christian <unk>: You know, we've always had the view that the high dose would be the would be the right dose.
Sean Nolan: And we'll talk through that more fulsome manner. Once we go through the data, but that's how we're thinking up at two P. M is there anything you'd add to that Sean what I would also add is that there is the translational data set right. So the animals to human translation that it comes to motor function and respiratory function. So we've seen some improvement there between the doses and then the other.
Christian <unk>: Thing is.
Christian <unk>: Yeah.
Christian <unk>: On the clinical data and obviously over time, we think it's going to mature and get better between the doses but.
Christian <unk>: Logically the higher dose also I think should add a further advantage purely because the.
Christian <unk>: The Florida, and Mississippi tool on the hydro levels. This heterogeneous complex disease.
Christian <unk>: Neurological and do you think that will also have a better clinical impact in that patient population is.
Christian <unk>: Thank you.
Christian <unk>: Thank you.
Speaker Change: The next question we have comes from solving Ritchie of Goldman Sachs. Please go ahead.
Speaker Change: Hi, This is lidia on free Salve in thanks, so much for taking my question and congrats on the update today.
Speaker Change: You plan to provide an update later this quarter could you just frame the bar for success and kind of how you're thinking about that.
Speaker Change: Of the recent regulatory feedback just in terms of the data that we can expect here. Thanks, so much.
Speaker Change: Sure I think what's going to be.
Speaker Change: Very helpful.
Speaker Change: For the market as to number one see what the natural history analysis that we've conducted.
Speaker Change: Highlights I think that's something that's been been missing.
Speaker Change: You know from frankly for the disease state for quite some time and so we will step through our analysis of that natural history and truly that underlies bolt the regulatory strategy and the clinical strategy and so the reason we want a package everything together is to start with just a clear basis.
Speaker Change: Fine on what would you expect to see in the natural course of the disease and even though the diseases heterogeneous the patients really at a certain point have a have a very clear.
Speaker Change: What type of a trajectory website.
Speaker Change: Secondly.
Speaker Change: As full then explain what's the regulatory details are so we've reached alignment on key framework, which what does that mean that means we've reached alignment on what the trial design as we've reached alignment on the primary endpoint. We've reached alignment on the study population. We've reached alignment on the estimated number of patients that will need to.
Speaker Change: <unk> achieved statistical significance.
Speaker Change: Well, you don't want to share that with all of you.
Speaker Change: And then with that we'll go through the clinical data both the long term low dose data and the high dose data looking through pipe, primarily the lens that the FDA has agreed to as a primary endpoint, which we think will be very predictive of.
Speaker Change: What does success looks like in the pivotal trial.
Speaker Change: It will give people a very good insight into the probability of success and also then the timeline to a potential BLA submission. So there'll be a lot there and that's why we wanted to share with everybody today, reaching this congruence with the FDA is fantastic it obviates the need.
Speaker Change: For an end of phase meeting, which you know when you add it all up could take potentially another quarter to get that wrapped up we've already reached that alignment and now that we can stop right into the protocol submission.
Speaker Change: That effectively is a 30 day clock.
Speaker Change: And assuming there's no.
Speaker Change: Issues.
Speaker Change: You know we would be able to then proceed with site activities and initiation. So a lots of update at the IRS off meaning but very exciting times for the program and we're poised to.
Speaker Change: Step into the part B and move us closer to.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: So much.
Speaker Change: Thank you. Thank you.
Speaker Change: The next question we have comes from Joe <unk> of Needham <unk> co. Please go ahead.
Speaker Change: Good morning.
Speaker Change: And my congratulations on the progress here.
Speaker Change: So you kind of made sense of timeline.
Speaker Change: <unk> question.
Speaker Change:
Speaker Change: Is there any specific feedback that the FDA may provide still posted a 30 day period on the study protocol.
Speaker Change: S P.
Gil Sukru: Yes, Gil Sukru secret I can tackle this one I would say that.
Gil Sukru: I'll just start with the framework that the end of phase meeting purpose is generally too.
Gil Sukru: Line on things or you have a missile alignment with the FDA in a meeting as needed to reconcile that so the good news is we've reached alignment with the FDA and really the key aspects of the trial design right. So we've got written agreement that the trial.
Gil Sukru: Zions is good we've gotten written agreement that the primary endpoint is ago. The study population and we've talked about the statistical analysis plan and you know we're in we're in very good shape there.
Gil Sukru: So really at this point, it's putting the detail into the protocol and making that submission so.
Speaker Change: I'd like you to comment on it if we're at this stage there could be potentially a little back and forth bus.
Gil Sukru: They wouldn't have told us to submit the protocol.
Sean Nolan: If there was something that could really be a showstopper, yes. So youre correct, Sean I mean, they would have asked us to come back.
Gil Sukru: To further review the protocol etcetera.
Gil Sukru: Stability with what had been originally proposed so the odds are that it's highly unlikely that they will have significant further comment they couldn't there couldnt be some correspondents say if you had a question or two but it's highly unlikely at this point.
Speaker Change: Thank you.
Gil Sukru: Thank you.
Speaker Change: The next question we have comes from Maury Raycroft of Jefferies. Please go ahead.
Maury Raycroft: Hi, good morning, Congrats on the update and thanks for taking my questions.
Maury Raycroft: Realizing there are more details to come on the trial design can you at least talk about what the primary endpoint will be and if it would include standardized clinical video showing milestone or functional gain.
Maury Raycroft: And then I don't know if theres anything additional you can say about the statistical analysis plan as it relates to the endpoints at this point.
Maury Raycroft: Yeah, I mean, I would say that you can expect with the primary endpoint is going to be consistent with what we've been focused on over the last 18 months or so which has been <unk>.
Maury Raycroft: Working towards an endpoint that is objective, it's clinically meaningful it's very easy to measure and it's important both to the patients their caregivers and the clinicians.
Maury Raycroft: And you know again without getting too far ahead of ourselves I would just say we've always wanted to be in a position where you could have a very efficient.
Maury Raycroft: Robust clinical study you know, we've always thought that a placebo was not necessary that a single arm could work here with the right controls.
Maury Raycroft: And so you know if that's the case you would want to make sure that there would be mechanisms in place where you would have appropriate.
Speaker Change: I asked mitigation measures video assessments and readers and adjudicated or so it would be appropriately bounded.
Speaker Change: So I think those are the details that we'll provide but we're in good shape on all of that in terms of.
Speaker Change: The alignment that we've obtained with the FDA.
Speaker Change: Got it that's really helpful. Okay. Thanks for thanks for taking my question.
Maury Raycroft: Thanks Maury.
Speaker Change: Okay.
Speaker Change: The next question, we have comes from <unk> <unk> of Wells Fargo.
Speaker Change: Go ahead.
Speaker Change: Great. Thanks for taking our questions.
Speaker Change: Was wondering how does the aligned.
Speaker Change: Design compare with your.
Speaker Change: Pozo or your <unk>.
Speaker Change: Desired design going into those into the meeting.
Speaker Change: And also it sounds like a natural history will be playing an important role. So just wanted to perhaps ask whether this is a single arm design and I have one follow up thanks.
Speaker Change: Yeah Yeah.
Speaker Change: I would say that the.
Speaker Change: The design that the company put forward is the design that the F D a endorsed.
So we we had some discussions around.
Maury Raycroft: The previous question for Maury, it's making sure that from a process perspective.
Maury Raycroft: Everyone was comfortable with what we're going to do and we achieve that but there was never any pushback from the agency they've always been very constructive and open minded to what we've put in front of them. They only requested data, which is obviously very justified and the data wasn't was.
Maury Raycroft: In two areas. One was we told them our promise with the natural history data and what that might show and we've put that in front of them.
Maury Raycroft: I would say agreed with what we've put in front of them and then the second piece was the clinical data and as our data have evolved we've continued to update them on what we're seeing and so it was really the combination of those two aspects of data that got us to this point where we.
Maury Raycroft: We had the alignment.
Maury Raycroft: And in obviated the need for.
Maury Raycroft: At the end of phase meeting.
Maury Raycroft: Oh, great, yes, so actually I am sorry.
Maury Raycroft: So I was going to ask you what was the second part of your question.
Right I was going to ask what might be the role of any data.
Maury Raycroft: That you know.
Maury Raycroft: Which might have played into the.
Maury Raycroft: Lack of a need for it.
Speaker Change: End of Phase meeting, so I think you've kind of answered that but let me also ask you know it's the lack of the end of phase meeting.
Speaker Change: And having anything to do with the FTA resource capacity.
Speaker Change: And.
Speaker Change: Also.
Speaker Change: Is it a course of a is it a general action on the indication which will.
We will look like for other sponsors.
Speaker Change: Also be the case and lastly, do you expect the harmonization of the endpoints across sponsors.
Speaker Change: Yeah in terms of FTE resources.
Speaker Change: What I can tell you is we received written.
Speaker Change: Written alignment before the announcements with Peter remarks, and in the departures. We subsequently have had interactions with the FDA, where they've maintained that posture. So we think that there is no relation between not having an end of phase meeting and resources I go back to <unk> comment earlier.
Speaker Change: Which is the reason for an end of phase meeting is generally to either get congruence or you are in.
Speaker Change: Opposition Youre not aligned on a key aspect and so you need to have a meeting to discuss that because we've had our mat we've already interacted with the F. D. A three times this year multiple times last year, we've had a very consistent and progressive discussion with them. So we've been work.
Speaker Change: King towards this for 18 months and the reality is we got there with them you know through this arm at mechanism and then there was no need for them to you now.
Speaker Change: Take the time to have an official meeting so to us it highlights.
Speaker Change: The robustness of the data that we've put in front of the FDA. Both in terms of natural history, and our clinical data to support what we wanted in terms of trial design endpoints et cetera and.
Speaker Change: We look forward to continuing to move things forward. So it's super exciting I again, I think keep in mind is usually if you're if you're doing an end of phase meeting I'm going to say, it's it's 70 day clock or so.
Speaker Change: We're now able to submit the protocol, which we say we're going to do this quarter.
Speaker Change: There's a 30 day wait period.
Speaker Change: Could ask us for a couple of clarifying.
Speaker Change: You know request, which we would do expeditiously or they could say nothing but in a very short period of time, we would anticipate being able to initiate site.
Speaker Change: Site activities get the pivotal trial up and running and you know we're on a very exciting pathway to get to a potential BLA.
Speaker Change: Great. Thanks for the color and congrats on the update thank you.
Speaker Change: Thanks, Jonathan.
Speaker Change: The next question we have comes from Amit <unk> of Piper Sandler. Please go ahead.
Speaker Change: Yeah, Hi, guys. Thanks for taking my questions and congrats on all the progress with one zero so.
Speaker Change: Sean maybe for the part B.
Speaker Change: A portion of the trial given its an amendment on D C.
Speaker Change: Seamless how seamless is it going to be to go to the part b with the current sites that are in the part a.
Speaker Change: You need to start with IRB approval for each site, including the part a site.
Speaker Change: And then the second question is.
Speaker Change: Given the significant number of patients in Europe, what are your plans to engage with EMA requirements. There. Thanks.
Speaker Change: Yeah and in terms of.
Speaker Change: What's nice about the India Amendment, we will leverage existing sites right because we've already been through the contract process they've already cleared.
Speaker Change: The initial.
Speaker Change: I I M DS within their institution. So you know we've already prioritized, how we want to triage and go through site activation, so definitely having the multiple sites up and running and dosing patients is going to be to our advantage.
Speaker Change: Might add additional sites beyond that you know to help make sure that as we open up enrollment for part B, which we can do in parallel we'd like to have the most.
Speaker Change: Expeditious you know enrolled.
Enrollment possible, but the fact that we've got multiple sites that are trained on the product.
Speaker Change: That already have these.
Speaker Change: A lot of the.
Speaker Change: Activities done in the past, we think will facilitate it and allow us to move very very quickly.
Speaker Change: <unk> also been in some of these sites have multiple patients well basically lining up so we could run multiple patients in parallel as long as they can handle the capacity.
Speaker Change: Exactly.
Speaker Change: And then Darren as it relates to EMEA Youre right I mean, there's a nice opportunity over in Europe. When you look at.
Speaker Change: Europe, plus U K, it's about the size of the U S. So it's a very significant patient population.
Speaker Change: We've got the U K activate and we've got the open CGA there and we've worked to I would say enable the E M. A.
Speaker Change: So we've got that going and again with additional capital.
Speaker Change: Potentially down the road.
Speaker Change: That's where we could expand our footprint. So we've been very disciplined with the resources that we've had we've focused on primarily on the U S. But in the background, but we haven't said a lot about it the regulatory team has done a great job of working in Europe too.
Speaker Change: You know put us in a position where we can move forward at the appropriate time.
Speaker Change: Thank you.
Speaker Change: The next question we have comes from Whitney <unk> of Concord Genuity. Please go ahead.
Speaker Change: Hey, guys I'll add my congrats on all the progress.
Speaker Change: Wanted to follow up on the interactions with Astellas I know you had previously talked about having kind of the amount of data or the type of data that you would need to start the clock on the potential opt in.
Speaker Change: This summer I guess is that still on track or has that been accelerated at all I guess given that the regulatory outcome here and and then have you been having conversations with them in the meantime, or is it that you'll deliver kind of the final package to them whenever whenever you have it.
Cameron: Yes, Cameron jump in here, but basically.
Speaker Change: The agreement is very specific in terms of.
Speaker Change: When when things get triggered and you are correct. There is a data package on pediatric patients that needs to be submitted to them.
Speaker Change: You know, which is which is forthcoming now based on the data that we have.
Speaker Change: I really can't comment on any discussions that we may or may not have had with astellas I would I would just simply say that we will execute the agreement as it as it's written and that's part of the process that we're stepping through at this particular point in time.
Speaker Change: Great. Thanks.
Speaker Change: Thank you.
Speaker Change: Thank you. The next question we have comes from Jack Allen of Baird. Please go ahead.
Jack Allen: Alright, Thanks for taking my questions and congratulations on all the progress made over the course of the quarter I just wanted to ask about some of the recent FDA interactions. You had mentioned that you had spoken with the administration and the proceeding.
Speaker Change: The marches.
Speaker Change: Sure.
Speaker Change: Love to hear any color you can maybe have as it relates to discussions post Peter marks his departure, how consistent the people you've been talking to have been at the FDA and if you plan to have any.
Speaker Change: Even informal interactions given that recent addition of vinayak or start to see better.
Sukru: Yes, Sukru help me out here, but.
Sukru: From the beginning our team has been very consistent.
Sukru: With FDA since we submitted the I M D.
Sukru: In terms of the review team and things of that nature.
Sukru: Because we have arm at the Culver Don has certainly been the official meetings you know she's been there in her capacity. So we've had again consistent senior leadership review I can say because we've got a question.
Sukru: Particularly during when Peter departed but Peter Peter was never in any of the meetings like that's not his his role easy setup to Nicole and the.
Sukru: And the teams beneath her.
Sukru: So that part has been very consistent and there really has been no departure no deviation from the conversations that we had going back to call. It.
Sukru: April of last year Everything's been consistent in what we wanted to do the strategy that we outlined and all again all we've ever asked for is to see additional data and the natural history analysis, which we have provided.
Sukru: Provided so so I would say.
Sukru: Through the process things have been very very consistent and the interactions that we've had after the departure of Peter.
Sukru: You would not have known that Peter had left so the team was.
Sukru: Bill very focused on what we were working towards there was no.
Sukru: Pause the meetings that we had were on schedule. The team was fulsome that showed up.
Sukru: And everyone was very engaged highly professional and we continue down the path. So we haven't seen any impacts with with these changes at FDA I think.
Sukru: You know in terms of additional interactions.
Sukru: The next interaction would be when we submit.
Sukru: The protocol and the C. P to the eye and D. And then there may or may not be back and forth. If they have some questions and we need to jump on the phone and work things true we will do that but it's also possible that they are comfortable with everything and we just proceed.
Sukru: So that's a little difficult to to answer that question and I would I would just say as it relates to <unk>.
Sukru: Besides I think as time has gone on and he said more publicly.
Sukru:
Sukru: His comments seem to dovetail in with with what.
Sukru: Dr. Mccarthy has said and that Theres a high a high.
Sukru: High degree of understanding that rare disease is different than large product markets.
Sukru: They understand that not all programs need a placebo control it's not appropriate.
Sukru: Particularly for some of the rare disease programs, what's really important is context.
Sukru: And a robust clinical trial design and we think context is important that makes a lot of sense to us and that's why I think the natural history data will make a lot of sense to people in terms of.
Sukru: Its importance on how we ultimately have gotten to this point and and hopefully beyond with the agency so worried.
Sukru: We feel right now we're in a really good spot the agency and all of these new players continue to talk about the importance of innovation and you specifically mentioned gene therapy. They talk about the fact that.
Sukru: They want to move therapies forward as quickly as possible and.
Sukru: We don't see that there's going to be any impediments based on our interactions today.
Sukru: Sucralose to give some color as well because he's the one in the meetings. Thanks, Sean what I would say is that when it comes to the FDA and see but the team that has been reviewing the ret program for gene therapy has stayed consistent so the clinical team out of the box cut steam so not concerned with it.
Speaker Change: Comes to any variability new elevations over time when it comes to Dr. Prasad I think he has a very bright young individuals who has done a lot of good research and the focus here is you know.
Speaker Change: Disease lung disease at a time to meet appropriate beta and then obviously proceed rapidly through the FDA review process.
Speaker Change: Even though there was a lot of noise I think when it was initially chosen.
Speaker Change: So it's very clear.
Speaker Change: Is that P is going to really make a differentiated culture that will rare disease review process.
Speaker Change: Yes.
Speaker Change: Alright, thanks, so much the color and congratulations again on all the progress.
Speaker Change: Thanks Jack.
Speaker Change: Thank you ladies and gentlemen, just a reminder, if you would like to ask a question today. Please press star and then one now.
Speaker Change: The next question we have comes from Joon Lee of <unk> Securities. Please go ahead.
Joon Lee: Hey, Thanks for the update thanks for taking my questions.
Joon Lee: Clinical data do you have any biomarker data from CSF or others that inform you that your construct as auto regulating Mexico to Etsy signed and are you able to indirectly at least approximate the level of <unk> being produced in this patients corresponding to the doses being administered and relative to do it.
Joon Lee: Wild type of individuals and as a quick follow up what would be the timeline for part D enrollment and study completion. After you are now.
Joon Lee: This quarter. Thank you.
Joon Lee: Yeah on the second part we would we.
Joon Lee: We will give more.
Joon Lee: <unk> on that once once we hear back from FDA.
Joon Lee: Or we don't once we get through the 30 day period, but I would say if thats. The case June then we would be.
Joon Lee: Initiating sites.
Joon Lee: Right away and potentially getting into dosing you know the fourth quarter of this year first quarter of next year.
Speaker Change: So it's a very short timeline to make that happen as a result, as it relates to the <unk> ill turn it over to Sue yeah. So Julien.
Joon Lee: It's a good question gets asked all the time.
Speaker Change: Sometimes it is.
Speaker Change: Norway to measure and ECP two levels in the CSF blood stream off sale and in the sales I'm talking about the neuron on the Astral side. It's intranuclear proteins that is there and then I think gets turned over very quickly so.
Speaker Change: When it comes to our product given how quickly. These patients is fun to gene therapy, given and particularly because our construct is also self complementary clinically.
Speaker Change: As you probably know the help restore sleep abnormalities autonomic dysfunction fine and Rosemont.
Speaker Change: And it is usually within the first four to six weeks post dosing and the clinical measures I think are going to be the biomarker at this point in time.
Speaker Change: Yes.
Speaker Change: Okay. Thank you.
Thank you.
Speaker Change: The next question we have comes from Silvan Chuckled Cohen with citizens. Please go ahead.
Speaker Change: Okay. Thank you very much and congrats on the update and thanks for taking my question.
Speaker Change: Maybe a follow up on <unk> earlier question I just wanted to see if there's any more color you can give us on the FDA feedback on the endpoints before you actually reveal the endpoint did they specifically I agree that it's not.
Speaker Change: That effort based and not objectives. Thank you.
Speaker Change: It's not effort based it is objective.
Speaker Change: And it's very clinically meaningful so again, we've highlighted silvan.
Speaker Change: So then I think over the last year, plus said the gains of function.
Speaker Change: Restoration of lost function is really something that's critically important to these patients.
Speaker Change: It's meaningful to the doctors.
Speaker Change: And it's also something when you start to think about even the payers.
Speaker Change: We were able to demonstrate that people are functionally improving.
Speaker Change: That that is going to be meaningful to that particular stakeholder group as well. So we'll outline specifically what this means and also how we would collect this data, but we've been doing it.
Speaker Change: Very analogous way in part a and then we will step through that when we present the data, but I think our view will be it should give a good lens. The part a data should give a good lens of what you can predict part b to look like.
Speaker Change: And we're excited to do that so again, we're pleased with Fda's alignment with this they've never been misaligned, it's only been.
Speaker Change: Give us a little bit more data and really it was they hadn't seen the natural history data.
Speaker Change: Until until this.
Speaker Change: This year, so again onwards for us in a great great question.
Speaker Change: Great. Thank you. Thanks, so much and congrats it sounds like a great update.
Speaker Change: Thank you.
Speaker Change: The final question, we have comes from Evan <unk> of BMO capital markets. Please go ahead.
Speaker Change: Hi, Marc Hoffman on for Edwin.
Speaker Change: And thanks for taking my question can you characterize your level of confidence in tissue I wanted to safety at this time with no <unk> or Sirius as today. It feels like we're getting to a point, where there is less risk, but just wanted to get your thoughts there and just a follow up to that can you indicate when the most recently dose patient was dosed again.
Speaker Change: I appreciate it.
Speaker Change: Yeah.
Speaker Change: On the safety piece, you know Sue maybe maybe you can take this this this question I would just say that keep in mind, we've now dosed.
Speaker Change: Our high dose patients.
Speaker Change: Those patients, which which is also comforting, but <unk>, perhaps you can give more color on given all your experience.
Speaker Change: Based on our data set is a vehicle that has no treatment emergent adverse events or dose limiting.
Speaker Change: Toxicity. So we have no concern given that the particular project is pretty benign.
Speaker Change: Efficacy is pretty obvious based on the data that they always reveal for the low dose the benefits follow up is the risk.
Speaker Change: Okay.
Speaker Change: Okay. Thank you.
Speaker Change: Thank you.
Speaker Change: Ladies and gentlemen, we have reached the end of our question and answer session I would now like to turn the call back over to Sean Nolan for closing remarks. Please go ahead Sir.
Speaker Change: Thank you very much operator, and thanks for everyone taking the time. This morning again I just want to say how pleased we are with the alignment we've obtained with the FDA. We look forward to the next steps team is working hard right now to finalize the protocol and the SAP.
Speaker Change: We are on track to make that submission this quarter again, which can enable us to begin to start site activation.
Speaker Change: Early is.
Speaker Change: Summertime, so look forward to the updates that IRS soften again, thanks for all your time take care.
Speaker Change: Thank you ladies and gentlemen, <unk> concludes today's conference. Thank you for joining US you may now disconnect your lines.
Speaker Change: Okay.
Speaker Change: Yes.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: Hum.
Speaker Change: Uh huh.
Speaker Change: Okay.
Speaker Change: Uh-huh.
Speaker Change: Uh-huh.
Speaker Change: Hum.
Speaker Change: Okay.
Speaker Change: Uh-huh.