Q4 2022 Taysha Gene Therapies Inc. Earnings Call
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Speaker 2: Greetings and welcome to the Taysha Gene Therapy's fourth quarter and full year 2022 earnings call.
Speaker 2: At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation.
Speaker 2: If anyone should require operator assistance during the conference, please press star zero on your telephone keypad.
Speaker 2: As a reminder, this conference is being recorded.
Speaker 2: It is now my pleasure to introduce your host, Haley Collins, Director and Head of Corporate Communications. Thank you, Ms. Collins. You may begin. You may begin.
Speaker 2: Thank you. Good afternoon and welcome to Taysha's fourth quarter and full year 2022 Financial Results and Corporate Update Conference Call. I'm Haley Collins, Taysha's recently appointed Director and Head of Corporate Communications. I will also be overseeing investor relations activities. I bring corporate communications experience in rare diseases.
Speaker 2: having previously served in a similar role at Jaguar Gene Therapy.
Speaker 2: I'm excited to join Tayshia at this pivotal time and look forward to working with the team to help bring potentially life-changing therapies to patients with rare diseases with high unmet medical needs.
Speaker 2: Earlier today, Tayshia issued a press release announcing financial results for the fourth quarter full year 2022. 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 Nagandharan, President and Head of R&D, and Cameron Alam.
Speaker 2: Chief Financial Officer. We will hold a question and answer session following our prepared remarks.
Speaker 2: Please note that on today's call we will be making forward-looking statements, including statements relating to the existing clinical data for TASIA 120 and the therapeutic and commercial potential of TASIA 120 and TASIA 102.
Speaker 2: These statements may include expected timing and results of clinical trials of our product candidates and other clinical and regulatory plans and the market opportunity for those programs. This column may also contain forward-looking statements relating to TASIA's growth, forecasted TASH runway and future operating results.
Speaker 2: 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 TASCHA's actual results to differ materially from those stated or implied in such forward-looking statements.
Speaker 2: 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.
Speaker 2: and the requirements of substantial funding to conduct our research and development activities.
Speaker 2: for a list and description of the risks and uncertainties that we face.
Speaker 2: Please see the reports that we have filed with the Security and Exchange Commission, including our annual report on Form 10-K for the year ended December 31, 2022. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 28, 2023.
Speaker 2: TASIA 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 3: Thank you Haley and welcome everyone to our 2022 fourth quarter and full year financial results and corporate update conference call.
Speaker 3: Today I will begin providing a brief corporate outlook for 2023. Then, Suku Nganiram, President and Head of R&D of Tayshia, will provide an update on our clinical development programs, followed by a financial update from Cameron Alam, our Chief Financial Officer.
Speaker 3: I will then provide closing remarks before opening the call up for questions.
Speaker 3: The actions taken earlier this year to improve execution and expedite progress with our two lean clinical programs in Rett syndrome and GAN are having a positive effect. For TASIA 102 and Rett syndrome, we remain on track to execute across our timelines for both initial available safety data.
Speaker 3: regulatory submissions this year in our ongoing Phase 1-2 Reveal Adult Study.
Speaker 3: Suku will provide further details here shortly.
Speaker 3: Fertatia 120 in GAN, an ultra rare disease with no currently improved treatments.
Speaker 3: We recently received constructive feedback from the FDA regarding our follow-up questions to the Type B and the Phase II meeting.
Speaker 3: We are completing a comprehensive review of the data from the ongoing natural history and interventional trial, including functional, biological, and electrophysiological assessments. The preliminary analysis appears encouraging, and we believe there are some compelling new findings that we intend to share with the FDA.
Speaker 3: to further discuss a potential regulatory path forward. Again, Suku will discuss this in further detail shortly.
Speaker 3: In the year ahead, we remain focused on achieving the anticipated near-term milestones in our Rett Syndrome and GAN programs and continue to work towards our mission of bringing transformational new treatments to patients with these devastating neurodegenerative diseases.
Speaker 3: I will now turn the call over to Suku to provide a more in-depth discussion of our Rett Syndrome and GAN programs. Suku?
Speaker 4: Thank you, Sean, and good afternoon, everyone. First, I will start with an update on TASIA-102, a gene therapy program for the treatment of Rett syndrome.
Speaker 4: As a reminder, TASIA 102 utilizes an innovative miRNA responsive auto-regulatory element or miRAIR platform designed to regulate the cellular expression of MECP2 for the treatment of rep syndrome.
Speaker 4: TESHA 102 has received orphan drug and rare pediatric disease designation from the FDA and has been granted orphan drug designation from the European Commission.
Speaker 4: In our Revealed Phase 1-2 trial in adult patients with Rett syndrome, we recently initiated screening for the first potential patient.
Speaker 4: And we anticipate dosing the first patient in the first half of the year.
Speaker 4: We remain on track to report initial available clinical data, primarily on safety for TASIA 102 in the first half of 2023 and plan to provide quarterly updates on available clinical data thereafter.
Speaker 4: Importantly, we recently submitted a protocol amendment to allow patients as young as 15 years old to be included in the study, which we believe will further expedite enrollment.
Speaker 4: In the second half of the year, we intend to continue dosing patients with threat syndrome in our revealed trial. The second half of the year, we intend to continue dosing patients with threat syndrome
Speaker 4: For our study of pediatric patients with Rett syndrome, we plan to submit a CTA to the UK HRA-PATESHA-102 in mid-2023.
Speaker 4: We also have an INB application submission to the US FDA planned in the second half of the year.
Speaker 4: Now let's turn to TASIA 120 for the treatment of GAN, which to reiterate is an ultra-rare neurodegenerative indication with no approved treatments or established regulatory pathways.
Speaker 4: TESHA 120 has received orphan drug and rare pediatric disease designation from the FDA and has been granted orphan drug designation from the European Commission.
Speaker 4: In regards to manufacturing, we recently submitted a CNC Module 3 Amendment submission to the FDA detailing our Commercial Process, Product Manufacturing and Drug Comparability Analysis.
Speaker 4: As Sean mentioned, we also received feedback from the FDA in response to our follow-up questions to formal Type D, end of Phase II meeting minutes.
Speaker 4: The FDA- clarified MFM32, the primary efficacy scale, discussed at the FDA Type B end-up phase two meeting as a relevant primary endpoint only in the setting of a randomized, double-blind control trial, while also acknowledging the research challenge in executing and enrolling such a study design with the ultra-annual nature of GANs.
Speaker 4: As such, the FDA 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 treatment effect that is self-evident and clinically meaningful.
Speaker 4: We are completing a comprehensive review of data from the ongoing natural history and interventional trial, including functional, biological, and electrophysiological assessments, which will inform our plans for future interactions with DFDA. The ongoing analysis includes functional assessments of NFN32, and the analysis of NFN32, and the
Speaker 4: and ataxia. As progressive gait and limb ataxia is a common clinical manifestation observed in patients with GAN that often leads to rough stimulation by the second decade.
Speaker 4: Additionally, we continue to analyze functional and structural aspects of the retina and optic nerve, given that GAN patients experience deterioration of visual acuity and optic nerve degeneration over time.
Speaker 4: We are also conducting several objective biological and electrophysiological assessments, including sensory nerve action potential, nerve and skin biopsies, ganglion cell and retinal nerve fiber layer thickness, brain and spine MRI images, and muscle responses to nerve activation. THIS rock
Speaker 4: to determine whether there is a relatively large treatment effect that is self-evident and clinically meaningful. We intend to continue a collaborative dialogue with the FDA regarding the potential registrational path to bring TASIA 120 to patients with GAN who to reiterate have no approved treatment or established regulatory pathway.
Speaker 4: We plan to submit a formal meeting request to the agency in the second quarter of 2023 to further discuss the potential regulatory pathways forward for this ultra rare disease. We plan to submit a formal meeting request to the agency in the second quarter of 2023 to further discuss the potential regulatory pathways forward for this ultra rare disease.
Speaker 4: I will now turn the call over to Cameron to discuss financials. Cameron?
Speaker 5: Thank you, Suku. Research and development expenses were $13.9 million for the three months ended December 31, 2022 compared to $37.9 million for the three months ended December 31, 2021.
Speaker 5: Research and development expenses were $91.2 million for the full year ended December 31, 2022, compared to $131.9 million for the full year ended December 31, 2021.
Speaker 5: The $40.7 million decrease was primarily attributable to a decrease of $20.3 million in research and development manufacturing and other raw material purchases and a $9 million decrease in license fees. The decrease in research and development expenses for the year ended December 31st, 2022 was also attributable to a $12 million decrease in license fees.
Speaker 5: and third-party research and development policies mainly related to non-clinical...
Speaker 5: in toxicology studies and a $4.7 million decrease in compensation expense as a result of lower headcount.
Speaker 5: Overall, lower research and development expenses for the year ended December 31, 2022 were partially offset by higher clinical trial expenses of $2.4 million and higher severance expense of $2.9 million in 2022.
Speaker 5: General and administrative expenses were $7.3 million for the three months ended December 31, 2022, compared to $11.8 million for the three months ended December 31, 2021. General and administrative expenses were $37.4 million for the year ended December 31, 2022.
Speaker 5: compared to $41.3 million for the year ended December 31, 2021. The decrease of approximately $3.9 million was primarily attributable to $5 million of lower consulting professional fees and reduced compensation expenses driven by lower headcount in 2022.
Speaker 5: Lower general and administrative expenses were partially offset by $1.1 million of severance expense.
Speaker 5: Net loss for the three months ended December 31, 2022 was $55.7 million, or $0.99 per share, as compared to a net loss of $50.4 million, or $1.32 per share, for the three months ended December 31, 2021. In November 2022, we recorded a $36.4 million non-cash...
Speaker 5: non-recurring impairment charge related to the North Carolina manufacturing facility. Currently, we are in the process of actively looking for buyers for the North Carolina manufacturing facility.
Speaker 5: The net loss for three months on December 31, 2022 was partially offset by revenue of $2.5 million recognized related to the Estella's transaction.
Speaker 5: Net loss for the full year ended December 31, 2022 was $166 million, or $3.78 per share, as compared to a net loss of $174.5 million, or $4.64 per share, for the full year ended December 31, 2021.
Speaker 5: As of December 31, 2022, Tayshia had $87.9 million in cash and cash equivalent.
Speaker 5: The company continues to expect that its current cash resources will support planned operating expenses and capital requirements into the first quarter of 2024. I will now return the call back over to Sean for his closing remarks. Sean?
Speaker 3: Thank you, Cameron.
Speaker 3: I am pleased with the progress we have made with our two lead programs during the first few months of 2023, including initiating screening of the first potential patient in the adult RET study and submitting a protocol amendment that should further expedite patient enrollment.
Speaker 3: For Gantt, we are encouraged by the constructive feedback received from the FDA and the preliminary assessment of the comprehensive data analysis to support a formal meeting request in the second quarter to further discuss the potential regulatory path forward. Our focus throughout this year will be on the execution and delivering across our planned milestones for...
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Speaker 6: One moment please while we pull for questions. Thank you. And our first question is from Yanan Zhu with............
Speaker 6: Wells Fargo Securities
Speaker 4: Please proceed with your question. Hi. Thanks for taking our question. This is Kuan Tong for Yana. So my question is on the red syndrome program. So given that a KDS-A bill is now approved for red syndrome patient a, it is slowly going to take over the a fever,
Speaker 7: 5 to 20, how would that affect your clinical study contact and enrollment, particularly for the UK study? And do you need to include debut into your trial design? Thank you.
Speaker 3: Thank you very much for the question. We've certainly given us a great deal of thought in our planning and I'd like to ask Suku to provide some perspective on that. Suku?
Speaker 3: question. We've certainly given this a great deal of thought in our planning and I'd like to ask Suku to provide some perspective on that. Suku? Yeah, thanks, Sean.
Speaker 4: This is an important question that you asked because I think getting a product approved for a terrible disease like Rett, I think is very important for the whole disease state and the patient population. What I would also identify is that by having a trophilinotide approved, it also increases the awareness of the disease state amongst the physician and patient communities.
Speaker 4: which could potentially increase the number of accessible, prevalent patients and also result in, I think, some serious discussion at the state and federal level when it comes to newborn screening, which could further increase the number of patients available from an incident standpoint. So what I'm saying is collectively this could be a real plus.
Speaker 4: for the whole disease community, but also for sponsors like us who are doing interventional trials. Now to address your question about whether, once you have an approved product like Trufluentide, where the mechanism of action obviously is very different from our product, PESA 102, which addresses the root cause of the disease.
Speaker 4: We would ideally like to treat patients that are treatment-naive such that we can optimize and show the FDA and other regulatory authorities and the patient communities and the healthcare providers who treat this disease that this product will have significant impact on clinical progression of disease. Now, that is the hope. For change as a new PIV diet, you can offer ones that are still 21 tossed with our Obama Single-
Speaker 4: If there is an approved product, there is always a possibility that we may have to have an arm which has a combination product evaluation as well. And that is something we would be happy to discuss further with the regulators and take it on a case-by-case basis. But my team is all considering this in the protocol design for the future. Sean, anything else you would like to add? The only other thing I would add is that
Speaker 3: that you can potentially access. And we experienced with Zolgensma studies that even with the addition of Spinraza, patients would be willing to either wait or wash out from taking those other medicines. So we'll certainly keep an active eye on the impact that Tofenotide is having.
Speaker 3: We've given it a great deal of consideration into our scenario planning for clinical trial designs, and we remain confident that we'll be able to enroll patients in the US and in other geographies including, you know, Canada and the UK. So thank you.
Speaker 4: the trials are very high due to GI symptoms. And I've forgotten the exact numbers, but you may have to look that up. I think it was anywhere from, I don't know, 70 to even 90% in some of the trials. So that may have significant impact on more patients being available, even though this product is available for patients with threat syndrome.
Speaker 8: Very clear, thank you.
Speaker 6: Thank you. Our next question is from Whitney E. Jem with Panaccord. Please proceed with your question.
Speaker 9: Thanks for taking the question. Excuse me. So, for again, you kind of listed out a lot of additional endpoints functionally biomarker, et cetera that you're looking at. And I'm just curious, are those things that were collected all the way along, hadn't been analyzed or focused on, or those things that you are...
Speaker 9: calling patients back in now to look at and will be comparing to natural history. And then part two of my one question is, is the goal there to kind of continue the dialogue with the FDA, use that data to potentially support filing or use that data to design another study?
Speaker 3: So I'll take a first look at that, Suku, and feel free to to opine. We're going to have to answer the first part of your question. This is data that's existing in the database. So these are patients, remember there's been 12 patients that have been treated. We've got the natural history before they were treated.
Speaker 3: then all the study visits over the course of time, in some cases many many years, and there are a multitude of assessments that were done and what Suku's team has been doing is is comprehensively and systematically going through all of that data.
Speaker 3: to fully assess it and to see if there are additional data points that can—or metrics—that can augment and further demonstrate the clinically meaningful effect and the objective measurement effect of—
Speaker 3: of the treatment on these patients suffering from GAN. And to answer your second question, I'll turn it over to Suku. The idea would be that we would submit a formal meeting request this quarter, or the second quarter.
Speaker 3: to dialogue with the FDA about this data and we will put forward after we fully have analyzed this, you know, our view on what we think is the appropriate pathway forward and you know that that could very well be you know trying to seek approval with the existing data.
Speaker 3: So we haven't made a final determination yet, but we're encouraged by the data that we've gathered thus far and how it's starting to line up.
Speaker 4: Sugu, what would you add or clarify to what I said? Yes, John , thank you. So as you highlighted, it's an ultra rare disease.
Speaker 4: with no available treatment, very small patient population. And the patients were treated, in general, they were more than six years of age. So what we've observed is a slowing of disease, as we've all previously talked about when it comes to MFM32. And as Sean pointed out, there were many efficacy endpoints in the protocol that the NIH designed.
Speaker 4: And it's that data set that we're looking at when it comes to functional, biological, and electrophysiological endpoints, but we're also doing some modeling work. And we think that comprehensive data analysis should give us enough information to go back to the FTN request, a meeting in the second quarter of this year, for further discussion on what is the best path forward.
Speaker 4: in a data set that we think could really make a difference in these patients' lives, especially given it's an ulcerative disease with no other treatments available. So cautiously optimistic as we collect all the data, work with the NIH, and then go to the FDA, hopefully, and hopefully move this program forward. Thanks for the question.
Speaker 4: that we think could really make a difference in these patients' lives, especially given it's an ulterior disease with no other treatments available. So cautiously optimistic as we collect all the data, work with the NIH, and then go to the FDA, hopefully, and hopefully move this program forward. Thanks for the question. Thank you.
Speaker 6: Thank you. Our next question is from Jack Allen with Baird. Please proceed with your question.
Speaker 10: Great. Thank you so much for taking the question. I'm going to stick with GAN here. I was wondering if you could provide an update as to where things sit as it relates to the Estellas option for GAN. How are you thinking about the XUS opportunity? And then what's the turnaround time for the meeting request and who have you been meeting with specifically at the FDA? I'd love to get any insights there.
Speaker 3: FDA is going to be there, it's premature for us to say. We could not definitively, you know, make a statement relative to that. You know, we'll do everything we can to make sure that the package that we put together is as compelling as possible based on both the natural history and the interventional data. And your point about Peter Marks's
Speaker 3: is a good one. I mean obviously we're headquartered in Dallas, the MDA conference was in Dallas. There was a lot of buzz about some of the comments that he's made about how to deal with ultra orphan diseases. And obviously we feel like this one fits the bill tremendously and that flexibility.
Speaker 3: May lend itself well to the to the program, but we also understand we have to make that that case there's new leadership there now with Celia Witten taking taking over and It'll think we're all you know watching to see what will what will happen
Speaker 3: And hopefully we can get some additional flexibility, as Peter's kind of outlined in many of his public remarks over the course of time.
Speaker 3: Um, Suku, do you mind taking on the other two questions from Jack? Jack, you might want to just, if you're on the line.
Speaker 4: Can you repeat the questions because that's a lot of questions that you asked.
Speaker 10: Thanks so much and I apologize I know we're still too limited to one but the other questions I had were surrounding the Estellis option where does that fit or where does that sit as it relates to GAN and then maybe if you could just touch on the XUS path forward for GAN and how you're thinking about potentially filing in Europe I would think. Thanks so much. Tom, do you want me to take that or would you like to take that?
Speaker 3: I'll take it. On the ex-US piece, Jack, we're not, we're focused right now on the US. So we have not had additional interactions with anyone overseas since the initial discussions, and we want to focus all of our efforts, energy, and resources right now on the US.
Speaker 3: As it relates to the Estellas option, you know, that is, we really haven't provided too much detail about that, but what I would say is that, you know, we're still in a window where Estellas has, you know, the option and the time to evaluate whether or not they want to opt in. I think...
Speaker 3: it stands to reason that they would likely
Speaker 3: you know, make a decision after we have this upcoming FDA meeting that we're planning to have. So we're planning to submit the meeting request in the second quarter.
Speaker 3: hopefully mid-ish year we have that actual meeting. And again, I can't speak for Estellas, but I would say around that time is when they would have the information to make a more fulsome decision on whether or not they want to opt in on the program. So it's still a very active opt in.
Speaker 4: as you know, could be 30 days or anywhere from 30 to 75 days, depending on the type of meeting request from the FDA. So.
Speaker 10: Thank you so much. I appreciate you taking the question.
Speaker 10: Thanks so much. Thanks for being a question.
Speaker 6: Thank you. Our next question is from Gil Bloom with Needham and Company. Please proceed with your question. The approached number wasciplinary3000 imports should be available via eRIBS and memberships will soon be national
Speaker 10: Hi, this is Robert on for Gil. Thanks for taking your questions. Can you just talk about the ex US market for Tayshia 102? And would you be open to partnering the program?
Speaker 3: Well, I would say that the opportunity is significant. I think when we talk about the fact there's approximately 20, 25,000 patients in the U.S. and E.U. combined, so the opportunity over there is significant. There's good infrastructure. There's good infrastructure.
Speaker 3: over there in terms of clinical study sites, treatment centers, the patients are well identified. So we're encouraged by the opportunity over there. It's one of the reasons, you know, we've focused our clinical efforts in submitting that CTA mid-year into the UK. Thank you very much.
Speaker 3: Just trying to think of the second part of the question.
Speaker 3: Well, the partnering aspect.
Speaker 3: I would say that that's something that we would potentially consider. I think you always have to look at all options, your current...
Speaker 3: your current capital situation and make a determination on resource wise, you know, is it and otherwise Is it better to partner that or better to keep it to yourself right now? You know the plans are for us and we're and we're you know, we have the we have the funding this year to execute the trial as we've outlined it the plan trial I should say
Speaker 6: with JMP Securities. Please proceed with your questions.
Speaker 10: Yeah, thank you. Thanks for taking my questions Just to come back to again. I think the last time the SBA I thought that you mod Modest or I don't remember exactly the wording effect on the MFO on the primary endpoint And that's why they wanted maybe a controlled trial
Speaker 10: But, I mean, obviously, those are just words. And so how do we know now that they're open to a strong efficacy measure that you have met the bar with these additional end points? Could you stack them together to show a strong outcome here with the data at hand? Or how do you imagine this will play out? Thank you. Well, I would say, first of all, that what the FDA said
Speaker 3: even subjective, you need to have a double-blind randomized controlled trial.
Speaker 3: So when we went back to them and we asked the subsequent questions, you know, I would say that the new news is that they restated the review on MFM 32, but then they said that they're willing to evaluate alternative trial designs.
Speaker 3: that are controlled, and a control can be natural history, as you know, that have endpoints that are clinically meaningful and essentially objective.
Speaker 3: And so, you know, that is a, I would call it a door that was, a new door open there, you know, opportunity wise, that makes a lot of sense to us.
Speaker 3: So that's incumbent upon us to determine what do we think is the data that would justify and address those two aspects? What is clinically meaningful and what is objective? And so with that I'll turn it over to Suku to just give you flavor of the totality of data that we're looking at.
Speaker 4: those remarks at the MD were very important and hopefully will have some strategic impact on any sponsor that's dealing with an ultra rare disease, GAN or otherwise. As Shawn pointed out, as we continue our in-depth detailed analysis, the big question here is it's not just a MFM32, there are multiple other efficacy endpoints.
Speaker 4: And the question is, will our intrathecal gene therapy actually show broad clinical impact, some or most of which could be collectively considered clinically significant, whether it's really in a very large way or even in a moderate fashion in an ulcerative disease that allows us to make a case on behalf of patients and as a sponsor of our effort with the
Speaker 4: for potential accelerated approval or an approval that is acceptable such that we can make this medicine available to the patient community. And as Sean pointed out, it's the collective breadth of data, I think, that could eventually make the case for this therapy or further review at the FDA and for us to make the case for the submission of a meeting with the FDA in the second quarter. So I hope you understand what I'm trying to explain. It's not just MFM32. There are multiple other end points that I think we should look at those multiple times. And I hope you'll follow Sean's point at the top of the room. Perhaps today, there are some maybe familiar same minute areas that shouldn't be seen for the com Forty one it seems like and maybe the New York Times
Speaker 4: that we've observed with the help of the NIH and other experts that are presenting this ulcerative disease called GAN that our product may have clinical impact. And I think that collective case is what may give strength to the potential review and approval of the product. So stay tuned, and I'm keeping my fingers crossed. That's what we can do for this creation community. Thank you. Great. Thank you very much.
Speaker 6: Thank you. Our next question is from Yun Zong with BTIG. Please proceed with your question.
Speaker 11: Hi, thank you very much for taking the question. So my question is on the RET syndrome program. And so the change in the patient age to treat patients as young as 15 years old, in addition to helping patient enrollment maybe, do you have any other goals that you would like to achieve in terms of treatment outcome analysis and
Speaker 4: The initial data, would that be safety only, or will you be able to provide any additional information? Suku, would you like to take this question, please? Yes, John , I will. I will, absolutely. So this is another very important question. So that was a very important clinical reason.
Speaker 4: That's my team and obviously as a sponsor, we decided to submit this updated version for amendment to Health Canada because by dropping the age to 15, and we do have free clinical data and other data that supports us doing this, it enables us to treat a younger group of patients.
Speaker 4: which we think in this neurodevelopmental disorder may allow us to have greater impact over time. So the question on the table is, A, by dropping the age and having certain endpoints in our efficacy measures and also evaluating safety, will we not only have access, hopefully, to more patients, given that it's now a larger patient pool,
Speaker 4: but could we also show greater clinical impact that goes beyond safety in a much shorter time frame? So the question is, when you treat adult patients who have more mature disease or more progressive disease...
Speaker 4: over the age of 18, will it take much longer for any product to have impact versus once you drop the age? Could you have much greater clinical efficacy impact? So I hope even though the initial data set that we'll accumulate over time will be safe to do it, the big question on the table is will we also show greater clinical efficacy impact? And my hope as a clinician is that is what we will also see which will allow us to show the strength of our gene therapy.
Speaker 6: Our next question is from David Huang with SMBC. Please proceed with your question.
Speaker 12: Thanks for the update and taking my question. I had one question just with Dan. Are you formally considering an accelerated approval pathway there? Is that something given the endpoints and the data that you are now reviewing?
Speaker 12: Do you think that path would be available to pursue? And if so, why or if not, why not?
Speaker 3: Suku, would you please take that question?
Speaker 3: Suku, would you please take that question? Yes, Shawn.
Speaker 4: I can only give you my opinion based on the data that I've seen and our overall regulatory discussions, right? So obviously, what we can do is look at our data set, see if the broad impact of our product, the gene therapy, is truly clinically meaningful. And then as for the meeting with the FDA, we can look at our data set and see if the
Speaker 4: And absolutely, we believe our product is truly making a difference in this ultra-rare disease, while there is no treatment option available, I would absolutely love to ask for the FDA to consider our products for accelerated approval such that we can make the medicine available to patients. But the caveat is this, right? So this I have to be very clear on. We have to have a collective data set that truly enables us to make a convincing case that is not the case, but is not the case. So, we have to be very clear on this. We have to make a convincing case that is not the case. We have to have a collective data set that truly enables us to make a convincing case that is not the case, but is not the case.
Speaker 4: with the FDA that this gene therapy qualifies by accident approval. So that is what we're hoping for, and that is the plan when we submit our request for an FDA review once we do complete our full analysis, okay? So I hope that helps, and I don't know if you wish to add anything more to what I said. Yeah, look, the only thing I would add to that is, when you think about some of the remarks from what Dr. Peter Marks has said multiple times publicly, if you think about the disease...
Speaker 3: aggressive.
Speaker 3: presentation we can based on data for patients and to get them this product as soon as possible given that there's nothing available at this particular point in time. So if we're convinced the data is compelling and meets the bar, we would push hard for something like that. For more information, visit www.ottobock.com
Speaker 6: Thanks for the question. Thank you. Our next question is from June Lee with tourist security.
Speaker 6: Thank you. Our next question is from June Lee with tourist security. Please proceed with your question.
Speaker 10: Hi, thanks for the update. You know, when you say in your press release that the FDA is open to regulatory flexibility in a quote-unquote controlled trial setting, does that necessarily refer to placebo controlled trial setting or can that include some other controlled setting? And if it's the latter, what could it be? Well, I'll give you my answer to that and Suku's answer.
Speaker 3: a double-blind placebo-controlled trial. And the language written in the responses that we got from the FDA are clear on those. When they were talking about MFM32, they were talking about a double-blind placebo-controlled trial. When they were talking about alternate trial designs that met MFM32, they were talking about a double-blind placebo-controlled trial.
Speaker 3: bar of clinically meaningful and objective endpoints, they talked about a controlled trial.
Speaker 3: So I think they're speaking to the letter of the guidance, but Suku I would ask you for further clarification on that.
Speaker 4: Yeah, thanks, Sean. So, given that it's an out-of-air disease, doing a placebo-controlled trial, I don't think will be practical and could take forever. So, if there are alternative study designs necessary or have to be discussed, the simplest would be, you know, to dose a few more patients where you already have pre-treatment natural history for comparison. So, basically, most patients take a
Speaker 4: With that caveat, our hope is that the collective data set that is submitted to the FDA will qualify for a serious review and potential appropriate approval if the FDA thinks that's the best path forward for the patient community. So I would leave it at that. And, Sean, is there any other question you wish me to address? So hopefully we addressed...
Speaker 4: our hope is that the collective data set that we submit to the FDA will qualify for a serious review and potential appropriate approval if the FDA thinks that's the best path forward for the patient community. So I would leave it at that. And, Sean, is there any other question you wish me to address? So I hopefully we addressed the question that was asked.
Speaker 6: No, I think you do. Okay, thank you. There are no further questions at this time. I would like to turn the floor back over to Sean Nolan for closing comments.
Speaker 3: Thank everyone for their time and interest in what we're trying to accomplish here at TASIA. I'm very pleased at the progress we've made in the short time period of 2023. We've got a long way to go. We're working hard and we look forward to sharing future updates with you in the coming months. Thank you all and have a good night.
Speaker 6: This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.
Speaker 1: I P.