Ladies and gentlemen, thank you for standing by. My name is Krista, and I'll be your conference operator today. At this time, I would like to welcome you to the Tenaya Therapeutics Interim Clinical Data for TN-201 conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question at that time, simply press star followed by the number one on your telephone keypad. If you'd like to withdraw that question, again, press star one. Thank you. I would now like to turn the conference over to Michelle Corral, Vice President of Corporate Communications and Investor Relations. Michelle, please go ahead. Thank you, Krista, and good morning, everyone. As introduced, I'm Michelle Corral, and your point of contact. If you have any follow-up questions after the call or are interested in speaking further with the team. It's been an eventful few days, and we are looking forward to reviewing the interim data from our MyPEAK-1 phase Ib/IIa clinical trial of TN-201 for MYBPC3-Associated HCM. These data were presented this weekend at the American Heart Association's scientific sessions during a late-breaker session devoted to the topic of advancements in HCM care. Joining us on today's call are Faraz Ali, Tenaya's Chief Executive Officer, and Dr. Whit Tingley, Chief Medical Officer. While the data we are disclosing will be described in full verbally, please note that during the course of today's talk, we will be making references to slides. A PDF file of these slides is available on the Tenaya website in the IR section under Events and Presentations. Picking up on slide two, you'll see a reminder: the information discussed during this call will include forward-looking statements which represent the company's views as of today, November 11th, November 10th, 2025. These statements involve certain assumptions, and we caution investors not to place undue reliance on this information. Please refer to today's press release as well as our filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by these statements. With that introduction complete, let me turn the call over to Faraz Ali for opening remarks. Faraz. Thank you, Michelle, and thank you to everyone for joining us today. Tenaya has made significant progress over the last year across our two Gene Therapy programs, TN-201 and TN-401, and we are pleased to be sharing the first of two meaningful data readouts with you today. After some brief state-setting remarks and a regulatory update, Whit will be walking us through the status of the TN-201 Gene Therapy program for MYBPC3-Associated Hypertrophic Cardiomyopathy and today's main event. A recap of the data presented this past week and the discussion of why we are excited about the continued strong emerging data package from this phase Ib/IIa clinical trial. On slide four, on Saturday at the American Heart Association's 2025 scientific session, Dr. Milind Desai, a renowned cardiologist, Director of the HCM Center at the Cleveland Clinic, and an investigator on the trial, presented interim data from the MYBPC3-associated clinical trial of TN-201 Gene Therapy. This was a late-breaker presentation on the main stage at AHA during the session dedicated to advances in Hypertrophic Cardiomyopathy care and in promising genetic medicine took a commanding spotlight. Simultaneous with Dr. Desai's presentation was the publication of these promising data in cardiovascular research, which you can see on slide four. Links to both the slides from AHA, which we are presenting to you today, and the publication are also posted to the Tenaya website. Today's presentation will also include a few extra slides of data and content that we believe are important but that could not quite fit through the 10 minutes available to Dr. Desai at the AHA presentation. Moving on to slide five. The data presented from MyPEAK-1 included longer-term follow-up from Cohort 1 patients that first looked at results from Cohort 2. For those following along with the presentation accompanying this call, on slide five, we're jumping right into the results at a high level. First, all patients on study really have objectively severe disease at significant hypertrophy levels that we will be putting into perspective over the course of this presentation. The unmet need is high. Second, TN-201 has been well calibrated at both the 3E13 vector genome per kilogram and 6E13 vector genome per kilogram doses. Further, through our experience in dosing patients, we have optimized our prophylactic immunosuppressive regimens and monitoring such that we have reduced steroid use without increasing AEs or sacrificing safety. Importantly, from the biopsies, MYBPC3 protein levels increased in all patients, including we can say confidently with the benefit of baseline biopsies. They did so in a dose-responsive manner. In fact, with two times higher transduction and expression observed in the first evaluable Cohort 2 patient. Importantly, the positive indicators of TN-201's activity from the biopsy that we reported earlier this year are deepening over time, and we're seeing multiple measures of disease moving towards normalization, including circulating biomarkers and hypertrophy and measures of burden of disease on daily living. We'll place the changes in hypertrophy findings into broader context towards the end of this presentation since it really defines this condition. We are very encouraged by the emerging safety profile and biopsy results that we can share with you today. Beyond safety and biopsy, we're pleased by the early but meaningful signs of clinical activity observed. Our next steps are to continue to follow the maturation of clinical data in these patients and to resume dosing once we have implemented certain changes to our protocol requested by the FDA. With that, we are transitioning. I've been told that my audio is a little bit choppy. I am not sure why. I will try to make a modest adjustment here. If that improves things, then my team will tell me if it does. On slide six, before we go deeper into these data, I'd like to briefly address a surprising but ultimately benign action taken by our reviewers at the FDA. In the course of proactive outreach to regulators to discuss data obtained to date, they obtained a request for certain protocol amendments in order to minimize potential site-to-site variability. Most of these changes were intended to standardize patient monitoring and individualized immunosuppression that we have successfully put into practice. During this time, while we're making those protocol changes, the enrollment in MyPEAK-1 is on clinical hold. We have already submitted a revised protocol to the agency in response to their requests. We agree with the recommended changes, which were consistent with our plans anyway as we look ahead to TN-201's future development. Importantly, there have been no recent safety events of concern related to TN-201. Prior to the FDA communication, the MyPEAK-1's independent DSMB endorsed enrolling patients in expansion Cohorts at either dose level and continuing the trial with no changes. We are working very collaboratively with the agency to resolve this matter swiftly and currently do not anticipate this action will have any impact for overall data development milestones and near-term data milestones and development timelines. On slide seven, given the lack of any recent treatment-related adverse events, the hold action was quite unexpected. Given the backdrop of certain safety events reported in the field, the FDA's caution is understandable. As we've shared with many of you since the summer when other Gene Therapy sponsors reported deaths or other severe events that appeared to be associated with their respective approaches to immunosuppression and the underlying disease, we do not see any direct read-throughs from those situations to our program. We believe Gene Therapy safety is multifactorial, and we have taken a very comprehensive approach to safety, summarized in slide seven, that takes into consideration factors like gaps in selection, cassette design, dose, immunosuppression agents, all against the backdrop of the condition being treated. Each of our trials includes its own panel of independent experts in cardiology, hepatology, immunology, and Gene Therapy. Safety Monitoring Board reviews safety data for each patient following dosing and looks per protocol at results from each cohort. The U.S. FDA is also kept informed periodically of any and all adverse events in our study, whether treatment-related or unrelated. As we prepared for our IND, we even surveyed other sponsors to learn from their experiences and designed our immunosuppression and monitoring protocol accordingly. As a reminder, for both TN-201 and TN-401, we utilize prophylactic Sirolimus and Prednisone that are administered in the weeks ahead of dosing and then continued thereafter and then tapered. Patients also have the option of a C5 complement inhibitor that can be used reactively on demand if needed. To date, we have not had a situation where that has been warranted. We keep patients in hospitals for close monitoring of any signs of unusual activity. As we've gone along in the clinic, we've increased the frequency of lab assessments and patient monitoring to enable swift interventions and to inform individualized tapering. We have learned a lot so far, and our learnings from patient monitoring and tapering are what we've been asked to protocolize by the agency such that should we expand to new sites in the future, we minimize the variabilities and the potential for variabilities in how immunosuppression is administered, monitored, and tapered from site to site. With that under our belt, I'd like to ask Dr. Whit Tingley to tell us about the TN-201 development program and specifically the data presented this weekend from the MyPEAK-1 clinical trial at AHA. Thank you, Faraz, and good morning to everyone on the line. Thank you for joining us. Those of you who have been following Tenaya will likely recognize slide nine, but as a reminder, MYBPC3-associated HCM is the most common genetic form of Hypertrophic Cardiomyopathy associated with 57% of familial HCM cases and estimated to affect 120,000 adults, adolescents, and children in the U.S. alone. As you will hear more today, this is a severe and progressive condition in which the heart walls become significantly thickened, impinging on the capacity of the ventricle to expand until it is too stiff to pump enough blood to meet the body's needs. The disease also causes fibrosis and leads to abnormal heart rhythms, heart failure, sudden cardiac arrest, and in the worst cases, death. In spite of innovations in the field, there is significant unmet need, particularly among patients with the non-obstructive form of Hypertrophic Cardiomyopathy. Non-obstructive disease accounts for 70% of all MYBPC3 cases. There are no approved therapies that address the underlying genetic cause of this condition. Our lead Gene Therapy program, TN-201, is the first treatment being developed to address genetic mutations that cause this disease. Slide 10 offers an illustration of its intended mechanism. Causal variants in the MYBPC3 gene fail to produce protein, resulting in low levels. MYBPC protein is essential for regulating heart contraction. It determines the force and speed of each contraction and relaxation based on the body's current needs: a little at rest, a lot during exertion. It does this by coordinating the thick and thin filaments of the sarcomeres in the muscle tissue. When there is not enough MYBPC protein, sarcomeres produce too much force overall, ultimately leading to cardiomyopathy. TN-201 directly addresses this phenomenon by delivering a full-length, healthy, and functioning copy of the gene to heart cells, which then produce MYBPC protein. The overall vision and design of TN-201 is to increase MYBPC protein levels, fix the cause of disease, halt progression, and potentially reverse symptoms, and do all this with a single dose of one-time IV treatment. A brief overview of the MyPEAK-1 phase Ib/IIa study is provided on slide 11. This is a multicenter open-label dose escalation trial designed to assess the safety and tolerability of TN-201. It is also designed to identify the optimal dose. Finally, it collects numerous data points for an early look at TN-201's activity, though the study is not powered for efficacy. I'm happy to say we've completed the dosing of both cohorts, one and two. Over the summer, the study's independent Data Safety Monitoring Board reviewed all available safety and activity data across both of these Cohorts and recommended the trial proceed per protocol with dosing of additional patients at either dose level in the expansion part of the protocol. There have been no meaningful safety events since that DSMB review in the summer. Now we'll turn to the new data presented Saturday at the American Heart Association meeting underway here in New Orleans. Slide 13 shows the baseline characteristics for the six patients from Cohorts 1 and 2, consisting of five women and one man between the ages of 27 and 63. All have objectively severe disease. All six have non-obstructive disease and are at high risk, requiring implantation of a cardiac defibrillator device to prevent sudden death. Four of the six have previously undergone myectomy and open-heart surgery to directly treat extra heart muscle at the outflow tract. Despite this, they remain symptomatic. All were experiencing symptoms of heart failure interfering with daily living and meeting New York Heart Association class two and three. Left ventricular mass index, a key measure of hypertrophy, is higher in these study participants than in most HCM patients. The data in this presentation includes over one year of follow-up for all Cohort 1 patients. Cohort 2, on the other hand, has a shorter follow-up of 26 weeks or less. Unfortunately, patient five has decided to withdraw from the study for unclear reasons and stop participating in assessments at the study center. However, she did successfully complete the immunosuppression regimen, and local safety laboratories have been very reassuring. All other patients remain on study and compliant with the protocol. Patient four's early post-dose biopsy was postponed for unrelated reasons, though it is not included in this presentation. Subsequent to this data cut, a seventh patient has been enrolled at the 6E13 vg/ kg expansion cohort. MyPEAK-1 primary objective is to establish the safety and tolerability of TN-201 at the two doses being tested. On slide 15, we detail the events observed on study across both Cohorts. TN-201 was generally well tolerated at both the 3E13 and 6E13 doses. No dose-limiting toxicities were observed. Nausea was the most common adverse event reported on study. Of the treatment-related adverse events, reversible and asymptomatic liver enzyme elevations, grades one through three, were the most frequent, occurring in four patients. One of these, a grade two transamination elevation, was classified as a serious adverse event because extra steroids were administered and monitored in the hospital setting for pragmatic reasons. The patient's enzyme elevation normalized rapidly following this treatment. Within Cohort 2, two patients have experienced lab abnormalities of complement activation starting a week after dosing. One of these was deemed grade one, mild, but classified as an SAE because the protocol-defined hospitalization was extended for further monitoring. All complement activation has resolved spontaneously without the need for any additional therapy or intervention. There were no signs of cardiotoxicities, including no declines in LV ejection fraction, no clinical myocarditis, and no ventricular arrhythmias. All six patients have successfully tapered off immunosuppression. Slide 16 summarizes our experience and progress optimizing the immunosuppressive regimen. The immunosuppression used in the first patient successfully controlled the immune response to TN-201, so we chose to make some changes in order to reduce the total amount of immunosuppression used. Over the course of Cohort 1, we switched to starting Sirolimus earlier, but at the same dose. We lowered the starting dose of Prednisone, and we increased the frequency of monitoring at the end of the taper. These minor adjustments resulted in faster tapers and lower total cumulative doses of steroid. As a result, the total immunosuppression used in Cohort 2 was lower than Cohort 1, better tolerated with better control, all despite the doubling of the TN-201 dose. Given the time constraints of the AHA presentation, TN-201 transduction of the heart data was not presented, but we have included it here for you today. Slide 17 shows robust transduction of the heart with TN-201 DNA levels well above the threshold set by our preclinical models. The mean vector copy number is 2.1 early post-dose in Cohort 1, and this increased in a dose-dependent manner in the first patient at the 6E13 vector genome per kilogram dose, as expected. As was shared at ACC in March, mRNA levels are clearly detectable early post-dose and increase over the course of the year. I note that our assays used for both DNA and RNA are specific to TN-201. They do not detect the patient's original DNA or RNA, and so the assays are zero at baseline, and everything we show here is derived from the Gene Therapy. The therapeutic protein, on the other hand, is indistinguishable from endogenous MYBPC3. On slide 18, we have the results of MYBPC protein analysis. Protein levels increased above baseline in all patients over time, and the higher dose of 6E13 resulted in the largest dose response, a 14% increase. In Cohort 1, patient three is the first to have pre- and post-dose protein levels, and the levels increased by 5% at one year. In Cohort 2, patient six's MYBPC3 level increased 14% from baseline within just 12 weeks, so more protein produced more quickly. Patient six is the only Cohort 2 patient with post-dose protein available. Patient four's biopsy was delayed, as I mentioned. We look forward to seeing additional protein data from Cohort 2 in the near future and watching for the impact of these protein level changes across all patients. Turning next to measures of TN-201 activity, starting on slide 19, we see some positive and promising early results on circulating biomarkers. All Cohort 1 patients had abnormal cardiac troponin levels at baseline. These troponins improved by as much as 74% to normal or near normal levels by the most recent visits. As a reminder, troponin is a plasma marker of ongoing cardiac injury. Among HCM patients, elevated troponins predict worse outcomes, such as ventricular arrhythmias, sudden cardiac death, and progression to end-stage heart failure. NT-proBNP, on the other hand, is a marker of heart muscle strain, and it can be sensitive to steroids, so it does increase in some patients at early time points in the trial. We are happy to see NT-proBNP levels improved at the latest time points, the most recent visits, in most patients with at least 26 weeks of follow-up. Echo measurements of hypertrophy improved or remained stable in patients with at least 26 weeks of follow-up. Most notably, as shown on slide 20, the reductions in posterior wall thickness that were observed when we reported data at ACC have further improved with time and with more patients. All three Cohort 1 patients have seen meaningful reductions in posterior wall thickness, ranging from 21%-39% at week 52. Left ventricular posterior wall thickness is an established risk factor for reduced long-term survival after septal myectomy in HCM patients, and these patients all fit that description. We are all encouraged by the changes we're seeing in LV mass index, with reductions in overall mass ranging from 12%-22% for the Cohort 1 patients or 2 of the Cohort 1 patients at week 52. New York Heart Association class improvements were measured briefly in the AHA presentation. On slide 21, we share more data showing the consistent improvements over time. New York Heart Association is a well-established classification of the impact of heart failure on symptoms affecting activities of daily living. At week 26 post-dose, NYHA had approved and improved in all patients, and by one year, all patients were Class 1, the best class, indicating no limitations from symptoms. The first two Cohort 1 patients, now out at 78 weeks, the change in New York Heart Association class has endured. In summary, on slide 22, TN-201 has been well tolerated at both doses. Our immunosuppressive regimen is working well, and it is now working with lower overall amounts. TN-201 is working as intended, delivering DNA to the heart and expressing mRNA and protein. Protein levels increased dramatically at the 6E13 dose in just 12 weeks. We look forward to seeing Cohort 2 data mature with time to learn whether the higher protein levels accelerate and increase the response to TN-201. We anticipate sharing this data as early as the first half of next year. Perhaps most exciting, among those patients with at least 26 weeks of follow-up, multiple measures of disease are moving together toward normal at the 3E13 dose level. We see responses deepening over time, consistent with other cardiac gene therapies for other diseases. We believe the improvements in Troponin, posterior wall thickness, and New York Heart Association class may be clinically meaningful, as these are all known risk factors for serious cardiovascular complications and reduced survival. On slide 23, before handing the line back to Faraz, I'd like to acknowledge all the contributors supporting this trial. First and foremost, the people with HCM who have participated in MyPEAK-1 and their families. Their contributions and efforts are fundamental to our shared mission of creating a Gene Therapy to stop this genetic disease. As part of the session at AHA, the very first patient in the world to receive Gene Therapy treatment for MYBPC3-associated HCM shared her remarkable story of resilience in the face of severe disease, which took her mother, unfortunately, at a young age. In my book, she is a hero. In addition, our mission would not be possible without the leadership of our investigators, the dedication of the site staff, oversight and guidance from our expert DSMB members, and careful data analysis from our partners at the Prevost Lab at the University of Vermont, the Brigham and Women's Cardiovascular Imaging Core Lab, and of course, our tenacious Tenaya team. Faraz. Thank you, Whit, and thank you for your leadership as well and your contributions to bringing this all together, both internally and externally. I will now make some comments over a few slides to try to put our program and our data into strategic and kind of clinical perspective. I'm going to now refer to slide 25, where we're putting the disease epidemiology into perspective. This slide provides a reminder that the indications that we're pursuing, including MYBPC3-associated HCM that we're discussing today, are important in part because they represent significantly larger indications versus those being pursued in other Gene Therapy clinical trials for genetic diseases, whether approved or in later stages of clinical development. The epidemiology of MYBPC3-associated HCM has been very well established through independent studies, and all of that work leads us to believe that there are an estimated more than 120,000 patients with this mutation in the U.S.A. alone. This is at least one reason why we think there is strategic and overall interest in this program and why the data we are presenting today are important. On slide 26, we're now trying to put the disease severity into perspective, and we're doing so here by comparing the average LVMI, left ventricular mass index, and the range of LVMI for the first three patients in Cohort 1 that have been dosed in our study, and we're comparing that to other studies. Those peer studies include contemporaneous cardiac Gene Therapy studies or cardiac myosin inhibitor studies in the obstructive or non-obstructive HCM population. What these data help illustrate is that, at least as measured by LVMI, Cohort 1 patients enrolled in the MyPEAK-1 study are significantly more affected and severely affected than those that have been studied by our peers and other studies. In fact, comparing the results of hypertrophy using LV mass or LV posterior wall thickness would lead to similar comparative results. As reminded us early in this presentation, these patients have continued to progress despite access to standard of care medications and despite successful myectomies that debulked their heart tissue and provided transient but important relief. We think this analysis speaks to the relentlessly progressive nature of this genetic condition that we believe can only be fully addressed with a genetic intervention like TN-201 that is trying to address the underlying genetic cause of the disease in these patients. Finally, on slide 26, we're trying to put the early performance of 201 into perspective as measured by both the relative and absolute decrease in both LVMI and LV posterior wall thickness as compared to the same peers referred to on the prior slide. On the left portion of the slide 26, we're showing the improvements in LVMI shared at the AHA. For two or three patients in Cohort 1, the relative reductions in LVMI are in line with cardiac Gene Therapy peers, and the average absolute reduction across all three patients in Cohort 1 is in line or even higher than what has been observed in studies of the cardiac myosin inhibitors such as Mavacamten or Aficamten. On the right portion of the slide, we're similarly showing that the improvements in LV posterior wall thickness, the relative reductions in hypertrophy, the relative reductions in hypertrophy here are better than all peers, and the absolute reductions are significantly higher than virtually all peer comparisons. Importantly, the reductions we're seeing in left ventricular posterior wall thickness are associated with improved long-term survival in HCM patients post-myectomy, as all three patients are now well below the threshold for left ventricular posterior wall thickness associated with higher mortality in patients post-myectomy. To be clear, our intention for presenting these data is not to take away from the clinical significance of the data from our peers. Quite the opposite. The data from these peers represent product candidates that have either already been approved in the case of Mavacamten or are in late stages of clinical development and product candidates that represent meaningful improvements in the lives of those patients. It is precisely for that reason that we feel our data, while early and only in three patients with at least one year of follow-up, represent a true signal of something quite meaningful. In summary, today, we have had the opportunity to present clinical data from the first three patients in dose Cohort 1 of the MyPEAK-1 study of TN-201 for MYBPC3-associated HCM. Against the backdrop of the uniquely high disease severity described on the prior slide and the comparisons we're making against our peers on this slide, we believe that the changes we're seeing in measures of hypertrophy are truly compelling. We are excited by the data being generated by TN-201 in adults with objectively severe non-obstructive HCM. At one year or greater, we're seeing robust and durable DNA transduction and mRNA expression, as well as protein level changes that track to the TN-201 mRNA expression. Clinically, there's evidence of multiple parameters moving towards normalization across different domains with biomarker changes, reduction in hypertrophy, and improvements in the burden of heart failure symptoms. With that, we're going to transition to Q&A. Operator, we're ready to open the call to questions. Thank you. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you'd like to withdraw that question, again, press star one. We also ask that you limit yourself to one question and one follow-up. For any additional questions, please re-queue. Your first question comes from Yasmeen Rahimi with Piper Sandler. Please go ahead. Good morning, team. Congrats on the really strong data, and thank you for the comparative slides that you put together. Very helpful. Team, I guess given Cohort 2, so remarkable protein expression, help us understand the way to really almost tripling of the protein, how we should conceptualize sort of what the clinical cardiac biomarkers and data points are potentially going to look like when you report out early next year. Maybe, and obviously, it's very clear from Cohort 1, the longer we go, the greater the treatment response becomes. Just help us conceptualize what expectations should be for Cohort 2. The next one is, based on your prepared remarks, it seems like the procedural paperwork submitted to the FDA is already in process. I just want to make sure that these commentaries that were made with regards to immunosuppression protocol for 201, and therefore there's no need for them to review the protocol for 401, just a clarification. The third one is, how soon can you engage with the agency on pivotal design and come back? Maybe, thank you, Yasmeen, for three very good and meaty questions that I'm sure many people have an interest in. Maybe, Whit, I'll ask you to first address the question about the FDA's action on TN-201 and then you read through to 401. Yes, we've had very productive discussions with the FDA on 201. They have not expressed any concerns about 401. We are partnering with them to basically formalize what we've been doing by interacting with sites directly, formalize that in the protocol in terms of just precise monitoring of these patients. This will benefit the 401 protocol as well. We will voluntarily update that protocol as soon as we have finalized the 201 protocol with the FDA. Again, the FDA has not expressed any concern about TN-401. Yeah, and yes, to add to that, really most of the things that were there was no new information on either 201 or on 401. Many of the changes, as I mentioned in my opening comments, we are aligned with that because those are things that we were thinking about doing anyway. You're always thinking about ways to tweak your protocol as you think ahead to future development, which we are on both programs. Some of the changes that we had already intended to put in motion or already had put in motion will certainly do that once we've got the final alignment and final review with the agency. All of that has been going very swiftly and rapidly. We do not anticipate any knock-on effects on TN-401 where patients continue to get dosed. To your first question, which is how do the changes in protein, how might that show itself in clinical data in Cohort 2? We are very pleased with the high both transduction and expression from the first evaluable patient. You are asking whether that might translate to different kind of clinical benefit. I think the short answer is time will tell. We do not want to project too soon whether we will see a greater magnitude effect or a faster kinetics of effect from the Cohort 2 data. Frankly, yes, we are just thrilled with what we are seeing from Cohort 1. I would also say that based on our experience and the experience of peers, it is sometimes hard to draw a straight line between dose, vector copy number, mRNA expression, protein, and clinical benefit. There is so much patient-to-patient variability. We are pleased with what we are seeing from Cohort 1. We're optimistic for what we're going to see from Cohort 2, but don't want to speculate too soon with too early a time point and not enough patients about what the trajectory, magnitude, and kinetics of Cohort 2 data may look like. Is there anything you'd like to add to that, Whit? I agree. Thank you. We asked you your third question, which is about future plans. I think we stand by what we have been saying all throughout this year and is captured in our public statements that in 2026, we aspire to have both the quantity of clinical data as well as the quality of clinical data that may allow us to engage with the regulators on this program for either future late-stage development in adults and/or in pediatrics, severely affected pediatric patients on whom we've presented data quite extensively about the burden of severity in the pediatric population. We believe we're still on track for that. In fact, this data presentation at AHA is a wonderful marker of progress of where we are. We will have full Cohort sets for data of dose Cohort 2 next year. At that point, if we're based on the experience of our peers, we may be in a position to engage with the regulators about what the design of future studies may look like, the use of surrogate markers, etc., etc. Too early to speculate now. We don't believe that the regulatory action taken has any impact on those forward-looking plans because the data from the patients already dosed is what we think will be most relevant. Of course, we're going to resume dosing once we've implemented changes. Clearly, we're thinking ahead to the future, yes, because it was our own proactive reach out to the FDA with our current data set that resulted in this request for protocol changes before we dose additional patients. We're aligned with that, and we're doing that. Hopefully, that answers all three of your questions. Thank you. Great questions. Thank you. Your next question comes from the line of Mike Ulz with Morgan Stanley. Please go ahead. Good morning. Thanks for taking the question. Maybe just a follow-up on the clinical hold. It sounds like you should be able to make some quick progress there. Any thoughts on when that hold could potentially be lifted? Is it weeks or is it months? Secondly, just prior to the hold, were you able to dose any patients in the expansion cohort at the higher dose? Just trying to get a sense of when you might get a couple more patients at that higher dose, which looks very promising. Thanks. Thanks, Mike. That's a great question. First, Whit, do you want to address just the question about the dosing of an additional patient in the expansion cohort? Yeah, we have dosed seven patients to date. We completed the planned Cohort 2 and have expanded that by one patient before the hold. We do have patients in the queue waiting. We are optimistic about resolving this with the FDA quickly. We appreciate and share their mission to optimize for safety and acknowledge they have moved very quickly. We've had more than one back-and-forth round with them and exceeding their usual timelines. I can't say when this will be finalized. We have submitted a revised protocol that we believe addresses all of their requests. They are actively reviewing now. We are cautiously optimistic that this will be resolved very soon. Very helpful. Thank you. Yeah, I agree with that, Mike, with the comments. It has been very productive, very collaborative, and very swift rounds of discussion, I think, in part because we're aligned with their thinking and in part because there is a shared understanding that the things that we're doing, while individually small, collectively, they'll just add up to more consistency in the conduct of our studies. We are quite aligned with doing that. There is really no kind of pushback between us and the FDA on the things that they're interested in learning more about and implementing. We are hopeful, but we can never put a date on it, Mike. Thanks for the question. Your next question comes from the line of Joseph Pantginis with H.C. Wainwright. Please go ahead. Hi, this is Sarah Onsford, Joe. Good morning, and thanks for taking the question. Also, regarding the clinical hold, just curious whether any of the patients that were dosed under your current or what will be the old immunosuppressive monitoring regimen, will any of those need to be, in terms of future analysis, will they be treated any differently, put into a separate subgroup from patients maybe added after these changes are made, or how should we think about those differences looking forward? Thank you. Yeah, I'll take that. Yeah, I'll just say quickly, the short answer is no. Good question, but the short answer is no. I wouldn't have any reason to believe that would be the case. I'll let Whit respond, and then I'll probably add to that. Go ahead, Whit. Yeah, you said exactly. That is a great question, but a very clear answer, no. These modifications are not major at all. We are not changing the immunosuppression regimen of Prednisone or Sirolimus, nor are we changing the doses. It has been a good discussion sharing with the FDA all the progress we've made with the adjustments, the minor adjustments that I described during the presentation part of the call. My sense is that they also find that very reassuring. The protocol amendment is more about making sure that stays consistent across all sites, and it's formalized in the protocol. As I said, we talk with sites regularly, and we've been managing this with them. It will be good to have it all explicitly spelled out in the protocol. There are other minor tweaks, but this does not affect the population that we're enrolling, and it certainly doesn't affect the interpretation of the results. Yeah, I think the only thing I'll add to what Whit just said is one, just this is a new review team for us. They are becoming familiar with our program for the first time. They respect that we know our product and our study very well. We respect that they are seeing things across sponsors that maybe they want to harmonize, right? Not only site-to-site variabilities left at the site level in our study, but maybe there are things that they're seeing across programs that they'd just like to tighten up based on the information that they have. I think there's a lot of mutual respect. We know our product and its profile, and they know what is going on across studies. I think there's a lot of mutual respect here. The other thing, so no changes are being made, as Whit described. However, I'd also like to point out that even in situations where changes have been made, which is not the case for us, that does not seem to have changed the ability of that data to be pooled for future pivotal studies. I am just referring to our cardiac Gene Therapy peers in this regard that even changes in manufacturing platforms, changes in immunosuppression regimen, changes in dose, that has not gotten in the way of data being pooled for the purposes of pivotal studies and looking at the totality of the evidence, which is very much on course for rare disease drug development and particularly for Gene Therapy drug development. We do not have any concerns in that regard. Okay, great. Thank you. Your next question comes from the line of Cory Jubinville with LifeSci Capital. Please go ahead. Hi, good morning, and congrats on the data update and your questions. Can you just speak to the differences that we're seeing in left ventricular mass index versus LV posterior wall thickness? I know typically LVMI is seen as what could be an approvable endpoint in these types of cardiac indications. Posterior wall thickness demonstrated these really profound improvements, but this was not the case for all patients in LVMI. Intuitively, I'd anticipate that these two endpoints would be pretty locked up with one another. I guess, are there any factors in your view that would drive a robust improvement in posterior wall thickness, but an increase in LVMI? I guess in your view, is one measurement more objective or cleaner to measure, for lack of a better term? Whit? Yeah, it's all objective. The wall thickness is cleaner than LVMI. That's a great word. A great question also. Thank you. The wall thickness is a one-dimensional measurement. You just put a ruler onto the image. LV mass index has to be calculated from several measurements that are multiplied. Small errors in each one of those can multiply out. It is more sensitive to the physiologic, what we say, the volume status of the patient, whether they're dehydrated or have extra fluid volume, extra blood volume. That just changes the shape of the ventricle. That volume or size of the ventricle is part of the equation for LV mass index. With small numbers like we're talking about now, we are really very focused on the wall thickness, as we're showing terrific improvements and consistent across patients with a consistent time course. As we get more data with more patients, we expect the LV mass to follow. Yeah, that's a great question, Cory. The only thing I'd add to that is it is actually quite remarkable when you look at the patient that has not yet had an overall reduction in LVMI is patient one. You look at that LVMI, and it's at 203. If you were to plot out all HCM patients, you'd see what an outlier that number is. It's incredible. It's maybe one of the largest ever seen. This is a patient who spoke eloquently at AHA. Her mother died before the age of 40, runs in her family, had a myectomy, felt better, still had symptoms, and really just felt like she needed more than what she had from the medications and from the myectomy. We're super pleased that in a patient that really would be described as refractory, and as Dr. Desai said, handed at AHA, headed towards potentially heart transplant, a single dose of TN-201 is producing the protein, and we're seeing a dramatic reduction in at least the left ventricular posterior wall thickness at this time. Who knows what will happen over time with this patient? This is with the other two patients who are also objectively severe, we see that consistency of both LVMI and LV posterior wall thickness. We will see more with time, including from dose Cohort 2. We're not overreading too much into one data point from one patient. Overall, it seems like directionally, many things are moving in the right directions for Cohort 1 patients, the circulating biomarkers, measures of hypertrophy, New York Heart Association Class. It's still at a relatively early time point with a small number of patients. Too early to say whether we will always have consistency between LVP, WT, and LVMI, or other measures of hypertrophy over time. It's a good question. Very helpful. Thanks. Your next question comes from the line of Sami Corwin with William Blair. Please go ahead. Good morning. Congrats on the data, and thanks for taking my questions. Given the FDA's clinical hold is based on the protocol uniformity, I was curious what the protocol is for using the complement inhibitor given the laboratory signs of complement activation we're seeing in Cohort 2. On slide 29, you suggest that you could have multiple pivotal studies, including one in pediatrics. I was just curious if you plan on treating a pediatric patient in the MyPEAK-1 study prior to those discussions with FDA. Thank you. Whit, maybe you take the first one first, and I might talk about the second one. Yeah, absolutely. To be clear, we have not had any cases of clinical TMA, any organ involvement. We can detect innate immune response as expected to TN-201, and that does include complement activation. As Faraz was saying, the FDA can't say, but we suspect and hope that they're integrating information across multiple AV programs to improve safety for all participants across all studies. Part of the discussion is how to best monitor the complement activation and be ready to use a complement inhibitor if it were to be needed. Again, we are very aligned with their thoughts on this and happy to implement the minor changes that they have proposed. Yeah, it's a good question, Sami. In the past, this is something that may not have even been caught in early studies of Gene Therapy, including high-dose Gene Therapies. Patients were being discharged before the time we now know that the lab values are increasing. We are fortunate that maybe there were not more cases of full-blown TMA and aHUS that had clinical sequelae, but that was not the case for us. Everybody, I think, is more consistently—I think that is where the FDA is trying to get to—that everybody more consistently monitors the same things, whether it is the specific points in the complement cascade, platelets, whatever. They just want to make sure that everybody, I believe, is kind of consistently looking at the same things and then consistently responding in the same ways, right? We are 100% aligned with that. We are glad to be implementing the changes. We believe that the changes that they're suggesting are with data from other programs that suggest that there may be an emerging kind of best-in-class approach to doing this in a more consistent and safe way across programs. Frankly, that's a gift to us now. Before we go into pivotal studies, we've seen some products in the case of Sarepta in the commercial domain, and then having to make changes in their immunosuppression regimen by the addition of Sirolimus, which we already have. In the case of Rocket, they had the unfortunate situation of adding something during the pivotal study to manage complement. I think that we are being handed a gift here with the opportunity to implement changes that the FDA thinks are the best for these patients and doing it now before we are in those late-stage clinical developments and before we are rapidly dosing in many patients, maybe in expansion cohorts. That is another perspective on all this. It is quite positive. The other thing regarding pivotal studies, adults and children, I think it is too early to say, Sami about whether we would first have to dose a patient in children before going into pivotal studies. Just a reminder, our current study is only focused on adults. It would require a change of the current study in order to start dosing children. We are not open to do that. Frankly, the endpoints are quite different and quite unique in some of the severe pediatric populations. It may not be as simple as just changing our current study to go to those, for example, very, very severe homozygous infants that die within the first days, weeks, and months of life. One thing, it is in the public domain that we have actually opened ourselves to compassionate use approaches. Families or patients around the world, through their physicians, can approach us about a compassionate use for those very, very severe, very rapidly progressive patients who, frankly, cannot wait until we are in a pivotal study in children. That is in the public domain. It is on our website. It is possible that we end up dosing a patient through a compassionate use pathway before we have aligned with the FDA on a pivotal study. That is one indication of intent. We do believe with these data that we have in the adults, there's justification, there's equipoise between efficacy and safety to give a shot to very young children who would otherwise die within the first days, weeks, and months of life unless they get a heart transplant, which is quite complicated for such young patients. Hopefully that answers your question, Sami. Yeah, very helpful. Thank you. Your next question comes from the line of Mani Foroohar with Leerink Partners. Please go ahead. Hey, guys, thanks for taking the questions. I guess one key one for me, just looking further out, there's been a lot of questions around the specific state of the programs now. More broadly, when you think about a regular choice path, we've seen from a couple of other companies in the space a mix of protein and LVMI as a co-primary endpoint. Would you expect that to be similar for you guys, or would you expect a different approach in terms of endpoints, co-primary analysis as opposed to some other arrangement of the endpoints? How do you think about potential regulatory path and endpoint construction here? I mean, we're pleased, Mani. I'll say a good question. One, we're pleased that both of our cardiac Gene Therapy peers for whom we have a lot of respect, Rocket and Lexeo, and their respective programs, Danon and Friedreich's ataxia, that both under the new administration, under new leadership at the FDA, both reaffirmed the alignment with the FDA that their co-primary endpoints of any level of expression of protein, not with any quantifiable threshold, at any level of expression of protein, along with an improvement in LVMI reductions of greater than 10%, are sufficient for or could set them up for potential accelerated approval based on surrogate markers. We're glad to see that reaffirmation. There have been some surprises in the space recently. It is nice to know that this was relatively recent. In the case of Rocket, it was reconfirmed after a very unfortunate safety event in their study. No dramatic changes were proposed to their study, to the best of my knowledge from the public statements you've made. It seems like there's some consistency here, Mani. What we certainly hope is that what's lost with the goose will be lost with the gander, and that will be also true for us. Each program needs to make the case for their own study, right? We have pointed out that the levels of hypertrophy we're seeing in these patients is uniquely high. If you look at the comparative data with Rocket and Lexeo, you can see that we're glad to see that our peers have gotten that alignment with those endpoints. We also are seeing changes in hypertrophy and a pattern that maybe some of it is similar to theirs, and some of it is unique to us, including those changes in posterior wall thickness, which does have a mortality benefit that is predicted based on the data of others. I think too early to declare exactly what our future pivotal designs will look like. Will it be LVMI? Will it be LVMI or any other measure of hypertrophy associated with long-term benefit? We're hopeful that we are going to, in 2026, have the quantity and quality of data, Mani, that will allow us to have that discussion with the FDA. We can continue to come back to that guidance over and over again that this is a 2026 problem for us, not problem, but opportunity. Nothing about the regulatory action changes that. Is there anything, Whit, that you'd like to add to those points or to make different points, including for the pediatric population? No, I agree. Great. That's helpful. Mani, does that answer your question? Yeah, it does. Thank you. Your next question comes from the line of Geulah Livshits with Chardan. Please go ahead. Good morning. Congrats on the data again. Thanks for taking the questions. Just to follow up on some of the previous questions on the left ventricular posterior wall thickness, again, you mentioned these patients declining below that threshold that's associated with mortality. Can you maybe elaborate a little bit on that from your discussions with investigators or clinicians? You expand on maybe the relative importance of that and the degree of risk reduction that you might see with incremental improvements there. Also, what about any other hypertrophy metrics that you're collecting? I think in the past, you may have reported data on septum thickness and things like that. So any other metrics that we can look forward to in future updates? Thanks. Great. Whit, do you want to take a first crack at that question? Yeah, absolutely. So yeah, there is data specifically for patients who have undergone septal myectomy, as our Cohort 1 patients have, showing that that posterior wall thickness is predictive of survival. And so we're very encouraged to see the reduction in posterior wall thickness consistently across all these patients, which could correlate with survival benefit in the future. We're cautiously optimistic about that. The other measurements of the septum, as you notice, have stabilized in these patients. It is interesting seeing the magnitude of improvement in the posterior wall being numerically greater than in the septum in these patients at this point. As I just mentioned, all of these patients have had open-heart surgery on that septum. It is possible that the leftover scarring and so forth means it will take longer for us to see large reductions in the septal wall thickness. That is something we will have to monitor with time. As discussed near the beginning of this call, the higher protein expression we have seen so far in the second cohort could lead to faster improvements and potentially larger improvements, although we do not know. We are very happy with what we are seeing with the 3E13 dose and look forward to sharing more data from the higher dose in the first half of next year. Yeah. The only thing I will add to that is the specific paper that we referenced there will point out that the threshold is 1.3 centimeters or 13 millimeters for posterior wall thickness. Above that, post-myectomy, if after myectomy you still have that much or more, that is associated with higher mortality. Of course, there is still elevated mortality in those patients, all patients, because they have genetic disease and they have thickened hearts. Within that, there is an even higher risk of mortality if you have a posterior wall thickness of 1.3 cm or more. In our first three patients chosen for Cohort 1, patient three is objectively above that threshold and comes down below that threshold by the one-year mark. For patient one, they were very close to that threshold and have come down to almost the normal range with dramatic reductions there. That is partly why we are—and then patient one, patient two was below that threshold and yet further, but still hypertrophied and came down well within the normal range. That is why we are pleased in focusing in on those measures of posterior wall thickness, partly because of that experience in the literature. I would also say that with septum wall thickness, in addition to what Whit said, we have also analyzed septum wall thickness across all of these programs. What we see consistently is septal wall thickness is something that everybody has seen varying degrees of changes, and our changes are very much in line with others. The septal wall thickness is also more—it seems to be more recalcitrant to major changes in the way that other walls of the heart are. That sometimes—and I do not exactly know the full biology behind it. In our case, it could be because the patients had myectomies, and so there may be some scarring in that. That does not explain that for all the programs that are represented here. It seems like ventricular IVS or ventricular septum thickness is something that does not move quite as much as other hearts or other walls of the heart. The data, the pattern that we would be showing here would be very similar. The reductions seen with TN-201 are quite consistent with, in many cases, better, both on an absolute and a relative basis than in these other studies. We have also made these comparisons with things not represented here, like ATTR cardiomyopathy and Fabry cardiomyopathy. We now have quite a deep data set of understanding. This is partly what will go into our thinking as we thoughtfully approach the agencies with our data in 2026, is what arguments we want to make about the best markers for potential accelerated approval and with what logic. That logic may overlap with what some of our Gene Therapy peers have done, but there may be some differences that are based on the data that are available in other studies as well as in our study and in the HCM population. That concludes our question and answer session. I will now turn it back to Faraz Ali for closing comments. Yeah, thanks for staying here. I know we've gone over. Thanks for joining us today and all the great questions. We've had an outstanding year of performance. I'm now referring to slide 29, the last slide in the deck. We only have one more exciting milestone left to check here for 2025, and we're looking forward to doing this again soon for the initial readout from a RIDGE-1 clinical trial for TN-401. As a reminder, those data will provide our first look at Cohort 1 safety and biopsy results. We have, of course, we've already been referencing several times on this call, exciting milestones ahead of us in the first half of 2026. As a reminder, these data milestones have not changed as a result of any recent regulatory interactions, and they're not impacted by the hold that we mentioned because these are data from patients who have already been dosed. That's what we're looking forward to in the first half. Of course, adding to that with the dosing of additional patients, and that data set would be more likely to mature later in 2026. We look forward to more data from the TN-201 program for Cohort 1 and maturation of clinical data from Cohort 2, including more biopsy data and changes in clinical parameters. We continue to believe that we have an exciting year ahead of us for both programs in 2026. We welcome the follow-up questions. I'm sure we didn't get to all of them today, and we hope to connect with many of you over the coming days. Please reach out to Michelle if you'd like to schedule some one-on-one time with our team to discuss these data and Tenaya's progress and our forward-looking plans. With that, we'll close. Thank you, everybody, for your time and attention, and thanks to the patients who have contributed to our results today. Ladies and gentlemen, thank you for your participation. You may now disconnect.