Good morning and welcome to Lexeo Therapeutics' webcast presentation on LX 2020 for the treatment of PKP2-associated arrhythmogenic cardiomyopathy. As a reminder, this call is being recorded today, January 12th. I would now like to turn the conference call over to Louis Tamayo, Chief Financial Officer of Lexeo Therapeutics. Louis, please go ahead. Earlier today, we released interim data from the Lexeo HEROIC PKP2 phase I-II clinical trial of LX2020 for the treatment of PKP2-associated arrhythmogenic cardiomyopathy, or ACM. The press release outlining the interim data update is available on our website at lexeotx.com, as well as the slides related to today's call. Joining us on today's call will be Nolan Townsend, Chief Executive Officer, and Dr. Eric Adler, Head of Research. Before we begin, I would like to remind you that this call will contain forward-looking statements regarding Lexeo's future expectations, plans, and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor Provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our filings with the SEC. With that, I would like to turn the call over to our CEO, Nolan. Thanks, Lou, and thank you all for joining us. Today, we are pleased to share preliminary data on the safety and efficacy of LX2020 across a meaningful sample of 10 participants dosed to date, eight of whom have at least six months of follow-up. Looking first at transduction and protein expression, we have observed mean increases in PKP2 protein expression, as well as robust vector copy number and exogenous mRNA at three months post-dosing, with dose-dependent increases between the low and high-dose cohorts. We are also seeing appropriate co-localization of the PKP2 protein within the desmosome using immunofluorescence. In terms of clinical measures, we are seeing early benefit in two key measures of arrhythmia burden associated with increased risk of poor outcomes, including sustained ventricular tachycardia, ICD shock, and sudden cardiac death. Premature ventricular contractions, or PVCs, have been stabilized or reduced in the majority of participants at latest visit, and we've observed a 14% mean improvement across participants in the high-dose cohort. Non-sustained ventricular tachycardia has also been stabilized or reduced in the majority of participants at latest visit, with a 22% mean improvement in the high-dose cohort. Finally, treatment with LX2020 has been well tolerated across all 10 participants dosed, with no clinically significant complement activation and no new serious adverse events to report. We are encouraged by these collective data on the therapeutic potential of LX2020, including those from relatively early time points in the high-dose cohorts, and we are eager to advance development for this therapeutic candidate as the data continue to mature. I will now turn the call over to Dr. Eric Adler to provide an overview of PKP2 ACM and to review these data in more detail. Eric? Thank you, Nolan. Arrhythmogenic cardiomyopathy is most commonly caused by mutations in the Plakophilin-2, or PKP2 gene, affecting approximately 60,000 people in the United States. PKP2 deficiency in ACM is a disorder of the cardiac desmosome, a protein structure which allows cells to adhere to each other and is strongly associated with fibrofatty infiltration of cardiac tissue. Patients with PKP mutations are at high risk for cardiac rhythm abnormalities, heart failure, and sudden cardiac death. Tragically, over 20% of patients experience sudden cardiac death as their first presenting symptom, which is why familial history and genetic testing is so critical in timely diagnosis of this disease. Following diagnosis, most patients with PKP2 ACM receive an ICD, or implantable cardioverter defibrillator. While this device can mitigate the risk of sudden cardiac death, it does not address underlying disease progression, with patients continuing to experience ongoing arrhythmia and associated anxiety. Additional medications, such as beta-blockers and antiarrhythmic drugs, have shown some benefit in managing arrhythmia symptoms but do not address the underlying genetic cause of disease or progression. When looking at arrhythmia burden, we often focus on three measures in order of severity. First, individuals with PKP2 ACM may experience frequent premature ventricular contractions, or PVCs. In fact, one of the minor diagnostic criteria for ACM is greater than 500 PVCs per day. A PVC is an extra or early heartbeat that originates in the ventricle, disrupting the heart's normal rhythm. These early beats may be caused in part by calcium ion instability, and as we will discuss, PVCs can go on to trigger more severe sustained arrhythmia. Non-sustained ventricular tachycardia, or NSVT, is another key measure in this disease, closely associated with poor outcomes such as increased risk of sustained VT, ICD shock, and sudden cardiac death. Non-sustained is defined by episodes that are self-terminating and last fewer than 30 seconds. Although brief, people with PKP2 ACM are more likely to feel episodes of NSVT compared to PVCs, which can contribute to significant physical discomfort as well as heightened anxiety regarding the underlying disease. PVCs can trigger NSVT events when the extra heartbeat continues for three or more consecutive beats, consistently overriding the normal heart rhythm. In some cases, ventricular tachycardia fails to self-terminate, which is life-threatening and can result in a third measure of sudden cardiac death. In individuals with an ICD, sustained VT can trigger an ICD shock to restore normal heart rhythm. People with PKP2 ACM are at particular high risk for sustained VT and may undergo surgical ablation to manage this risk, although recurrence after ablation is very common. As mentioned on the previous slide, PVCs may trigger VT, so the two measures are related but driven by potentially different mechanisms. Think of PVCs as a spark and VT as a fire. One PVC may not be hugely clinically significant alone, but patients with a high PVC burden are at high risk for development of both ventricular tachycardia and heart failure. PVCs may initially arise due to calcium ion leak, disrupting the heart's refractory period and depolarization. Calcium instability due to PKP2 deficiency is likely due to downstream proteins, not PKP2's direct function in the desmosome, so we hypothesize it may take more time to observe significant reduction in PVCs to normal levels in this disease. When a PVC meets another underlying vulnerability, this is when a fire or when VT can occur. In PKP2 ACM, one key vulnerability is slowed electrical conduction caused by the destabilization of the desmosomal complex due to PKP2 deficiency, which is essentially a scaffold protein. Another example is the development of scar tissue or fatty fibrotic tissue, which can disrupt the normal flow of electrical signals throughout the heart. When a PVC meets a vulnerable area of the heart like this, a re-entry loop can also occur so that the premature beat propagates and contributes to re-excite the heart consistently. This combination is what leads to VT. Given the different mechanisms of these endpoints, we hypothesize that VT could be reduced if vulnerable areas of the heart are improved, even if high PVC burden persists. Looking briefly at the natural history of disease, you can see on the left that individuals with PKP2 ACM tend to experience high and persistent PVC burden, though there is significant variability both between individuals and within the same patient over time. It's important to note that activity and exercise significantly influence measures like PVCs and NSVT, so it can be hard to separate lifestyle factors from underlying disease progression. What you can see in the chart on the left is a reduction in PVCs immediately following diagnosis, usually because healthcare providers recommend a cessation of exercise, and some patients may begin other therapies, including beta-blockers or antiarrhythmic drugs. However, following this initial intervention, PVC burden persists and even appears to increase after four to five years. The middle graph illustrates risk for severe VT, which is higher with a high PVC burden, plotted on the x-axis. PVC burden alone does not fully explain arrhythmic risk. As you can see in the orange and dark gray lines, patients who experience NSVT are significantly more likely to develop VT than those without NSVT, even if their daily PVC burden remains the same. Finally, on the right, we are sharing some preliminary data from the Lexeo-sponsored snapshot prospective natural history study. 15 patients is a relatively small sample, but what's interesting about this dataset is that it includes individuals further along in their disease progression, eight years from diagnosis on average, and it also quantifies NSVT burden rather than reporting as a binary outcome, which is how it is most often presented in the literature. Here you can see that PVCs and NSVT both increase over a 12-month period, and each are associated with greater VT risk. Importantly, arrhythmia burden persists or progresses in some patients despite consistent use of beta-blockers or other antiarrhythmic drugs, highlighting the need for disease-modifying therapies. LX 2020 is designed to treat the root cause of PKP2 ACM by delivering a full-length PKP2 gene to cardiomyocytes. We packaged the full-length PKP2 gene in an AAVrh10 vector, which has an increased affinity for cardiomyocyte cells in the heart, allowing us to use relatively low doses compared to commercially approved gene therapy treatments. LX 2020 also includes a cardiac-specific promoter to further localize expression in the heart, which we believe could support a more favorable safety profile while still delivering efficacy in treating this cardiac disease. LX 2020 is currently being evaluated in the HEROIC PKP2 phase I-II clinical trial, an open-label, single-arm, multicenter trial designed to assess the safety, tolerability, and preliminary efficacy of this therapeutic candidate with two-dose cohorts. This study is focused on adults with a documented PKP2 mutation, an existing ICD, and no pre-existing immunity to the AAVrh10 vector. 10 participants have been dosed, including three participants in cohort one at the low dose of 2E13 VG per kg, and seven participants in cohort two and three at the high dose of 6E13 VG per kg. On this slide, you can see the baseline characteristics summarized across participants in the low and high-dose cohorts. These characteristics are consistent with the clinical manifestations of PKP2 ACM, and you can see that these participants are pretty advanced in their disease progression on average, especially at the high dose, with a mean of nine years since diagnosis and significantly elevated arrhythmia burden. Importantly, I will note, nine of the 10 participants had no limitation from heart failure symptoms yet, as measured by the New York Heart Association Class, which is consistent with arrhythmogenic cardiomyopathy, where arrhythmia burden presents earlier in the disease, and end-stage heart failure may not develop in all participants or within the decade following initial diagnosis. Here you can see the baseline characteristics for each individual participant who was dosed, as well as some relevant medical history related to arrhythmia burden, sustained VT, ICD shock, and ablation. You can get a sense of the advanced disease progression in these individuals. For today's presentation, safety data is summarized for all 10 participants who were dosed, while efficacy data is inclusive of those participants with at least six months of follow-up as of the data cutoff date of January 7, 2026. At the bottom of the table, you can see the latest visit for each participant. I will now share safety data. LX2020 continues to be generally well tolerated across all 10 participants at both dose levels, and we have not observed any clinically significant complement activations or incidences of TMA. We did observe elevations in liver function tests, or LFTs, in 5 participants treated at the high dose, consistent with what we would expect with gene therapy treatment at this dose. All five were treated successfully with modified immunosuppression per the trial protocol. For 3 participants, the elevations occurred following steroid taper and resolved after the reintroduction of low-dose prednisone treatment for a few weeks. In 2 participants, elevations occurred prior to steroid tapering and resolved with increased prednisone and sirolimus treatment. All of the elevations have since resolved without other complications or hospitalizations, and no other medications were required for resolution, nor were any serious adverse events observed following the LFT elevations. Finally, one previously disclosed grade 3 serious adverse event of sustained ventricular tachycardia was observed three months after dosing in a single participant in the high-dose cohort and assessed as possibly treatment-related, though the event is consistent with the natural course of PKP2 ACM and its known clinical manifestation. The participant was successfully treated with antiarrhythmic medication and discharged with no additional intervention required, and no new serious adverse events have been observed, so we are confident in the favorable safety profile of LX2020 to date. Turning now to the evidence we've collected with cardiac biopsies, on this slide you can see the robust transduction and transcription observed in all participants. I'll remind everyone that participant three in the low-dose cohort declined the post-treatment biopsy, so we do not have any bioanalytical data for this participant. Unfortunately, we did not have sufficient tissue to perform VCN analysis for participant one in the low-dose cohort either, but looking at the available data on the slide, you can see meaningful increases in both vector copy number and exogenous mRNA consistent with PKP2 transduction and transcription. Looking at the mean values, you can also see clear evidence of a dose response. Looking at PKP2 protein expression, again, we are seeing mean expression increases across participants with a greater response at the high dose. As I mentioned previously, PKP2 ACM leads to the replacement of healthy cardiac tissue with fatty fibrotic tissue, which can contribute to sampling variability and sample quality issues with cardiac biopsy tissue. We believe that it's what's driving the results for participants four and five because a reduction in PKP2 expression is not logical, and both of these participants do demonstrate LX2020 transduction and transcription with the VCN and mRNA results. In these two instances, it is likely that we happened to analyze a sample with a greater percentage of fat or fibrotic tissue, which is confounding the Western blot results, but looking across all samples, we are encouraged by the evidence of increased PKP2 expression and dose dependence. Finally, looking at immunofluorescence staining, you can see appropriate co-localization of PKP2 protein at the cardiac intercalated disc after treatment. Essentially, these images show us that PKP2 protein is going to the right place after treatment with LX2020, and it's traveling alongside other important structural proteins in the desmosome and gap junction, such as connexin-43 and N-cadherin. Where you see clear lines, particularly in the merged images, you can see the intercalated disc where cardiomyocytes connect both mechanically and electrically, allowing the heart to beat in synchronized fashion. We've chosen participants four and five here for illustrative purposes, but appropriate co-localization of PKP2 protein is consistently demonstrated across our patient population. Turning now to the clinical data, we have observed a reduction or stabilization in arrhythmia burden across participants, with a greater mean effect in the high-dose cohort. PVCs are reduced or stable in seven of eight participants, with a mean improvement of 14% at the high dose despite a relatively earlier follow-up. Even more important is NSVT, which is a major risk factor for sustained VT, and where we see reduction or stabilization in six of eight participants, including a mean improvement of 22% at the high dose. The most significant reduction in VT in participant four also appears to be associated with modest gains in cardiac function, as assessed by right ventricular ejection fraction, although the majority of patients remain stable with respect to RVEF. Looking at these data over time, you can see improvements in arrhythmia burden on average and evidence of a clear dose response. On the left are PVCs measured at baseline, six months, nine months, and 12 months, including participants who have reached at each time point to date. You'll see the mean across all patients, as well as the mean for each of the two-dose cohorts. The right-hand side presents the same view for NSVT events over time. Looking at the high dose in red, there is clear clinical benefit and a dose response in terms of reducing arrhythmia burden and potential evidence of greater improvement over time. We look forward to seeing these data mature and also adding participants nine and ten to this emerging picture. Even with some measurement variability, the directionally consistent improvements observed across measures of arrhythmia burden and cardiac function give us early confidence in the potential treatment effect of LX2020. Finally, looking at EKG data and other clinical measures, participants appear stable over time. You can see the mean per dose cohort, and the dots represented individual participants at baseline and latest visits. The left-hand side shows QRS duration. The majority of participants start and stay within the normal range as of latest visit. We had previously reported an improvement for participant one, which you can see in the purple dot, but looking across the sample, we are largely seeing stabilization on this measure of electrical function. On the left, T-wave inversion is also largely stable across participants, with minimal change from baseline. No participants experienced any change in New York Heart Association Class, and in fact, seven of the eight participants started at class one, so they continue to report no signs or symptoms of limitations from heart failure. While these measures remain stable overall, we are most encouraged by the observed reductions in arrhythmia burden, including reductions in more severe NSVT events, which are both clinically relevant and highly meaningful for patients. I'll now turn the call back to Nolan to close. Thank you, Eric. I believe these interim data demonstrate an exciting emerging profile for LX2020, with favorable safety, robust transduction, increased PKP2 expression, and clinically meaningful reductions in arrhythmia burden. In terms of next steps, we recently completed enrollment of the HEROIC study in Q4 2025, with the final two participants, participants nine and ten, dosed using drug supply produced with our final manufacturing process. This process demonstrates higher potency and higher yield relative to earlier lots, so we look forward to reviewing data for these participants in 2026, including cardiac biopsy data in the near term. Looking ahead, we expect to receive twelve-month follow-up data for all high-dose participants by Q4 2026, at which point we plan to provide a subsequent data update. I'd like to close by thanking the study participants, caregivers, investigators, and other members of the ACM community who have helped us to reach this exciting milestone. Those impacted by PKP2 ACM are central to our mission, and we are committed to advancing the development of LX2020, given the urgent need for treatment options. I will turn it over to the operator to help facilitate the Q&A portion of today's call. Thank you. If you'd like to ask a question, please press star one one. If your question hasn't answered and you'd like to remove yourself from the queue, please press star one one again. One moment while we compile the Q&A roster. And our first question comes from Paul Matteis with Stifel. Your line is open. Hi, this is Matthew on for Paul. Thanks for taking our question and congrats on all the progress. So, two questions from me. The first is, what gives you confidence that we might see further benefits on PVC and NSVT in the high-dose cohort at twelve months, given the protein expression already seen in the earlier biopsy? Then the second is, staying on the biopsy, the PKP2 expression, how does that compare to wild type in terms of percent of normal, and at what degree of PKP2 expression do you think you start to see benefits? Thank you. Thank you. Thanks for the question. First on time course, I don't think there was a predetermined time frame in which we would expect to see resolution of this underlying biology of the disease. I mean, the best indicator we have for the time course would have been from murine models, where we saw improvement at three months, but obviously that does not translate directly to the human context. The best indicator we have currently is what we're seeing in NSVT. We're seeing a time course of improvement. At nine months, for example, at the high dose, we're seeing greater reduction in NSVT than we're seeing, for example, at six months and versus baseline. That's a trend that we would expect to continue as we go out to 12 months and longer time points. With respect to the biopsies, I guess you're asking on average, what percentage of normal are we achieving? Or, yeah, but irrespective of that, I don't have that number at my fingertips there. I actually think it could be calculated from the slides, but in general, it's not clear to us that this is a disease where it's completely resolved at a specific value of PKP2 expression. In particular, because we're taking biopsies from the septum, but this is a disease mediated by the right ventricle. While this is a good surrogate for expression in the right ventricle and the septum, we may not be accurately capturing the amount of protein that we're seeing in the septum, but in the right ventricle, sorry. As you can see, we're getting robust PKP2 expression, we're getting robust mRNA, and also we're seeing a dose-dependent response across the biopsies and then across the endpoints that we're evaluating from a clinical perspective. I think the question here is more about time. These are early time points. Six months is the earliest time point where we can begin to evaluate efficacy, and so we are seeing an increased response over time, in particular with NSVT. I think we'll keep our eyes on this data and keep our eyes focused on the twelve-month time point where we'd expect to see an even greater response. Thank you. Thank you. Our next question comes from Brian Skorney with Baird. Your line is open. Brian, if your telephone's muted, please unmute. Yes, thank you. Good morning, everyone. Thank you for taking the question and congrats on the data. Can you just review how frequently you have NSVT and PVC data measured in the studies at every three months, and how are the PVC and NSVT measurements being done? Is the PVC at 12 months, for instance, measured for 24 hours going into the visit, and NSVT is the seven days before the visit, or is it over a longer time frame and then being sort of adjusted for the 24-hour, seven-day average? And then just going back to the time course of NSVTs over time, it does definitely look like longer follow-up shows greater reduction, but there's also this shrinking in, and at six months, there's that one outlier with an 80 NSVT increase at six months bringing up the means. So, I was just wondering, is that true? If you look at NSVTs on a patient-by-patient basis, particularly in the high dose, is it very clear that you're seeing a decline on an individual basis? So, Brian, first on the NSVTs, yes, we're measuring them every three months. And maybe, Eric, you could speak to the time. It's a seven-day Holter and an average. So, they're measured for seven days, and then we come up for a 24-hour per day number for NSVT and VT. Does that answer the question, Brian? That answered it on that. What about on a patient-by-patient basis? Is it clear that there's a decline over time in measurements? Yes, absolutely. Yeah, you can see, yeah, as you can see, we have the error bars on the slide that shows that with the temporal changes, and you can see on a patient-by-patient average, it does decline over time. Yeah, so we are seeing a deeper response at nine months versus six. So, that is a trend that we're observing in the data. Great, thank you. Thank you. Our next question comes from Kristen Kluska with Cantor Fitzgerald. Your line is open. Hi, good morning, everybody, and congrats on these data. I was hoping we could talk a little bit more about the relationship between NSVTs and SVTs, particularly how to think about the reductions here and ultimately down the line how that may reduce the probabilities of SVTs occurring. I know there's really no approved drugs that have looked at this, but I'm curious if there's any research that can really contextualize some of the benefits you are seeing. Thank you. Yeah, so the definition of non-sustained ventricular tachycardia is more than three beats, and basically three consecutive PVCs. And the definitions of sustained VT, it's a little murkier, but generally around thirty seconds is what most people will say is sustained VT. So, you can see that they're just essentially the same process. It's just temporal. One is lasting longer than the other. So, there's a clear relationship between NSVT and sustained VT. It's just the amount of time that they last. So, having non-sustained VT is a harbinger that most clinicians would say that would predict sustained VT. Thank you. I mean, I might just add to that, the sustained VT obviously is more concerning regarding the patients receiving shocks. And one of the things we've mentioned is that none of our patients in this trial have received any shocks from their defibrillators, so suggesting that there's no sustained VT in this cohort of 10 patients thus far. Thank you. Our next question comes from Chris Raymond with Raymond James. Your line is open. Hey, thanks and congrats from us on the data as well. Just maybe looking ahead a little bit, this might be early to sort of ask this question, but any plans maybe, or are you thinking a little bit about how your next trial might look in terms of patients with more severe disease? And can you maybe talk about the enrollment, sort of what you have to solve for there, just given that patients with more severe disease obviously have more events and just kind of how that might work? And then maybe a question on how you and the FDA might be thinking about PKP2 protein expression. Is it the totality of VCN, mRNA, and PKP2 protein, or is there some other measure that we should be thinking about going forward? Thanks, Chris, for the question. So, I think it's our perspective that the patients we've enrolled, in particular in the high dose, are pretty severe in terms of their disease burden. Typically, they have very high PVCs at baseline. 500 is a threshold for patients to be diagnosed with arrhythmogenic cardiomyopathy along with several other criteria. Some of these patients are starting with PVCs in the thousands. One patient as high as 6,000 PVCs. Most of the patients have meaningful non-sustained VT burden. Some of the patients have reduced ejection fraction, which is a structural measure. So, they are presenting with pretty meaningful signs of arrhythmogenic cardiomyopathy. We would say that they are severe, probably not in the latest stages of the disease, but they are pretty severe. So, I think we're trying to understand the effect size across the range of patients presenting with this disease. We have some patients that are a bit earlier. We have a number of patients that are later. And so that picture, I think, will forward into a discussion with the FDA. On your second question for the next trial, I do think it's early to come to any formal conclusions on this. I think we believe non-sustained VT would be a good endpoint to build a future study around, but there are possibly others here that could be important, such as RVEF and maybe some of the patient-reported outcomes as well. With respect to protein expression, I know that our FA study and I believe another study are using protein expression as a co-primary endpoint. I think there are some questions that we would need to discuss with the FDA about the use of protein expression as an endpoint in a pivotal trial. As you can see, there's a different pathology here in arrhythmogenic cardiomyopathy. The fibrofatty deposits are one factor. The fact that the patients start with highly variable pretreatment baselines is another factor. So, the question of what's this target level you need to reach in PKP2 expression relative to these variable pretreatment baselines is definitely another question here. I believe that this one as well would be potentially a bit larger study than, for example, what we are undertaking for Friedreich ataxia. Obviously, adding biopsies to a large study increases the study execution, some of the study execution challenges as well. I think those are all the factors we'll be considering as we talk to the FDA this year about next steps in the program. But I would just note that we believe NSVT is an important endpoint in this disease, and showing an improvement in NSVT, as Eric was just describing, can potentially be a good surrogate for sustained VT and obviously then for ICD shocks. We've not seen any patients with ICD shocks in our study to date across 10 patients treated. We have patients that are out to 12 months of treatment follow-up. Thank you. Thank you. Our next question comes from Moritz Reiterer with Guggenheim Securities. Your line is open. Hi, this is Moritz. I'm for Debjit. I got two questions. First, in your natural history study, what does the intrapatient variability NSVTs over time look like? And sort of related to that, what's your threshold for defining a patient as stable when it comes to NSVT versus improving or getting worse? And then the second one, I believe you've already mentioned this during the Q&A, but just to confirm, you did not see any ICDs fire in any of the patients throughout the trial period, correct? Sorry, so there were a few questions there. We may have to ask you to repeat some of them, but the first on the last one with ICD fires, correct, we did not see any patients with ICDs that fired in the trial. In terms of variability in the natural history, we don't have that information. It's still emerging. We don't have that information available yet. But you could see in both NSVT and PVCs, there was an increase over a twelve-month time period in the fifteen natural history patients. Could you repeat the other questions that you mentioned? Yeah, it's related to the intrapatient variability in NSVT over time. I was just wondering, you referred to some of the patients earlier on as stable when it comes to NSVT. So, I was just wondering, how do you define a patient as being stable? At what point is the effect size, the delta still defined as stable versus what do you see as an improvement or getting worse? We haven't set strict criteria around stable, worse, or better, but you could imagine certainly 10%-20% differences wouldn't be considered meaningful, or we have a patient with two NSVTs going to four in terms of the materiality of that change in two, is a question from a threshold perspective. We're encouraged by the fact that for some of the patients with the highest NSVT burdens, like patient four, patient seven, and so on, we're seeing reductions in NSVT there in a double-digit% range. Yeah, and I think it's really important to look at absolute change in NSVT in particular. So, if these numbers are low to begin with, like you have one patient that goes from two to four, is that really meaningful or is that the percentage is high? But the reality is that's not particularly clinically relevant and seems more like noise, as opposed to you see patients going from like 169 to 44, like it's unequivocally a large reduction. Thank you. Thank you. Our next question comes from Geulah Livshits with Chardan. Your line is open. Good morning and thanks for taking the question. Can you expand a little bit more on your hypothesis of why the kinetics of PVC count improvement could be later than NSVT? And what are your expectations for the kinetics for things like T-wave inversions, QRS duration, and right ventricular function? Yeah, great question. I think you have to remember that they're fundamentally different biological processes here. So, PVCs is really an intracellular process in which trafficking proteins that go along with the desmosome regulate depolarization and lead to early after depolarizations, which cause PVCs or delayed after depolarization. So, that process is quite different than when you have entrapment of an arrhythmia leading to non-sustained or sustained VT. So, we think it's quite possible that though you might not be able to suppress the initial PVC, the spark, that you can still suppress whether that spark becomes a fire and is sustained. Got it. And then how does that relate to the potential kinetics for those other metrics? Yeah, I think those other metrics, you can imagine those are. A surface EKG is capturing the entire ventricle, and you can imagine that it would just take longer to change, for example, a T-wave, which is reflective of the entire myocardium. So, it's logical to me that that type of remodeling could just take. You're talking about overall large structural changes to impact that, which may take time. Got it. Thanks. Thank you. As a reminder, to ask a question, please press star one one. Our next question comes from Michael Okunewitch with H.C. Wainwright. Your line is open. Good morning. Mike Okunewitch from H.C. Wainwright. Can you please share the baseline PVC burden and NSVT frequency for each of the five high-dose patients, or at least give us the range and the median? Because kind of without baseline levels, it's hard to judge how meaningful the 14% and 22% mean changes are. And also, were the PVC NSVT measured by Holter versus ICD interrogation, and were med/ablation stable over follow-up? And basically, I'm pretty much asking because Holter versus ICD can capture arrhythmias differently based on the monitoring window, which kind of affects how comparable the percentage changes are. Thank you. So, just to clarify, baseline PVCs are on the slides. So, if you look at slide 16, the number on the left side of the arrow is the baseline PVC value. So, we're simply calculating the percent change from that value on the left relative to the value on the other side of the arrow, which is the latest visit. Which is the latest visit? Can you repeat the second question? Sorry. I was just asking if the PVC NSVT were measured by Holter versus ICD interrogation, and if there were any meds/ablations, all the meds and ablations were stable over follow-up. Yeah, so in regards to your first question, they were measured by a seven-day Holter and then averaged to give you a 24-hour, which I think is the right way to do it. So, it gives you an average for this as opposed to just one random 24-hour measurement. In terms of the second question, I think this is all disclosed on the slides. Again, there's minimal use of antiarrhythmics to patients on antiarrhythmics out of the entire cohort. Great. Thank you very much. Thank you. Our next question comes from Rohan Mathur with Oppenheimer. Your line is open. Hey, it's Rohan on for Leland. Thanks for taking my question. Just on mRNA expression and PKP2, based on the current levels of PKP2 expression you've shown and the VCN numbers there, do you expect those numbers to stabilize over time? And if so, would you still expect to see a greater degree of cardiac remodeling with the extended time of exposure? Thank you. Yeah, I think it's a great question. This is obviously an early time point. Most of the patients are at six, especially in the high-dose cohort where you only have two patients at nine months. We do expect, as you can see, this deepening and improvement, especially as we get out, as we look at non-sustained VT, that we do expect over time that this indeed should get better. Obviously, the data will be the data and that will tell us, but we think it's quite promising that over time you see these reductions. Do expect. We're hopeful that that's going to occur. We're seeing it, I mean, already, in our opinion. If you look at the high-dose mean NSVT change, we're seeing a greater effect at nine months versus six on average. More to come. It's a small end, but one would expect that as these fibrofatty deposits are cleared, as we've seen in the animal models, you begin to see even a greater response. I think it's a function of time. Again, as we've mentioned, this is the earliest time point where we could begin to evaluate efficacy. So, to see these early signals at patients that are primarily at six months is encouraging. With a clean safety profile and good protein expression. So, yeah, I think all these things are aligning for us. Thank you. Thank you. As a reminder, to ask a question, please press star one one. Again, that's star one one to ask a question. I'm showing no further questions at this time. I'd like to turn the call back over to Nolan Townsend for any closing remarks. Okay, well, thank you everyone for joining this morning. We appreciate the interest in the program and we're excited about this program going forward. I mean, I'd say we're looking at a set of patients here in this disease, and if you look at their baseline characteristics and some of their past treatment history, a lot of them have ICD shocks, sustained VT in their treatment history. They have high both PVC and non-sustained VT burden. And here, we're seeing in this early data that we are reducing premature ventricular contractions. We're reducing non-sustained VT. We've had no ICD shocks through the duration of the study. So, we think we're seeing a positively emerging clinical picture here and obviously alongside a very compelling safety picture for gene therapy at this dose. And so, we're excited about the next steps in the program. As we mentioned, we have patients nine and 10 that have been dosed with a final commercial process for final manufacturing commercial process, which is yielding higher potency. So, we'll have that data forthcoming into patients. And then we have the twelve-month data across the entire study that would be coming in the second half of the year. So, a lot of exciting future moments for this program, including a conversation with the FDA about the registrational study. So, thank you for your interest and for the interest in the program and the company. So, thank you very much. Thank you for your participation. You may now disconnect. Everyone, have a great day.