Tenaya Therapeutics, Inc. ($TNYA)

Thank you for standing by, and welcome to the MyPEAK-1 interim data call. [Operator Instructions] I'd now like to turn the call over to Michelle Corral, Vice President of Corporate Communications and Investor Relations. You may begin.

Thank you, Rob. Hey, everyone, and thank you for joining us today. I'm Michelle Corral, as he said, Vice President of Corporate Communications and Investor Relations at Tenaya. Today, we are excited to share interim data from both cohorts of our MyPEAK-1 Phase Ib/II clinical trial of TN-201 gene therapy for potential treatment of MYBPC3-associated hypertrophic cardiomyopathy or HCM. While the data we are discussing today will be described in full verbally, please note that during the course of today's call, we will be making references to slides. A PDF file of the slides accompanying this webcast is available on the Tenaya website in the IR section under Events and Presentations. Before we dive in, let me remind you that the information discussed during this call will include forward-looking statements, which represent the company's views as of today, June 3, 2026. 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. On the call with me are Faraz Ali, Tenaya's Chief Executive Officer; Dr. Kathy Ivey, our Senior Vice President of Research; and Dr. Whit Tingley, Tenaya's Chief Medical Officer. With that business out of the way, let me turn the call over to Faraz Ali for opening remarks. Faraz?

Thank you, Michelle. Good morning, everyone, and thank you for joining us today. We're incredibly excited to share today's TN-201 update in MYBPC3-associated hypertrophic cardiomyopathy, as you know, a genetic heart disease driven by insufficient MyBP-C protein. On Slide 4, we remind you of the scale of MYBPC3 mutations within the broader context of HCM as well as some of the defining characteristics and the toll of this disease on patients' lives. MYBPC3-associated HCM is a chronic progressive condition, affecting an estimated 120,000 adults, teens, children and even infants in the U.S. alone. And for those with mutation, we know disease progression is more rapid, and that their risk of serious cardiac events is far greater than those with other forms of HCM. The prognosis for those diagnosed at younger ages is even more grim, as we will cover in more detail later. Turning to Slide 5. In MYBPC3-associated HCM, the mutated gene involves a deficit in a key sarcomeric protein needed to regulate the heart's contraction. Without that protein, the heart contracts at excess force. And over time, the walls of the left ventricle thicken or hypertrophy, reducing the ability for the heart to fill with sufficient oxygenated blood to meet the body's demand. The result of this progressive condition is heart failure and other comorbidities. We believe TN-201 has the potential to fundamentally change the trajectory for these patients by delivering a fully functional MYBPC3 gene to the heart muscle cells, increasing MyBP-C protein levels and potentially halting or even reversing the course of genetic ACM with a single treatment. Importantly, TN-201 is targeting the underlying cause of the disease. And therefore, its impact is not dependent on phenotype. While great inroads have been made in the availability of myosin inhibitors for obstructive disease, 70% of the patients with the MYBPC3 mutation have the nonobstructive form of the disease. Today's update represents a significant milestone for our program, one that we believe highlights the growing strength and consistency of treatment data for TN-201. Since we last shared data at the American Heart Association meeting in November 2025, we have meaningfully extended follow-up across both those cohorts, with some patients now reaching up to 2 years of observation at the 3E13 vector genome per kilogram dose, and up to 1 year for those who received TN-201 at the 6E13 factor genome per kilogram dose. On Slide 6, we summarize the key findings for the compelling data set we are sharing today, which show consistent improvements in cardiac structure, including reversals in multiple measures of hypertrophy sustained over extended follow-up, reductions in symptom burden for all patients and emerging improvements in functional capacity, particularly among those at the higher dose level. From biopsies, we continue to generate evidence that TN-201 is reaching the heart and robustly transducing and expressing in cardiomyocytes. We are also pleased with the continued tolerability profile across both those levels as we expand enrollment and gain additional experience with the therapy. Together, these findings support our expectations that TN-201 can drive a meaningful and durable impact on disease burden, which is especially encouraging given the limitations of today's standard of care. Now with that, let me turn the call over to Whit Tingley, who will walk you through these compelling data in greater detail. Whit?

Thank you, Faraz. I will begin with a reminder of the trial design on Slide 8. MyPEAK-1 is intended to characterize the safety of 2 different doses, 3E13 and 6E13 vector genomes per kilogram of body weight. In addition to dose finding, the trial collects heart biopsy data to give us a set of pharmacodynamic and includes several exploratory endpoints measuring changes in key parameters. The ultimate goal of treatment is to see multiple parameters of disease biomarkers, echo measures, symptom burden, all improving with directional consistency within each patient and across all patients. We have completed enrollment of both initial dose cohorts, and we are currently enrolling patients in our 6E13 vector genome per kilogram expansion cohort. The data presented today includes safety, biopsy and clinical results from 6 of the 7 patients enrolled. Slide 9 shows the baseline characteristics for the patients in MyPEAK-1 who have more severe disease than the average HCM patients, consistent with their genetic mutations. All patients enrolled to date have nonobstructive hypertrophic cardiomyopathy. Four of the 7 previously undergone myectomy. Their ages at the time of enrollment range from 27 to 63. They all have march hypertrophy with elderly past well above typical HCM patients. And they all have symptoms of heart failure that impact the activities of daily living as measured by the New York Heart Association Classification. The majority of my people on patients entered the study with elevated cardiac biomarkers. On Slide 10, we show cardiac troponin eye levels at baseline and most recent visit. Troponin is a marker of injury to the heart cells. We follow it closely in ATM method as a known prognosticator for increased risk of adverse cardiac events. In the chart, you can see troponin levels declined or remained essentially stable in all but one patient. Patient 7 in the high-dose cohort had a large and rapid drop. NT-proBNP is the circulating biomarker that indicates strain at the heart muscle and is known to be sensitive to diverse factors, including immunosuppression. NT-proBNP has declined from baseline in 3 patients. On Slide 11, we turn to a critical assessment in hypertrophic cardiomyopathy, cardiac [indiscernible]. All patients treated with TN-201 show improvements in hypertrophy. That means the defining characteristic of this condition, LB mass and thickened wall, have been reduced. On the graph, we show the decrease in left ventricular mass index, a measure of the proportion of the LV size normalized to the total body surface area. Elevated LVMI is a strong independent predictor of cardiovascular events like heart failure and sudden cardiac death. All patients entered MyPEAK-1 with severe hypertrophy, making these reductions in LVMI all the more important. For the first 2 patients dosed, the improvements have been maintained through year 2. Four of 6 patients have 10% or larger reductions in LVMI. But we're not just seeing a decrease in a single measure, we see corresponding improvements in wall thickness as well. For example, the thickness of the intraventricular septum, or IBS, decreased in 5 of the 6 patients. Other echocardiographic measures of cardiac structure and function remains stable. Taken together, these positive changes in hypertrophy suggest that favorable cardiac remodeling is taking place consistently and persistently over time. For context, on Slide 12, we have mapped the average reductions in LVMI, posterior wall thickness, LVPWT and IVS thickness for our MYBPC3 patients in comparison to reported average changes for the cardiac myosin inhibitors pulled from available published data. With the caveat that cross-trial comparisons are always limited by differences between the trial and therefore, can risk over interpretation, we do see that the decreases in hypertrophy after TN-201 compare favorably to the results reported for the cardiac myosin inhibitors. We are certainly excited by these data, particularly the durability of changes in Cohort 1 and the pace and depth of changes emerging in Cohort 2. We certainly also want to know that patients feel better, and we are encouraged by the early changes in the symptom burden. On Slide 13, we're measuring how patients are feeling using 2 measures. New York Heart Association class, a physician assessment of how disease affects daily living, and the Kansas City Cardiomyopathy Questionnaire, a well-validated measure used to assess all status, symptom burden and quality of life among cardiomyopathy patients, including HCM. Most importantly, I'm happy to share that all patients in MyPEAK-1 are feeling better and experiencing fewer symptoms by at least one of these measures. Starting on the left, all but one patient is now New York Heart Association Class I, meaning that although they started the trial with heart failure symptoms affecting daily activities, they now have no limitation on daily activity. On the right hand of this slide, we're sharing more encouraging new data. 2/3 or 4 out of 6 MyPEAK-1 patients report meaningful improvements in their clinical summary score. KCCQ Clinical Summary Score uses a 100-point scale from very poor to poor, fair, good and excellent, with approximately 25 points between categories. A 5-point difference is considered the minimum change in score that is clinically meaningful. Patients in MyPEAK-1 started the study with scores as low as 22 points in the very poor category at baseline. Four have had meaningful improvements, and their scores now range from 78 to 100 points, meaning their symptoms and quality of life are now in the good to excellent category. I'd like to underscore the consistency among Cohort 2, whose average change from baseline was an impressive increase of 36 points. This exceeds the typical change seen in the placebo arms of blinded HCM studies. Now let's turn to Slide 14, where we share results from 2 tests used to evaluate exercise capacity, 6-minute walk distance and cardiopulmonary exercise testing for Cohort 2. A majority of patients receiving the high dose of TN-201 showed improvement and at least one measure of exercise capacity. As to Cohort 1, not shown there are several factors that may be confounding their functional performance, given that we're seeing improvements in other parameters for patients in that cohort from founders include comorbidities and unrelated medical events during the study. Of note, Cohort 1 patients received more immunosuppression for a longer duration than Cohort 2, which can impact exercise capacity. We are actively enrolling new patients at the 6E13 dose level to further understand the positive observations we have seen so far, and we plan another data readout later this year. Now I'd like to ask Kathy Ivey to speak about TN-201's pharmacodynamics. Kathy?

Thank you, Whit. I'm glad to share the details of the data we have obtained from heart biopsies. Turning to Slide 16. In MyPEAK-1, cardiac biopsies were collected from patients 1 and 2 at 8 weeks post dose and again at 52 weeks. All other patients were biopsied prior to dosing and are intended to be biopsied 2 additional times, with the latest being at 52 weeks. The biopsy collection and analysis process was described in more detail in our RIDGE-1 data released webinar on May 15. But in brief, during each biopsy procedure, 6 to 8 small snips of tissue, about 1 millimeter in size, are collected from the septum using a catheter. Each of these valuable tissue samples is preserved and allocated to a specific quantitative analysis of DNA, RNA or protein. The graph at the top of Slide 16 shows the number of TN-201 transcript per microgram of RNA from the 6 patients at their earliest and most recent biopsies. Importantly, the RTQPTR assay used is designed to specifically detect TN-201 and not detect mRNA from the endogenous MYBPC3 gene. Therefore, these results provide clear evidence that TN-201 gene therapy is reaching the heart, entering the cardiomyocyte and producing messenger RNA, which ultimately provides instructions needed for the heart muscle to produce my MyBP-C protein. Notably, the average TN-201 mRNA levels in Cohort 2 at the most recent visit were about 2x higher than that of Cohort 1, reaching up to 3.2E6 in patient 7. And those higher mRNA levels in Cohort 2 were achieved at an earlier time point. DNA transaction levels not shown here were also higher in the second cohort, confirming the expected dose response. The lower graph shows the ratio of MyBP-C to myosin heavy chain peptides as determined by a liquid chromatography in that spectrometry. Normalization to myosin heavy chain, which is a protein restricted to cardiac muscle cells, helps to account for differences in the cellular composition among biopsy samples. We also analyzed multiple samples for protein where possible, and consider the average value to help account for variability. As intended, TN-201-derived MyBP-C protein is indistinguishable from endogenous B protein. Acknowledging that the variance between and among samples, patients and clinical sites complicates interpretation, we nevertheless detect an average overall increase in total MyBP-C protein in both cohorts over time. And consistent with the mRNA results, the protein increase in Cohort 2 is comparable to Cohort 1 even at an earlier post-dose time point. Together with the latest clinical data, the totality of the DNA, RNA and protein data from biopsy samples support that TN-201 is reaching and having effects in the heart. I'll now invite Whit back to review results of safety and tolerability.

Thank you, Kathy, for that clear explanation of our biopsy results. Before handing the call back to Faraz for closing remarks and the Q&A, I'd like to cover 2 slides on TN-201 safety, starting on Slide 18. Safety is our primary objective, and I'm very pleased to report that there are no new safety events since our last data presentation in November 2025. TN-201 has been generally well tolerated at both doses, and the few adverse events related to treatment have primarily been filed, manageable or reversible. The most common AEs associated with treatment have involved safety laboratory values, such as elevated liver enzymes, low platelet count or elevation in complement factors. Platelet and complement changes all self resolve without need for treatment. As for the elevated liver enzymes, these were asymptomatic and responded well to steroid treatment. Patients in MyPEAK-1 received sirolimus and prednisone prophylactically before TN-201. As shown in Slide 19, we refined our dosing and monitoring resident during Cohort 1 to reduce the overall need for immunosuppression. As a result, we've been able to taper immunosuppression faster in Cohort 2 than Cohort 1 despite the higher dose of TN-201. This limits side effects and is clearly better for patients. Faraz?

Thank you, Whit. Turning to Slide 21. As we continue to build the data set, what stands out to us is the consistency of effect we are seeing across multiple measures of disease, from cardiac biomarkers to cardiac structure, to how patients feel and function in their daily lives. This is especially true for patients who received the higher dose of 6E13 vector genome per kilogram. We believe this growing body of evidence reinforces the core promise of TN-201, namely, that our onetime gene therapy has the potential to modify the underlying biology of disease, rather than simply manage symptoms. As we look ahead, we have every reason to believe that TN-201 could have a positive impact on any patient with the MYBPC3 mutation causing HCM. Today, we are treating adults with either phenotype. MyPEAK-1 has thus far enrolled only nonobstructive patients, as we would expect, given that this phenotype is much more common among the MYBPC3 variance and the lack of available nonobstructive treatment options. Turning to Slide 22. We also have long maintained that the significant unmet need in severe and rapidly progressive pediatric patients demands and answer and presents an important opportunity to fast track our late-stage development. It is with the sense of urgency that we initiated the MyClimb natural history study even before we started dosing adults with TN-201 in the MyPEAK-1 interventional study. MyClimb has thus far enrolled more than 220 patients at 29 sites in 4 countries. That includes retrospective patients who have already unfortunately passed due to their disease as well as prospective patients who could be eligible for future pediatric studies. Now that we are generating increasingly positive efficacy and safety data with TN-201 in adults, we're excited to engage on next steps in that direction and to explore multiple possible pathways ahead to pivotal studies in adults or severe pediatrics. And on the topic of pivotal path, one of our key goals as a company this year is to engage with regulatory agencies on our growing body of evidence and to pursue alignment on a path forward. We are indeed engaged in such discussions and which are, by their very nature, iterative, and we expect to provide an update by year-end. However, in the meantime, we have 2 encouraging new items related to this to share on Slide 23. First, the European Medicines Agency, or EMA, has granted TN-201 prime designation. Prime designation is intended to offer early and proactive support to sponsors in order to accelerate the review and progress of promising new medicines. We have long considered the EU as a near-at-hand extension of our U.S. development program and utilize the MyClimb study as a means of establishing a relationship with KOLs and leading cardiomyopathy treatment centers, which, given the nature of medicine there, tend to be more consolidated versus a mix of centers of excellence and community docs we have in the U.S.A. Exciting, TN-201 has also been accepted into the FDA's new RDEP process for the indication of severe biallelic pediatric patients. RDEP stands for rare disease evidence principles, and as part of the agency's effort to provide sponsors with additional guidance on the development of genetic medicines for ultra-rare and severe genetic diseases typically affecting fewer than 1,000 patients in the U.S. The process enables early and ongoing collaboration with the agency, align our regulatory strategy, trial design and approaches to generating convincing approvable evidence from multiple sources. Turning to Slide 24. As a reminder of the opportunity in severe pediatric patients, we offer a snapshot of how we're thinking about the treatment of children with MYBPC3 mutations. We estimate that there are approximately 3,000 diagnosed patients under the age of 18 in the U.S.A. alone at any given time. We know that younger age of diagnosis leads to worse outcomes, a faster pace of disease progression and higher risk of heart failure, arrhythmias, symptom burden and hospitalization, transplant or death. And what we've learned from MyClimb is that there is an opportunity for further refinement within that population. Outcomes defer even within the severe population based on genotypes. For example, 85% of severe pediatric patients who are homozygous, die or require transplant before the age of 1, and 64% of compound heterozygous [indiscernible] experienced heart failure-related hospitalizations before age 10, and 27% required transplant or died. These data from the MyClimb Natural History study offer the tantalizing possibility of being able to show movement on hard clinical endpoints sooner versus a natural history, and then expand to additional populations among additional patients under the age of 18. As a reminder, there are no approved condition-specific treatments for these very severe pediatric patients, leaving a clear and urgent need. That sense of urgency among families was illustrated by the results of a survey of patients of young children with severe cardiomyopathy that confirms high interest in gene therapy. The survey was conducted in collaboration with the Children's Cardiomyopathy Foundation and the DTC Clinic, a center of excellence taking care of such patients. We shared these results via poster at the recent ASGCT conference, and it is available on our website. As a reminder, in addition to being admitted into the RDEP process for biallelic patients, we have received rare pediatric disease designation, which offers another incentive for pursuing the subgroup as a potential first path to approval in the form of a priority review voucher. So in addition to continuing to enroll adults in the 6E13 vector genome per kilogram cohort -- expansion cohort and engaged with the regulators on the data being generated from MyPEAK-1, we are actively exploring the advancement of TN-201 in a severe pediatric population as a key component of our pivotal trial planning and strategy for achieving a potential approval for TN-201. While these are still early data from a small number of patients, we believe the breadth, depth and consistency of the signals we are seeing provide increasing confidence in the potential of TN-201, and support our ongoing development strategy. Turning to Slide 25. As we look ahead, we remain focused on: continuing enrollment in the higher dose expansion cohort, generating additional follow-up to further characterize durability and dose response and engaging with regulators on the path forward for this very promising program. Finally, on behalf of the entire Tenaya team, I'd like to express our gratitude to the MyPEAK-1 and MyClimb investigators and their clinical site teams. As always, a special note of gratitude to the patients and their families and caregivers. These individuals are at the heart of Tenaya's purpose. And without their willingness to believe in our mission and join us in our efforts, these data would not be possible. With that, we have concluded our prepared comments. Operator, let's now open the lines for Q&A.

[Operator Instructions] Your first question today comes from the line of Mike Ulz from Morgan Stanley.

Maybe just one on protein expression, just for the 2 patients in Cohort 2 that didn't experience an increase. Just curious if there's anything unique about those patients or any interpretation as to why that might be?

Mike, thanks for the question. And for that, I'll first turn it over to Kathy Ivey?

Yes. So I don't think anything about the baseline protein expression was particularly remarkable, although it's perhaps notable that patient 4 had the highest baseline protein that we detected in any of our patients at baseline. But yes, I think the evidence that we see from clinical improvement suggests that our detection of protein may just be a limiting factor here, and we think there really are underlying increases in protein over time.

Yes, I agree. Thanks. Thanks for the question. I mean, overall, the RNA data and the totality of the data, including the transaction data that we don't -- we haven't shown here, just support that overall, we're getting higher transduction and RNA expression at the higher dose. And so the -- we do believe that, obviously, we're adding protein to these patients' hearts, and the clinical results seem to bear that out.

Your next question comes from the line of Thibaut Pardo from LifeSci Capital.

So when you look patient by patient, how should we reconcile improvements in hypertrophy measures with some mix changes in feel and function measures beyond the immunosuppression in Cohort 1, how that could affect, for example, the [ 6 ] minute [ walk ], particularly patient 6 and how we saw increases in -- or decrease in hypertrophy, but the 6-minute walk did not improve.

Yes, it's a great question, Thibaut . Good to hear from you. For that, I'll turn it over to Whit.

Yes. As we noted, the changes in exercise capacity depends on multiple factors and can be confounded by underlying comorbidities or adverse events unrelated to the trial that can occur during the course of the trial or even right before an exercise assessment. Overall, though, we are very pleased, as you now see improvements in multiple parameters and consistent improvements within patients and across groups.

Yes. Good. Thank you, Whit. And just to add to that, Thibaut, I think, I mean our results in some ways are -- they -- you can also make in comparison with what has been demonstrated with myosin inhibitors. The -- they've shown their functional improvements, that's why they've been approved, but the level of high purchase fees are not quite as profound on average is what we're being able to demonstrate early on. So this is an imperfect relationship, it's an important overall relationship, but an imperfect relationship at any individual patient level between the level of hypertrophy reduction you might see and the level of improvement in some functional measure, like 6-minute walk test or [ pVO2 ], that's been seen in other studies and versing it here, too. So ultimately, the totality of the evidence does suggest that we are getting patients are moving them in the right direction by modifying the underlying disease.

Your next question comes from the line of Whitney Ijem from Canaccord Genuity.

Congratulations on the update. In particular, congrats, I guess, on progress on the pediatric side. And just wondering if we can get any more color there in terms of the discussions with regulators and maybe what feels like pushback? Or -- you kind of talked about the iteration, what needs to be iterated? It feels, in particular, on the back of some of the natural history data you presented, that there could -- should be a faster kind of more straightforward path. So are we thinking about that correctly? Or what's been the pushback? Why haven't you treated any pediatric patients as yet? And what do you need to do to get there going forward?

Whitney, thanks for the question. Let me first -- I'll turn it over to Whit again, and then I'll add some comments on top of that. Whit?

Yes. We're having productive discussions. I think when you say pushback, I would say we are aligning on a path forward that will -- for pediatric development that will be tailor-made for TN-201 therapy. So that process can take a little while.

Yes, I agree. It's not pushed back at all. Whitney, in fact, I would say quite the opposite. The inclusion of TN-201 in this new program, RDEP, that was introduced by this -- FDA, is actually -- we take it as a positive sign that they understand the severity of this rare disease population and very severe population, and want to work with us, actually. And as we pointed out, there's heterogeneity within this group. As we show in the MyClimb data, some patients, you could have a hard endpoint like survival, others who are on [ bads ] might have different end points and some -- yet other patients present on a structure that's more consistent with the adults. So I think there's nuances here in this population, and we're very pleased with the engagement that we're having. And so the devil is always in the details. And so it's iterative not because of push back, but because actually, in many ways, this is the first time that, to our knowledge, somebody is trying to align on something with this kind of rapidly progressive early severity, including kids who are dying in some cases, as early as the first few days, weeks and months of life. We haven't dosed any patients in a pediatric study yet because we haven't initiated one. We would initiate a pediatric study only under the side of full alignment on the design of pivotal studies to support that population. And so we would only either amend the current study or launch a new study with that under our belt. So just please, rest assured, we -- the iteration is a good thing.

Your next question comes from the line of Mani Foroohar from Leerink Partners.

I know it's been touched on a little bit, but wanted to circle back, first on the data -- so with 3 -- it looks like 3 of your patients in Cohort 1 sort of increase in protein, quite robust results, bouncing around by time point as you expect versus [ close to 1 ] I think in Cohort 2, though, again, obviously not a perfect metric. But the Cohort 2 patients, to my eye, did better from functional endpoints. Can you just sort of a little bit test that on how to interpret this? And then I have kind of a follow-up on broader strategy.

Yes, sure. Thank you, Mani. Good to hear from you, and thanks for the question. Let me turn it over to Whit to sort of share his impressions of the differences between Cohort 2 and Cohort 1.

Yes, we are seeing our early signs that patients may be responding more strongly and more quickly to the higher dose. We can see that in how they're reporting their symptoms. We can see that in hypertrophy measures. And as you're noting, we're seeing encouraging signs for a functional assessment. As it's still early, there's still more functional assessments we need to get from the high dose. We need longer follow-up, and we are dosing additional patients in that high dose port to fully understand it. But the overall trend appears to be better efficacy at the higher dose. And as we mentioned, is very well tolerated. So very encouraging overall. The RNA results are also encouraging for that cohort, the protein, clearly, more data will help.

Yes. The only thing I'd add to that is that, while on the functional side, we didn't yet quite see those same improvements for Cohort 1, but the reductions in hypertrophy in a patient population that has some of the most hypertrophied hearts steadied when we compare to other peer programs. That is meaningful, as in many cases, as we've shared in the past, reductions in hypertrophy below certain levels are predictive of better long-term outcomes for these patients, including survival benefits. So we are very pleased with the improvements we're seeing in Cohort 1, and even more pleased with what we're seeing in Cohort 2. It sounded like you had a follow-up question, Mani?

I do. I guess I had a separate question. Obviously, the meaningful [indiscernible] between NHCM and OHCM, especially around structure. As we think about your continued engagement with the FDA, what are the range of, sort of strategies you could pursue in terms of separate studies, multiple cohorts or a stratified approach to a single study. These are clearly very different patient populations in terms of tempo of response and underlying clinical course. Just walk us through what the possible outcomes and development strategies might be to serve patients with different needs of underlying clinical forces.

Yes, great question. And again, I'll first turn to Whit to see if he'd like to comment on that. On Slide 22, we lay out the different populations that I think you're referring to, Mani, nonobstructive and obstructive adults and then the adolescents, teens, and infants. So Whit, anything you'd like to add about our development strategies in the different groups and different studies or one study with different subtypes or subgroups?

There are different possibilities. As you know, we are necessarily going to have to follow the path that CMI followed. We have -- as you are suggesting, we have [ curated ] discussions ongoing with regulators, but still in the discussion phase, so it would be premature to hint any potential direction.

Yes. But needless to say, I mean, Whit, I would agree. And I think the -- these are different populations, as I pointed out, Mani. And the end points that might be most relevant are going to be different. For example, you can't measure pVO2 and 6-minute walk test in a homozygous infant. That's obvious, right? So the -- what we're going to study in these different populations may be different. And then there's a little bit of logistics of how do you -- what's the best way to incorporate these different groups, whether in some groups, you address by amending MyPEAK-1 or other groups require just an entirely separate study because the sites and the end points are just completely different. So I think more to come on this front, Mani, as the day -- as the year progresses and as we provide updates on our -- where we have aligned with the FDA on endpoints and design of pivotal studies and with specific populations. We continue to see that severity of the -- and the unmet need in the pediatrics as something we've been talking about, frankly, consistently for probably the last 5 years since we first launched the MyClimb Natural History Study. So more to come on that front.

Our next question comes from the line of Yasmeen Rahimi from Piper Sandler.

Really profound changes and feel and function of the patients. I mean putting that slide you have, 13, into perspective, right, you're getting normalization of patients feeling and functioning good. Question for you. Just one minor. If you see patient #6 really changing KCCQ Class 1 normalization. Maybe why have -- but then the 6-minute walk test regresses. Like what is the disconnect in that patient where everything is tracking well, but then the 6-minute walk, for some reason, goes down instead of going up, even though everything else is really astonishing. And the second question is, given the KCCQ data in the NYHA class responses, could we -- is it fair to think about in the future when you think about a pivotal study, and we have seen pivotal studies, right, in nonobstructive with the CMI that sponsors have peak KCCQ as a key regulatory endpoint. Would love to get your thoughts on the data that you just reported on Slide #13, if that's the way we should be thinking about primary endpoint selections for the pivotal programs and the robustness of the effectiveness that you're seeing? Sorry for these long-winded questions.

Yes. Always good to hear for you. Thank you for the question. Again, I'll turn it over to Whit to take a first response.

Yes, very good question. Certainly, to your second question, Kansas City Cardiomyopathy Questionnaire, as [indiscernible] as a potential pivotal endpoint. New York Heart Association class as well. And so these are certainly on the table as options for pivotal study. And then in terms of parsing out a patient, patient [ 6 ] was improving in multiple domains. That a 6-minute walk test is encouraging at that particular day. I would encourage you to sort of think about integrating the preponderance of the data. Again, as a patient is reporting their symptoms, it's not limited to one activity or one particular day. So when they say they're feeling better and their physician has interviewed them and found they're less limited on daily activities, that carries a lot of weight, and individual exercise capacity measurements can be confounded. We've seen from the CMI data, some published data. We'll show the individual changes, in pVO2, for example, and there's a huge range, up and down, amongst these individual patients. And that's not a drug effect or lack thereof, that's the variability of where people are at on that particular day of the test.

Yes. Whit, thank you. I agree. As we said earlier, I think there's -- any given patient will have some variability. We know some of these patients or a team does intimately know, aware of other commodities they may have that may impact the individual results. So we look at the totality of data and we're pleased with what we're seeing, Yasmeen. And then again, yes, KCCQ in endpoint, 6-minute walk test, pVO2, but I will go back to you on the pediatric population, those might not be as relevant, particularly as we're talking about very severe on patients. So we always said that -- when we set out to do MyPEAK-1, we always said it was going to be a data-rich study, and that we were looking at a lot of things. And I think you're seeing the fruit of that bear out being able to now describe improvements in circulating biomarkers and multiple, in many cases, multiple forms of hypertrophy and now multiple ways of capturing both feel and function. This is exactly what it's set out to do, and this will help us inform those selections as well as design of future pivotal studies in different subpopulations. And so we're exactly where we wanted to be with the data set that are maturing. Still early days, and we look forward to providing more updates in the second half of the year.

And that concludes our question-and-answer session. I will now turn the call back over to Faraz for closing remarks.

Yes. Thank you, Rob. Thank you all for joining us on the call today. Exciting results on top of the exciting results we delivered for TN-401 just a few weeks ago. So a great first half of the year for Tenaya, and an even more exciting second half of the year to come. We look forward to meeting some of you over the coming days, weeks and months and diving deeper into the data and answering your questions, and to providing additional important clinical and regulatory updates on the TN-201 program and the 401 program in the second half of the year. With that, have a good day.

This concludes today's conference call. You may now disconnect.