Hello, and welcome to Edgewise Therapeutics' investor event. My name is Sarah, and I'll be the operator for today's call. I would now like to pass the call over to Edgewise Chief Financial Officer, Mike Carruthers. Please go ahead when you're ready. Thank you, Sarah. Good morning, everyone. Welcome to Edgewise Therapeutics' conference call to discuss our sevasemten update for our Becker and Duchenne muscular dystrophy programs. This morning, we issued a press release which outlines these updates. You can access the press release, as well as the slides that we will be presenting today, by going to the Investors and News section of our website at edgewisetx.com. A replay of the event will also be available as a webcast on our website. Joining me today are Dr. Kevin Koch, President and Chief Executive Officer; Dr. Joanne Donovan, Chief Medical Officer; Dr. Behrad Derakhshan, Chief Operating Officer; and Dr. Alan Russell, Chief Scientific Officer. As a special guest, we have leading neuromuscular expert, Dr. Barry Byrne, Professor and Associate Chair of Pediatrics and Director of the Powell Gene Therapy Center at the University of Florida. Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements that are subject to a number of risks and uncertainties. These may cause our actual results to differ materially, including those described in our reports filed with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements and Edgewise disclaims any obligation to update the statements. I'll now turn the call over to Kevin. Thanks, Mike. For the introduction, I'd like to thank you all for joining today. I'm happy to be able to report that sevasemten continues to show significant promise for the treatment of Duchenne and Becker muscular dystrophy. We report today new positive observations in our open-label extension study, MESA, and new three-year data from our 12-patient ARCH-MESA trial. We had a positive interaction with the FDA, which provided a clear path to approval for sevasemten, and are on track to deliver top-line data on our confirmatory pivotal Grand CANYON study in the fourth quarter of 2026. On the Duchenne front, I'm happy to be able to report that we observed a clinically meaningful decrease in functional decline in a broad population of Duchenne patients when compared to natural history, and have identified a target dose for phase III. We will discuss with the FDA timing and study designs for the pivotal studies in the second half of this year. Turning back to the details of the unmet medical need in Becker muscular dystrophy, Becker is a devastating disease affecting over 12,000 adolescent boys and men in the prime of their life, which has no approved treatment option today. Over a multi-year period, these patients can completely lose their ability to lead independent lives, often leading to complete loss of ambulation and a shortened lifespan. Sevasemten is a drug with an entirely novel mode of action, and we believe this mode of action can address these unmet medical needs. The FDA has provided us fast-track designation for sevasemten because of the severity of Becker muscular dystrophy. I'd like to turn our attention to some of the details of what we'll discuss today in the Becker program. Sevasemten continues to demonstrate a favorable safety profile for up to three years of treatment from the ARCH studies. In the new open-label data in both the ARCH and CANYON studies, we see sustained disease stabilization in a population that would expect to lose function significantly over time over this timeframe. We built a prognostic model of natural history using a database of academic modeling of Becker patients and have been able to demonstrate that we are significantly altering the disease trajectory in these patients. We had a positive type C meeting with the FDA that provided a clear path to sevasemten registration with the potential to accelerate timing to the Becker launch. Finally, we're on track to provide top-line data in the fourth quarter of 2026. We've enrolled over 175 patients. We have that powered at greater than 98% to deliver a statistically significant difference in North Star versus placebo. I'd like to now hand it over to Joanne Donovan to discuss the details of the program. Good morning, everybody. First, I'm going to discuss the CANYON study. Like Kevin said, that is moving into the MESA study. The CANYON study was a phase II multi-center study to look at sevasemten safety and effects on biomarkers in adults with Becker. The primary endpoint was pre-specified and was change from baseline in CK, averaged over six months, six, nine, and twelve. It was not powered for North Star. The key inclusion criteria was we were looking at ambulatory males from 12 to 50 with a dystrophin mutation and a Becker phenotype, not on corticosteroids, and with a North Star between five and 32. That is because natural history told us that that was the group of patients with Becker who are in the decline phase and have a reproducible natural history. We enrolled 40 adults and 29 adolescents and studied them for 12 months. Adults were on 10 milligrams of sevasemten, and adolescents were on one of two doses. On the next slide, we show the primary endpoint. CK was decreased from baseline by 28%, which was statistically significant, and TNNI2, which is specific for fast myosin, decreased by 77%. Again, statistically significant. Importantly, the functional data shows that the North Star over 12 months in these participants was stable. The placebo group decreased approximately what you would expect from natural history. The point estimates from natural history studies show mean annual decreases between 1 and 1.7, and that is shown by the green triangle. The placebo was consistent with that. The difference between placebo and active treated was 1.12 North Star points. That had a p-value of 0.16. These patients moved into the MESA study, the open-label extension. In fact, the patients from all of our Becker studies are moving into the MESA study 99% of eligible participants are currently enrolled, and that is as of March 2025. We're giving you that because that's the data cut corresponding to the data when everyone in CANYON has reached six months, a full six months of MESA. What happened to them when they continued on sevasemten in MESA? What we see is that the active treatment group continued to be stabilized and in fact increased by a North Star difference of 0.8 versus baseline 18 months before. The placebo group that had declined was increased by 0.2 points since the initiation of sevasemten at the 12-month point. Looking at this duration is particularly important because 18 months is also the duration of the Grand CANYON study. We're showing stability over that time point. We have developed a predictive model to look at North Star changes and use that to contextualize what we've seen compared to natural history. We've worked with investigators at the University of Leiden. This was presented at MDA in March, and we looked at their natural history over up to five years to develop a predictive model based on age, functional measures that explained most of the variance in North Star. We validated this against publications showing other natural history data in patients with Becker. What this gives us the ability to do is look at each individual and predict their North Star trajectory. We'll do this for our patients in ARCH as well as in CANYON. In CANYON, after 18 months, these participants were predicted to decrease a North Star of 2.2 points. We were enrolling patients that were predicted to decline consistent with the natural history. That's the actual patients that we enrolled. In fact, they increased by 0.8. That's a very meaningful difference for patients to change over that period of time. You heard before about our ARCH study. That was two years open-label study. Those patients have also continued in MESA, and 11 of 12 are dosing now out at 36 months, and they are stable over time. The North Star change at three years is 0.2 points, and the predicted decrease is over four points. Again, the treatment group with sevasemten is continuing to diverge from natural history. What I'd like to do is actually ask Dr. Byrne to comment on what's the meaning of those kind of changes for men who are living with Becker. Thanks, Joanne. Certainly, the evidence that you've just shown about stabilization is really important in what is an inexorably progressive disease that has important consequences for the quality of life in patients living with Becker. Just as is shown on this slide, even moving one point from unable to or to a compensated performance of that skill on the North Star can enable someone to become a community ambulator, get up off of a chair, or live without direct assistance even in something like independent personal care. I think we've seen this even in feedback from patients that these are important changes. I'm really delighted to see the data thus far and now this large number of men with Becker dystrophy. Thank you. We took this to the FDA and had a successful type C meeting. The FDA reviewed the data for consideration of an accelerated approval and thought really that the CANYON data alone was insufficient for an accelerated approval. Actually, they said North Star is a clinically meaningful endpoint for traditional approval. They encouraged us to continue to share the natural history prospective modeling, the MESA data ahead of the completion of Grand CANYON. We will be working with them on that. They emphasized their support for Grand CANYON for the design of Grand CANYON so that it has potential as a single adequate well-controlled trial to support marketing authorization. We are quite interested in the recent developments that are positioned to potentially shorten approval time. We already have fast track with rolling submission as well as exploring other options to accelerate the path to approval in a potential first therapy for this disease that has no approved therapies. We have fully enrolled Grand CANYON with 175 patients. Based on the data from CANYON, in many of the same centers, we're able to look at the powering again, and the study is powered at over 98% to get a significant difference, a statistically significant difference, assuming the mean difference of 1.7 extrapolated from the CANYON findings over placebo at 18 months. That study is ongoing and moving towards having top-line data in fourth quarter of next year. Okay. Thanks, Joanne. I think there's been tremendous excitement from the physicians and the patients around this data set, and really the potential of sevasemten being the first therapy to treat Becker patients. We've demonstrated over the past couple of years long-term safety and reduced biomarker responses in the ARCH study and trends towards improvement in function over a 24-month period. In CANYON, the first placebo-controlled study in the Becker population, we met our primary endpoint of CK lowering. We showed stabilization of the North Star with a trend towards improvement versus placebo over 12 months, and the placebo acted just as predicted from natural history. The first time we've seen that in a placebo-controlled study. The ARCH and MESA data and CANYON MESA data, the long-term extension, continues to show positive trends in North Star, demonstrating sustained disease stabilization, continued slowing of progression. Finally, Grand CANYON is highly powered, show a statistically significant difference in North Star versus placebo over an 18-month period. We've had good progress with that program, very few dropouts. It's moving along very quickly and well. The regulatory path is clear. There are no approved therapies. It's a rare disease population, over 12,000 patients in the major markets. We've completed what we believe is a successful type C meeting where the FDA provided us a clear path to approval. I'd like to turn our attention now to the Duchenne population. Duchenne continues to be a devastating disease of young boys and adolescents. Despite recent approvals, there remains a significant unmet medical need with over 35,000 patients in the three major markets. What's really unique about the sevasemten mechanism is that it's mutation agnostic, meaning it can treat all Duchenne patients. In fact, we believe because of the foundational nature of this mechanism, it can be used in combination with things like exon skippers with steroids. We are the first company to evaluate this novel mechanism or any novel mechanism in combination and on top of gene therapy-treated patients. It is a very exciting time. I just want to remind you about how Duchenne muscular dystrophy progresses and what is the origin of the disease. Now, Duchenne muscular dystrophy is a genetic disease where patients are missing a key structural protein called dystrophin from their skeletal muscles. When a patient with Duchenne actually contracts their muscles, they hypercontract certain fibers, and those fibers are then damaged. Go to the next slide. Those fibers turn on a set of remodeling and mechanisms that look to replace that fiber. What first happens is that these little dots on the left are contractures, which are the broken down fiber. You need to have an immune response to actually clean up that fibrotic damage and then replace that fiber. What happens in Duchenne muscular dystrophy is that the regenerative processes are overcome by this damage process, and you replace the normal fibers with fat and fibrotic tissue, which leads to loss of function in muscular dystrophy. On the right, you see that sevasemten, which can decrease the contraction of the muscle by a very small extent to completely block the muscle damage response in the muscular dystrophy skeletal muscle tissue. This leads to the potential benefit of sevasemten in patients. How do you develop a drug in this space, and how do you get to the right parameters to run a phase III trial in muscular dystrophy? In phase II, what we really want to do is explore a range of doses to assess the safety and identify a potential beneficial dose for patients in phase III. A couple of really important things to determine. One is what's the target patient population? What is the age range? What is the severity range of the patients you want to treat to create a homogeneous patient population to increase the odds of seeing statistical significance? We want to understand what's the background therapy of these patients. We've studied extensively patients on a background of steroid, a background of patients who have been on exon skippers, and a background of patients who have been on gene therapy. We also want to try to understand at the same time what might be the primary and secondary endpoints for a phase III design. We'd also like to understand, can we do this quickly? How do we dose range as rapidly as possible? We took a task to have a three-month placebo-controlled period to evaluate biomarkers from dose selection followed by an open label period. As you remember from the Becker study, the biomarker response occurs very rapidly, and we thought we could understand the biomarker response and then translate that into functional benefit in the patient and understand how we would dose the drug. Finally, an added complexity to this particular trial is that the FDA recommended that we transition all subjects to the highest tolerated dose in the open label extension after an adequate safety review. What we did in both LYNX and FOX is do an intrapatient dose escalation going up to a maximum tolerated dose and then going back down to what we think was the target dose to study that in greater depth. What we will be talking about today is 18-month data in the LYNX study in patients on a background with steroid and exon skippers and 12-month data from patients who have been treated with gene therapy. With that, I will hand it over to Dr. Donovan and talk about the details of the study. Thank you. This is the design of the LYNX study. Our primary endpoint was safety, and the goal was to look at biomarkers and function over the longer term and to select a dose for phase three. We enrolled boys aged four to nine, ambulatory, on stable dose steroids largely, and with certain functional criteria. That was the case for cohorts one through five with increasing doses. We also enrolled a cohort that were not on steroids, that were steroid naive, and they were dosed at a dose of 5 milligrams. As Kevin said, in the open label extension part of the study, we dose escalated. With the DMC, we were changing doses and then moved to the target dose. On the next slide, we have the baseline demographics of the participants enrolled in LYNX. Now, interestingly, although the enrollment range was four to nine, the age was shifted towards the upper end. Overall, the age was 7.5. I'm going to particularly focus on cohorts two and three, which were the cohorts that were largely dosed with the 10 milligram dose. For about half of that 18 months Kevin talked about, have been on the 10 milligram dose. That gives us the most information about that. The functional measures are shown here, and about 15% were on an approved exon skipper. On the next slide, here's the safety. This is the safety in the placebo-controlled period where you can compare across. It was benign, basically. It was well tolerated in the placebo-controlled period at all doses. We did see the most common adverse events have been dizziness and somnolence that we saw more at the higher doses, again, transient and mild. In the open label period, the safety profile was similar. I point out this is data cut from May from last month, and this is interim data. It will continue to evolve. We looked at biomarkers and, again, based on our experience in Becker and initially focused on that. What we did see with CK, we did not see changes even up to the 30 mg dose. We moved up to see if we could see more biomarker changes since it was well tolerated in the placebo period. TNNI2, we did see a profound decrease at the higher dose and a tendency towards a decrease at the 15 mg dose. What was quite interesting on the next slide was that in the group that was steroid naive and only on 5 mg, we still saw a 52% decrease in CK and a 65% decrease in TNNI2. This is relatively small numbers, but it does raise the possibility that steroid use is actually masking sevasemten effect on biomarkers. I would call your attention to that with the Becker participants, we observed significant decreases in CK and TNNI2, and these folks were not on steroids. We were basically in the position to shift to functional measures to look at dose selection, basically. On the next slide, what are we going to use in functional measures? We are trying to look at small numbers of patients. We, of course, included the North Star Ambulatory Assessment that you are quite familiar with. We also included the stride velocity 95th centile, which is becoming more prominent. You've heard about this in other Duchenne studies as well. In contrast to looking at the North Star at a single point in time when the patients are at the clinic site, this is looking over three weeks and basically looking at peak ambulatory performance over 100 hours of typical activity of daily living. EMA, in fact, has approved this as a primary endpoint in Duchenne studies. Importantly, it's more sensitive so you can look with smaller numbers and over shorter times to avoid single-day variability. What we saw then in the cohorts is shown here. SV95, that's the change from baseline in the meters per second, the 95th percentile of velocity, stride velocity in these boys. In the doses between 2.5 and 10, we see stability. It was even up a hair at the 10 milligrams at three months. These are small numbers. You can see single digits, basically. What we did see in the 15 milligram and 30 milligram group was what was ultimately shown to be reversible decline in the SV95. When we saw this, we decided that we would move all of the cohorts into either the 5 milligrams or the 10 milligrams for further study. As I mentioned, cohorts two and three were on 10 milligrams for the majority of the time. Some of them started out on 5, as you can see on the bottom of each graph. Because we were stepping up in dose, all of the cohorts were exposed to higher doses of sevasemten in the red area, either at 15 milligram or in cohort 5 at 30 milligram. When looking at cohort two and three, I think it capitulates the whole story that we saw stability with 15 milligrams, we see a jog down. Then when they move to 10 milligrams, they are improving. In fact, at the end of 18 months, they are basically stable compared to their baseline. The gray line indicates the natural history, and this is from the EMA approval document. It is quite meaningfully different. Those are the 95% confidence intervals on the SV95. This is the 23 patients in cohorts two and three. You can see at cohort one, they did not do quite as well. Again, they did better when they moved to 10. Cohorts four and five saw an initial decrease and an improvement to better the natural history once they were back on the 10 milligram dose. This is a very powerful dose selection tool to be able to identify that 10 mg was the appropriate dose moving forward. What about other measures? The North Star, we, of course, this is open label. We do not have a placebo group. We compared it with the multivariate regression model that was published in 2022, again, based on individual baseline functional measures, age, height, and weight. The boys on sevasemten in cohorts two and three decreased a North Star by 1.5 points over the 18 months. That is about one point per year. This is in boys that are almost eight at the start, so an average of over nine towards the end of the 18 months. One would have predicted that they would have declined by about three and a half points over that 18 months. We are seeing that the observed with sevasemten was better than predicted, much as we saw the observed with sevasemten for SV95C was better than the predicted or the natural history. We also saw that four stair climb remained stable with less than a second increase over the 18 months for these almost eight-year-old boys. We also did further analyses to look at sensitivity of the North Star, basically. We looked at boys with different data cuts above and below North Stars of 25, above and below age seven. We found that consistently the difference between the observations with sevasemten versus the predicted favored sevasemten by more than a couple of North Star points over that period of time. We're going to move on to the FOX study and looking at boys that were previously treated with gene therapy, I should say, in adolescence as well. Primary endpoint was safety. We enrolled ambulatory individuals between ages 6 and 14 that were previously treated with gene therapy with an interval of more than two years after study drug administration. That was to look at a point where the biomarkers are stable and they were relatively far out from the doses of steroids. Here, they're on a stable dose of steroids. We enrolled 32. Again, we looked at the same endpoints as within the LYNX study. About two-thirds of the patients had been on ELEVIDYS in clinical trials previously, with a quarter in the Pfizer clinical trials and 9% in Solid clinical trials. Their baseline data, as shown here, of course, they're older. These boys are 10 on average. We're looking at 10 and 11-year-old boys starting from a North Star in the low to mid-20s and with those functional measures that are somewhat decreased compared to those in the LYNX study. How do we, first of all, safety? What we saw was that we had seen in LYNX that there was a slowing down in the highest dose cohort. We saw this more profoundly in the boys in the FOX study. There was, as I mentioned before, dizziness and somnolence and a slowing down. We moved those individuals down to the 10 milligram dose within six months and actually within three months for the 30 milligram group. We are looking now at 12-month data and trying to put that in context, which is admittedly difficult because there is not data in the natural or the "natural history" after gene therapy. What we could find after two years is on boys that had been previously treated with ELEVIDYS. There were a couple of posters that have been disclosed in boys following two years after treatment and three years after treatment. Those are not the same groups, but they are relatively robust, 63 in one and 50 in the other. In fact, the boys in FOX are likely to have been included because they were mostly from those studies. Between baseline and year two, there was improvement. Between baseline and year three, there was a decline. The net change appears to be down. Again, not a perfect comparison, but just trying to get a sense of what's happening to these boys out at past year two. In fact, the boys in the FOX are now looking at the period four to five years post-gene therapy. Rise from floor appeared to have an increase and 10-meter walk/run. That's consistent with, as you get older in the natural history, there's more decline. That's not a surprise in non-gene-treated therapy. What we did see in the boys in the FOX study was over the year, and that was a year that included that period when they were on the higher doses, a net decrease of North Star of 2.4 points. The change in rise from floor and 10-meter walk/run, the change was less than a second on those. They appear to be relatively stable. This is not a perfect comparison. On the next slide, what we are weighing here is our functional observations in the LYNX and the FOX study that do support that 10 mg dose. What our plans going forward are to continue open label dosing with the boys and adolescents that are currently in the study. We are looking to design the phase III in the best way possible. We are completing a population PK model to look at whether the 10 mg dose is exactly correct for the youngest boys and whether we need to do weight-based dosing in very young boys. We are going to explore the primary and secondary endpoints with regulatory agencies and continue to look at this against the evolving therapeutic landscape in Duchenne. Our plan is to go to the FDA in the fourth quarter for a meeting to discuss the Duchenne phase III design and move on from there. With that, I'd like to ask Dr. Byrne to comment on kind of where this all fits in the Duchenne landscape. Thanks, Joanne. Great job in reviewing a complex set of studies. The rigor of FOX and LYNX has helped establish a dose across a wide dose range, which has not been commonly done in Duchenne studies to be economical with the study complexity. These studies covered that entire range, which I think helped find the strike zone for sevasemten that establishes what is the best balance between target engagement and the effect on fast-twitch fiber contraction. Knowing the dose now enables a phase III study to go forward with also what has been learned in more high-resolution assessment of clinical outcomes that are clinically meaningful. The SV95C seems to really have emerged as the best way to collect more meaningful data in a real-world setting than single assessments done at a study site for the North Star. This collective data is really providing insight into what boys can do when they are in their home environment. I think it is really well-positioned to develop sevasemten as an early option for patients with Duchenne. I think also the data regarding the concomitant use of glucocorticoids, it may become preferable in early diagnosis to begin treatment with sevasemten as opposed to the significant impacts on growth and bone health of the early use of glucocorticoids. Certainly, now four states initiating newborn screening for Duchenne. This is another opportunity to understand better how to manage Duchenne diagnosis at an early age. I think we're seeing a paradigm evolve in SMA that makes a lot of sense that there will be a combination of therapies like sevasemten offers, has been shown in the FOX study to have an adjunctive effect in the context of an additional disease-modifying therapy. I'm quite excited about how this will proceed. I know it's been a complex area in Duchenne compared to the more homogeneous findings and dose selection in Becker, but I think it's really well-positioned to move forward quickly now and get the benefit of sevasemten in this patient population that continues to have significant unmet need. Thank you, Dr. Byrne. That's a really great overview of the opportunity here. I really appreciate it. We've had a great first six months and delivered on everything we were expecting to. We provided data on FOX and LYNX. We've gotten FDA feedback on the approval path for sevasemten. In our Grand CANYON study, recruitment is complete, and we're progressing effectively with a readout in the end of 2026. We reported on our SIRIS data of 28-day readout in April. We're on track to file an IND for our second cardiovascular candidate. We've positioned in HFpEF and other heart failure syndromes. In the second half of 2025, we have a couple of key milestones. We'll be providing an update on the 12-week data, part D of the 7500 program and non-obstructive HCM. This is an update. We have been treating patients at 25 mg for the past month and a half or so and have just started screening in the part D aspect of the SIRIS study. We expect to file the IND and initiate clinical trials with our cardiovascular candidate. Finally, we expect to be able to deliver on a phase III and initiate a phase III in 2026, an obstructive and non-obstructive for 7500, and also a phase II trial in HFpEF with our cardiovascular second-generation molecule. Of course, we hope to be able to initiate a phase three in Duchenne in 2026. At the end of 2026, we're on track to provide Grand CANYON results in the Becker program. An exciting year is upcoming. Looking forward to the presentations of the data. We're very well capitalized, executing on all these important milestones. We have $624 million in cash equivalents. We have no debt and 105 million shares outstanding. We have cash runway through 2028, which would include two phase III in HCM, the launch of the sevasemten program in Becker, and completion of the phase III in Duchenne. Additionally, a phase II study in HFpEF with our cardiovascular second-generation molecules. Very well-financed for a number of milestones through 2028. It will be an exciting time for the company. I would like to thank you for your attention. I will now turn it over to the moderator for questions. Thank you. If you would like to ask a question, please press star one on your telephone keypad. We ask that each person asks only one question. Please be sure to unmute your line when called upon. Thank you. Our first question today comes from the line of Joe Schwartz with Leerink Partners. Please go ahead. Your line is now open. Hey, everyone. This is Whelan from Joe. Thanks for taking our question and congrats on the progress here. One for us, I guess, just on the FDA's decision regarding the potential for accelerated approval. Could you please provide any additional color on why they may have decided the CANYON data were insufficient? Was there any one specific hang-up for the agency, such as the sample size or the duration of follow-up, or was this more multifactorial? I guess from our end, considering the favorable safety profile, the fact that the pivotal data are about a year and a half away, combined with the unmet need, we were cautiously optimistic that the FDA would be amenable here. Any additional color would be helpful. Thank you. I'll provide my opinion. I think the biggest point they made was there was a very strict interpretation of wanting to see statistical significance in a controlled study on a functional endpoint. Hitting 0.2 or 0.16 was not sufficient. I do not know if this is absolutely true, but perhaps having the readout of the phase III so close to the accelerated approval as they get closer and closer together, perhaps was not interpreted in our favor. As opposed to our thought was we were primed for a confirmatory study. Given the place where the FDA is today on the risk tolerance, perhaps they thought they would just wait and not put themselves in a position where they would have to withdraw support for the program if they gave an accelerated. Perhaps a different environment at the FDA than we had anticipated perhaps four months ago. That's probably the best color I can provide. Great. Thank you. The next question comes from Laura Chico with Wedbush Securities. Please go ahead. Your line is now open. Hi. This is Dennis on for Laura. Thanks for taking our question. So just on DMD, as you evaluate the LYNX and FOX data, could you expand further on how you see the target population for a pivotal study? What are the key inclusion and exclusion criteria to implement to ensure that you identify the population most likely to realize benefit? Joanne, why don't you provide that feedback? Maybe Barry can also provide what he's seen. Yeah. I think where the general consensus is moving is that to get a more homogeneous population, probably need a bit older boys that have been enrolled. Including the youngest group is somewhat problematic because you have the mixture of kids going up in North Star and indeed in SV95 and then going down. It makes it harder to pull out the signal. It is all about signal to noise. That noise of people going in two different directions becomes problematic. I think that is the way that we are moving towards. We are looking at a broad population in terms of background therapies, such as discipline-targeted therapies as well. That is what we are thinking. We are going to include the endpoints, of course, that we have seen. We are impressed with the performance of SV95, even in very small groups here, to be able to distinguish changes. We need to discuss that with regulators, certainly. Dr. Byrne, do you have any additional comments? Yeah. I can add some color to that. I agree with Joanne that instead of having more homogeneity, we will add to the level of confidence in the outcomes. There is a counterbalancing factor that I think one of the reasons we have not seen the magnitude of effect of some of the therapies that have been applied in late school age in the six, seven, eight-year-old group is because there is probably some degree of irreversibility in Duchenne that has not been appreciated previously. It was always assumed that regeneration muscle would have sufficient plasticity that it could overcome any fibrosis or fat conversion that happened even earlier than the time of diagnosis. There may be a benefit to having both populations, those that are more homogeneous, and then an early intervention group. Certainly, this might be an opportunity coming from the program, the states where newborn screening is being initiated. Obviously, those younger patients may not have the same reliability in terms of the clinical outcome measures, but the functional outcome measures like SV95C, ultimately, in a preschool population would be a very interesting data set. Yeah. I think also, certainly, with discussions with the EMA and the FDA in regards to the role of SV95, as Joanne described, the SV95 is considered a primary endpoint in the EU, but it's under evaluation within the FDA. I think that's a very direct question to the FDA that we'd like to hear their commentary on in the coming months when we get feedback from them. The next question comes from Tessa Romero with JP Morgan. Your line is open. Hi, Kevin and team. Good morning, guys. Thanks for taking our question. Kevin, maybe you can walk us through, really, what were the key pushes and pulls that ultimately got you over the line to say that a pivotal trial in DMD is the right next step for Edgewise? What was that key finding or observation that ultimately drove the decision here? Thank you. I think from our perspective, we've achieved a threshold of seeing a two-point change versus natural history across populations in the DMD space. And we saw a level of consistency between functional endpoints that would make us believe that we could design a trial. The question does become of perhaps the timing of this, which we haven't really addressed the timing of when should we start this study. We think it's a worthy study to run. The question is, when will we start it? Is it better as a lifecycle management aspect for this drug, or is it something we should invest in earlier? I still think that we believe the investment would make sense in Duchenne. The question is when. We still need to hear from the regulatory agencies, what's the bar from the regulatory agencies, and also what is the competitive landscape over the coming year or two? I think it's a tough call with some of the changes that are occurring, perhaps additional demands. We're seeing functional benefit as opposed to simply surrogate marker benefit for approval that may be coming. It's a big question mark for what the environment's going to look like a year or two from now. I think that this is what we're weighing over the next couple of quarters. We need additional feedback from the regulatory agencies about how they view the space, what's the bar. Thank you. What I would add, though, is that this company was founded on the commitment to muscle therapies and to developing something in the Duchenne space. What we want to do is make sure that we run the right study and have the right information to go ahead. That's what we've been doing. As Barry said, this was a complex study. We're going to continue to gain information. We're going to continue to figure out a way to design, hopefully, what will be a positive phase III study. That's our goal. Thank you. Thank you, Tessa. The next question comes from Leonid Timashev with RBC Capital Markets. Please go ahead. Your line is open. Hi, guys. It's Anishan from Leo. Thanks for the updates this morning and for taking our questions. Just a couple of quick ones from us. Given that you saw some dose dependence on biomarkers like CK and TNNI2, how does steroid use play in here? Would it truly have a masking effect or a synergistic effect with Seva? As we think about patient cohort stability longer term with NSAA benefit, how can we be sure it's due to Seva and the mechanism over typical patient heterogeneity playing in your favor? Thanks so much. I don't think we have a lot to say about the mechanism for the biomarker. What I would say, and perhaps Alan can comment, we are looking at a number of other biomarkers and other proteins that move in the right direction, even at the lower doses as well. It is more complex than we had anticipated. Yeah. I think it's a complex situation with steroids. Perhaps they are masking the pharmacological effects of the compound, which is definitely apparent when you look at the functional endpoints. It's something that we're digging into right now. Certainly, what we're seeing in longer-term data that we'll give you updates on later is movement in these biomarkers. They just take longer. The steroids are having a complicated effect perhaps on the membrane. I think that we have plans of we've collected things like the CardiOmix platform, the SomaScan platform, as well as longer-term biomarker data. It does appear that over time, some of the biomarkers deepen. In particular, the SomaScan fingerprint over time seems to move the patients towards a more normal phenotype than from the Duchenne phenotype. I should also point out that the fingerprint of a gene therapy-treated patient is somewhat different than the proteomic fingerprint of a non-gene therapy steroid background patient. There is a level of complexity of what these drugs do. In all cases, it appears over time that we move the fingerprint of the patient population we are looking at to a more normal phenotype, which I think is reassuring. It takes some level of time to see that fully form. This is partly one of the reasons why we continue to dose in the open-label extension. We want to either see those biomarker responses deepen and also see continued stabilization. Of course, as you go out in the Duchenne populations for longer and longer time periods, the delta of what you anticipate their decline should be should increase, which gives us much greater confidence in running a phase III study in one of these patient populations. Also, in thinking about the design, we're also contemplating you probably need at least 18 months, which was the duration of the juveni-set study in the older boys. These are all considerations for the phase III design, which these types of things and continued dosing of the current patient population will give us additional information. Thank you so much. The next question comes from Kripa Devarakonda with Truist Securities. Please go ahead. Your line is open. Hey, guys. Thank you so much for taking my question. I have one question on the accelerated approval feedback that you got from the FDA for BMD. I wanted to dig a little deeper into the comment in the PR, where it says that the FDA is encouraging Edgewise to continue to share data from the open-label extension and the modeling data from natural history. Does that mean there is a potential to revisit the accelerated approval even ahead of Grand CANYON data? At what frequency would you be able to show the FDA these data? Thank you. I have a follow-up. The cadence of the data cuts, the next data cut will be in probably the beginning of the fourth quarter. We can have that ready for a discussion with the agency the first quarter of 2026. I think they gave us some really clear guidance that they wanted to participate in helping us build the model that would be most supportive of both the MESA and Grand CANYON data from a standpoint of natural history. They view the model that we've built as one where they would like to have participation in building that model and how it would support both of the potential filings. With fast-track designation and also with the newly announced, although a little bit undetermined, voucher program where the FDA will look at data early to speed up approvals, we think that we'll be able to provide them portions of the NDA or the portions of the filing earlier and then be able to jump off from a positive Grand CANYON result, ultimately getting us to market in a more rapid way. I think this is really under, I think it's a moving target at the moment of exactly how the FDA might work with sponsors to accelerate marketing approvals. I think they seem quite open and interested in driving this kind of interaction. We'll see. To be determined. Okay. That's very helpful. I have a follow-up question for Dr. Byrne. You mentioned the potential for sevasemten to be used in early age instead of steroids. What would you need to see to be able to do that? Would you need to see a head-to-head study? Thank you. Kevin, do you want to comment? I can chime in. Go ahead. I think that there is. Yes. In order to, we've talked about and thought about younger boys, for sure, and whether there's interesting data that something like SV95 can actually look at changes even in as young as one and a half-year-old, which is, of course, very exciting to be able to try to intervene and preserve muscle early. I think those are all things that we are thinking about. We need certainly to understand the dose and the PK modeling to be able to go down to lower ages. It's something we'll certainly be talking about with experts like Dr. Byrne. Yeah, I agree that this is an exciting area to expand into. It's probably not on the immediate horizon because of the complexity of understanding the PK at that age and the proper dose. It's an area where there certainly is an exciting opportunity. Great. Thank you so much. The next question comes from Yas Rahimi with Piper Sandler. Please go ahead. Your line is open. Hi, team. This is Liam on for Yaz. Congrats on the data. Just to run it back to the Type C meeting, we're just wondering if the FDA specified if they need to see a specific delta on the NSAA change in order to support approval in BMD and whether they mentioned any key secondary endpoints they'd be looking for as well. I think that they were looking for statistical significance in a functional endpoint and that North Star was an appropriate endpoint for a full approval. Beyond that, they were, I feel, reasonably confident that even a one-point change would be meaningful because I think we brought along a Becker patient to speak to the FDA. I think they were compelled by that conversation of what a one-point change means to a Becker patient. I do not think the magnitude was in question. It was the demonstration in a well-controlled placebo-controlled trial that you would see statistical significance. I think we have designed that into phase III. You have to look at this disease as the decline occurring over a decade, over two decades. If you can alter that slope of decline, you know that the adolescents are starting in the 30s in North Star. You know that the guys in their 40s are down in the single digits predominantly. If you can decrease that decline, that has a clear, meaningful effect on that. I do not think that we have been questioned about that by the FDA. Thank you so much. The next question comes from Cory Kasimov with Evercore. Please go ahead. Your line is open. Hey. Good morning, guys. Thanks for taking my question. I want to also ask again on the approval pathway for Becker and this new voucher program that you mentioned as a potential way to accelerate a review now post-Grand CANYON. Did the FDA specifically mention this program, this opportunity to you? If so, is there any sense on what you would have to do to implement it and when you would start submitting other aspects of an application package prior to the readout of Grand CANYON if this is indeed a viable program for sevasemten? Thank you. Yeah. This actually came out after we had actually spoken to the FDA. This was not offered up as an option. I think it is unclear at the moment what that program will look like ultimately. We're certainly in the throes of thinking through how we would approach the FDA for discussions with this new program. There is very little information. This came out, I think, about a week or so ago. It is in congruence with the idea that the commissioner has the seeking way to accelerate approvals. From that standpoint, it's reassuring that we should be in a position to have data early and provide modules of the filing to them to review more quickly. That may take time off the back end of the Grand CANYON results. I think it's to be determined. Okay. I guess at this point, though, then, would you prefer the default position that investors take, which is what we're taking already, but the default position kind of across the board is that the Grand CANYON study will be the pivotal study to enable a full approval and just assume a normal timeline off of that that has the potential to be accelerated? Yeah. I would suspect I think that's the base case that we're looking at. Okay. Yeah. Perfect. Thank you. The next question comes from Paul Choi with Goldman Sachs. Please go ahead. Your line is open. Hi, everyone. This is Khalil calling in for Paul. Thank you so much for taking our question. I kind of want to circle back on that in terms of the BMD filing strategy. You mentioned earlier in the call that you're looking at other options for accelerating it even if it is a full approval. Are we sort of correct in assuming that that is not going to include any kind of statistical amendment to the study, but rather potentially exploring options like acquiring a priority review voucher or something like that? Just a little more color would be helpful for us as we think about this timeline going forward. Thank you so much. I think that we are in a position where we are moving ahead with our CMC package to make sure that that's available well before any potential filing as well as the rest of our package. We are looking at ways of exploring getting the statistics ready for the FDA to accelerate once we have the Grand CANYON study. They are interested in engaging on the natural history study. That always gives us an opportunity to discuss more accelerated pathways. As you know, fast-track is the presumption that when you file with fast-track, you get the priority review. Yeah. Fast-track in and of itself provides the opportunity for a priority review and additional conversations on a regular basis with the agency. They have been open to having these conversations. Got it. Thank you so much. The next question comes from Moritz Reiterer with Guggenheim Securities. Please go ahead. Your line is open. Hi. This is Moritz from Debjit's team. Thanks so much for taking our question. I would like to come back to the steroid-naive cohort on the DMD side. Do you have functional data from that cohort as well? If so, do you see sort of a similar delay on the efficacy, the functional efficacy of sevasemten in steroid-treated versus steroid-naive patients? If so, what might that mean for the phase III design as well as the overall role of sevasemten in DMD? Yeah. The patients who are not on steroids that are relatively flat SV95 over the three-month period, it was a very small group. Some of those patients moved on to take steroids post three-month period. I think the ends are quite small. We would need to add additional patients in the non-steroid cohort to get additional information. I think we are capable of running a trial in steroid-naive patients. I think there are places in Europe as well as alternate places in other parts of the world where steroids are not utilized to the same extent as they are in the U.S. That is to be determined. As you might imagine, it's a relatively complex regulatory path within the U.S. to actually move forward with a non-steroid-treated population. It is intriguing, the magnitude of the biomarker response and what we've seen with very early studies in small ends. Yeah. The original design, what we were asking ethics committees, was basically to delay the treatment with steroids for 16 weeks. That was deemed appropriate. They did have the option that was written into the protocol of starting at 16 weeks. A couple did. The numbers become very, very small. As Kevin said, they're stable. They seem to be very stable over time. The next question comes from James Condulis with Stifel. Please go ahead. Your line is open. Hey. Thanks for the update. Thanks for taking my question. Just another on Becker. Just curious, in your discussions with regulators, did the baseline imbalances on North Star and CANYON come up at all? Kind of along those lines, I guess, as you think about the phase III, should that imbalance color our view at all of the 12-month effect size? Or is it really not all that important? Just curious of any color and curious of the KOLs and any thoughts also. Thanks. It actually did not come up with FDA. I would say that, remember, the CANYON study was 40 patients, three-to-one randomization, and two cohorts. That is where randomization does not always operate perfectly with small numbers like that. In the Grand CANYON study, we have 175 patients, two-to-one randomization. So 120 randomized to one group, approximately 60 to the other. That should not happen with that large number of enrollees. Thanks. Thank you. There are no further questions at this time. I would like to pass the call back over to Kevin Koch for closing remarks. Please go ahead. Thank you for your attention. Great questions. I think we have a really exciting set of programs here at Edgewise, making great progress. I look forward to speaking with you in the future. I would really like to thank all of our supporters, our shareholders, but in particular, the employees that actually work for Edgewise and their families and the hard work there was to provide all this information to you all today. I think even more importantly, it is the patients and their families that took the time to participate in our studies and the physicians who manage these studies to bring these new therapies to patients with high medical needs. I'd like to thank you all for your attention and look forward to speaking to you in the future. Thank you. That concludes today's webinar. Thank you for your participation. You may now disconnect.