Hello, welcome to Edgewise Therapeutics Investor Event. My name is Telepan, I'll be your operator for today's call. I would now like to pass the call over to Michael Carruthers, please go ahead when you're ready. Thank you, Telepan. Good morning. This is Mike Carruthers, Chief Financial Officer at Edgewise Therapeutics. Welcome to our call to discuss our positive 12 month top-line results from the ARCH Open Label study of EDG-5506 in individuals with Becker muscular dystrophy. You can join this conference call on Edgewise website at edgewisetx.com. We're using slides to accompany our remarks today, which can be downloaded from the investor relations section of our website. A replay of the conference call will also be available as a webcast on our website. I'd like to introduce Edgewise presenters today, including President and Chief Executive Officer, Dr. Kevin Koch, as well as our Chief Medical Officer, Dr. Joanne Donovan, and Dr. Behrad Derakhshan, our Chief Business Officer. Dr. Alan Russell, our Chief Scientific Officer, will also be available to answer questions as needed. As a special guest, we have Dr. Craig McDonald, Professor and Chair, Department of Physical Medicine and Rehabilitation at the University of California, Davis, who is joining us today. Before I turn the call over to Kevin, I want to remind everyone of the following safe harbor statement: "The matters we discuss today include projections or other forward-looking statements about the future results and research and development goals at Edgewise. These statements are estimates based on management's current expectations and involve risks and uncertainties, which could cause them to differ materially from actual results. We refer you to risk factors discussed in our filings with the SEC, including our annual report filed on Form 10-K on February 23rd of this year, and other Edgewise filings with the SEC. These filings identify important risk factors that could cause actual results to differ materially from those in our projections or forward-looking statements. Edgewise specifically disclaims any obligation to update any forward-looking statements except as required by law. I'll now turn the call over to Edgewise CEO, Dr. Kevin Koch. Thank you, Mike. As an introduction to Edgewise Therapeutics, we are a clinical stage biopharmaceutical company focused on the discovery and development of orally active, innovative therapies for the treatment of severe and debilitating muscle disorders with high unmet medical need. Our platform capabilities include a seasoned management team with decades of success in drug discovery and development, a scientific team with a deep understanding of the biophysics of novel molecular mechanisms to treat disease, access to an array of genetically engineered animal models of muscle disorders, and a team of world-class drug discovery scientists and clinical development experts. We believe that EDG-5506 has the potential to become a foundational medicine for the treatment of several different diseases in muscular dystrophy. We have expanded our pipeline. As of January, we announced that our first cardiovascular candidate EDG-7500 was moving into preclinical development, and we plan to file an IND for this agent this summer, starting with new normal, healthy volunteer studies in the fall. Here's our pipeline. From a standing start, from a novel concept, we now have EDG-5506 in three different indications in phase II clinical development: in Becker muscular dystrophy, in Duchenne muscular dystrophy, and in limb-girdle muscular dystrophy 2I and McArdle. EDG-7500 is targeted for hypertrophic cardiomyopathy, and we have a third program with an undisclosed molecular target. Next slide. I'd like to say a little bit about muscular dystrophy and why we believe that EDG-5506 will have a profound effect in this disease state. Muscular dystrophies are a set of genetically driven diseases where there are key structural proteins of the sarcomeric complex that are missing or mutated, which drive an aberrant stress response when the muscle contracts. This stress response leads to damage to the muscle, ultimately replacement of the muscle with fat or fibrotic tissue over a period of time, and then ultimately loss of function. Damage to the muscle precedes loss of function. EDG-5506 is a novel investigational, orally administered allosteric, selective fast myofibril type II myosin inhibitor. EDG-5506 is designed to limit muscle damage, protect and normalize the muscle, block the loss of the muscle, and also provide either enhanced function or a disease arrested disease progression. We believe that this is a in Becker muscular dystrophy, that it is a severe disease. It has been provided Fast Track designation by the FDA. We have evaluated EDG-5506 in multiple muscular dystrophy indications. We have a secure patent life out to 2039, subject to extensions. Now I'd like to introduce Craig McDonald to give us an overview of the Becker muscular dystrophy space in disease. Great. Thank you. It's great to be with you all this morning. To give you an overview of Becker muscular dystrophy, this is a progressive muscle disorder caused by mutations of the dystrophin gene that produce a protein with decreased function. To remind you, like Duchenne muscular dystrophy, Becker is an X-linked recessive genetic disorder. It's caused by an in-frame mutation of the dystrophin gene, affecting the body's ability to produce dystrophin. The age of symptoms usually range from five to upwards of 60 years of age. Typically, the symptoms begin between the ages of eight to 13, whereas in Duchenne, the symptoms would typically begin before the age of four. The patients will present with focal muscle damage, usually affecting more proximal muscles, of around the pelvic girdle and thighs, of the lower extremities and the shoulders and elbows, in the upper extremities. Walking problems in Becker patients usually are noticed by age 15, and loss of ambulation often occurs in young adulthood. The most common cause of death in Becker is heart failure from cardiomyopathy. Here's just a quote from a neuromuscular specialist in Europe: "Becker may be considered milder than Duchenne, but that doesn't mean it's any less devastating." I could really speak to this as I follow a number of patients with Becker muscular dystrophy in my clinic, and several actually have developed, you know, very severe weakness in early adult years. There are several that have actually developed very severe heart failure and have actually ended up with cardiac heart transplantation. Next slide. Here you can see an adult individual walking with Becker muscular dystrophy. You can see the compensation that they utilize, where they really throw their legs out in front of them and actually land on an extended knee. They don't have any knee flexion that occurs during the gait phase. Their... If you look at them from the side, they actually have a great deal of lumbar lordosis in the spine as an additional compensation for walking. This individual literally has a very little volitional quadricep strength, but through compensations, they're able to maintain walking for many years. And then, like Duchenne, the 12 year-old boy on the left actually is presenting with Becker muscular dystrophy with a positive Gowers' sign because he rolls over from a sitting position onto his front, gets wide-based, and literally has to push off the knee in order to get to a standing position. Becker individuals have ongoing contraction of these muscle damage, resulting in, like Duchenne, fibrosis, replacement of muscle fibers by fat and connective tissue, progressive loss of skeletal muscle function, severe disability, and early death. Next slide. Physicians often indicate that like Duchenne, their diagnosis is often delayed. Usually, the diagnosis is made around seven years of age with patients with Becker muscular dystrophy, where there's no known family history. The treatment often focuses on symptomatic management. As in Duchenne, there's really a diagnostic journey or diagnostic odyssey that patients will experience. Primary care physicians will oftentimes refer patients. At around seven to eight, there will be identified weakness, and perhaps there may be an existing family history, which may cut down on this diagnostic journey. They're referred to a community neuromuscular neurologist. Oftentimes, the diagnosis may take longer because there's perhaps other disorders such as limb-girdle muscular dystrophies, which are considered in the diagnostic workup. Newborn screening, which really will be spurred by approval of the first gene therapy, where it will be shown to be efficacious, say, below the age of two, will undoubtedly drive a much earlier diagnosis of Becker muscular dystrophy. The patients ultimately are diagnosed through genetic testing. We rarely will do muscle biopsies. In terms of treatment or management, the overall treatment at muscular dystrophy centers of excellence or academic centers would really be for the most part symptomatic and supportive management, where patients are followed yearly. Oftentimes, these patients may not historically even perceive the need to continue to go to their neuromuscular specialist on a regular basis. In many instances, they're oftentimes lost to follow-up for a number of years. I've had a patient that was lost to follow-up for seven or eight years, and unfortunately came back and was in really quite severe presymptomatic heart failure. It's really important to follow these patients on a regular basis. Now that we have a number of emerging therapeutics, I think treatments such as EDG-5506, which really we're able to perform clinical trials in will make these patients, I think, have provide them with motivation to follow up on a more regular basis. I think what's really quite clear is that newborn screening is going to drive the diagnosis into the first few months of life. In terms of overall prevalence, a 2022 systematic review and meta-analysis of DMD showed the overall global prevalence to be 1.6 per 100,000 people. There's about 5,000 BMD patients in the U.S., 4,500-6,500 in the EU, in U.K., based on country-specific and global estimates. Really there appears to be large geographic disparity in prevalence, which suggests really there's a high rate of under diagnosis. Overall, there's over 12,000 patients with Becker muscular dystrophy in the U.S., EU, and Japan. Which would compare to perhaps 15,000 patients with Duchenne in the U.S. Next slide. This is some MR data, magnetic resonance imaging data on both Becker and Duchenne patients. These patients will actually show diminished function in the setting of a great deal of muscle loss and fat replacement. This is the fat fraction of the various muscle groups in Becker muscular dystrophy and Duchenne muscular dystrophy. Really, the average fat fraction in Becker patients is quite similar to that we see in Duchenne. In selected muscles here, for instance, in the vastus lateralis, which is highlighted, there's actually greater than 50% fat fraction in an ambulatory Becker population, whereas in Duchenne, that fat fraction is generally between 25% and 50% This really demonstrates the ability to compensate for really great degrees of focal muscle loss just because of perhaps some greater preservation of surrounding muscles, which can be used for compensatory strategies. The point here is there really can be even greater fatty accumulation in selected muscles compared to Duchenne muscular dystrophy for a given functional status. There you see the MR images on the right, showing the great degree of fatty infiltration into the muscle, the fat showing up as the whitish colored tissue. Next slide. Here we have the assessments that are performed in dystrophinopathy. Like Duchenne, the North Star Ambulatory Assessment is a well-established, well-validated measure of global function in both Duchenne and Becker. This really can be clinically meaningful, even in a real-world context. Just to remind you, there are these 17 functions that range from those that are most challenging, lost early in the disease, such as hopping, standing on heels, rising from the floor, running, and jumping. Then those that are the least challenging or lost late in the disease, such as rising from the chair or walking and standing. The North Star is scored on a three point scale, with each activity scored either a two, where it can be performed normally. A one point score means there's an adjustment due to weakness, so there's difficulty in performing the function, but the function can be performed. A zero is complete loss of function. Just to try to translate this to really a real-world context, if you look at jumping, hopping, and running, this would translate to individuals having difficulty playing sports. Standing on heels can translate to difficulty on uneven ground, cycling difficulty with other functions such as going up over curb cuts, even. If you look at the box stepping functions, that can translate to real-world mobility tasks such as stairs, sidewalk, and curbs. Even, obviously, standing from a chair would translate to inability to use a toilet independently, getting out of bed, using public transportation to get around. Obviously walking, some short-distance walking, like going out to the mailbox, or going on short-distance hiking or everyday mobility would be impacted. Obviously, even standing function would be manifested by inability to stand, to groom, prepare meals, adapt to a mobility or transfer device. Here's a quote from an individual living with Becker: "As far as how Becker impacts my day most, it would be from the very beginning, the moment I wake up, I have to have help from my wife to get up, go to the bathroom, get dressed, get to my wheelchair. It impacts my day, really every day, right from the very beginning." If we could go to the next slide. In terms of the natural history data, with the North Star Ambulatory Assessment, these individuals will show decreasing function as there's loss of muscle fiber and increasing muscle fat. About 30% of patients will have NSAA values, which are quite high up where the normal peak value is 34, and they'll have values of, say, 31-34, where they're at near maximal NSAA values. They've not really reached a threshold that leads to rapid functional decline, and they can stay quite stable for many years. About 70% of individuals with Becker have NSAA values below 32. They've lost muscle mass and have more fatty infiltration, and their progression is actually progressively lost, but progressively lost in a very predictable manner over time. As you can see, the natural history data showing losses over 12 months. This predictable decline in function in the majority of Becker patients facilitates really a highly focused clinical trial design and allows us to actually conduct a clinical trial and actually power a clinical trial. I think given the progression, I think we've been thinking more in terms of perhaps an 18 month trial rather than 12 month trial. Here's the spaghetti plots on the natural history data that has been made available. The Padova, Duchenne, Becker Natural History study is really the most comprehensive of its kind and demonstrates that NSAA decline is very consistent in Becker patients who are already progressing. They lose about 1.22 points per year, which is a clinically meaningful change. The observations from the Padova group are further validated by a separate independent natural history study from Erik Niks and colleagues, who observed 2.5 point decline over two years. Very similar decline. What's really quite striking is if you look in this patient population with NSAA values from 10-32, again, 1.22 point decline, but the standard error of the change is really quite tight in this population. Unlike Duchenne, which would have a much higher degree of variability and a much higher standard error, in part, given the age range of the patients being evaluated. We're assessing adults here, which are much more easily assessed in a reproducible and standardized fashion. Also, the decline is really quite predictable and really quite tight in terms of the standard error of the measurement. Next slide. To contextualize the NSAA scores, we looked at baseline NSAAs in Becker adults enrolled in Edgewise studies to date. We asked a question: at different NSAA scores, perhaps at 10 point decrements, what functions are completely lost, and what functions require some degree of compensation, or would be scored a North Star score of one based on muscle weakness? While this is a cross-sectional look at function, we know from natural history that patients that do decline 1.2 points a year, would decline about 10 points over eight years of disease progression. If we go to the next slide, here is actually the NSAA individual values, sort of, grouped in these buckets of patients, where group one are those that have scores, greater than or equal to 30. Here you can see that really, they're able to perform most functions, quite normally. Maybe just a few functions are performed with difficulty or with compensations, but they've not really lost any functions, the vast majority of patients. When you get to group two, which have scores between 20 and 29, here you can see that there's really quite a number of the NSAA functions which are performed with difficulty due to muscle weakness and are actually performed with compensations, as shown in the light green percentile bars. Really very few patients have actually lost, completely lost, function. Here, the weakness is definitely evident. As we moved into the teen scores from 10 to 19, here you can see that there's most patients have begun to lost loss function. In fact, many functions have been lost in these patients. Many functions are performed with difficulty or with compensation. There's clear evidence of beginning of lost function here, and essentially all functions, many functions are performed with compensation. When you get below a score of 10, essentially the patients have lost most of their functions. There's a few functions that are still able to be performed with compensation, but the vast majority of functions have been completely lost. Patients have really minimal ability to complete most of the ambulatory activities on the NSAA. Next slide. Just to end, here's again a couple of patient quotes which really highlight the impact the loss of ambulation has had on daily living. One patient says, "The first thing I did, was, when I started walking with a cane, and then gradually, probably six years ago, for long distances, when we went somewhere really hilly, started using a mobility scooter to get around. Then, where I worked, it was a pretty big building, so I started using that at work. Then recently, I also sometimes used an electric wheelchair." This other patient says, "There's a lot of things you've got to consider once you have to start to use mobility devices. You have to consider where you're going, if it's accessible. A lot of things you don't have to consider before, so there's probably been. That's been the biggest hurdle for me recently. It's just one of those things you have to just learn to be okay with, because sometimes the world is not, it's just not built for people that are, disabled. With that, I'll finish, and pass the presentation over to Dr. Donovan. Good morning. I'm pleased to share with you the top line 12 month results from the ARCH Open Label Becker Study. The study, just to remind you of the design, this is an open label, single center study of EDG-5506, to assess safety pharmacokinetics of EDG-5506 in adults with Becker. Primary objective was safety tolerability at 12 months, and with the key inclusion criteria were that they had a dystrophin mutation, age 18 to 55, and a phenotype of Becker. There weren't specific timed measures that include them. This is a broad group of patients with Becker. As you can see, what we did was we started with a dose of 10 mg, upped that at two months to 15 mg, and then to 20 mg at six months. We have a sense of what's happening in terms of biomarkers and function at the different doses. The data I'm presenting today is at 12 months. What these patients look like at baseline, you can very much see from what Dr. McDonald's described. These guys are in their mid 30s, and in terms of function, their 10-meter walk, run is prolonged. Only half of them could rise from the floor, and their average North Star was 15. Advanced in terms of losing functions, in terms of compensating for functions. Consistent with that loss of muscle, their serum creatinine is decreased compared to normal. They still have ongoing muscle damage, as evidenced by an elevated serum CK, and DEXA confirmed the loss of lean body mass. These patients, if you look at them and compare them to with those that are enrolled in clinical trials for Duchenne, they are all in the functional decline part of their disease course. In fact, many of them would not even be eligible for Duchenne studies. They're more advanced than that. In the next slide, first, safety. EDG-5506 was well tolerated at all doses. No dose reductions, adjustments, no discontinuations, and no SAEs. The particular adverse events that we saw were really typical of what you would see over a year. Dizziness and somnolence were previously the most common side effects. We saw those early on in the treatment course, typically within a few days of increasing a dose, but not with chronic dosing. On the next slide. The fundamental issue in Becker is contraction-induced muscle damage. What that does, it causes excessive degeneration, particularly of the fast muscle fibers. What that does is it leads to membrane injury and subsequent release of muscle injury biomarkers into the circulation, showing here CK, myoglobin, fast muscle troponin. We can look at those to determine ongoing muscle damage in muscular dystrophies. What did we see in this study? EDG-5506 led to a sustained decrease in biomarkers of muscle damage after 12 months of dosing. This is individual values on the left here of CK and fast skeletal muscle troponin. You can see consistent decreases in these patients. The mean decrease in CK was 37% after 12 months. The mean decrease in fast skeletal muscle troponin, now specifically demonstrating target engagement, was 79% at 12 months. Interestingly, the individuals with the highest baseline values show the greatest biomarker effect, again, supporting protection against activity-induced muscle damage. When you look at this over the 12 month period, it's quite interesting. This looks at the different doses. 10 mg for the first two months, 15 mg for the next four months, and then 20 mg. What we see is that the biomarkers of muscle damage are essentially maximally decreased even after two months of dosing at the 10 mg daily dose. You really do not see meaningful further decreases in CK, fast skeletal muscle troponin, or myoglobin. What you do see is that there are rapid, significant, and sustained decreases in these biomarkers of muscle damage over the course of treatment here. What do we see in terms of function? We see the North Star showing stabilization and a trend towards improvement. There was a mean positive 0.4 improvement, and what we have on this graph is. I'm showing you the line. The blue line shows the linear regression of the time points that we see over 12 months. Consistent improvement over neutral. In fact, what that needs to be compared to is the decrease that one would expect in natural history, that you saw with Dr. McDonald's slide. The average from two studies is minus 1.2 points per year. You see that continuing to diverge from the effect or the change in NorthStar. Showing the individual points here with the 95% confidence intervals. When we look at it on an individual basis, we see that three-quarters of the patients either were neutral or actually improved, and that's not what we would expect from the natural history. On the next slide, you should remember what Dr. Craig McDonald showed. The natural history declines very consistently in the range between 31 and down to four, where the patients were in this study. In fact, we are seeing that contrary to this, we're seeing three-quarters of the patients either stable or improved. In the next slide, some of the other functional measures that we've looked at, 100-meter timed test velocity is stable, no significant change over 12 months. We're seeing grip strength. Again, no change over 12 months. It's maintained over all of these dosing levels. In terms of symptoms, we also looked at pain scores in these patients, and that is a hallmark of Becker muscular dystrophy. We've looked at that with the PROMIS-57. These also trended better after 12 months, and actually quite soon with EDG-5506. And anecdotally, that's what we've heard from the investigator that people feel better on the drug. Looking at this in terms of how are we going to determine a dose for future studies? We've shown you before that the target muscle concentrations in preclinical models of efficacy were between 1 and 4,000 nanograms per gram, with corresponding plasma concentrations of 30 to 90 nanograms per milligram. What we did in phase 1 was to look at muscle biopsies in both patients with Becker as well as healthy volunteers. So that gives us the information of where we should be in the 50 to 70 nanogram per ml range for maximal efficacy. It's highly concentrated in muscle versus plasma. So that's shown here in the target human muscle exposure range, and that's spot on what we see with the 10 mg dose. So that's very consistent with what I just showed you with the biomarkers. We see maximal changes with that dose and no further changes beyond that. To summarize, what we have seen in the ARCH study is we've checked all the boxes here. We see safety. It's been well tolerated at all doses. With biomarkers, we've seen rapid, sustained, and significant decreases in multiple biomarkers of muscle damage, disease progression. In terms of function, we've seen stabilization of functional assessments consistently with trends towards improvement in NorthStar, and particularly compared to the natural history data that you would expect. We've identified a pivotal dose for future studies. We see the maximal biomarker response even at the 10 mg dose, and we see PK/PD relationships that are also supportive of selecting this dose for a pivotal cohort. We have identified the key factors that encourage us to design a potentially registrational trial. What's next? First of all, in ARCH, we are continuing ARCH, and we have expanded it to 24 months, and we have moved the patients back to the 10 mg dose on that. That is the dose that we believe going forward is the ideal dose. Moving on to the CANYON study, which is in process. On the left, we had initially planned this study to look at doses of 10, 15, and 20 mg, with a primary endpoint of CK at 12 months. We're also looking at adolescent Becker patients at doses of 5 and 12.5. What we've done is we've amended this one year part of the CANYON study for the adult doses. We've eliminated the 20 mg dose and consolidated the other two cohorts to a 10 mg dose. Primary endpoint remains CK as a measure of muscle damage, but we're also continuing to look at North Star, and that's an important secondary endpoint, as well as 10 meter, excuse me, a 100 meter timed test, as well as other biomarkers of muscle damage and MRI. What we'll get from this, importantly, is to be able to look at these data, placebo-controlled data, at 12 months, and this will further inform analysis of a GRAND CANYON pivotal cohort that's potentially registrational. I'm gonna show you that design on the next slide. What ARCH has enabled us is to identify the key factors for a pivotal cohort. It's going to be a global study. We've expanding the number of sites, placebo-controlled, to assess the efficacy and safety of EDG-5506 in Becker. We are looking at adult Becker patients because we understand the natural history in adults. North Star is between five and 32, not on corticosteroids. We have identified North Star as the primary endpoint at 18 months, and we are using secondary endpoints of the 100-meter timed test, biomarkers of muscle damage, and MRI. We are enrolling the 10, up to 120 patients, and this is powered at well over 90% for observing a difference corresponding to the natural history North Star decline of 1.2 points per year. We are very conservatively estimating the to power this study. We've spoken, we've vetted this with regulators, we have agreement in terms of the North Star at 18 months, as well as other key measures, key design aspects of the trial. We're very encouraged moving forward to be announcing this, and looking forward to starting to enroll this later this year. I'd like to turn this over to Dr. Derakhshan to tell you more about what we think is the opportunity in Becker. Thanks, Joanne. In the next set of slides, we're gonna provide you with an overview of the commercial opportunity for EDG-5506 in Becker alone. Slide 38 provides a high-level summary of the qualitative and quantitative blinded market research we've conducted to better understand the unmet need in Becker and how EDG-5506 could shape the future treatment landscape. We also conducted a patient engagement project, as well multiple Becker focus groups, to understand the patient experience in terms of disease burden and to further characterize the unmet need. We leveraged the collected feedback from physicians and patients to refine our clinical development plan in Becker and ultimately also refine our target product profile. On slide 39, we asked physicians to highlight what they considered to be the major unmet needs in the management of Becker patients. Unsurprisingly, the lack of an approved therapy, particularly one which is disease-modifying, was ranked as the major cause of frustration. They also highlighted that the lack of comprehensive Becker natural history has made it difficult to predict phenotype and understand disease progression. Although some acknowledge that the recent independent datasets from Dr. Erik Niks and Dr. Luca Bello are starting to shed some light on this. A common theme among physicians, but also something we hear regularly from individuals with Becker, is they often feel ignored, particularly in light of the disproportionate attention given to individuals with Duchenne, both by industry and advocacy groups. Lastly, as Dr. McDonald pointed out, Becker is typically diagnosed around age seven and can take several months from suspecting someone has Becker to confirming they actually have the condition. With the advent of newborn screening, however, physicians believe Becker diagnosis challenges will gradually be overcome. Slide 40 exemplifies one of the frustrations voiced by physicians and patients. As you can appreciate, to the best of our knowledge, there are only three agents in development for Becker, with EDG-5506 being the most advanced molecule in development and the only one physicians are familiar with. Many of the KOLs were aware of the recent data disclosures and expressed excitement at EDG-5506's potential in Becker. In the next slide, in slide 41, we've summarized the feedback from physicians who were presented with a blinded target product profile, highlighting some of the key attributes of EDG-5506. EDG-5506's mechanism of action was viewed favorably, and reducing contraction-induced muscle injury resonated with interviewed and surveyed physicians. Intuitively, preserving muscle function was considered an important treatment goal for Becker patients, and physicians considered that the NSAA is the best tool to assess efficacy of EDG-5506 in Becker, with the goal of disease stabilization relative to a decline in the placebo group considered a win. EDG-5506's safety and tolerability profile and ease of administration were also considered highly attractive attributes. Overall, there was general enthusiasm around EDG-5506's disease-modifying potential in Becker, and physicians would ultimately like to prescribe it to all of their Becker patients as soon as they're diagnosed. Slide 42 highlights the sizable opportunity in Becker. With approximately 12,000 BMD patients in the U.S., EU4, U.K., and Japan combined, and the lack of approved therapies, we believe that the addressable pool of Becker patients at launch could be approximately 8,500 patients. Physicians indicate that approval of EDG-5506 would shift their behavior on how they manage Becker, with 80% stating that they would proactively reach out to their BMD patients lost to follow-up, to offer them EDG-5506. You heard some of that from Dr. Craig McDonald earlier. While it's clear that the opportunity in Becker alone is significant, let's not forget that DMD gene therapies are creating individuals who have a phenotype resembling Becker and, in many cases, a severe Becker patient. These individuals provide additional upside. Finally, on slide 43, we wanted to illustrate that care for Becker patients is highly concentrated across the U.S., EU4, U.K., and Japan, with significant overlap with DMD care centers, suggesting that a lean and focused sales force could adequately access both patient groups. That's it from me. Back to you, Kevin. Great. Thanks, Behrad. We have a busy set of milestones next 12-18 months. Initiation of GRAND CANYON, our pivotal cohort in Becker, should occur sometime third quarter, beginning of fourth quarter of this year, on the back of the CANYON study. We'll be initiating our phase I clinical trial, probably in September timeframe with EDG-7500, our cardiovascular asset for the treatment of hypertrophic cardiomyopathy. Our Duchenne phase II study is recruiting aggressively, and we expect to have three month dose-ranging data by the end of this year. Three important milestones for the company in the rest of 2023. We plan to report our Becker ARCH data at the 24 month time point, sometime perhaps this time next year. We have an ongoing DUNE study, which is an exercise challenge study looking to expand the opportunities into other muscular dystrophies including Limb-Girdle type 2I in McArdle. We have the CANYON 1, 2 study. Cohorts 1 and 2 is recruiting, and we should be complete this summer with a readout in the third quarter or so of 2024. Finally, we should be putting out phase I safety and perhaps efficacy data for EDG-7500 in the second half of 2024. We're very well capitalized to execute on these important value-driving milestones across both EDG-5506 and EDG-7500, with $328 million in cash and a runway through 2025. In conclusion, I'd like to thank personally everyone who's chosen to support our mission, particularly our talented and dedicated employees and their families. Most importantly, I'd like to thank our patient community, clinical trial investigators, trial participants, as well as the shareholders for continued confidence and support. It's been an exciting time here at Edgewise, and I truly believe we are at the cusp of demonstrating the potential of a novel therapeutic agent that could fundamentally improve the lives of patients in need of more effective treatments. Thank you all for joining the call. Be happy to take any questions. Thank you. If you would like to ask a question, please click the Raise Your Hand button at the bottom of your screen. Our first question comes from the line of Tessa Romero from JP Morgan. Please go ahead. Your line is now open. Kevin and team, can you hear me okay? Yeah. Yes, we can. Good morning, Tess. Morning, Tess. Great. Well, congratulations on the data, guys. Really nice presentation as well. Dr. McDonald, while we have you, thanks for being here. A couple part question for you, if I could. We'd be very interested to hear how your impressions have evolved over time, and as we think next about CANYON, what would be a clinically meaningful result on NSAA that would represent a win for patients? Specifically, what delta are you looking for between the placebo and drug arms here? Generally speaking, what duration of treatment do you think you need before you can see a clinically relevant effect? Those are great questions, and I think what we've been learning by actually applying the NSAA over time, both in terms of our natural history studies, using it as a prognostic indicator for likelihood of loss of really meaningful functions. Also, as we have gotten into some focus groups of patients with dystrophinopathy, we know that even a one point change on the NSAA is clinically meaningful to a patient in the real-world context. That could be, you know, losing a function or perhaps experiencing more difficulty with an individual function. I think in terms of the. I mean, I would certainly power a study on the order of a delta of probably 1.5 points, say, at 18 months, that would essentially equate to, you know, relative disease stabilization. Based on our 12 month natural history data, we know that patients lose about 1.22 points over the course of 12 months. If you stabilize the disease, which I think stabilization is a win in my mind, the delta value then would be, you know, essentially 1.22 points over 12 months, and, yeah, on the order of 1.5 points over 18 months. I think if you, if you hit a statistical significance with a delta of that magnitude, I think certainly that would be considered to be clinically meaningful and evidence of disease stabilization in the overall population. What we've learned in the actual Becker trials that I've participated in is, you know, given the relatively slow progression of the disease course, we know that we're better off conducting trials over, say, 18 month period of time. We've also learned that patients are, you know, probably willing to have placebo exposure for that period of time before transitioning onto to the actual drug during the open-label extension period of time. I think there have been Becker trials previously conducted, which have been of just 12 months duration. And some of those trials have shown signals, but I don't think we really have the understanding of the NSAA in a Becker population that we have more recently with the Bello data and the data from Erik Niks. And then also our emerging data from the Edgewise trials has also, I think, been very helpful in terms of understanding the applicability of the North Star to a Becker population. Hopefully, that answers your question. Thank you. The next question comes from Will Soghikian from SVB Securities. Please go ahead, your line is now open. Will, we can't hear you. Can't hear you. Hi, your line is now open. Please unmute. Hi, can you hear me now? Yeah. Yes, we can. Hey, Joseph. Sorry about that. It's Joseph Schwartz. Congrats on all the progress. A question for management, and then for Dr. McDonald, a follow-up. For management, I think CANYON can enroll up to 50 patients, 32 adults and 18 adolescents. Given the wide age range of those who are eligible, I was wondering if you can talk a little more about who is represented in the 12 patients reported here. Do you see any patterns amongst younger or older patients? When will we see data on the rest of the cohort? What are the biggest factors that you will need to pay attention to as you expand from a 12 patient cohort in CANYON to a 120 patient study in the pivotal trial? Thank you. Let Joanne take a crack at that, and I'll follow up. These patients are in the Open Label ARCH study and are distinct from CANYON. There are patients that are enrolling in the CANYON study in cohorts corresponding to doses of 10 and 15, and those are being consolidated at the 15 dose. That's a blinded, placebo-controlled study. We have baseline data for that, but we have no data over time in that population. The interesting thing is that we will this is essentially, we're potentially adapting GRAND CANYON, and we'll have more information to make sure that we are adequately powered, that we've got the right analysis, and we'll have that well before the GRAND CANYON cohort is final. That will further inform our analysis of GRAND CANYON. To be, Joe, to be clear, the CANYON 1 and 2 has been consolidated to the 10 mg dose. That's 32 patients, three to one randomization, treated to placebo. That will read out for one year. We're just about to complete the enrollment of that 32 this summer. The adolescents are a separate group. They're being treated differently at 5 and 12.5 mg. Those patients tend to decline rather slowly, there's no good natural history for that group. They do have typically elevated biomarkers relative to the later-stage patients. We get additional information as to a different population with even higher biomarkers than the relatively advanced adult patients. We're looking at those two populations, the key readout will end up being the 32 patients from, what is it? 18 to 50. Mm-hmm. Which should be completed by the end of July, and we should be able to read out third quarter of next year. Thank you. The next question comes from Laura Chico, Wedbush. Please go ahead. Your line is now open. Hey, Laura, we can't hear you. Hi, Laura. Please unmute. Yeah. The next question comes from Leonid Timashev, RBC Capital Markets. Please go ahead. Your line is now open. Hey, guys, can you hear me okay? Oh, sorry. Yes. Hey, Laura. Go ahead, Laura. What are you asking about? Leonid? Hey, guys, I apologize for. Hey. Can you hear me okay? Yeah, we can hear you, Laura. Sorry, for the Edgewise team, can you just talk a little bit more about your recruitment timing, expectations for GRAND CANYON, given that's 120 subjects? Could you speak a little bit more, are you planning on collecting outcomes data like events of cardiomyopathy? For Dr. McDonald, just curious, you made some contextualization on NSAA between the BMD populations and the natural history and what Edgewise studied. Do you have any comments in terms of, is there any extrapolation that can be made from this BMD population to what a DMD population might be like? Thank you very much. Mm-hmm. Joanne, why don't you take that? Yes, yes, we are, we are collecting a number of other outcome measures and PROs. We know we're collecting the right things in GRAND CANYON. In terms of our recruitment, we are increasing the number of sites, we're increasing the number of countries, and we will have more information when we provide additional details later in the year on GRAND CANYON in terms of the recruitment timeline. The in terms of the cardiomyopathy question, we are following as a safety measure. We are with cardiac echo. You may remember that pre-clinically there was a benefit in terms of decreased fibrosis in the animal models in terms of even though there isn't a direct interaction with cardiac myosin. Craig? Yeah, I think the question was extrapolation to a DMD population. I think obviously based on, you know, the NSAA values that we see in the Becker patients that are being targeted for these trials, we're trying to focus on those Becker patients that have a little bit of decrement in function and are in the decline phase of the disease. I think in order to learn more from a Duchenne population, I think taking patients in the ambulatory phase that have sufficient muscle fiber to treat and preserve. I think the Duchenne trial I believe is gonna be targeting sort of that patient population kind of in the later part of the first decade, up to about age 10 years, I believe. We'll learn a lot from that population. Most of the ambulatory Duchenne patients would be, you know, predictably, you know, showing some degree of decline. Obviously, in the Duchenne population, you would need to be able to demonstrate treatment effect really on top of standard of care steroids because it would not really be ethical to design a Duchenne population in a steroid-naive patient population. I think, you know, interestingly, we have all these dystrophin restoration strategies, either exon skipping and emerging gene therapy. Based on what we're learning from our experience with Becker-like dystrophinopathy, I think there's real potential here to be used really in a synergistic manner with a dystrophin restoration strategy to treat these patients with a compound that actually protects against contraction-induced injury. I would fully anticipate patients with Duchenne who have low levels of dystrophin or even more impressive amounts of micro-dystrophin could potentially benefit from this therapy. Thanks, Craig. That's right, it's up to their 10th birthday. We are enrolling patients in the 4 to 10th birthday range. To remind folks on the call, because of this early, rapid, sustained decrease in biomarkers, we can look at these kids over three months in a placebo-controlled study in order to understand PK and dosing for a pivotal study. That's what we're getting out of this phase II in Duchenne. Thank you. Thanks, Laura. The next question comes from Leonid Timashev. Please go ahead. Your line is now open. Please unmute. Hey, guys, Leonid here. Thanks for taking my question, and congrats on the data. I guess I wanted to ask on some of the regulatory interactions you may have been having with the FDA. I guess just to start off, I mean, what's the sort of level of engagement you're having with the agency across, you know, different levels of leadership there? Then, you know, sort of following up on that, you know, can you talk about what the agency is expecting from GRAND CANYON? Is this a study that could potentially support full approval or an accelerator approval? In terms of the dosing, was the 10 mg kind of driven by the FDA, or was it something that- ... you guys decided on. I'm just curious why, given the sort of clean safety profile, not to go with an intermediate dose? Then maybe lastly, you know, given that Becker and Duchenne are sort of a continuum of the same disorder, do you have any view on whether, you know, data you might gather from Becker or vice versa can be supportive for the other indication, not just from a safety perspective, but also from an efficacy data set as well? Thanks. That's a lot of questions there, Leonid. You know, I think the discussions with the agency were productive and quite positive, I think. They were particularly interested in the natural history, since there was no real natural history in NSAA, they really gravitated towards the Northstar as the primary endpoint. They saw all of the safety data and agreed with us that there really was very well-tolerated molecule from 10 to 20 mg in the Becker population. That was very positive. I think in general, we've looked at the data and cut it many different ways and seen that this biomarker reduction is very rapid and occurs with the 10 mg dose. There's no need to go to the 20 mg dose. Looking back at the concentrations within the preclinical models, we think the sweet spot that would capture most of the patients would be the 10 mg dose. We made that choice ourselves. As far as whether or not these trials would end up being registrational, we believe that we're very, in fact, overpowered for GRAND CANYON, and that much of this will translate to the Duchenne population. We would anticipate when we're looking at the Duchenne population, we'd get up to a perhaps what we think is the maximal level of biomarker reduction, especially on the troponin endpoint. We'd probably go up one dose group above that to know that we've reached the peak and then back down to what we think is a maximal level, and hopefully, we're anticipating that will cross into the same exposure range as we're seeing in the adults. You know, I think in regards to how this Becker data might translate over to Duchenne, I think clearly, you know, there's been an adamant discussion of gene therapies and exon skippers creating Becker patients. I think it's completely rational to say if we provide benefit to a Becker patient, we should treat every exon skipper and every gene therapy patient. Whether or not you can expand the label into that direction, I think depends on the data and we certainly will be treating in the next year, gene therapy patients and exon skippers are part of our phase II dose ranging design in Duchenne. Thanks for the question. I think I got them all. Yep, got them. Thank you. Thank you. The next question comes from Srikripa Devarakonda, Truist Securities. Please go ahead and unmute. Thank you so much for taking my question, and congratulations to the Edgewise Therapeutics team on these data, and thank you for the presentation today as well. This is for Dr. Donovan. Quick question. I think maybe a little bit of it was addressed previously, but I just wanted to try and understand. It's 12 patients of data. I know it's hard to say, but do you see any characteristic that determines who responds and who doesn't respond? You have six patients showing improvement, three patients who were stable. Also, is there a correlation between reduction in the biomarkers and improvement in the NSAAS scores? Apologies if I missed it. A question for Dr. McDonald. Can you talk about how often steroids are used in BMD patients versus DMD? I know the trial is not enrolling patients on steroids, but do you think their prior history with steroids could make a difference to how well they respond to EDG-5506? Thank you. There's a few questions there. Thank you for those. In terms of the biomarkers, since there is consistent reduction of the biomarkers, it's difficult to show any correlation because pretty much everybody goes down. It just can't show a correlation there. In terms of the responders, what we have seen is that it's not the folks with the highest exposures. It's actually the lower exposures, consistent with the 10 mg dose. That gives us confidence there, based on what we're seeing in the functional measures. In terms of age, not really seeing any particular correlation. Most of these guys are in their thirties. In terms of baseline function, we see that the ones who have more severe disease actually have good response as well. We see it across the, the range of, the baseline NorthStars. Did I get all your questions? Yes, you did. Thank you. Okay. Yeah, I think there was a question for me about the steroid experience with Becker muscular dystrophy. I would say that really very few Becker patients are on steroids. I would say that it's probably less than 10% of all Becker patients that we encounter in clinic are currently actively on steroids. That's because, you know, with a really a slowly progressive disease that's going to continue. To be compatible for, with a long life, and decades of disease progression. These patients just don't tolerate the accumulated toxicity of steroids over, you know, many, many decades. In terms of the weight gain, the loss of bone mineral content, and fracture risk, and the Cushingoid features, the issues you get into with weight gain and also relevant degree of insulin resistance, and so forth. It's really in my experience, it's very few of the Becker patients are on steroids. There's a few centers around the world that have been treating some of the Becker patients with the high-dose weekend regimens of steroids. One of the things that's been striking to me in the few patients with Becker that we do see on steroids is just the variability of steroid regimens. Some of the patients are on weekend regimens, some of them are on daily regimens, but really quite low doses that might translate to 0.25 mg per kilogram. Whereas a Duchenne population of prednisone, where a Duchenne population we started at 0.75. I think from a trial design perspective, to include that small proportion of Becker patients that are on steroids, with the widely discrepant steroid doses and regimens that they're on, plus just the real, you know, limited proportion overall of patients that we see with Becker that are on steroids. I think it makes perfect sense to actually conduct a GRAND CANYON in a, you know, essentially a non-steroid treated population. I think the last question was, yeah, you know, would you expect the treatment response to be any different? I think if you wean patients off for, you know, several months from their steroids, and they're completely off steroids, we've known in our Duchenne experience that really the benefit of steroids doesn't really continue past when you taper those steroids off. I think if there was a Becker patient that was tapered off of steroids for a number of months, I don't think that should, you know, impact the efficacy of the steroids. There are some companies that are looking at other steroid alternatives in Becker populations down the road. I think Edgewise seems to be well positioned here to look at a steroid-naive population of Becker treated patients. Thank you. Thank you so much, Dr. McDonald. Thank you. The next question comes from Rob Palermo Goldman. Please go ahead and unmute. Hey, guys, Rob on here from Arda Ural. I just had one question: How do you think about the landscape in muscular dystrophy with an approved DMD gene therapy? Thanks, Rob. I think, I mean, looking at the rate of uptake, I think it will be measured until the EMBARK study comes out. Don't think there'll be a particularly rapid uptake for the drug. We already know from our discussions with the parents of patients with gene therapy-treated kids, is that we know many of them are progressing. We also know that their biomarkers of muscle damage are relatively high, north of 5,000, approaching 10,000. In fact, they would probably be diagnosed as Duchenne patients even after the gene therapy. I think that there's an opportunity for us to treat patients who have had previous gene therapy, especially looking at those that might be in a decline. Those patients may be on the older side, perhaps seven to 10 or even 12 years of age. I think that our Becker data is highly supportive of that we can stabilize disease in a declining population. I believe that our drug will become a standard of care ultimately in post gene therapy treatment. I also believe we have an extensive possibility prior to gene therapy, because if we preserve muscle up to say adolescence, we ultimately could provide the gene therapy, and you've had less dilution of the gene therapy. I think there's an argument to be had that treatment early with EDG-5506 would be highly beneficial, would become the backbone of therapy in Duchenne. Thank you. If I could just provide just, you know, a little additional color to that. I think that, you know, we're already as physician scientists, clinical investigators, you know, we're already starting to think about questions like, you know, would gene therapy potentially be steroid sparing, you know, in a Duchenne population? You know, starting to think about designing trials in terms of, you know, perhaps randomizing patients to different dose reductions of steroids, you know, to try to decrease side effects and toxicity in those populations. I think the other issue is that, yeah, you know, there's also a lot of talk about, you know, trying to develop, you know, ability to repeat treatment of gene therapy down the road, whether it be with plasmapheresis or immune modulating therapies. You know, we don't know when that would become necessary, you know, how many years down the road, whether it be, you know, decades potentially down the road. You know, wouldn't it be nice if you know, could combine treatment of a gene therapy treated population with EDG-5506, and perhaps, you know, either delay the need for retreatment or perhaps even, you know, prevent the need for retreatment for many, many years or decades? I think these are all things that, you know, would be in my mind. Obviously, you know, the gene therapy-treated patients, you know, are treated perhaps, you know, as we get to treatment, in the neonatal phase, you know, perhaps you could produce more of a true Becker phenotype. You know, keep in mind, Becker patients have the in-frame mutation from the time of fetal development in every one of their muscle cells. To think that you treat a Duchenne patient at age 10 or 12, or age eight with gene therapy, you know, they still have, you know, a great degree of loss of muscle fiber and fibrosis. You know, the data I think that came out of Sarepta really indicates that in the declining phase of the disease, the hope is really stabilization, not necessarily improvement of function. I think this really does have sort of a place and a potential role, you know, in the context of an overall population, many of whom, you know, could potentially down the road benefit from gene therapy. That would be sort of my perspective on this. Thanks, Craig. Thank you, Rob. Thank you. We do have a follow-up question from Laura Chico, Wedbush. Please unmute and state your question. Hello, Laura, please unmute and state your question. 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. Well, I'd like to thank the employees, collaborators, and especially our patients and their families for participation in our trials to facilitate our quest to create new medicines for the treatment of disease with high unmet medical need. I'd like to thank everyone who joined the call today. We'll close now. Thank you! Thank you. That concludes today's webinar. Thank you all for your participation. Thank you.