Astria Therapeutics, Inc. (ATXS) Earnings Call Transcript & Summary

Let's go ahead and get started. Good morning, everyone. Hello, I'm Jill Milne, the Co-Founder and CEO of Catabasis Pharmaceuticals. Welcome to our Duchenne muscular dystrophy and edasalonexent focused event. We're pleased to have you join us today. Before we get started on this sad but patriotic day, September 11, 2020, we would like to acknowledge and remember those that were lost on this date 19 years ago. Today's event is being recorded. It will be available for replay on the Investor Relations section of the Catabasis website after the event. At the end of today's presentation, we will be hosting a live Q&A session. Please feel free to submit questions throughout the event using the ask a question box on your screen. During this morning's discussion, you can read the full forward-looking statements by accessing this presentation on our website. I'm pleased to introduce our speakers for today. We are joined by 2 individuals deeply connected to the Duchenne community: Dr. Craig McDonald, an internationally recognized DMD key opinion leader; and Mindy Cameron, a parent of the Duchenne patient that has extensive direct experience as well as rare disease nonprofit experience. Dr. Craig McDonald is joining us today to provide a clinical overview of Duchenne muscular dystrophy. Dr. McDonald is a well-recognized expert in DMD care and in clinical trials. He is a professor and the Chair of the Department of Physical Medicine and Rehabilitation, a professor of Pediatrics and the Director of Neuromuscular Disease Clinics at the University of California Davis. He also is Chair of Synergy, a Duchenne natural history study. Dr. McDonald has made significant contributions to clinical care and the development of drugs for rare diseases. He has been a PI for numerous clinical trials in DMD, including our Phase III PolarisDMD trial for edasalonexent and is well-known to regulatory authorities throughout the world. We are very pleased to have Craig as part of our event this morning and to continue to receive his valuable input on our program in DMD. Mindy Cameron is joining us to share her family's experiences and her view as a deeply knowledgeable caregiver about what the needs are for Duchenne patients. Mindy has a 19-year-old son that is affected by Duchenne. She also has more than 15 years of experience working with nonprofit organizations in the DMD, rare disease and disability areas. Two of my Catabasis colleagues will also speak today about edasalonexent: Dr. Joanne Donovan, who is our Chief Medical Officer and Senior Vice President of Clinical Development; and Andrew Komjathy, our Chief Commercial Officer. Now let's review the agenda for this morning. We have put together today's event to provide a deep dive into Duchenne muscular dystrophy and edasalonexent, a potential new therapy being developed by Catabasis. Dr. McDonald will start off our day with his extensive knowledge of Duchenne muscular dystrophy. Joanne will review our clinical development program for edasalonexent, including our current Phase III PolarisDMD trial. Mindy will then share her perspective as a caregiver and her family's experience with DMD. Andrew will provide an overview to what we see as the potential commercial opportunity for edasalonexent. We will then have an open question-and-answer period where you can submit a question for any of our speakers, and I will finish our session with a few concluding remarks. Let me start by introducing Catabasis and edasalonexent. At Catabasis, we are working together to make a difference in patients' lives by discovering and developing life changing therapies. We have assembled a leadership team with deep expertise in the science of NF-kappa-B and neuromuscular disease and, importantly, in the development and commercialization of rare disease therapeutics. Our lead program is edasalonexent, a potential foundational therapy for all patients affected by Duchenne muscular dystrophy. Edasalonexent is an oral small molecule being evaluated in Phase III to determine whether it can slow disease progression and have positive effects on muscle function. Our Phase III registrational trial in DMD is ongoing with top line results expected in Q4 of this year. We are dedicated to the Duchenne community and have an active pipeline that represents our commitment. In addition to our current trial in ambulatory boys affected by Duchenne, we are planning a trial to evaluate edasalonexent in nonambulatory patients in collaboration with Duchenne UK, and we are planning to explore edasalonexent in other muscular dystrophies where NF-kappa-B may be activated as part of the pathogenesis. At Catabasis, our vision is to build a global rare disease company, and I'm pleased that we have the opportunity to share an important component of that vision with you today. I would like to start by addressing 2 questions: Why Duchenne muscular dystrophy? And why NF-kappa-B? Why are we working in DMD? Duchenne muscular dystrophy remains the most common rare neuromuscular disease that affects young children. Duchenne muscular dystrophy is a rare disease with a significant unmet need. But unlike so many other rare diseases, this is an active landscape for patients, advocacy and manufacturers, including Catabasis, because there are so very little available for patients and the medical need is urgent. The global therapeutic market value is estimated to exceed $4 billion in 2023. There is currently no cure for Duchenne, and there is a need for therapies that can slow disease progression and improve muscle function for the thousands of boys and men that are affected. We find this compelling, and we are working tirelessly to provide a positive impact in this landscape. Our vision is to develop a therapy for all patients affected by Duchenne that can slow disease progression, that can enable boys to walk longer and that can enable young men to live independently longer. And the next question, why are we targeting NF-kappa-B? Activated NF-kappa-B is a key link between the lack of dystrophin and the resulting manifestation and progression of Duchenne. It is important to remember that in DMD, the absence of the dystrophin protein is necessary, but it is not sufficient to drive disease progression. Typically, young boys with DMD are not symptomatic in their first couple of years. However, without dystrophin, mechanical stress from everyday activities like walking and running chronically activates NF-kappa-B, which leads to progressive deterioration of skeletal muscle. By inhibiting NF-kappa-B, edasalonexent has the potential to limit muscle degeneration, promote muscle regeneration and reduce inflammation in fibrosis to improve muscle function supporting patients' daily activities and to slow disease progression. Edasalonexent has a unique mechanism of action, designed to provide targeted NF-kappa-B inhibition and improve muscle function. Inhibiting NF-kappa-B with edasalonexent is a mechanism with the potential to benefit all patients with Duchenne and, therefore, would not be limited to patients with specific mutations. The chronic activation of NF-kappa-B is a critical component of disease progression in Duchenne. Not only does NF-kappa-B negatively impact skeletal muscle function, it also is a critical component of cardiac disease and a factor in bone health in DMD. We are targeting NF-kappa-B in DMD with edasalonexent because of the potential for broad therapeutic effects. We believe that inhibiting NF-kappa-B with edasalonexent has the potential to improve skeletal muscle function, preserve cardiac function and reduce the risk of fractures. There are currently few options available to treat Duchenne in all boys regardless of their underlying dystrophin mutation. Catabasis is committed to developing an effective, well-tolerated foundational therapy in DMD for patients, families and health care providers. We see the key aspects of a foundational therapy as something for potentially all patients throughout their lifespan with broad benefits of good safety profile and the ability to be used with other therapies. Our vision for edasalonexent is as a foundational lifelong therapy for all patients regardless of mutation type. As we just reviewed, we believe that edasalonexent has the potential to address the multiple key systems affected by the disease, including skeletal muscle function, cardiac function and bone health. We are developing edasalonexent as monotherapy but do see great potential for use in conjunction with other therapies, in particular, the dystrophin-targeted therapies such as Exon skipping agents and gene therapy. As we have seen to date, the safety profile for edasalonexent has been favorably differentiated from currently available therapies and those in development. We see edasalonexent for the treatment of Duchenne as a substantial commercial opportunity in the U.S. and globally. I am pleased to now introduce our next speaker, Dr. Craig McDonald, to provide an in-depth information on Duchenne muscular dystrophy from his experience as a clinician.

Thank you, Jill. It's really a pleasure to be with you this morning. And I'm going to be sharing a clinical overview of Duchenne muscular dystrophy. As a matter of disclosure, I've done consulting work on Duchenne muscular dystrophy clinical trials for a number of pharmaceutical companies and have also received research funding for the conduct of clinical trials from a number of companies. Duchenne muscular dystrophy is a rare, relentless and fatal disease of boys and young men. It results in progressive paralysis, ultimately respiratory failure and cardiomyopathy and premature death. And as seen in these muscle biopsy pictures on this slide, you can see that there's a progressive loss of muscle fibers and also replacement of those fibers by fat and connective tissues as the fiber dies. So as a consequence of dystrophin, there's a segmental necrosis in muscle cells. So the reduced or absent dystrophin leads to a mechanically weakened plasma membrane. That muscle membrane is prone to focal tears during normal contractile activity. And this results in a massive influx of extracellular calcium and activation of proteolytic enzymes. The activation of NF-kappa-B and Duchenne muscular dystrophy is a key factor in disease progression in both skeletal and cardiac muscle. So with the absence of dystrophin and normal mechanical stress of muscle fibers, there is activation of NF-kappa-B, an increase in inflammation, an increase in degeneration of muscle fibers, a decrease in the capacity of muscle fibers to regenerate. And ultimately, the NF-kappa-B actually will ultimately lead to decreases in dystrophin production, particularly in patients with Becker muscular dystrophy or those with dystrophin-targeted therapies. And so these micro RNAs, which are actually produced will actually lead to ultimately dystrophin reduction and dystrophin production. So NF-kappa-B is really a key factor in disease progression with Duchenne patients. There are fairly stereotypic stages of Duchenne muscular dystrophy disease progression, which are really captured by a number of clinical milestones. The -- early on, the impaired ability to hop, run, jump, rise from the floor; the loss of ability to rise from the floor and stair climb, ultimately, loss of ambulation; a loss of overhead reach; a loss of hand-to-mouth function and distal hand function; and, ultimately, a reliance on noninvasive mechanical ventilation or BIPAP initially at night time and subsequently during day time and night time. And then ultimately, premature death due to respiratory failure or insufficient cardiac function. With regard to the early stage of delayed and impaired acquisition milestones and motor skills, this is really captured predominantly by the North Star Ambulatory Assessment, which has been increasingly used in clinical trials. The North Star is a validated scale, specifically developed to measure physical performance in ambulatory boys with Duchenne. It's a holistic measure. It actually measures 17 domains of function. It's patient centric. It was selected as a meaningful endpoint with both patients and caregiver input. It's been shown to be reproducible. Studies show that the North Star is reliable and measuring change over time. And the edasalonexent trials, the North Star, has been indeed demonstrated to be reproducible. The North Star is a widely accepted measure. Catabasis was an early adopter of the North Star in their clinical trials. Many other clinical trials in Duchenne are now using the North Star as a primary endpoint, including the emerging gene therapy trials. And then finally, it's been recommended as a key clinical trial endpoint by both the FDA and the EMA. And we use it in our daily practice in our care of Duchenne muscular dystrophy patients. The North Star is a composite endpoint. It evaluates physical function with -- across these 17 tests with increasing difficulty. The most difficult items to perform, such as hopping and running and jumping are lost earlier in the course of the disease. The other items, such as walking and standing are less difficult to perform, and those are lost later in the course of the disease. The scoring on the North Star is simple. It's scored on a 3-point scale, 0, 1 or 2. A 2 is a score where a patient is able to perform the function normally. A score of 1 means that the patient is performing the function with difficulty or with a compensation. And a score of 0 would indicate the patient is unable to perform the activity, and there is a complete loss of function of that with regard to that item. Here is a video actually showing illustrative tests. Here's a patient standing from supine or rising from the floor. You can see with hip extensor weakness, he has to push off the knee. He has impaired ability to sit from a seated position without the use of the arms. Here, he's trying to jump, also demonstrating difficulty with the hopping on 1 leg. Here he is with a fairly characteristic gate pattern during ambulation and then the stair climbing as well as stair descending item on the North Star. Here is data that's actually recently been published by the U.K. North Star Group showing natural history North Star data. You can see with multiple patients, hundreds of patients that have been evaluated at the North Star, there is a maturational component to the North Star with progressive decline. But much of this data has actually been obtained in steroid-treated patients. And those patients will oftentimes demonstrate a continued maturation at ages 4, 5 and 6. We've had a different experience with on steroid-treated patients. So just to demonstrate this, nonsteroid patients may never develop the ability to hop. Here is a steroid-treated patient demonstrating on the left, the ability to hop on 1 leg. Again, on the right, here is a steroid-treated patient demonstrating the ability to jump. And here is a child very young, actually demonstrating a compensatory strategy to rise from the floor. Because of hip extensor weakness, you'll see a push off the knee in order to get to a standing position. And then many nonsteroid treated patients never developed the ability to run with build feet off the gram, but here is actually a steroid-treated patient demonstrating the ability to run with both feet off the ground. That's another item that's tested on the North Star. The North Star is a reproducible measure. This has been demonstrated in studies in the academic community. And also, recently, in the edasalonexent Phase III PolarisDMD trial, North Star scores were shown to be reproducible with no systematic differences between screening and baseline, regardless of age or the baseline North Star. So on the left, you can see this really nice reproducibility comparing the screening scores with the baseline scores. And then to evaluate this as a function of age, the data on the right actually demonstrates that there really isn't greater discrepancies between screening baseline seen in, say, 4 year olds or 4.5-year olds or younger patients on the North Star. So we see nice reproducibility really regardless of age. There has been, I think, popular perception that there is a distinct maturational trend in the North Star, which occurs in 4-, 5- and 6-year olds, but this is largely based on experiences with steroid-treated patients with Duchenne. And the more recent data actually comparing the North Star changes in steroid-treated and steroid-naive patients actually demonstrates here that when you get -- by the time you get to 4.5 years of age, you're really seeing no improvement on the North Star. This is the blue data points. And you can see with 4.5, 5, 5.5 and 6-year olds, patients who are steroid-naive are actually showing negative scores over time or negative changes in the North Star over time. And in fact, the -- if you look at the 6-year-old data from natural history studies, the data from the MoveDMD trial actually compares really quite favorably in terms of 1 year changes in North Star over time. So why would we wish to develop an alternative to standard-of-care steroids? And it's really due to the really quite problematic side effects that we see with glucocorticoid treatment. We see significant osteoporosis and fractures, weight gain and obesity, problems with high gain, growth retardation, delayed puberty, iatrogenic adrenal suppression with steroids, significant behavioral issues really concerning and problematic cushingoid appearance, hypertension, metabolic syndrome, glucose tolerance. And then with some steroid regimens, we see cataracts as well. The North Star has actually been evaluated using a shift analysis, looking at the numbers of functions that are gained or the number of functions that are lost. And here in patients that are younger than the age of 7, again, in largely steroid treated patients, you can see there is a preponderance of activities, which actually show gains in function across the 17 items. But there are some patients that are actually showing shifting down or lost of function. But again, this is largely steroid treated data. And again, once you get to 7 years of age, even in steroid treated patients, we're seeing a preponderance of activities are actually shifting down or actually being lost over time in Duchenne muscular dystrophy. So to conclude, the North Star is reproducible at younger 4- to 7-year-old Duchenne patients. Nonsteroid-treated Duchenne patients lose function earlier in a predictable manner. There's an earlier peak North Star at a reduced level, and that's associated with more rapid disease progression. In this earlier peak, North Star with reduced level and subsequent decline is often seen in nonsteroid-treated patients. And also, we see delayed time to reaching peak function typically associated with those higher peak values and the slower rates of subsequent decline in patients with more mild disease progression. What about the minimal clinically important difference in the North Star? So what would be a clinically important treatment difference? For the regulatory authorities, oftentimes, the focus is on statistical differences between a treated cohort and a placebo cohort. But to the clinician and to the patient, really, I think the minimal clinically important difference is really a key concept. And this is the smallest change in the treatment outcome that an individual patient would identify as being important, life-changing or would impact their quality of life. And there's been different approaches, statistical distribution approaches anchor-based approaches where changes in the North Star are actually related to changes on other motor function tests or perhaps are related to health-related quality of life measures. And then consensus-based approach is using a Delphi methodology where patients or their parents are interviewed to determine changes that would be meaningful to them. And I think really the focus has been more on these anchor-based and consensus-based methodologies. So just to show you the actual publish data on minimal clinically important differences in the North Star. If we look at the anchor-based methodology, a change of 2.2 points would be considered to be clinically meaningful. Using the consensus-based methodology, a change of 1 to 2 in on the North Star would be clinically meaningful. And this makes sense to me clinically for a patient, a loss of 1 function would imply a decrease of 1 point score in the North Star, a deterioration of 2 functions would imply a decrease of 2 points on the North Star. So just to illustrate this in the following videos, the video on the left is a patient who, most days, would score a North Star score of 2. He's able to rapidly rise on the floor barely pushes off the knees. Some days, he might push off the knee. Other days, he might not but generally would have a North Star score of 2. The patient in the middle actually uses a compensatory strategy to rise from the floor. You'll see the difficulty he has. He gets into a wide-based posture. He'll push off the knee because of hip extensor weakness and gets to a standing position. This patient would score a 1 on the Northstar. And the patient on the far right actually has lost the ability to stand from supine. And you can see he's unable to stand from supine within 30 seconds. And you can see the incredible difficulty he has to just simply transition from the floor to a standing position. And this patient would be given a score -- a North Star score of 0 on the stand from supine. So again, you can see the clinical meaningfulness of just a 1 point change on the North Star. Moving on to later stages where we're seeing ambulatory decline in function of these patients may be losing the ability to rise from the floor altogether or losing stair climbability. And one of the key clinical endpoints used in younger patients or the time function test, particularly in a population that's 4 to 7 years of age. And the key time function tests include the time to rise from supine, forced stair climb and the 10-meter walk run test. A younger steroid-treated patients who were 4 to 7 years of age with Duchenne often improve their on their time function tests and acquire functions on the North Star due to maturation. But nonsteroid-treated 4 to 7 year olds will typically lose function as measured by the time function test. The time function tests have also shown to be prognostic and can actually be a hallmark for the onset of functional deterioration in a Duchenne population. So here's data from our synergy natural history study showing the proportion of patients that actually lose the ability to stand over the next 12 months as a -- on the y-axis versus their actual standing times on the x axis. And you can see with this data on over 230 patients, when patients actually transitioned past a 5-second stand from supine time increasing proportions of patients will lose standing ability over the next year time. So this has actually become a hallmark for onset of functional deterioration in Duchenne patients. Similarly, the stand from supine time actually is prognostic and predicts the probability of losing ambulation 2 years later. This is data showing the proportion of patients that lose ambulation, again, from the synergy network when you have a standing time of 10 seconds or greater, you start to see patients losing ambulation over the next 2 years. And again, here is data from the synergy natural history data showing the stand from supine times compared to healthy, typically developing controls, which are the blue data points. The Duchenne patients are the red data points and the 5th to 95th percentile distribution for the typically developing population is again shown. And what you can see is even at age 4 years of age, if you look at the standing time as a percent predicted value, the vast majority of Duchenne patients are below the fifth percentile in comparison to healthy, typically developing patients, and they'll actually show a deterioration subsequently even after age 4. Similarly, with time to run or walk 10 meters, the blue data points are the healthy, typically developing patients. So you could see, even in age 4, the vast majority of Duchenne patients are below the fifth percentile and actually increasingly become even more impaired relative to a healthy, typically developing population subsequently. So these time function tests actually can be used to demonstrate a treatment effect in Duchenne patients between the ages of 4 and 7 years of age. Just to illustrate this, here's data on the 10-meter walk run test, the blue data points, the controls, they're all functioning around a 100% predicted value. Whereas the Duchenne data points in the red are actually showing a progressive deterioration with age relative to the controls even as young as 4 years of age. To demonstrate the effect of glucocorticoids, which inhibit NF-kappa-B, which reduce NF-kappa-B on function, quality of life and survival. We've published the experiences in a real-world setting in the lancet recently in 2018. And what we did is we actually looked at milestones of disease progression based on time function tests and actually showed that those milestones were actually very closely correlated with health-related quality of life measures as shown on the right side. And if we look at these data, this is data showing the proportion of patients. The red are those treated with steroids. The blue are those that have not been treated with steroids. And if we look at the proportions that transition to that milestone of a 5-second stand time from supine time, you can see the effect the steroids have in prolonging the transition to that milestone. And in the nonsteroid-treated patients, even at 5 years of age to younger than 5, they're beginning to already transition to that 5-second stand from supine time milestone. Similarly -- and if you look at a 10-second stand from supine milestone, steroids also prolong the age at which that transition occur. And then steroids have also -- in the next slide, we see the data on loss of ambulation. Steroids have been shown to prolong loss of ambulation by 3.5 years, really showing proof-of-concept that if we can inhibit NF-kappa-B, we can have significant impact on these critical milestones of disease progression. Finally, in terms of extrapolated to older patients with Duchenne dystrophy, there is linkage of the timing of functional deterioration and the loss of key milestones in the later disease course in Duchenne muscular dystrophy. So for example, if you look at the age at loss of ambulation, that's actually closely linked to the future age at loss of hand-to-mouth function, which, again, is a key function in terms of quality alive for a nonambulant Duchenne patient. Similarly, the age of loss of ambulation is predictive of subsequent pulmonary decline. The age of onset of a 1 liter lot of capacity has been associated with a significant increased risk of death, a fourfold increased risk in Duchenne patients. And the Blue Kaplan-Meier curve shows that the -- shows the proportion of patients reaching that 1 liter critical threshold of lost ambulation before the age of 10 versus those that have lost the ambulation at 13 years or later. So if you lose ambulation earlier, you'll tend to transition to really a dangerously low lot of capacity subsequently in the disease course. So I'd just like to acknowledge the other members of our EC Davis Neurovascular research team and thank you for the opportunity to share some of this experience. And I'd like -- and I'm pleased to now transition to our next speaker, Dr. Joanne Donovan, who is the Chief Medical Officer at Catabasis. Thank you very much.

Good morning, everyone. My name is Joanne Donovan, and I'm the Chief Medical Officer at Catabasis. I'm pleased to be joining you today to share information about edasalonexent and our clinical progress to date. Edasalonexent has been studied in both adults and pediatric subjects with more than 150 years of cumulative exposure in Duchenne patients thus far. Here is a summary of our clinical development of edasalonexent to date. We initially started in adults and then moved into DMD patients. Our first trial in patients with MoveDMD, a Phase I/II and open-label extension trial of edasalonexent. This morning, I will share these results, which informed the design of our currently ongoing and fully enrolled Phase III PolarisDMD trial. GalaxyDMD, our open-label extension trial is also ongoing and enrolling boys who completed the Phase III trial. We also have a drug-drug interaction study with corticosteroids underway to inform how best to administer these 2 therapies should that be needed. I will start today by reviewing the design of our ongoing Phase III PolarisDMD trial. The PolarisDMD trial is a 12 months double-blind, placebo-controlled trial and is intended to support global registration. It is fully enrolled with 131 boys aged 4 to 7 up to their 8th birthday, who have not been on corticosteroids for at least 6 months. Boys on a stable dose of eteplirsen were also eligible to enroll. And these patients were stratified and will not be included in our primary analysis. Our Phase III trial incorporates 2:1 randomization with 2 boys receiving edasalonexent for each boy that receives placebo. At the end of 12 months of treatment, all boys and their eligible siblings have the option to enroll in GalaxyDMD, the open-label extension trial to receive open-label edasalonexent. Top line results from PolarisDMD are expected in the fourth quarter of this year and are intended to support an NDA filing in 2021. We understand that the COVID-19 pandemic has impacted many clinical trials. We're pleased that we were able to maintain our time lines and continued execution of this trial throughout the pandemic. We believe our Phase III PolarisDMD trial has several advantages with respect to the pandemic, including that enrollment was completed in 2019, clinical trial site visits are only every 3 months and patients take the oral study drug at home. Together with our clinical trial sites and consistent with recent regulatory guidance, we have developed and implemented contingency plans as needed to enable the continued conduct of the Phase III PolarisDMD trial and the open-label Galaxy trial. These steps include the option to deliver study drugs to a patients home, increased flexibility in the timing of patient visits and utilization of telehealth. Our priorities are and will continue to be focused on the safety of patients as well as maintaining study integrity. In the Phase III PolarisDMD trial, we opened 40 clinical sites globally, and patients were enrolled in all 8 countries at 37 sites. The majority of our sites are in the U.S., where about 2/3 of the boys are enrolled. Europe and Israel enrolled an additional 1/4 of the boys; Canada about 8%; and Australia about 4%. We're very pleased with the strong interest from investigators and families in our Phase III trial, which enrolled considerably faster than other clinical trials with common patient population. The primary endpoint of the Phase III PolarisDMD trial is changed from baseline of the North Star Ambulatory Assessment for edasalonexent compared to placebo at 52 weeks. The North Star is comprised of 17 activities as shown here and is regularly performed as part of clinical practice. For the Phase III trial, the North Star is evaluated by trained clinical assessors that were specifically trained for evaluating this endpoint in the clinical trial, and the evaluations are also captured by video so that the trainers can modify -- can monitor the assessors. The secondary endpoints are 3 age-appropriate time function tests as outlined in the FDA guidance for developing treatment with 4 DMD: the time function tests are shown here, the 10-meter walk run, the fourth stair climb and time to rise from supine. Unfortunately, as Dr. McDonald showed you, boys affected by the DMD lose ground in their speed to perform these functional tests compared to their unaffected peers. We expect at the time of the top line results that we will have results from the North Star, the time function test and safety and tolerability. We have also included additional assessments in areas that are important to families affected by DMD that are potentially differentiating growth, bone health, cardiac function and patient-reported outcomes. We have poster presentations with our collaborators on preclinical bone and cardiac effects being with edasalonexent at the upcoming World Muscle Society Congress in a couple of weeks. The cardiac assessments in PolarisDMD include a 48-hour monitor that the boys wear at baseline, 6 months and 12 months in the trial to enable the capture of both resting heart rate and heart rate variability. The bone measurements include dexa scans of bone density and lateral flying fills. We, of course, are also measuring, monitoring safety and tolerability throughout the Phase III trial. The primary endpoint, the North Star Ambulatory Assessment is a validated scale specifically designed to measure the physical performance of ambulatory boys with Duchenne. We chose it as our primary endpoint because of the meaningful assessment for patients because it reflects measures of everyday life. It's also widely accepted and recommended by both EMA and FDA. As Dr. McDonald mentioned earlier in data from the Phase III trial before treatment at baseline and at screening, the North Star demonstrated consistency and reproducibility. Let's go to our earlier-stage trial, the MoveDMD trial. The results informed the design of the Phase III trial. The MoveDMD trial was designed in 4 parts so that we could use MRI as an endpoint at 12 weeks compared to placebo and then explore functional assessments over a longer period of time in the open-label extension. An off-treatment control period for many of the patients, which averaged over 6 months in duration, allowed us to compare the results of edasalonexent in the same boys before and after receiving edasalonexent. This trial enrolled the same patient population as we've enrolled in the Phase III trial, boys aged 4 to 7 up to their 8th birthday, that had not received steroids for at least 6 months. Here, we have a summary of the clinical trial results from the Phase II MoveDMD trial and open-label extensions. Across all the measures, we saw a consistent support for positive effects from edasalonexent. We confirmed NF-kappa-B target engagement and saw improvements in biomarkers such as C-reactive protein, a global marker of inflammation and also muffle enzymes. Let's review these results in more detail. The next slide shows the data from the 4 functional assessments that were used in the Phase II MoveDMD trial and a open-label extension. First, let me explain how the trial was designed. We designed the MoveDMD trial to allow us to select natural history data in these boys before they receive edasalonexent. The gray lines on the left side of each of the graphs shown here show how the boys were functionally declining during its off-treatment control period, while the green lines showed slow disease progression and an overall stabilization on edasalonexent for these same boys. The same trend was observed with all 4 functional assessments. The North Star force stair climb, 10-meter walk run and time to stand. Recall, the North Star is the primary endpoint in the Polaris Phase III trial of edasalonexent, and the 1-year results on North Star in the MoveDMD trial were used to power our Phase III trial. We also looked at MRI T2 in the MoveDMD trial as a marker for muscle health as it measures inflammation and fat in muscle. In natural history studies of boys with Duchenne, the MRI T2 signal increases over time as muscle is replaced by inflammation and fat. The increase in MRI T2 correlates with the loss of functional ability. The primary endpoint in the Phase II portion of the MoveDMD trial at 12 weeks was the change in MRI T2 for boys on edasalonexent compared to placebo. The data were directionally positive but not statistically significant. Using the boys as their own control, though, comparison of the MRI T2 changes on edasalonexent to the off-treatment control period was statistically significant. The off-treatment control comparison continued to be statistically significant for the rate of change in MRI T2 on edasalonexent and extended throughout 72 weeks, consistent with the functional results. The gray bar represents the annualized increase in MRI T2 in the boys in our trial before treatment with edasalonexent. The green bars then show the annualized rate of change following treatment with edasalonexent, showing that MRI T2 was significantly improved following edasalonexent treatment. We did not incorporate MRI into the Phase III trial because it's not yet an endpoint that regulators accept and due to the complexity of performing MRI in young boys across many sites in multiple countries. In young boys with Duchenne, the muscle -- the levels of muscle enzymes in plasma are significantly elevated as a result of leakage from damaged muscles. In the MoveDMD trial, all 4 muscle enzymes, including creatine kinase, or CK, decreased following treatment with edasalonexent. The decreases were statistically significant, following 12 weeks of dosing and the effect was durable through 72 weeks of treatment. Turning to safety. Edasalonexent has also been well tolerated to date through more than 150 years of cumulative exposure in patients with DMD. We see this as an important attribute as we aim for edasalonexent to be a foundational lifelong therapy for Duchenne. The majority of adverse events on ESL and extent have been mild in nature. And the most common treatment-related adverse event was diarrhea, generally mild and transient. We saw no serious adverse events on edasalonexent in MoveDMD, and we've not seen adverse trends in chemistry, hematology or measures of adrenal function, including cortisol and ACTH. Edasalonexent does not act through the glucocorticoid receptor. Boys in the MoveDMD trial grew similarly to unaffected boys with height increasing an average of 2 inches per year and weight increasing by an age-appropriate 3-pounds per year, both in line with typical height and weight increases of unaffected boys. An area that's important in DMD is cardiac health. Unfortunately, cardiomyopathy is the leading cause of mortality in DMD. Preclinically, inhibiting NF-kappa-B has shown positive effects on cardiac fibrosis in mouse and dog models of DMD. Elevated resting heart rate is an initial manifestation of cardiac disease in DMD and has been shown to be associated with an increased risk for subsequent cardiomyopathy. The boys in the MoveDMD trial had elevated a resting heart rates at baseline of 99 beats per minute. And the mean resting heart rate significantly decreased, approaching age normative values of about 92 beats per minute. We're starting cardiac effects in more detail in the Phase III trial. Given that we use results from the Phase II trial to power the Phase III trial, an important question we wanted to answer was whether the phase 2 trials enrolled similar patient populations. When we compared the baseline populations of the Phase III PolarisDMD and Phase II MoveDMD trial, we saw that the boys had similar baseline characteristics. The analysis shows that the Phase III trial enrolled the expected patient population, and when baseline age and function were compared, there were no significant differences between the 2 trials. Both trials were similar in previous corticosteroid usage as well. We believe these findings support the assumptions on which the Phase III trial was powered. Our goal for edasalonexent seems to be a foundational therapy for all of those affected by Duchenne, and we plan to further study edasalonexent in both ongoing and planned clinical trials. The edasalonexent clinical development program is designed to address a broader patient population than 4 to 7-year-old boys up to their 8th birthday who are enrolled in Polaris and MoveDMD trials. In the GalaxyDMD open-label extension trial, boys are able to enroll after completing the MoveDMD or PolarisDMD trial as well as their eligible brothers aged 4 to 12 years old. We're also planning a trial in nonambulatory patients with DMD that is expected to enroll those age 10 and older. First, let's look at the Galaxy trial in more detail. We designed the GalaxyDMD trial to provide open-label edasalonexent to boys that have participated in our clinical trials. We were asked by the families of participating boys to also provide their other sons with edasalonexent after they had the experience of completing the MoveDMD trial. And we've been able to incorporate this request in our open-label extension trial. The GalaxyDMD open-label extension trial enrolled boys who completed the MoveDMD trial and their eligible brothers. Boys to complete the PolarisDMD trial and their eligible Brothers also have the option to enroll in GalaxyDMD. Boys for whom as indicated are able to initiate treatment with approved exon skipping therapies for Galaxy while returning -- continuing to receive edasalonexent. Earlier this year, we were thrilled to announce our partnership with a leading European patient advocacy organization, Duchenne UK, to evaluate edasalonexent in a trial and in nonambulatory patients with Duchenne. We recognize the need for a well-tolerated treatment for all patient populations that has the potential to slow disease progression and to preserve muscle function by benefiting both skeletal muscles as well as cardiac function. Duchenne UK granted us over $600,000 in funding to support patient and clinical trial site costs. We're incredibly fortunate to have the opportunity to partner with Duchenne UK for this important work and appreciate their deep commitment as we work together to bring treatment options to all patients. This trial is planned to assess safety, pharmacokinetics and measures of function, including upper limb, cardiac and pulmonary function in nonambulatory patients with Duchenne. The trial is designed to be a 1-year randomized, double-blind placebo-controlled trial in nonambulatory patients. The trial is expected to initiate next year, and we are working on the clinical trial design with experts. We're also getting input from the Duchenne community and patient advocacy organizations about the best approaches to minimize the burden of participation in clinical trials and as well as trial design considerations in the current COVID-19 environment. We look forward to sharing more details about the trial plans in the coming months. To summarize, edasalonexent is an NF-kappa-B inhibitor, which can limit muscle degeneration, promote muscle regeneration and reduce inflammation and fibrosis. It's currently being studied as a potential foundational treatment for DMD in the Phase III PolarisDMD trial, and top line results are expected in the fourth quarter of this year. The primary endpoint is the North Star Ambulatory Assessment because it is a widely accepted, validated and reproducible measure that's relevant and meaningful to patient lives. Our clinical results from the MoveDMD trial have been promising. And in those studies, all measures of functions stabilized compared to the declines observed during an off-treatment control period. Additionally, edasalonexent has been well tolerated for more than 150 years of cumulative patient exposure. We plan to continue to study edasalonexent in the GalaxyDMD open-label extension trial and in nonambulatory patients with Duchenne in an upcoming trial in partnerships with Duchenne UK. Thank you very much to patients and family to advocacy organizations and to clinical trial site staff and investigators for their support of edasalonexent and for enabling our clinical development program. I'd like to introduce our next speaker, Mindy Cameron, who's the mother of a 19-year-old son affected by Duchenne and will share her families experience and story. Thank you.

Thanks, Joanne. Hi, everybody, and thanks for letting me tell you a bit about Duchenne muscular dystrophy from a mother and caregiver's perspective. What my family has experienced about Duchenne over the past 19 years will help you better understand what it's like to get this diagnosis. And while no 2 Duchenne experiences are the same, I do believe my family's story is a very typical one. I'm going to show you this first slide because this is a picture back -- way back from 1983 at my high school graduation. That's me and my siblings and my parents. I show you this picture because we were just the picture of typical back then. We had no idea that a gene mutation that would cause pretty severe devastation for one of my parents grandchildren was already present in our family tree. As we would discover around 8 years after the birth of my second son, Christopher, I discovered that I am a carrier of Duchenne muscular dystrophy. I had my first son in 1996. He was a big strong boy. He hit all of his developmental milestones and walked at around 11 months. But as you can see, my second son also appeared very typical, beautiful, healthy, very normal. Looking back, I think there were subtle signs that something was different. He didn't hit his developmental milestones. He didn't roll over. He did not crawl. He was later walking, and he was not speaking by the time he turned 2. And so a few months after turned 2, we started looking into why he was having these developmental delays. After a series of specialist visits, we were given the diagnosis of Duchenne muscular dystrophy. And as a parent, you hear a lot of terrifying words and phrases during this diagnostic period, words like deteriorating and dying skeletal and cardiac muscle cells, limited regeneration of muscle cells, the likely loss of ambulation at age 12, need for ventilatory assistance by the mid to late teens, significant loss of upper body strength by that same time, very probable scoliosis that will require dangerous surgeries, the loss of the ability to eat due to lack of strength and lack of ability to swallow, debilitating and painful muscle contractures and intensive caregiving requirements by his mid-teens that would require many lifestyle adaptations for the whole family, adaptations to the home, the lifestyle, financial health, everything. And then the worst of it was the likely loss of life due to cardiac or respiratory failure by the early 20s. And then to top that all off, there was no cure or no treatments. We were told that there was 1 possible treatment option, corticosteroids, that had been shown to slow the effects of the disease. But they came with significant side effects, including slowing or stunting of growth, effects on mood and behavior, delay or loss completely of puberty, thinning of bones, bad bone health, multiple fractures. We had eye issues like cataracts and glaucoma, high blood sugar, high blood pressure, significant weight gain, cushingoid facial appearance, suppressed adrenal gland function, skin problems, excess hair growth. These were all things that we had to consider as our boy played with his train set in his diaper. I think any parent would tell you that the decision to use corticosteroids is a pretty difficult one. But we were also told that recent discoveries about Duchenne had led to a growing field of research. So we went on the steroids. We hoped and prayed that more treatments and more options would become available, and we filled our life full of fun and adventure for our 2 boys and really tried to keep Duchenne and the thought of the future at bay. We also threw ourselves into all the advocacy efforts that were underway, and we really tried to find out as much about research possible approaches at treating the disease and clinical standards of care. We wanted to make sure that our son got the best available care out there. And as is common with boys with Duchenne, around the age of 8, Christopher started having difficulty walking any sort of distance whatsoever. So we got him his first mobility device, which is here, the little scooter. As you can see, he still looked very good. He wasn't really having visibly any of the side effects of steroids. It was also during this time that I found out I was a carrier of Duchenne. And as a side note, I did enter a study later -- several years later about carriers and possible emotional and physical impacts of carriers. And I had found out that I have significant cardiac involvement as -- because of my status as a carrier, and that is also a story that is very common and very shared among carrier moms. And I wanted to give a shoutout to my son and countless other boys that were participating in natural history studies, research studies about outcome measures, lab tests, dosing studies during this era. A lot of these kids were not even 10 years old yet, and they were going to clinics across the country and participating in these studies that really did lead to the development of clinical standards of care, outcome measures, natural history studies, all these things that we were beginning to understand were going to be necessary for drug development and industry interest in this disease. And I just want to say these guys are all heroes. And without them, I'm not sure we would be where we are today. I'm very grateful to my son and everyone else that did this kind of work back in the early 2000s -- early to late 2000s. If you looked at a description of Duchenne online, you would see over and over again that the average loss of ambulation is between 10 and 12 years old. Almost like clockwork, Christopher fit into this category. The picture of him on the right is very typical of a late ambulatory Duchenne boy, the chest out, the arms back, wide stance, waddling gate. This is also the time that he lost the ability to get off the floor. If he was on the floor playing with Legos or toys, he would be unable to get up. He couldn't rise from a chair. He was frequently falling. And the falls, at this stage, are pretty gruesome. They can't catch themselves when they fall. So when they fall, they tend to fall hard and they plop. And it's usually a terrible sound somewhere in the house. He was holding on to walls while he was walking. He couldn't carry anything while he was walking. He wasn't safe in the bathroom. And we knew that all the signs were there that he was late-stage ambulation at this point. And then as is also common, 4 months before his 12th birthday, he did fall while trying to sit on the couch, and he sustained this leg fracture. We tried everything to rehab him to get him to walk again. We tried standing wheelchairs and hoists and walkers and anti-gravity treadmills and physical therapy. You can see in this picture, in this collage that he was fitted for his own power chair at that time. We know that once boys sit down for good, they start having all kinds of health difficulties. There's more cardiac involvement. There's more bone deterioration, contracture start forming. So parents try everything they can to keep these boys walking for as long as they can. But in many cases, including ours, these attempts are pretty futile or, at best, very short lived. And Chris never did walk again after this fracture. While that was devastating for us, he was actually glad that he didn't have to worry about walking and falling and hurting himself anymore. A few years later, he did get hurt again. And this time, it was a real doozy. We were at a power soccer tournament, and I was trying to transfer him from his soccer chair into his power chair. And I very, very lightly dropped him, and he ended up having to sit on the floor while I got some help. Unbeknownst to me at the time, 2 bone fractures occurred during that slight contact with the floor. Things that would have never ever broken bones in a person with normal bone health, fractured these 2 bones. Those fractures led to a very serious condition called fat embolism syndrome that resulted in his heart and lungs stopping. He was put on life support for 2 weeks. Fat embolism syndrome, really, it still happens. It's the ultimate example of how dangerous fractures can be in these boys. We still lose far too many boys from episodes of falling and resulting fat embolism syndrome. I also wanted to talk a little bit about the other pictures on this slide. You can see that the disease was really starting to affect him, and the steroid regime he was on was really starting to affect him as well. He was starting to gain weight. He need a nighttime ventilation assistance, BIPAP. He was getting the cushingoid facial features, and he -- puberty was not even on the cards. The boys get checked for puberty development because the steroids tend to delay that, and he wasn't even on the scale yet, and he was 15 at this point. So despite all these difficult challenges and changes that Duchenne brought into our lives, one remarkable thing did remain constant, and that was the work that advocacy was doing for support for advancing clinical studies, for providing seed money for research and drug development. It was a remarkable community. And when we were diagnosed back in 2004, this slide will give you a good idea of what we heard as parents. This is what our perception of that world was. There were no enrolling clinical trials. Step code on read through research was looking promising. Exon skipping, which is a drug tech -- a drug approach now was just an idea. Almost all of our studies were in mice. We didn't have anything going on in large animal models even. We had no certified care centers. We had scarce community connections. We had an incomplete understanding of what corticosteroids did and their long-term effects. There's a mistake here on this slide that it says scare education about care and available resources and services. I left that on there. I noticed it, but I thought scare was more appropriate than scarce. There was no DMD patient registry, but we were starting to understand that we were going to need a registry, and we were going to need natural history studies in order to get interest in this disease and drug development. And we just have tremendous community resilience and hope. It is a tremendously strong, educated and inspirational community. So I mean, I think Duchenne families learn early on that they really have to embrace every day and make every day count. My son is now in college. He's happy. His health is stable for the moment. But he's just one such young man of thousands, and he's just one young man that's waiting for better options for treatment. He's just one young man of thousands with DMD that want a healthier and longer life. It so happens that Monday was Duchenne -- World Duchenne Awareness Day. So I wanted to end on that slide. I hope you know more about what this diagnosis means for families now. Thanks for your time. And I want to introduce Andrew Komjathy, the Chief Commercial Officer at Catabasis.

Thank you, Mindy, for sharing your story. It's my pleasure to speak to all of you this morning and share what we believe is an exciting and highly attractive potential commercial opportunity for edasalonexent and Duchenne muscular dystrophy. As we work on our plans to embark on the potential launch of edasalonexent action and the transition of Canada basis from an R&D organization to a fully integrated biotechnology company, we've identified and defined the critical success factors that lead to a focused and successful orphan drug launch. There are 4 factors that I will cover today: first, that a high unmet need exists in the patients that we seek to serve; second, that patients who could benefit from edasalonexent are properly identified and diagnosed; third, that patients will have access to excellent care and can be managed in established centers of excellence; and finally, that patients, caregivers, their providers and payers recognize they have a choice in therapeutic treatment -- of a therapeutic treatment option that they all value. Over the next 10 minutes or so, I'll provide some more context to these critical success factors and how we believe edasalonexent and our plans are laying the foundation and the important groundwork to make this a foundational treatment in Duchenne muscular dystrophy. As Jill, Dr. McDonald and Mindy shared earlier, there remains a very high unmet need in Duchenne. Although current Duchenne treatment guidelines describe steroids as the standard of care, the physicians and caregivers must balance their risk benefit profile. Additionally, as Mindy mentioned, some patients may be treated with mutation-specific treatments targeted at dystrophin production. In the U.S., there are now 3 FDA-approved exon skipping agents that are appropriate for approximately 20% of the Duchenne patient population. And in Europe, ataluren is approved for use in about 13% of those patients. Although approved, additional studies are required to confirm clinical benefit for these treatments. So to summarize, there remains a high unmet need within the Duchenne community for treatment options that could benefit patients, either as a monotherapy or in combination with other treatments. The second critical success factor mentioned earlier is a well-defined patient population. The incidence of Duchenne is well studied and is well known. It affects 1 in approximately 3,500 to 5,000 boys globally. This equates to a prevalence of about 15,000 males in the U.S., 19,000 in Europe and approximately another 35,000 males in other countries with established access to rare disease therapeutics. The patient journey, although different for each boy has also been defined primarily based on ambulation, which roughly correlates to age. As been told earlier, most boys are diagnosed by the age of 5. And as this slide illustrates, boys with Duchenne begin to lose ambulation and eventually lose upper limb and respiratory function in the later stages of the disease. And many, unfortunately, die of cardiac disease by the time they reach their 30s. It is estimated that approximately 40% of the global prevalent population is ambulant. Equally important to the identification and characterization of the patient's journey is strong advocacy. Over time, the Duchenne community has developed a strong global network of advocacy organizations. At Catabasis, we're extremely grateful and proud to have developed many strong relationships within this advocacy community. We firmly believe that one of the key reasons we successfully enrolled the Polaris Phase III DMD study so quickly was due to the relationships we developed with those important advocacy groups, and we are all so appreciative for all their insights and their support. The third factor I mentioned earlier was access to focused and holistic medical care. There are approximately 100 to 200 identified treatment centers across the U.S. that currently treat and see over 80% of DMD patients. This structure will allow us to plan for and deploy a focused targeted field sales effort. This similarly will be the case for our medical affairs team operating under Joanne's leadership. Many Duchenne -- European Duchenne patients, like their U.S. counterparts, also have access to expert care and treatment. Last year, we completed market research in 5 countries in Europe: the U.K., France, Germany, Spain and Italy, where we learned that 85% to 90% of all diagnosed Duchenne patients in these 5 countries also have access to expert care and treatment. Like the U.S., we confirm that there are approximately 185 to 200 concentrated centers of excellence or treatment centers in these 5 countries. The final factor we've identified for successful commercialization and access, and probably the most important one is how do all of these stakeholders perceive the value of a treatment offering. Edasalonexent's potential efficacy and safety profile offer some very important points of differentiation. First, promising efficacy as measured by a clinical outcome endpoint, one where patients and caregivers have reported that a 1- to 2-point change in NSAA represents a meaningful impact of function. Second, it's been well tolerated to date with over 150 patient years of exposure across all clinical trials. Third, it's a potential foundational treatment for all Duchenne boys regardless of dystrophin mutation. Fourth, its mechanism of action suggests that it has the potential to be used alone or in combination with other therapies. And finally, it may offer an age-appropriate development allowing boys to have the potential of growth and weight changes similar to unaffected boys. We believe that edasalonexent's potential value proposition is both significant and meaningful. Over the last 2 years, we've conducted extensive qualitative global blinded market research with 3 critical stakeholder groups: the physicians who treat these patients, the payers that determine reimbursement and access for these treatments and the patients, caregivers and advocates, like Mindy, who are looking for therapeutic options to meet the high unmet need in this community. Our research was blinded, meaning that stakeholders did not know the name of the product or the company, and we did not know the stakeholders who were interviewed by these third-party agencies. Our objectives included obtaining an assessment of the blinded edasalonexent target product profile, including the proposed primary and secondary endpoints, safety profile, mechanism of action and dosing, an assessment of efficacy for the Phase III Polaris DMD as well as the extrapolated efficacy from Phase II MoveDMD trial and an assessment on the probability for use and reimbursement. Given our focus today is primarily on our first potential commercial launch anticipated here in the U.S., I thought I'd focus on what we learned in the past year with the U.S. DMD treating physicians. The chart on the left indicates how DMD physicians weigh the importance of treatments and the clinical trial attributes that demonstrate clinical value. We confirm that clinical efficacy and safety carried significant importance, but also that they consider the mechanism of action and quality of life of treatments almost as important. They were particularly interested in the potential of a treatment that could benefit muscle function without the side effects of a steroid. Not surprisingly, the U.S. payers are currently skeptical about treatment outcomes within Duchenne clinical trials. As you can see from the ranked importance of the clinical trial attributes in DMD, payers have voiced their preference to having therapies that could demonstrate efficacy and safety with supportive long-term functional benefit. Despite limited disease awareness, payers echoed the DMD prescribers feedback that steroids are not ideal and that they are also receptive to a new therapy that can demonstrate functional benefit without the side effects of steroids. The most important voice that we heard from in our research was that of parents, caregivers, advocates and the patient community. There was consensus among caregivers and advocates in the community in general. Not surprisingly, they are interested in the benefits of slowing the clinical progression of this disease and accomplishing that without the adverse events associated with steroids. The one quote from an advocate summarizes the research quite well. I think this is something families would get excited by. I look at it, and I'm very hopeful and excited. We believe the market research we've conducted across these various stakeholders validates our belief that edasalonexent has the potential to provide value to physicians, payers and, most importantly, a choice for parents and patients and caregivers in the treatment of Duchenne. As we have researched the potential value edasalonexent could provide in Duchenne, we have assessed pricing ranges of the currently commercially available treatments in Duchenne as well as comparable analogs in cystic fibrosis and spinal muscular atrophy. As this slide illustrates, the DMD treatments and those in similar disease states have commanded pricing ranges between $100,000 and up to, and in the case of gene therapies, in excess of $1 million. We believe that the potential profile that edasalonexent could provide Duchenne patients would represent a significant value offering of the currently available treatment options. In conclusion, we are very excited about the potential for edasalonexent and the important role it can play as a foundational treatment in Duchenne muscular dystrophy. We will continue to focus on these 4 critical success factors as we prepare for commercial launch. I want to thank all of you for the opportunity to share our plans with you, and I look forward to future updates as our plans progress. At this point, I'll turn it back to Jill for Q&A. Jill?

Thank you to all of our speakers today, and thank you to the audience for all of the questions we've received so far. Let's jump in and answer as many as we can right now. Let's see. We received a number of questions on the North Star Ambulatory Assessment as an point. These fell into 2 categories for the most part, so let's see how we'll queue this up. What would we consider a success in the Phase III PolarisDMD trial? And what is considered clinically meaningful with regard to the North Star Ambulatory Assessment? I'll let Joanne Donovan, our Chief Medical Officer, to address what we consider success in the Phase III trial and then hand it over to Craig after that to address the second part of the question around clinically meaningfulness -- clinically meaningful changes in the North Star. So first, Joanne?

Hello there. Thanks for the question. So we would basically consider a statistically significant difference between the active treatment group and placebo to be a home run. That's what we're looking for. That's what we're looking -- we know that the regulators are looking for. I'll turn it over to Dr. McDonald.

Yes. Thanks, Joanne. Again, I think the -- hitting statistical significance, I think, from a regulatory perspective is really critical, but I think from a clinical perspective, when I treat patients, I think a 1 to 2 point change of a treatment over the course of 12 months, that could translate to essentially a deterioration of 1 to 2 functions or a complete loss of a function going from, say, a 2 down to a 0 or losing 2 functions going from impaired function and losing complete loss of 2 functions. And I think this is a measure we use now in a day-to-day basis in our clinic environment. We -- many of the assessments we can get a sense of in the exam room and so I think a 1-2 point change has been shown to be clinically meaningful, both from a -- in the academic community with regard to test development but also looking at the results from interviewing patients as well as their caregivers.

Thanks, Craig. Thanks, Joanne. I'll address this next question to Craig while we're on the North Star Ambulatory Assessment as an endpoint. The question, Craig, is that the NSAA seems to be a very consistent measure. Do variations in genetic mutations affect the North Star score? And if so, by which subtype more or less? Craig?

Yes. I think we're gaining increased data with regard to specific mutation effects on the North Star. I think that the best natural history data seems to indicate that patients that have naturally occurring exon skipping, such as exon 44 skip amenable mutations, there's also patients with exon 337 deletion. These patients tend to have a little bit more mild progression. This has been shown on a variety of endpoints, including the North Star. There are also a number of genetic polymorphisms that seems to be affecting disease progression as well. But I think, fortunately, this is a very robust trial design that Catabasis was put together with large numbers of patients enrolled. And I think that this allows really for some of these mutation subtypes to be -- will likely be balanced between the treatment group and the placebo group. And I think the disease progression is really fairly well characterized in this age group. And I don't think that genetic subtypes are going to impact the study results that we see here.

Great. Thank you, Craig. And I suppose, let me direct this question to Joanne as it's related to that question around variability of patients entering the trial. So the question is, were there entry criteria that would sort of minimize the functional differences among patients being -- entering into the clinical trial. I think if I understand that correctly, that was the question. Joanne?

Yes. So we basically replicated the design of our Phase II study that we powered the Phase III study on. We did limit the change in -- that they needed to be able to rise from the floor in less than 10 seconds. When we look at the baseline characteristics of the 2 trials, though, we thought that they were essentially -- they were statistically drawn from the same population. We did not see a meaningful difference despite going from U.S. sites only to sites across the world. So that's very reassuring.

Great. Thank you, Joanne.

Can I just comment, Jill?