Good morning or good afternoon, depending upon where you are. I want to thank you for joining today's call. I also want to thank PPMD for making this presentation possible and look forward to your questions at the end. Today, we will present an update on deramiocel for the treatment of Duchenne muscular dystrophy, including our updates on our most recent data presented at the World Muscle Society in Hiroshima, Japan last week. Next slide, please. Next slide, please. This is Capricor's standard forward-looking statement that we present as a publicly traded company. To remind you, our filings are up to date and available on the SEC website. Next slide. As you just heard from Eric, joining me on today's call is Dr. Nathaniel Hogan and Dr. Adam Sullivan, two of Capricor's Lead Biostatisticians, as well as Dr. Craig McDonald, our National PI, who hails from the University of California, Davis, as well as Dr. Chet Villa, a Pediatric Cardiologist from Cincinnati Children's Hospital Medical Center, obviously in Cincinnati, Ohio. We are looking forward to updating the DMD community on the recent developments around deramiocel, including what has been submitted to the FDA. We will not take questions today regarding our interactions with FDA, as they are sensitive, and it is important to maintain that confidentiality. Thank you for respecting that guidance, and we look forward to providing updates as they become available on our BLA application. Now, let's talk about deramiocel and Duchenne muscular dystrophy, the important topics of today. Next slide, please. While we were disappointed in the vote by the Advisory Committee, we were pleased that the FDA recognized and heard the voices of the patients, primarily in the open public hearing, and decided to extend the PDUFA date to November 22nd in order to review the additional data from the open-label extension and the supportive evidence that HOPE-3 did in fact demonstrate a clinical as well as statistically significant effect on treating both upper limb dysfunction in a primarily non-ambulant DMD population, and also in treating the cardiomyopathy associated with DMD. We believe exciting OLE data presented today will be important in moving that program forward. To remind you, the HOPE-3 data showed a 4.55% improvement in Performance of the Upper Limb 2.0 in those treated with deramiocel at 12 months compared to a placebo group based on the statistical analysis plan we submitted, which was statistically significant, showing the trial met its primary efficacy endpoint of Performance of the Upper Limb 2.0. We use percent change from baseline as the primary efficacy endpoint because as data continues to emerge, it appeared that the best way to assess the Performance of the Upper Limb and also the clinical meaningfulness to a person with DMD, primarily based on the work of Aviva Gillman and Anna Mayhew, published in 2025. However, we saw statistically significant and clinically meaningful improvement in absolute change from baseline in PUL 2.0. No matter how you look at it, the data shows a benefit in sustaining upper limb function in those with advanced DMD. I do not have to reiterate this to you, but HOPE 3 represents one of the largest DMD datasets ever collected, and therefore, there is true strength in the data, as you will see in the presentation from Dr. Nathan Hogan in a few minutes. FDA granted us a refinement of the indication from cardiomyopathy to one more focused on what HOPE 3 was powered to detect, which was a change in upper limb function. The new indication, therefore, is for treating those with upper limb impairment at ages greater than nine, which encompasses a large proportion of those with DMD. Next slide, please. As I just mentioned, the new refined indication is treatment of upper limb impairment in those older than age nine. How did we get there? Let me provide some context, please. Most of you know we filed a BLA based on the HOPE 2 and the HOPE 2 OLE results based on recommendation from FDA that we do so. Upon their review, they decided the dataset was too small and issued a CRL in July of 2025 asking for a new trial with DMD cardiomyopathy as the primary efficacy endpoint. However, since we had a complete dataset in HOPE 3 and 106 of you had enrolled in that study, we offered them HOPE 3 as a way to cure the CRL. They agreed and requested we leave the indication as DMD cardiomyopathy and maintain the primary efficacy endpoint as PUL 2.0. They stated in writing regulatory flexibility when they reviewed the data. As you know, based on their briefing book for the Advisory Committee meeting, their interpretation of the HOPE 3 data was very different from ours, primarily based on the fact that they used a statistical analysis plan, version 1.1, that was never meant to be applied to the full dataset. In addition, the key secondary endpoint of HOPE 3 was the left ventricular ejection fraction in the ITT population. ITT is intent to treat, and that means everybody that enters into the trial has to be analyzed. One-third of those in the intent to treat population had healthy hearts. While the data was strongly suggestive of clinical benefit, the strictest interpretation of that data did not show left ventricular ejection fraction as statistically significant. However, and I want to reiterate, that is essentially a numeric interpretation because you cannot make a healthy heart healthier. This made interpretation of the voting question by the Advisory Committee regarding cardiomyopathy as an approvable endpoint more challenging. Today, Dr. McDonald will show data that those with DMD cardiomyopathy had sustained and statistically significant improvements in heart function as measured by left ventricular ejection fraction, which is the most important group to assess the benefits of deramiocel in treating the cardiac dysfunction associated with DMD. You will also see that the upper limb data continues to be strong and that there is the durability of effect. We are delighted that based on the strong support from the DMD community and the major unmet medical need, the FDA allowed us to submit a major amendment. The data submitted to the FDA and those data from the open-label extension recently presented at the World Muscle Society will be shown here today for you. Next slide, please. To remind you and for your review, the results from HOPE-3 were recently published in The Lancet, one of the top medical journals in the field. We will not focus on that data today except to provide the context I mentioned earlier. We are proud of the results from HOPE-3 and believe that The Lancet reviewers carefully assessed the data prior to accepting the manuscript. Please feel free to reach out to us at Capricor or any of the authors of the paper for further context around the HOPE-3 data should you have any questions after today's presentation. Next slide, please. To remind you, we have been looking at treating DMD for a long time now. What we take great comfort in is the consistency of the data across multiple clinical trials, as well as over 1,000 infusions over eight years. Each clinical trial from HOPE-2 onwards showed clinical relevance with at least a one point change in the Performance of the Upper Limb 2.0 in those treated with deramiocel compared to the placebo group or the natural history cohort. In a few minutes, Dr. McDonald will show you what a one-point change looks like, and many of you on this call can tell us what a one-point change feels like. Importantly, one key element of alignment with the FDA has been that a one-point change in the PUL 2.0 is clinically relevant. I would like to thank you for taking time out of your day to join us and hear about the new data from the open-label extension and also why we believe in the strength and the lack of fragility of the HOPE-3 data. Now, I will ask Dr. McDonald to present the new two-year open-label extension data from the HOPE-3 clinical trial. Thank you. Craig? Great. Thank you, Linda. I am really pleased to be able to present these updated data that really focus on longer-term treatment effects in the HOPE-3 trial participants. I will be discussing today an overview of the HOPE-3 open-label extension study, where patients were followed out for an additional year after the original randomized placebo-controlled clinical trial. We will discuss some HOPE-3 open-label extension skeletal muscle upper limb functional results, as well as some cardiac MRI results. We will also provide some update with regard to the open-label extension safety data as well. Next slide. Before I get into the data, what I would really like to emphasize is that a one-point change in the PUL 2.0, there is no question, has been determined to be clinically meaningful. The FDA has actually provided feedback to Capricor on a number of occasions, written feedback that they believed a one-point change in the PUL 2.0 was clinically meaningful and clinically relevant. In addition, I was actually quite pleased to see that the FDA actually, in their slide presentation, actually stated in their slides that they believe that a one-point change in the PUL 2.0 was clinically meaningful and clinically relevant. Just to illustrate this actually demonstrates on one of the functions of the PUL, the bringing hand to mouth function, which has been deemed by the DMD community to be one of the most important of functional issues related to quality of life in a non-ambulatory population, the ability to bring the hand to the mouth and feed oneself independently. On the left, if we could click this first image here. This patient actually is bringing the cup fully to the mouth without compensation. They actually have a 200 g weight in that cup. They are easily able to bring that cup to the mouth without any compensation. This would be scored as a score of two on the bringing hand to mouth function. If we go to the next slide, this is a patient with more advanced DMD. This patient actually is still able to bring the hand to the mouth, the cup to the mouth, but they do so with compensation. As you can see it here in this image, they have to lean forward quite a bit. They use their other extremity to help bring the arm up to the mouth. They would actually be scored as a one-point score on the bring hand to mouth function. The difference between the first image, the first video, and the second video is essentially a one-point change in the PUL 2.0 assessment, going from a score of two, normal ability, to a score of one, with difficulty and compensation. I think most of you will agree that the differences there are certainly clinically meaningful to a patient with Duchenne. If we can go to the next slide, I would like to, again, just bring people up to date with regard to the phase III open-label extension study design. Year one compared patients who were treated with deramiocel with placebo in a double-blind fashion. Essentially, these patients were followed for 12 months. They remained blinded to the treatment effect. The clinical investigators, the clinical evaluators, all remained blinded to that treatment effect. The placebo patients then essentially had a delayed start in beginning deramiocel. After 12 months, they actually transitioned to open-label extension treatment, where they were actually treated with deramiocel. The other patients that actually were originally treated with deramiocel continued on deramiocel. We can actually see the treatment effects over two years in the deramiocel-treated patients. In the original placebo patients, the delayed start patients, we can actually essentially look at the treatment effect with each individual patient, and the impact of treatment for that patient transitioning from placebo to deramiocel. There were actually 98 patients, 49 per group, that actually entered the second year of the study. 82 of those patients completed a full two years of study, 40 of the early treated patients and 42 delayed treatment patients. There were some patients that actually right around this time, there was an FDA approval, with accelerated approval, for instance, for gene therapy. Patients opted to transition to commercially available treatments such as gene therapy. But 82 patients actually completed a full two years of study. In addition, 85 of the patients actually had cardiac MRI obtained at month 12, 40 of the early treated patients, 45 of the delayed treatment patients. Then 69 of those patients went on to have MRI scans at month 24. 31 in the early treatment, and 38 of the delayed treatment patients had cardiac MRI studies at month 24. If we could advance to the next slide. I think an important consideration is what is the balance of the patients that actually were the early start patients versus the delayed start patients? The patients on average were 15 years of age at randomization. 84% of the patients were non-ambulatory in both groups, or not walking independently. If you look in the early start treatment patients versus the delayed start treatment patients, they are actually quite well balanced on age at randomization, 15.3 years versus 14.4 years. The age at DMD diagnosis was very similar. The percentages of patients who were non-ambulatory, 83.7% of deramiocel early start patients versus 83.7% of the placebo delayed start patients. Their PUL entry score, the proportion of patients that had PUL entry scores of two to three, were quite well balanced between the two groups. Also the proportion of patients that had PUL entry scores of four to six. Those scores would be patients that were able to reach up to the shoulder, to the scalp, or fully overhead. The proportions of the patients were very similar across the two groups. In fact, the total PUL 2.0 score was well balanced across the two groups. Importantly, there was a group of patients that had genetic mutations that were actually predicted to be slow progressors. Just one of the patients in the deramiocel early start group were in the slow progressor group. And five of the delayed start patients who were originally in the placebo were actually in that slow progressor group. So that distribution of slow progressors actually favored the placebo, at least in the first year of the trial. In terms of proportions of patients on standard of care, systemic oral corticosteroid treatment, 100% of the deramiocel treated patients, 98% of the placebo treated patients were on standard of care steroids. Next slide. Just to remind you, the HOPE-3 clinical trial actually did meet its primary pre-specified endpoint, which was a change in the PUL 2.0 total score. This study originally was actually when we expanded the cohort to a full 106 patients, the study was actually statistically powered to show a 1.1 point change difference in the PUL 2.0 score. The original powering of the study was actually based on the ability of the study to show a 1.1-point treatment effect on the PUL 2.0. There was some confusion, I think, in the AdCom over a 1.5-point change, but the study was actually statistically powered to show a 1.1-point change. In fact, in the pre-specified primary analysis, which was percent change from baseline, there was less decline in the treated patients versus placebo by 4.55%, a P value that was statistically significant using the pre-specified primary endpoint analysis. As a pre-specified sensitivity analysis that was submitted prior to the unblinding of the study, there was actually a sensitivity analysis based on the absolute change in the PUL 2.0. In fact, that absolute change actually was 1.1 points. So there was 1.1 point less decline in the treated patients versus the placebo patients. That P value also meant statistical significance, nominal statistical significance of 0.05. I think it's rather remarkable that the study was powered to show a 1.1-point change on the PUL. That was the original hypothesis of the study. Indeed, that's exactly what we showed in this phase III randomized placebo-controlled trial was a 1.1-point change on the PUL 2.0, which again, has been deemed by the FDA, as well as investigators in the field, to be clinically meaningful. If we go to the next slide. Before we advance, if we go back one slide, I want to just make the comment that even though both groups here appear to be declining, there's about a 57% slowing of the rate of decline in the deramiocel-treated patients, over a 50% slowing of disease progression in the deramiocel-treated patients. When you think about that, when you actually treat patients over many years, when you have a slowing in the rate of progression, there tends to be a cumulative effect over time. So the difference between the treated patients and the untreated natural history controls, or what would be expected in a Duchenne population, the actual magnitude of that treatment effect becomes greater as you follow patients out to two years and three years of time. If we could go to the next slide. This actually shows the HOPE-3 open-label extension results, really showing that the benefit really is associated with the treatment with deramiocel, and not just simply the passage of time. So if we look at the data first on the left, these are patients, actually the delayed start patients that were placebo in the first year. So the dotted line is that patient group's disease progression over the first year of the trial. The red line is that same group's treatment progression over the second year of the trial after they've started on deramiocel. The difference we actually see over a 12-month period of time is actually a 1.56-point difference. So they actually do much better. They have much less slowing in progression in the second year of treatment, which is when they start deramiocel, shown in red, as opposed to the placebo year, which is the dotted data shown there on the left. Interestingly, when you look at the patients treated with deramiocel over the two-year period of time, really comparing their disease progression in their first year of their treatment with deramiocel versus their disease progression in their second year treated with deramiocel, we see very similar slowing of rates of disease progression comparing their first year of treatment on deramiocel, shown in the dotted line, versus their second year treated with deramiocel. So the difference here at 12 months is really quite negligible. There's really no difference in their first-year disease progression versus their second-year disease progression. I want to point out here that the axes, the scales of these two graphs are actually different. There really is slowing of progression there seen in the deramiocel-treated patients. We see very similar data looking at the mid-level PUL data with essentially a 0.9-point treatment difference and a percent change value almost 7%, comparing their first year of treatment versus the second year of treatment. We're not only seeing a change in the open-label extension with deramiocel treatment on the total PUL, but also on the mid-level PUL as well, which has actually been chosen to be a primary endpoint in many emerging new Duchenne muscular dystrophy clinical trials looking at the non-ambulatory Duchenne population. If we could go to the next slide, please. Importantly, are these results really quite robust in terms of is this just a function of some peculiar features of the placebo-treated patients? What happens when we actually compare the long-term treatment effects with deramiocel, both on the delayed start patients shown in the solid red here, and the deramiocel treated patients shown in the solid blue, with natural history data, published natural history data that has been following patients with Duchenne over a full three-year period of time. That data is actually shown in the black dotted line there. This was actually data published by Capricor fairly recently in 2025. The predicted change over both a two-year period of time, and three-years period of time, it shows almost an eight-point decline in the Performance of the Upper Limb over 36 months, and a greater than five-point decline in the Performance of the Upper Limb over the two-year period of time. In addition, there has been recent prognostic modeling data that has been published and actually has been put together by the Analysis Group, a very sophisticated group of statisticians that have been doing a lot of work in Duchenne dystrophy. In addition, working with data from Erik Niks in Europe, where they've actually developed a prognostic model showing based on the initial baseline characteristics of each individual patient, what would their predicted 12-month and 24-month trajectory be with the Performance of the Upper Limb? That's the data shown in the dashed line there, the red dashed line and the blue dashed line. Essentially, if you take each patient's individual baseline characteristics, how severe they are, what their clinical characteristics are at baseline. In this case, we compare the solid blue line, which are the two-year deramiocel treated patients with the prognostic model for that group over two years. You get a -3.4 point decline in the deramiocel treatment, whereas you get a -5.88 point decline over a two-year period of time in the prognostic modeled patient. Similarly, in the delayed start patients, the solid red line there, I think which is really quite striking, is those placebo patients actually followed the published, and the predicted trajectories during the first year of treatment. Those lines almost completely are superimposed or overlapped. As soon as the delayed start treated patients start deramiocel, you can see in the red solid line there's almost a hockey stick phenomenon there, where the patients all of a sudden start to progress more slowly over time. You can really see the deramiocel treatment effect there as those patients transition from placebo treatment to their second year of treatment. Again, those patients compared with their prognostic model, it's not quite as robust a treatment effect as we see with the two-year deramiocel treated patients. But nonetheless, they have a -3.7 point decline versus the prognostic model of -5.3 points. That's with only one year of deramiocel treatment with the delayed start. I think the key takeaways here is these early start patients show a -3.4 point decline versus a 5.88 point decline after two years of deramiocel treated patients. The delayed start patients, again, are showing a -3.76 point decline versus the prognostic model, where there's a 5.35 point decline after switching at month 12. The decline slows once placebo patients start on deramiocel. These open-label model-based comparisons, as well as the comparisons with the published natural history data, are actually quite supportive of the randomized HOPE-3 clinical trial results. If we go to the next slide, I'd like to now turn our attention to the really important cardiac MRI data. While the BLA amendment has really switched the focus to the upper limb because there's really more robust upper limb data, I think it's still important to point out that we're still quite optimistic and quite excited about the treatment effects we're seeing with cardiomyopathy. Just to remind you, in the clinical trial, if we actually look at the patients that actually had impaired cardiac function when they entered the study, there were 64 patients out of the 106 patients in the clinical trial that actually had impaired cardiac MRIs and had evidence of cardiomyopathy. If you look at the deramiocel treated patients from the clinical trial, they had essentially complete stabilization of the progression of their cardiomyopathy over 12 months, whereas the placebo-treated patients declined as anticipated. That treatment effect is about 2.8%. The data that has been published by my cardiology colleagues, Dr. Sasso and his group in collaboration with Dr. Villa and others, has shown that about a 3% change in cardiac MRI is actually predictive of a significant improvement or a difference in long-term survival. This 2.8% change, although it seems modest, is actually clinically significant in terms of being predictive of survival. Statistically, this was statistically significant in the clinical trial. When you look at the overall population of all 106 treated patients, that looked at patients who actually had normal hearts at entry into the study, and you wouldn't have ever designed a study necessarily to show a cardiac treatment effect by including patients that already had normal hearts with a short-term trial over, say, just a 12-month period of time. So it wasn't surprising that we see a more robust treatment effect with the cardiomyopathy population. If we go to the next slide. Again, when we look at the open-label extension cardiac MRI data in both the ITT population, these are the patients, again, that included patients that did not have cardiomyopathy. We see a 1.8% predicted change or percent change in cardiac left ventricular ejection fraction. At month 12, there was a 2.4-point treatment effect. We are still seeing a 1.8% treatment effect there. If we go to the cardiomyopathy population, we are still seeing, again, a 2.7% change treatment effect on left ventricular ejection fraction over 12 months and a nearly 2% change over 24 months. Again, I think these data really do point to continued preservation long term out to 24 months of cardiac MRI left ventricular ejection fraction. It stayed near the baseline with patients on deramiocel, whereas the matched patients from the external natural history controls actually continued to show more significant decline over that 24-month period of time. Next slide. Again, to summarize the safety results, what this infusion actually involves because of concerns about hypersensitivity reactions. We treat patients with a single dose of oral prednisone and antihistamines, as essentially they take either one or two single administrations just prior to the infusion. H1 and H2 blockers to help prevent reactions. They usually get their deramiocel infusion over 60 minutes time, and then they are observed for about a two-hour period of time by the care team following the infusion. The long-term open-label extension data shows that the side effects were well-balanced between groups, mostly mild, short-lived, and manageable. The hypersensitivity reactions were generally mild to moderate reactions. Premedication with the high-dose oral steroids and the H1, H2 blockers largely reduced the severity and the occurrence of these hypersensitivity reactions. As we follow patients now in the HOPE-2 and HOPE-3 open-label extension trials out to a period as long as five years, we have seen no known long-term safety concerns with deramiocel, which I think is really important to point out. Next slide. With that, I would like to transition to Dr. Nathaniel Hogan in biostatistics from Capricor Therapeutics. Thank you, Dr. McDonald, and good morning or afternoon, wherever you may be. Over the next few slides, I will walk you through two pieces of work that we have delivered to the FDA after the Advisory Committee. The question behind both is pretty simple. Is the reported benefit of deramiocel real, or could it depend on how the analysis was planned and conducted? Next slide, please. We know the Advisory Committee left many of you with questions about our statistical choices, and we have heard that concern from families and clinicians. We take this very seriously, and our aim today is to show you exactly what we did and what we found. The word that came up most at the Advisory Committee was fragility, which is the worry that a result might rest on a few patients or one analysis decision. We responded with two deliverables. The first is a robustness report on HOPE-3 alone, which tests whether the primary result holds when the assumptions and choices behind it may change. The second is an integrated summary of efficacy, which pools HOPE-2 and HOPE-3, so we can look at the effect with more total patients in a single analysis. Let me take those two in order. As Dr. McDonald discussed earlier, the primary endpoint in HOPE-3 is the PUL 2.0. It's a validated score of upper limb function. Can a boy lift his arms, bring a cup to his mouth, use his hands, et cetera? Our pre-specified analysis showed deramiocel slowed the loss of that function, as Dr. McDonald mentioned, by about one point over a year. One point, as we've mentioned on this scale, is clinically meaningful and relevant. Next slide, please. Here's the key idea. The hallmark of a fragile result is a treatment effect that moves drastically when you change analysis decisions. Whether you swap the model, handle missing data, maybe the benefit shrinks materially or even disappears. So we tested the many choices and options in the HOPE-3 analysis to see if the treatment benefit disappears or even favors placebo. These analyses are agnostic to any statistical analysis plan. Instead, they explore all the different choices made when modeling the data to see if any of those choices display fragility. We ran more than 600 alternative analyses. We varied the model, the missing data approach, the patients included, and how progression is defined. Every dot on this chart, on this slide, represents one of those analysis results. The position left to right marks the magnitude of the treatment effect that the analysis results in. The size of the dot represents the number of analyses that produce the estimated treatment effect. You can see that the vast majority of analyses show a treatment benefit at or above one point, with none even approaching the zero line, which represents no benefit. In other words, HOPE-3 simply does not show the signature or hallmark of fragility. What that tells us is that the differences in P values presented by us and by the FDA at the Advisory Committee are more a result of disease heterogeneity and the sample size. They're not the result of an unstable or spurious treatment effect. The size of the benefit is stable, and a larger study would make these analysis choices less impactful on the P values. This is exactly what the integrated analysis that I'll show next lets us test by combining data from both HOPE-2 and HOPE-3. Next slide, please. HOPE-2 and HOPE-3 were both placebo-controlled trials of deramiocel and DMD with the same dosing, administration, and assessment, so they can be analyzed together. The table shows who contributes to each. 62 boys on deramiocel and 64 on placebo had PUL assessments. 45 versus 50 with evaluable cardiac MRIs, and 35 in both groups who already had cardiomyopathy at baseline. For a rare disease, this is a very meaningful sample. Next slide, please. This is the main pooled result of the PUL 2.0 total score. Blue is deramiocel and red is placebo, and the vertical axis is estimated change from baseline, so down means losing function or progression. Both groups decline, but at 12 months, patients on placebo have lost about two points, and those on deramiocel less than one. The difference is 1.29 points with a P value of 0.0087. Another way of saying that is if the drug did nothing, a gap this large would appear by chance less than once in 100 times. As a percentage of the score, deramiocel preserved about 5 percentage points more function with a P value near 0.005. This is the same effect size that we saw in HOPE-3, but now just with more patients and a clearer P value. That is precisely in line with the picture we just presented by the robustness analysis on HOPE-3. It is important to note we see similarly strong results in the mid-level PUL when pooling the two studies, which is also consistent with the HOPE-3 results. Next slide, please. Now, the same stress test on the pooled data, and this is where we address the Advisory Committee concerns one by one. Each row here is a pre-specified alternative to a question raised in the Committee. How to treat missing composite values, recomputing the slow progressor flag, a different correlation structure, keeping visits after prohibited therapy, and two conservative missing data assumptions that assume dropouts behave more like placebo patients. All of these are modeling or analysis decisions. In this forest plot, the dot and capped lines are the estimated benefit and accompanying 95% confidence intervals. Zero means no effect, and the dashed line at one signifies the clinically meaningful threshold. Every estimate, as you can see, of the treatment benefit lands between 1.1 and 1.3 points above the clinically meaningful threshold. As important, every P value is below 0.02. All eight analyses on the pooled data demonstrate an even more consistent treatment effect, supporting the benefit of deramiocel for treating skeletal impairment in DMD. Next slide, please. The last piece is cardiac function, which for most families we know matters a great deal. Left ventricular ejection fraction, or LVEF, is the share of blood the heart pumps with each beat, and in DMD it falls steadily, as shown by natural history, generally, like Dr. McDonald mentioned, about two to three points per year. The left plot shows the full population. In this population, deramiocel is essentially flat at 12 months, while placebo declines about two points. This results in an estimated difference of 2.2 percentage points with a P value of 0.05. Importantly, the sickest five patients, those with the lowest LVEF, were all randomized to deramiocel in HOPE-3, which makes this result even more striking. On the right, the trajectory of patients who already had cardiomyopathy at baseline is also displayed. The difference at month 12 is 3.1 points favoring deramiocel with a P value of 0.04. Again, natural history in non-ambulant DMD consistently shows decline of a couple points per year, so holding LVEF steady is a real change in their trajectory. Next slide, please. To sum it all up, we tested the HOPE-3 result more than 600 ways, and the effect did not materially move, which is the opposite behavior of a fragile result. Furthermore, we increased the sample by pooling with HOPE-2, and the same treatment effect appeared with an even stronger P-value, confirming the original uncertainty was not about the efficacy of the drug, but rather about sample size. This is a common concern in rare and heterogeneous diseases. We ran every sensitivity analysis that was a topic in the committee, and all eight agreed, confirming the benefit of deramiocel. The cardiac data point the same way. We wanted to put all that in front of you transparently. Now I'll turn the time back over to Linda. Thank you, Craig, Dr. McDonald. Thank you, Nathan. These are important data that we've made available. I know there's a lot of it, so happy to take some questions. Also please feel free to reach out individually and independently. I guess where I'd like to close is to extend our gratitude to the Duchenne community for signing up for the clinical trial, for showing up at meetings, for reaching out to the FDA, for continuing to be a voice of advocacy for yourselves, for the unmet medical need. For those of you that are in this later stage Duchenne population, I looked out at your faces when I presented at MDA. I looked at your families and your faces at the open public hearing, and I can tell you that we will continue to work as hard as we can to make deramiocel available to you should you and your physicians decide that would be part of your care paradigm. We also want to thank PPMD and all of the other organizations that have worked with us over these many years now as we continue to develop deramiocel. With that, I'll stop, and I will ask for questions, which we can hopefully answer and clarify for you. Yeah. No, thank you for the presentation. That was a lot of data, so we're going to, I think, walk back through some of it just to make sure everyone understands. But that was pretty robust. So if we could go back to maybe the baseline characteristics slide, there's a few I want to walk through real quickly. While we're doing that, though, Linda, on the webinar a few times was mentioned PUL versus the mid-level PUL, and just for families who maybe don't know what that is and the differences there, could you just talk about that and the significance of something- Yeah like the mid-level PUL? Yeah. I think for those of you that aren't aware, the Performance of the Upper Limb is a metric that was developed based on activities of daily living to assess upper limb function when ambulation or ambulatory tests cannot be performed adequately. It's broken into three domains, shoulder which is obviously your shoulder and starts with the ability to raise your arms above your head, as you just saw me do on camera. Mid, which is your arm, which would be representative of being able to move essentially your elbow function, and that would be eat 10 bites or being able to drink or do other tasks that involve your arm. And then wrist and hand, which are the fine motor movements that are controlled by your wrist and hands. The mid-level PUL is very important because it's considered to be a Goldilocks zone. Shoulder declines very rapidly, and sometimes it's hard to catch changes in. Wrists and hands, muscle function declines very slowly, so you need longer time to study it. Mid-level PUL with the arm changes are typically able to be caught at least in some version within a year, and are also really relevant to quality of life for reasons that Dr. McDonald mentioned. I hope that clarifies, Eric. Yeah, no, that's very helpful. Thank you. I wanted to start here because there was a question in the chat around number of patients that were not ambulatory, and so just wanted to make sure that they saw that it was around 84%. There was also a question around the age range of what the oldest patients in the study, or youngest and oldest. The youngest patient in the HOPE-3 study was 10 years of age. The youngest patients in the HOPE-2 study was nine years of age. Just to clarify here, I know Craig had mentioned it, but when we are talking about slow progressor as one of the characteristics, can we just define that really quickly for everyone? Craig or Nathan, I do not know which one of you would be better able to take on that slow progressor term definition. Maybe Craig, from a clinical perspective. Yeah. From a clinical perspective, that would essentially include genetic mutations that were predicted to be more associated with a slowly progressive disease course. For instance, there is literature on exon 44 skip amenable mutations. Some of those exon 44 skip amenable patients have very characteristic Duchenne-like progression. Some of them actually have a bit more slow progression. We did not want to exclude particular genetic mutations in the trial, but we did actually define some of those mutations as associated with slow progressor, and that defined this sort of slow progressor subgroup. We did not necessarily originally stratify based on that. We stratified based on PUL entry scores. I think that's another really important point to make with regard to the importance of looking at the primary endpoint, which is upper limb function. The whole study was powered and stratified really to show an effect on upper limb function, not necessarily cardiac MRI function. Essentially, if you look at the placebo group in the original trial, there were actually five patients in placebo that actually had mutations that were pre-specified to be associated with more slow disease progression. There was only one patient in the deramiocel treatment group. This would favor actually the placebo group over deramiocel, but even with that imbalance, five patients versus one patient, we still were able to show a statistically significant treatment effect in the randomized placebo-controlled trial with deramiocel treatment. Thanks, Craig. Yeah, that's really helpful. It might be the next slide. It's basically the first, the PUL data. Okay, maybe one more. Yeah, so here. I just wanted to make sure that families understood because I think this different way sometimes of some of the data being presented with the overlap here. On the left-hand side where you presented this data, just so they're aware, that first dotted line on the delayed start, those are the patients who were in the placebo group, so not receiving anything. We see that there's, roughly we'll say, that two-point decline. Then the red line is at that point, after the 12 months started on treatment, and then what was a more sharp decline slows to this, again, roughly 0.5 maybe. We're seeing a change in the rate of decline, essentially between those That's right. the year one when they're not treated and then when they are put on treatment. That's right. That's what we've seen consistently. I think my last slide, which don't go to because I think this is an important slide to stay on, shows that we consistently see slowing the rate of decline year over year over year. In some of the OLE patients from HOPE-2, we've seen that for five consistent years. Best way to look at this graph, and I know it's complicated, it's even hard for us sometimes, is to look at the left graph with the red line. As the same patients, red line is year one on placebo, dotted line is year two on deramiocel. No. Yes. Sorry. The opposite. Dotted line is year one on placebo. Red line is the placebo patients that have shifted over to treatment with deramiocel. What we can show using zero as the baseline is a delay in the rate of decline. On the right side, again, you're seeing the exact same paradigm, but these are patients that have had two years of deramiocel treatment. The most important thing is that the dotted line is their first year on deramiocel during the randomized portion of the trial, and the blue line is during the open-label extension on the second year of deramiocel. So those guys have two years of treatment, and what you can see is there's no difference in their response between year one and year two. So that's really important to acknowledge here, that there's really no difference in the treatment between year one and year two, with a significant delay in disease progression over both years. Yeah. So the rate of decline is staying consistent when on therapy, which, as Craig mentioned, the hope with something like this is, and we talk about this, we try to convey this to the regulators a lot from the community perspective, and I think, Craig, you did that nicely in terms of the cumulative effect, that if we can slow the disease, these things might drastically push out disease milestones, even though it's still a decline, but the rate of decline is changing, which is important. It is. Then if we go forward, maybe one more to the modeling, I just wanted to make sure families understood. So the black dotted line here is actual patient data from a natural history versus the dashed lines, which are modeled data. So, what was projected to be similar to the patients in the study. Yeah. Yeah. Go ahead, Craig. I could take this one. Yeah. I think the black dotted line is the published natural history data, which I think shows a linear decline occurring continually over three years. When you take natural history data like this, and what was done here is data from Eric Niks, who has a really robust data set, actually took that data, and then essentially what they did is they developed a prognostic model, for what an individual patient, what their trajectory or their progression would likely be over the course of 24 months based on their baseline characteristics, how strong they were at baseline, what their initial PUL score was, their PUL entry score, and other age-related factors and so forth. For each individual patient, you can actually get a projected disease decline or trajectory over the next 24 months, what each patient would be predicted to do over the next 24 months. The solid line data here is the HOPE-3 OLE data. The blue line is the patients on deramiocel for all two years of the follow-up. The red line, which is you see that hockey stick phenomenon where the patients slow their progression, are the placebo patients that had delayed start in their treatment. Rather than taking an external control population and try to cherry-pick out a group that would be so-called propensity matched to that group, a very non-biased way of looking at a treatment effect over a longer term open-label extension time is to apply a prognostic model to those patients that you follow for a long period of time. In this case, you can see pretty clearly that both the deramiocel two-year treated group and the delayed start group both have much slower rates of decline than the prognostic model shown in the dashed lines would predict them to experience. Thank you. This comes up a lot, I feel, in presentations where we, again, due to patient or population size, we have to do some of this work, and it is really helpful, but I think it can sometimes be a little bit confusing. I appreciate the unpacking of that. On the robustness analysis and the integrated summary of efficacy, just I guess for families, because we do not necessarily have this come up a lot as we go through the process of regulatory decisions and some of this. Just for maybe families understanding, is this something that is specifically asked of the agency for you to do, or is this something that as Capricor to try and address some of the concerns that were raised in the AdCom that you all undertook to present? Yeah. They didn't specifically ask for this. What we did was offer it, and then we submitted it. So it's been submitted to the FDA as part of the package for the major amendment to help them sort through the data that was presented as part of the original BLA. But they didn't specifically ask for it. We just gave it to them for additional clarity. Then some of the other questions we had come in. So there were questions around while you have the PDUFA date coming up in November, questions around plans for non-U.S. approval for deramiocel. Yeah. So, we are now starting to explore the rest of the world. We focused really hard on the United States. We're now going to be spending some time working to get this outside the United States, both to Europe and Japan, and the rest of the world. We look forward to that opportunity and to updating the community as those advances become available. Then you said it at the start of this, that as this submission, the label would be solely for the upper limb impairment, not related to the DMD cardiomyopathy. There was a question, though, if you're expecting the agency to further review the cardiac data along with the upper limb data with this submission. We certainly submitted it, and one of the points that we wanted to provide in clarity to the community and to the FDA is that, and I think I mentioned this in my introductory remarks, but it's really important, so I'll state again, the key secondary endpoint of the HOPE-3 trial was left ventricular ejection fraction, but it was in the intent to treat population, the entire population. If you look at those that already have diagnosed cardiomyopathy, which were two-thirds of those in HOPE-3, and continuing into the open-label extension, you actually see a really robust and clinically meaningful and statistically significant effect. As a result of that, we're hoping that the FDA will look favorably on that. We don't know. What we're focusing now is the primary efficacy endpoint, and the powering of the trial was on upper limb impairment, and we look forward to getting the label for that. Then we'll continue to pursue cardiomyopathy in the future. If you have a few more minutes, because I realize we hit 2:00 o'clock, there were a couple other questions. Of course. We're available. Okay. This first one was just around potential for deramiocel to be used in combination with other therapies other than the steroids which were included in the trial. Both from a would they work well with other treatments theoretically, and then is there any safety concern about potentially combining them with other approved Duchenne therapies? That is our goal. Our goal is that they will receive combination therapy. Deramiocel is specifically anti-fibrotic and immunomodulatory and should work well with both exon skippers, in which we have significant amount of experience with patients being on exon skippers and deramiocel. Then gene therapy which has more of a limited experience. I think there has been a few patients that have had both the gene therapy and then later in the course of the disease process received deramiocel. But there certainly should not be any safety effects. We have not seen any yet. Of course, we will keep track of that and monitor carefully for any safety concerns. Again, I think it is important to point out that treatment with deramiocel would not actually preclude a patient from future treatment with a gene therapy product. There would be nothing from a safety point of view that would make you ineligible for a gene therapy treatment. I think there have been gene therapy clinical trials that companies have run where they actually have had previous treatment with a cell therapy like deramiocel to be an exclusionary criteria. The main reason for that was just that they did not want patients in their trial that were treated with deramiocel at the same time that could perhaps have more slow progression that could make their study design problematic. But I think there is really nothing from a scientific or a safety point of view that would make a patient not be able to benefit from a future gene therapy. We certainly have had patients treated with both exon-skipping drugs as well as deramiocel. What is the frequency of administration again? The current paradigm is four infusions per year, so once every 12 weeks. There was a question on, so you had the lower limit of age in the study, but is there potential either from a labeling perspective, or would future studies have to be conducted of looking at deramiocel in younger patients, and is there potential for benefit in a younger cohort? Yeah, there's definitely a potential for benefit in the younger cohort, and our plan is to develop a clinical development program for deramiocel in the younger kids, of course post PDUFA, for this later stage non-ambulant group, for really which there is nothing approved specifically. So we're looking forward to providing an option for them should the FDA consider that a possibility, and then we'll move on to the younger kids in the near future. Great. Well, I thank you for staying on a little bit longer to answer some of those other questions that were there. Thank you everyone for joining us today. If you do have additional questions, please send them along to us. We'll try to pass them onto the Capricor team. The recording of this will be available on the website probably in the next week or so. I want to just thank everyone for joining us, and as any additional updates come ahead of the November date, we will be sure to share those with the community. Again, thank you. Thank you, all of you. Thank you, PPMD, and we look forward to providing more updates as they become available. Have a great rest of your week. Bye, guys. Thanks, everyone.