Capricor Therapeutics, Inc. (CAPR) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and welcome to the Capricor HOPE-2 Trial 1-year Final Data Results Update Call. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to turn the conference over to our host, Mr. A.J. Bergmann, Capricor's Chief Financial Officer.

Thank you, and good morning. Before we start, I would like to state that we will be making certain forward-looking statements during today's presentation. These statements may include statements regarding, among other things, the efficacy, safety and intended utilization of our product candidates, our future R&D plans, including our anticipated conduct and timing of preclinical and clinical studies, our plans to present or report additional data, our plans regarding regulatory filings, potential regulatory developments involving our product candidate and/or possible uses of existing cash and investment resources. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the SEC, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, and we disclaim any obligation to update such statements. With that, I'll turn the call over to Linda Marbán, CEO.

Good morning, and thank you for joining us today as we share an update on the final results of our HOPE-2 clinical trial which investigated the use of CAP-1002 in patients with DMD. I am joined today by Dr. Craig McDonald, our National PI from the University of California, Davis, who will be presenting 1 of the 3 late-breaking abstracts in an oral presentation at the World Muscle Society today on the HOPE-2 clinical trial, highlighting the improvements in cardiac and skeletal muscle function in patients with later-stage DMD, primarily those who are non-ambulant. Shown here on the summary slide with an overview of Capricor and our current development programs. As you can see, we are developing 2 products CAP-1002, our cell therapy and the focus of today's call as well as an engineered exosome platform technology based on the concept that exosomes are nature's perfect delivery vehicles for biologics, primarily nucleic acids and proteins. But before I turn the call over to Dr. McDonald's, we are pleased to announce that the HOPE-2 data shows that we hit the primary efficacy end point of the performance of the upper limb, mid-level version 1.2 with a p-value of 0.01. There were also other endpoints in both skeletal and cardiac muscle function that achieved statistical significance. We are delighted with the success of the HOPE-2 clinical trial, but more importantly, on the clinical meaningfulness of the degree of improvement, which, as you will see, shows a 71% slowing in the decline in the function of the upper limb. This data sets the stage for HOPE-3 our planned Phase III pivotal study, which will commence once we have secured an agreement with an appropriate partner. For some additional context on the final data readout, I would remind you that originally, HOPE-2 was designed in an 84-patient double-blind, randomized, placebo-controlled clinical trial. However, we capped enrollment at 20 patients after an interim analysis at 6 months was already showing clinical relevance. As a result of the strength of this data, we had multiple meetings with FDA and in working with them and a committee of advisers we hired an independent statistical consulting firm to validate the HOPE-2 data as we pursued accelerated approval. In their analysis, the statistical firm found that the original statistical analysis plan was based on the proposed 84 patients, not on the 20 patients who received either CAP-1002 or placebo. Once they adjusted the model for sample size and performed the appropriate statistical analysis, they determined that the significance of the data went from p equals 0.08 to p equals 0.01, thus concluding that the trial hit its primary efficacy endpoint I want to point out that while the magnitude of the difference in raw performance of the upper limb or PUL score between the treated and the placebo patients has not changed from any of the previously reported data. The statistical analysis now demonstrate that the data is significant with a p-value of 0.01 for the PUL 1.2 mid-level. Simplifying this a bit more, in this analysis, there is a 1 in 100 probability of finding the result we found just by chance alone. Now I would like to provide additional clarity as to why these new statistical analyses were performed. The additional analyses were performed because the original statistical analysis plan for the 84 patients did not call for testing to see if the data was normally distributed, which, for reference, means that it is shaped like a traditional bell curve and is likely to occur more naturally with larger data sets. When the data is normally distributed or shaped like a bell curve, certain statistical tests are determined -- are performed to determine significance, but when the data is not normally distributed, other statistical tests have to be performed and those are called nonparametric statistics. When our statistical consultants originally looked at the HOPE-2 data, it became clear that the data was not normally distributed and therefore, required nonparametric statistical testing, the results of which you are seeing here today and reflects what we believe to be the most accurate representation of the effect of CAP-1002 in DMD. In addition to being presented at this prestigious scientific conference, The data is also currently under review at a major peer-reviewed journal. Now it is my pleasure to turn the call over to Dr. McDonald for a full presentation of the data.

Thank you, Linda, and good morning. I'm now on Slide 5. My name is Dr. Craig McDonald from the University of California, Davis, in Sacramento, the Capital City of California and I would like to thank Capricor Therapeutics and also the World Muscle Society and Congress organizers for giving me opportunity to present exciting late-breaking results of the Capricor HOPE-2 trial, which was a multicenter, randomized clinical trial of IV administration of human cardiosphere-derived cells for late stage Duchenne muscular dystrophy. Now on to slide 6. These are my financial disclosures related to this specific talk. Next slide. So CAP-1002 is a biologic consisting of allogeneic cardiosphere-derived cells or CDCs, which are manufactured from donated human heart muscle. The cells are infused intravenously and they do not act by stemness or engraftment in the host tissues, but rather these cells hone to the pulmonary vasculature with a secrete what are called exosomes or membrane-bound vesicles that are essentially nonimmunogenic. These exosomes contain microRNA, non-coated RNAs and proteins that are immunomodulatory and have other disease ameliorating properties on dystrophic muscle. CAP-1002 has been investigated in multiple independent clinical trials and has been used in more than 200 human subjects. Next slide. So the exosomes have been shown in preclinical animal models of dystrophinopathy to prevent muscle fiber loss, reduced stress caused by overproduction of reactive oxygen species and nitric oxide. They reduce inflammation, they improve mitochondrial function, they improve microvascular ischemia and reduce fibrosis. And these are actually targets of multiple therapeutics that are currently under development in the Duchenne space. Next slide. So the target population for this clinical trial was late ambulatory patients with impaired upper limb function and non-ambulatory patients with impaired overhead reach, but retained hand to mouth function. I think it's important to point out that this probably represents upwards of 60% or more of the entire Duchenne population. And these are patients that have often not been included in clinical trials historically as very few randomized trials have actually targeted this late ambulatory and non-ambulatory population of Duchenne muscular dystrophy, whereas there is just incredible burden of disease. Next slide. The primary efficacy endpoint was the mid-level Performance of Upper Limb version 1.2. And this was 1 of the first trials ever conducted in Duchenne muscular dystrophy to use both the Performance of Upper Limb or PUL versions 1.2 and the recently validated PUL 2.0 as clinical endpoints with the mid-level PUL 1.2 used as the prespecified primary endpoint. And again, the PUL 2.0 was -- had recently been validated, so we were able to incorporate this as an additional endpoint simultaneously measuring both the PUL version 1.2 and the PUL version 2.0 in this clinical trial. This endpoint actually focuses on shoulder dimension items, such as reaching above shoulder height and reaching overhead, use of upper limb weights, mid-level items, which often will require intact elbow function to be able to perform these items and then distal level items as well. Next slide. The inclusion criteria for the study included a PUL entry-item of 5, where the patient had impaired -- some degree of impaired overhead reach. And patients were included who had PUL entry scores down to a score of 2, where they had retained hand-to-mouth function. This excluded patients with full overhead reach who may not change in terms of their upper limb function over a 1-year clinical trial. And it also excluded those patients with only retained distal hand function due to floor effects of the measure. Next slide. Now the HOPE-2 clinical trial design. The design was a Phase II randomized, double-blind, placebo-controlled trial. 150 million cells were delivered intravenously every 3 months for the first 9 months, and the primary efficacy endpoint was assessed after 12 months. Nine sites in the United States participated in this multicenter clinical trial and a total of 20 subjects were enrolled. The mean age of the patients at baseline was 14.3 years. All patients were on corticosteroids and 80% of the patients were entirely non-ambulatory at the time of study entry. First, I'd like to present the safety results. A total of 69 infusions were completed and the investigational product was well tolerated throughout the study. with the exception of hypersensitivity reactions, which seem to be lessened by pretreatment with high-dose steroids, oral steroids and HT blockers, no safety signals were identified with the CAP-1002 product. Next slide. So now the efficacy data. In terms of the primary efficacy endpoint, the PUL 1.2 mid-level dimension was utilized. Here are the 12 months results for the prespecified primary endpoint, the mid-level PUL 1.2. The CAP-1002 patients are presented in the left in the blue line and the placebo patients are depicted in the orange line. As you can see, there is a divergence between placebo and CAP-1002 patients, which occurs fairly early on, and by month 12, there was a 71% slowing in the PUL 1.2 mid-level domain. And this actually translated to a treatment effect of 2.6 points in the CAP-1002-treated patients in comparison to the placebo treated patients at 12 months with a p-value of 0.01. So this was felt to be highly clinically meaningful in terms of what we know with regard to the PUL 1.2 mid-level domain. Next slide. Here, we present results of the PUL 1.2 combined total dimension score. This combines the elements of the shoulder dimension, the mid-level and the distal dimension. Similarly, there was a statistically significant preservation of the total PUL 1.2 score with 70% relative slowing, a 3.2 point relative improvement in total PUL score and a p-value here of 0.02. Again, 1 point change on the PUL 1.2 total score has been deemed to be clinically meaningful by academicians in this space. Next slide. What about the PUL 2.0 total score, which will be the primary endpoint in the HOPE-3 trial? Again, there was a statistically significant preservation of the total PUL 2.0 score was 70% relative slowing, a 1.8 point relative improvement in total PUL score and a p-value of 0.04, again showing relative preservation of upper limb function relative to placebo-treated patients. Next slide. Here, our forest plot data showing 95% confidence intervals of all dimensions of the Performance of Upper Limb versions 1.2 and 2.0 values to the right favor CAP-1002 treatment, the p values are shown on the right. And as can be seen here in the data both the total PUL 1.2 and the total PUL 2.0 showed statistically significant treatment effects. And in fact, all PUL dimensions were responsive to CAP-1002 and with the exception of the distal level items, which were well preserved in both groups, the placebo-treated group and the CAP-1002 treated group at baseline. Future studies will use the total PUL 2.0 as the primary efficacy endpoint. Next slide. What about cardiac function as determined by cardiac MRI evaluations. Impressively, left ventricular ejection fraction by cardiac MRI showed 107% relative slowing with a preservation of left ventricular ejection fraction by 4% relative to placebo with a p-value of 0.002. So again, the -- as you can see there, the CAP-1002 treated patients really maintain stable cardiac function over the course of the 12-month trial, whereas the placebo-treated patients declined in their left ventricular ejection fractions by 4%, and we had a highly statistically significant p value. Next slide. here are the forest plot data across all cardiac MRI parameters with the values to the right of midline favoring CAP-1002. So as you can see, really across virtually all cardiac measures of both cardiac structure and cardiac function by cardiac MRI, there was statistically significant treatment effects favoring CAP-1002 with the values of the left ventricular ejection fraction and the confidence interval for that shown at the very top of the forest plot graph here. The bottom value shows essentially a grand mean combining all cardiac measures, again highly statistically significant with a p-value of 0.007. Next slide. What about cardiac biomarkers? We evaluated the CK-MB fraction, which is a ratio of the creatine kinase-MB to the total creatine kinase percentage, which is a validated biomarker for cardiac injury. This biomarker showed a significant reduction in the CAP-1002-treated patients relative to placebo with a p-value of 0.02. So again, the cardiac biomarkers also showed evidence of a treatment effect favoring CAP-1002. So in conclusion, CAP-1002 cell therapy appears to be safe and effective in attenuating deterioration of upper limb and cardiac function in late-stage Duchenne muscular dystrophy, a population that has largely been neglected by clinical trials and have an incredible burden of disease. A therapy that stabilizes or reverses cardiac deterioration while also improving upper limb function would be unique in its ability to address synergistically the tremendous burden of disease seen in non-ambulatory Duchenne muscular dystrophy patients. Currently ongoing extension studies may confirm therapeutic durability and safety of CAP-1002 beyond 12 months in non-ambulant Duchenne muscular dystrophy patients. Hope 3, the Phase III pivotal study of CAP-1002 in Duchenne muscular dystrophy is currently in its planning stages, and we're very excited about that. Additional placebo-controlled trials will be needed to assess the benefit and risks of CAP-1002 in younger ambulatory patients. Thank you very much, and I'll now turn things over to Linda Marbán.

Thank you, Craig. As usual, it was a really terrific presentation of the data and the World Muscle Society I'm sure were equally excited by the data presentation. We submitted the data you have just seen to the FDA. And while FDA recognized the strength of the data as well as potential clinical significance in Duchenne muscular dystrophy, nonetheless, they felt that the sample size is too small to grant accelerated approval and so requested that we conduct an adequate and well-controlled Phase III clinical trial. I want to now provide a brief overview of our planned HOPE-3 pivotal trial and the next steps in this program. Our Phase III trial is designed to enroll approximately 65 to 75 patients and is also designed based on the data that was presented today. We are targeting enrollment at up to 20 U.S. based sites in order to enroll the study as quickly as possible. Based on the feedback from FDA, we will be using the full PUL version 2.0 as the primary efficacy endpoint, which to remind you, also achieved statistical significance as well as clinical relevance in the HOPE-2 clinical trial. We also have included a variety of other secondary cardiac and skeletal endpoint. Based on the strength of this data, we have been in active discussions with several potential partners, and our goal is to secure our partner before we commence enrollment. We are also working with Lonza, a global leader in cell manufacturing as we continue to move towards potential commercialization. I want to thank you for your time and attention today. And of course, finally, I want to especially thank the patients and their families for their participation in this study as well as all of the investigators specifically Dr. McDonald. We will now open up the line for questions.

[Operator Instructions] Our first question is coming from the line of Joe Pantginis with H.C. Wainwright.

Congratulations on the data. I think this is a very exciting and I don't know if you wanted to comment on this, but the fact that this is such a relatively small study and being able to show stat sig, I think, is quite promising. So I have a few questions, and it's nice to talk with you again, Dr. McDonald. First, just from a demographic standpoint, 20% of the patients were ambulatory. Just curious about the distribution of those patients with regard to active versus placebo?

Yes, the...

So..

Go ahead, Linda.

Go ahead, Craig.

Yes. So first of all, just to comment, these ambulatory patients that were included in this trial were specifically targeting late ambulatory -- the late ambulatory population that had 10-meter walk/run times of greater than 10 seconds. So these would be patients that would be destined to lose their ambulation very rapidly, virtually 100% of these patients lose ambulation altogether within 2 years. And they also are patients that begin to show impairments of the upper limb using instruments such as the PUL 1.2. So it was a relative -- a relatively small trial altogether and the ambulatory patients comprised 20% of the total population. They were well balanced. We didn't really see significant differences in the treatment effect among the ambulatory population versus the non-ambulatory population. There did seem to be a nonresponder patient that had, in retrospect, lost ambulation actually very early even though they were treated with steroids. So we're beginning to realize that there are probably patients with Duchenne that had very severe phenotype and very severe and rapidly aggressive disease progression that probably are not particularly responsive to steroids and perhaps are not patients that we would necessarily want to target for inclusion in a clinical trial. And in fact, I think looking at early loss of ambulation, say, ambulation before the age of 7 or 8 even while treated with steroids may end up being an exclusion criteria for many clinical trials moving forward. But I hope that answers your question.

No, it certainly does. That's great color. And then I guess my next couple of questions and thank you for your patience in advance, I guess, want to be quite patient specific or patient prospective basis. Obviously, there's a broad audience on this call and the data and charts are quite compelling. So I guess when you talk about a 1-point change being clinically meaningful based on feedback from the academic community, and you've shown a delta of 2.6 points. How does that really translate to the day-to-day life of these patients?

That's a great question. These PUL items actually [indiscernible] do correlate with the ability to improve activities of daily living, such as being able to brush the teeth, to feed oneself. And ultimately, what we find with the PUL is that the PUL is highly predictive of future loss of hand-to-mouth function, and that hand to mouth function has been determined by the patient advocacy groups to be highly clinically meaningful to Duchenne non-ambulatory patients. It's almost like loss of ambulation to the earlier younger ambulatory boys. The complete loss of hand-to-mouth function makes somebody all of a sudden dependent on others for feeding, scratching their nose, scratching their scalp or doing -- their hand to the scalp to be able to comb their hair or even to be able to brush their teeth independently. And so these are the types of functions that we're actually seeing in the extension phase that are actually seem to be being well maintained or even improving in the non-ambulatory patients. And I think the vast majority of patients have opted to continue on the extension phase and they actually seem to be pretty happy with the treatment of, at least, in our experience treating 8 patients of our center.

Got it. Got it. And in the slides and the data presentation, the data were presented essentially independently. But if I'm overreaching, please do let me know. But I would like to think that being able to maintain or reduce the degradation of PUL certainly could be linked to the cardiac results that you've seen here in maintaining ejection fraction, for example. So it's almost as if there's a positive 1-2 punch with regard to the mechanism of action here that if you can sustain the cardiac function that certainly should be able to contribute to PUL. And then with that in mind, this was over 12 months. So I was just curious about when you looked at the degradation of the cardiomyopathy in these patients, how did that translate to sort of the expectation of natural history on how quickly the cardiomyopathy could progress?

Well, we do know that the left ventricular ejection fraction will relentlessly progress and decline in Duchenne patients, a 55% value is a normal value. So you could imagine that if you're losing 4% per year, you're going to fairly rapidly move into that period where you're going to be below 40% or below 35% and really can start getting into trouble in terms of need for medications, even development of symptomatic heart failure in these patients. And we know that while we've been able to adequately prolong life with provision of noninvasive ventilation, patients with Duchenne still continue to die at a fairly young age due to the progression of their cardiac disease even in the setting of ventilating them with noninvasive ventilation. So I think that families and patients are very concerned about the progression of their cardiomyopathy even with treatment with cardiac medications and so forth. So I think this -- if you look at the data, and maybe we could even just queue up slide 18, A.J. But if you look at that treated patient, they're essentially stable, completely stable with regard to their left ventricular ejection fraction, which certainly is not anticipated by natural history, and the placebo-treated patients continue to have this decline, which is very characteristic in terms of the natural history data that we know where they lost essentially 4% on the ejection fraction over the course of the trial. But that was a great question.

Got it. And then my last question for you, it's just a logistical question and then 1 quick 1 for Linda, if you don't mind. Have you been monitoring or is there a potential based on these clinical results as with regard to durability and over time, to potentially reduce corticosteroid use?

That's a really good question. All these patients were treated with corticosteroids and they continue to be treated with corticosteroids. The side effects in the non-ambulatory population are pretty horrific in terms of weight gain and fracture risk and so forth. I'm -- I can't necessarily say that we're at a point where we could actually eliminate corticosteroids, maybe it may have a positive effect in terms of dosage required. We do -- we are seeing a lot of activity in the Duchenne space with regard to alternative corticosteroids regimens, and even use of designer corticosteroids. So I think in future, perhaps either a reduction in dose or perhaps either a shift to a less toxic form of a corticosteroid maybe we would likely anticipate with these patients.

Thank you very much for indulging me, Dr. McDonald. And Linda, very quickly, I was just curious, the cardiac component of CAP-1002 there that you're showing in the DMD patients, obviously, has been building in a positive sense over time. How has your -- how have your discussions with the FDA evolved over time with regard to placing more importance on the cardiac measures, even though the primary endpoint is PUL 2.0?

Yes. So that's been a really interesting conversation. So while the reviewers at FDA are intrigued and very positive about the cardiac implications of the data. And I think because we've done so much work on the mechanism of action of CAP-1002, which we have shared with FDA, they're very comfortable with the idea that the cells via their exosomes are actually addressing issues both in cardiac and skeletal muscles. So I think they really are looking forward to seeing the development of that program. We did decide to stick with the primary as the Performance of the Upper Limb 2.0 because the mountain that 1 has to climb to get a therapeutic or drug approved by the FDA in cardiac, it is just still so draconian. They really haven't caught up with the times, and they look for mortality-based endpoints. And of course, in a clinical trial paradigm, that is very hard to achieve. So we have decided to focus the primary and the Performance of Upper Limb as clinically relevant data and now 2 clinical trials and ones that have direct impact on the function of the boys and young men with DMD. It's a really great target. And then we got the added sort of 1-2 punch of the cardiac benefit, which could extend the quantity as well as the quality of their lives. And I'll just add 1 more point there. One of our advisers, Dr. Lee Sweeney, who is very well known in the Duchenne space, has often said that if gene therapy is ever successful long term in the DMD population, they're going to need their hearts to be stronger and better functioning even more than they do now as they are relatively sedentary. So we're very excited about the opportunity to work with all the other players in the space as CAP-1002 will be adjunctive to any of the therapies out there.

Our next question is from the line of Dr. Mark Swaim with Torrey Hill Capital.

This is for Dr. McDonald or Linda, a wonderful data set. Nothing succeeds quite like success and I'm happy for you. I wanted to ask if you had a sense of timing of onset of effect of the cardiosphere after infusion. Is it different in these older patients with more advanced disease as compared with patients examined in other trials? Or does it take longer to begin working in them?

I think I'll try and take that question and -- go ahead, Craig. Go ahead.

Yes. I mean, my sense, both to look at the data in treating patients is we start to see some clinical effect even after the first dose, so over the first 3 months that after that first dose. And I think the data would support there even as a fairly early divergence in these patients, and they start to sort of subjectively report benefits. It seems like at least after that first infusion, if indeed, they were active treatment patients. Now that we have open label extension, we know they're getting the therapeutic and we've had them on sort of an off-treatment phase where I have seen continued deterioration in their upper limb function. And then all of a sudden, with that first infusion, you start to see reports of some benefits. So I think it seems to be a pretty rapid onset of clinical effect. Linda can you comment from your perspective?

Yes. It is always most important here is the clinical perspective. We do get feedback from families that they start to see [indiscernible] very soon after the first infused and sort of as a stabilization that continues with the repeated infusions. And that's very similar to what we saw in the original HOPE-2 clinical trial where within the first 6 weeks, we were already seeing improvement in the Performance of the Upper Limb that continued out to 3 months, and metered out over the next 9 months, which is why we decided to dose every 3 months. But the answer is that it begins to work very quickly. Thank you so much, Dr. Swaim.

That's gratifying to know. I have 1 other question, maybe more for Linda, but I'm curious, this recalls for speculation, but your cardiologic shrewdness in our conversations over time has always impressed me. And I wonder given that cardiac muscle and skeletal muscle are not the same thing histologically, do you think it's possible that were cardiosphere infusions to commence early enough in the course of Duchenne patients life that you could really possibly even avert the horrible cardiac outcome? Is that possible?

That's our goal over time. So we ended up treating originally and have continued our commitment to the later-stage patients, those that are primarily non-ambulant. Because when we first entered the space and wanted to examine the impact of CAP-1002 on the cardiomyopathy, these were the most needy patients. But our goal, of course, will be over the next few years to indication expand to the younger kids. And yes, our goal is to attenuate cardiomyopathy, so that they can maintain good cardiac function throughout their lives.

And I'm very happy to hear the data. Congratulations.

Next question is from the line of Alan Leong with BioWatch News.

Congratulations on the reanalyzed data. You caught my attention with the commentary on the placebo patients starting the extension trial phase. Just wanted to have it confirmed and also a little bit finer grain. You reported that when CAP-1002 introduced to them, there was a subjective relief. Let me just kind of take that a little further. Did you see the expected changes towards disease stabilization in the placebo patients or even improvements? Or do you see continuing greater separation between the groups during the extension results?

Yes. So we haven't done a full data analysis of the extension patients. What I can tell you is that everybody was off therapy for at least 9 months. And so all of them pretty much showed a decline as they were off the therapeutic. And we are seeing positive trends in terms of reports by patients and the extension phase. So we really don't know exactly what that data is going to look like. The 1-year data will be available in the first quarter of '22 for the extension study, and we'll be able to look at that a little more carefully then.

The data departs from a normal distribution, and you got much greater statistical significance. So there's a significant departure from the normal distribution. I realize that this is going to be a little bit speculative with the small data, but what distribution better describes the data?

Yes. So we're very lucky today to have Dr. Suzanne Hendrix of Pentara, the statistical consulting firm that did these analyses. And Suzanne, can you answer this question, please?

Yes, certainly. So when we look at the distribution of the patients from the 2 studies. In the placebo arm, we see distribution that's very close to normal. In the active arm, we see that all but 1 patient didn't decline hardly at all. They have negative 2 up to improvement and 1 person with a negative 10, which was the lowest score in the placebo arm. So essentially, what's happening is we have a nonresponder in the active arm that causes a huge skew tail with just that single person and the placebo group is normal. And if that person were taken out of the active arm we would also have normality there, but they're really just all piled up together between negative 2 and positive 1.

See a better way to handle the outlier.

Yes. Essentially, what happened was the outlier was having high, high influence, but it was really only a single individual. And so what Dr. McDonald said earlier about trying to understand why someone might be a nonresponder would be important, but the distribution is really a single outlier with a distribution that's all clustered around 0.

Your commentary is helpful. Congratulations. I look forward to the continuing journey.

At this time, I will turn the floor back to management for closing remarks.

Thank you for joining us today for this update on our HOPE-2 clinical program. Thank you, Dr. McDonald, for sharing your time so early in the morning, and congratulations on the World Muscle Society presentation. Thank you, Dr. Hendrix, not only for joining us this morning, very early, but also for your work with us, which has helped to define our program moving forward, and we look forward to a long collaboration with you. And again, I'd like to reiterate my thanks to the patients and to their families. And to all those out there who email me on a regular basis with children with DMD. We're working as hard as we can to get it to you. We look forward to providing you with further updates on this program we hope that you stay healthy and well during this challenging time globally. Thank you.

This concludes today's conference. You may disconnect your lines at this time, and thank you for your participation.