Parent Project Muscular Dystrophy (CAPR) Earnings Call Transcript & Summary

All right. It looks like we have a good number of folks in here. So hello, everyone. Welcome, and thank you for joining us this afternoon for this webinar with Capricor Therapeutics. I'm Eric Camino, I'm PPMD's Vice President of Research. I'm joined from PPMD by Pat Furlong, our President and Founder. Joining us from Capricor, we have Linda Marban, who is the CEO. And during our question-and-answer portion, we will have Mark Awadalla, who is the VP of Clinical Operations; and A.J. Bergmann, who is the Chief Financial Officer. The webinar today is around Capricor's investigational product, CAP-1002 with some updates from their HOPE-2 open-label extension as well as their ongoing HOPE-3 pivotal investigational -- or pivotal Phase III trial. We will have an open Q&A at the end of the webinar. So if you have any questions that come up during the presentation, please put them in the chat box. We're going to try to get to as many of those questions we can in the Q&A. And then, we are recording this webinar. So, if you have friends or family who this would be relevant for, please direct them to PPMD's website. We will have this up likely in the next week, so they can go back through and see any of the material. So with that, we're going to get started, and I'm going to hand it off to Linda.

Good afternoon, good morning, wherever you are. Thank you, Eric and Pat for agreeing to host Capricor once again to give a webinar for an update to the Duchenne community about the progress of CAP-1002 in DMD. As you know, we are a publicly listed company, NASDAQ listed, CAPR is our symbol, and all of our filings are up-to-date with the SEC for your careful review. Shown today, we're going to be talking about a variety of topics, focusing primarily on our progress with FDA in getting CAP-1002 across the line to registration. I'll be giving an overview of the therapeutic, talk about our relationship with FDA and our recent alignment with them. Share a brief review of the clinical data, especially focusing on the open-label extension data, which I think profoundly shows the impact of CAP-1002 in slowing the progression of Duchenne. Then we'll talk a little bit about HOPE-3, and finally, our manufacturing paradigm, because I know many of you have questions regarding that. I'll go relatively quickly so that we leave plenty of time for the many questions and answers -- for your questions and my answers. Okay. So Capricor, who are we? What are we? What are we doing? We are currently based in San Diego, California. We moved there about 2 years ago from Los Angeles, although we remain in Los Angeles with a footprint for our manufacturing program. As many of you know, we have been working in the Duchenne space now for multiple years. So, we have multiple clinical trials showing the same basic data, which is the slowing of the disease process. We published our Phase 2 data in the Lancet. I've shared that data many times here and in other places, but it showed a 70% slowing of the disease process in terms of the disease of cardiac cell muscle function, and then 107% flowing or a 7% improvement in cardiac function. I'll show you some of that data. We are expanding our platform with our exosome technology. I won't be focusing on that today, but look for that to be coming in the future. And we have a variety of partnerships that have helped drive the company forward. And most importantly, we've strengthened our balance sheet, so we have plenty of capital to deliver upon our milestones. Let me just tell you briefly about CAP-1002. CAP-1002 is a cell therapy, but it is not a stem cell therapy, and I think that's really important to understand. What CAP-1002 does, and we have hundreds of papers literally describing everything from the discovery -- the eureka moment of discovery of what we now call CAP-1002, the science version, is the cardiosphere-derived cell or the CDC. What we understand is that these cells go in and they drive cellular repair. They help skeletal muscles regenerate themselves, driving cells back into what we call the cell cycle, which is cells making new ones up themselves. We have data showing that the exosomes that are released from CAP-1002 actually can penetrate into the satellite cells of skeletal muscle, driving them to recreate themselves, so helping to restore muscle function. The other part of CAP-1002, and I think is probably the most important part is that, it actually slows the inflammatory process. Now as you all know, with Duchenne, it is 2 sides of a very difficult coin. One is the lack of dystrophin, which is driving a lot of the damage that you see, muscle being broken down. But as muscles are broken down, that stimulates the immune system, which means that you have a lot of inflammation. One of the reasons why steroids have been so effective in delaying the disease process and even with all of their side effects, families choose to have their children on steroids for that reason. CAP-1002 is immunomodulatory. So it actually doesn't just work as anti-inflammatory, but we also see that it helps to drive the part of inflammation that drives repair processes. And that's really important to understand the difference between pure anti-inflammation, suppressing all inflammation, and immunomodulatory, which is suppressing bad inflammation, but encouraging sort of the good part of the process that drives repair. And finally, we have multiple disease designations with FDA that are important to drive the program forward, Orphan Drug designation, Rare Pediatric Disease Designation, which means we qualify for a coupon upon approval. And the most important is RMAT designation. Only 30% of those therapies that apply for RMAT designation get it. It is like breakthrough for cell and gene therapy, and it has allowed us a preferred access to FDA, as we have built CAP-1002 moving forward. So, one of the great things about CAP-1002 and why many of you are excited about it in the community, is that it's a really easy infusion protocol. Right now we're doing once a quarter, so every 3 months. It's a simple IV infusion. It's 150 million cells per dose. There is an oral premedication regimen that is required prior to the infusion. This is primarily to just suppress the body, sort of say, wait, you're putting extra cells of protein in me, and I don't know what that means. So it helps to fight off any allergic reaction that somebody might sustain. And because of our very strong scientific background, our stance on trying to reduce any type of safety issues, we're very proud to say that in over 140 infusions, we have no treatment-related SAEs, especially in the HOPE-2 open-label extension phase. So long-term infusion in our open-label extension patients and no treatment-related SAEs, which is a great success for us and also, of course, for you. So there's been a lot of questions about CAP-1002 and our path with FDA. And I know that's -- the main reason that I've been getting a lot of questions -- and I decided that we needed to do this webinar, because now they start with cohort A and cohort B, and what is cohort A and what is cohort B, and why aren't you going for accelerated. And so, I wanted to today use this as a foundational forum to address your questions. So number one, we are really glad to say that FDA has said that we can use the data from our Los Angelesbased manufacturing plant to apply for a BLA. This is the fastest direct path, and direct I mean full approval to get a BLA. This is a big win, and I'll explain why as I move forward. Cohort B is going to be happening and is starting very soon actually with manufactured product from our San Diego plant, and that is only necessary for expansion of commercial manufacturing. Now many of you know and I know the whole space has been following this, because even companies like Sarepta have been dealing with [indiscernible] switch facilities for manufacturing of a biologic. FDA usually wants clinical data from that facility for approval. Because of our strong safety and efficacy profile, FDA was willing to say they will give us the BLA from our clinical grade facility, our L.A. facility, and then only use the clinical data from cohort B to support that, and then we can have that facility that has larger-scale commercial manufacturing. Now many of you have been asking me, well, what about accelerated, what about accelerated. You almost have a fully enrolled cohort A, why aren't you taking the safe and efficacious products to FDA for accelerated like others in the space have done? Well, what we're saying, is that we are working directly with FDA. We're going to be showing them some of the data. We have shown them some of the data that I'm sharing with you today. And we believe that our clinical data supports accelerated approval. And certainly, we'll be pursuing that as aggressively as we can with the Food and Drug Administration. All right. So, now that I've given you the background, now let me take you through a little bit about why we're so excited about this opportunity for CAP-1002. This is a complicated slide. Many of you -- in fact, I would surmise to say most of you have seen this data before. And so, we put it together in sort of 1 slide, and I'll go through it a little bit slowly for you so that you have a sense of the success of CAP-1002 in DMD. We've done 4 clinical trials in Duchenne muscular dystrophy at this point, focusing primarily on the later-stage patients that are either non-ambulant or going towards becoming non-ambulant. We also are focusing hard on those that have the cardiomyopathy associated with Duchenne, because that is where we have seen also tremendous clinical, but of course 3 clinical benefits. HOPE-Duchenne was a randomized open-label study done at Cincinnati Children's Hospital. It was a one-time infusion of CAP-1002 into the coronary vessels, so like a stud being placed of 75 million cells. This was our primary study that drove our program forward and we learned so much from that program. One, we learned that not only did CAP-1002 work in the heart, which was what we expected, but it also worked in skeletal muscle, which our preclinical data had predicted, but nothing is as good as clinical data. We saw in our non-ambulant patient population there are improvements in the performance of the upper limb, specifically arm and hand, mid and distal. And in this one-time infusion where we studied the subjects over the course of 1 year, we saw the most improvement within the first 3 months. This drove us back to the bench to work on dosing studies, to work on safety studies, and we did all of those as required to move into HOPE-2, which became a randomized, double-blind, placebo-controlled trial. We had some HOPE-2 at 20 patients because of capital resource reasons. We fully believe that had we had the capital to be able to fully enroll HOPE-2 to the 84 patients we originally intended, it probably would have served as a registration study. Even with just the 20 subjects that we had in HOPE-2, we saw a remarkable improvement and enough good data to publish it in the Lancet. This study was our most important study in terms of defining dose and delivery, because we were able to, based on those bench studies, deliver cell 4 times a year. We were able to double the dose to 150 million cells because we were able to back that [ at ] the heart and use a simple IV infusion. Not going to spend a lot of time today in mechanism of action, but what we learned between HOPE-1 and HOPE-2 is that the mechanism of action of CAP-1002 is mediated by the exosomes released by the cells. Exosomes are tiny vesicles released by cells that carry nucleic acids and proteins that drive cellular behavior. And I can talk to you about that either in the questions or individually as questions arise, or please feel free to read our papers. What HOPE-2 showed is a 71% slowing of the disease process in terms of the mid-level performance of the upper limb, statistically significant, both in the 1.2 version of the performance of the upper limb, and then the full pole, the 2.0 version, which is our Phase 3 efficacy end point in HOPE-2 as well. And most importantly, we also showed improvement in left ventricular ejection fraction that is the gold standard measurement technique of how the heart meets the needs of the body. That was not only numerically very statistically significant, but we actually saw an improvement of ejection fraction, which as many of you know, does not happen naturally in Duchenne muscular dystrophy. Then we did the HOPE-2 open-label extension. We made CAP-1002 available to anybody from the original HOPE-2 study that wanted to participate. 13 originally took the offer. 1 patient withdrew early because he didn't want needles in his arms anymore. Some of you probably understand that. We then have 12 patients that are in the third year of open-label extension. Some of you have already entered into the fourth year of open-label extension, which really does great things for our long-term safety profile. And I'm going to show you a snippet of that data in a minute, so I won't spend too much time on that right now. And then finally, what we hoped to be will our last clinical trial before this is available, broadly an approved therapeutic, is HOPE-3, which is ongoing and almost fully enrolled. So, I want to spend just 1 minute sharing the open-label extension with you. Many of you know, I'm a scientist by background. And so, nothing speaks to me more loudly than data. We saw the HOPE-2 data, it was 20-patient study. This study, as I mentioned, was published in the Lancet. The data was extraordinary. But you always say small study, small numbers, what does that actually mean? And what we learned -- and the open-label extension, which I'm going to be showing you in a minute, is that CAP-1002 really does seem to reverse, or at least attenuate the progression of Duchenne. A boy that -- a young man that selected to be in the open-label extension study had to wait 1 year for treatment. That was largely, again, for the capital reasons by the time we could get the open-label extension started. Everybody, whether they had been in the original CAP-1002 group or in the placebo group had to wait about 1 year. And as I mentioned, they've been on it now for several years. I did show in [ total ] the data at the PPMD Annual Meeting this past summer. So I won't spend a lot of time on it. But I wanted to show you this data, and this is some of the data that we believe could potentially drive an accelerated pathway for CAP-1002. So what you see here is what happens to people when they are on CAP-1002. So this is just the open-label extension data at 24 months. The dark blue line that you see here are the subjects that were in the original CAP-1002 group, and the light blue line here are the original placebo group. Now shown for your reference is the HOPE-2 data of the placebo group. So the light blue and the red are the same people. And then the dotted line is what the progression was during the off time in the placebo patients. So you can see that there is a significant impact. It's a 64% attenuation, the progression of the disease in the placebo -- original placebo-treated patients and the CAP-1002 patients are stable too. So there's no difference in their disease progression over 24 months, whether you're original CAP-1002 patient or whether a placebo patient. Now all of you have probably seen that if you started with CAP-1002, you still ended up better 4 years later in total disease score, and I don't show that data today for maintaining revenue. But what I can say is that there's still a statistically significant difference in the placebo -- between the original placebo group and both groups that are on open-label extensions. So, we see a significant mathematically as well as a functional difference in those that are on CAP-1002. And then finally, this was also shown in June at the PPMD meeting, but I'll highlight here, and we do have a little bit of new data here, which is that we saw a 66% slowing of the disease process in left ventricular ejection fraction. Not all of the 12 patients were able to sustain an MRI. So we have 9 patients here. 6 patients improved in terms of their ejection fraction where we saw 3 patients declining. 2 of those may have been far enough along in the cardiac disease process that -- they may not have been able to be pulled back from here. And the third patient we're still watching very carefully. We're not sure that the measurement was entirely accurate. But shown here on this kind of yellow green line, which I think is fascinating data, is new data from Cincinnati Children Hospital. We did this study in conjunction with Chet Villa and the statistics team at Cincinnati Children. It's a natural [ HOPE-3 ] study of several thousand MRIs looking at left ventricular ejection fraction in Duchenne muscular dystrophy in a basically mass patient cohort. And what you see is that most people with Duchenne see a decline in their ejection fraction, and the average score is about 0.75% decline per year of life. So any improvement suggests a treatment effect. So, we are laser focusing on the cardiomyopathy associated with Duchenne. Of course, that's a secondary endpoint in the HOPE-3 clinical trial, which I'll talk about in a minute. And we look forward to be able to provide skeletal as well as cardiac muscle improvements with CAP-1002. So everybody says this now, it's becoming sort of the local expression for Duchenne [indiscernible] muscle. We've been saying it for a long time, people on CAP-1002 experienced a slower progression of the disease quite significantly, both mathematically and clinically. We're very anxious to get those of you that qualified for it on to CAP-1002 and then get it across the line for registration so more of you can be able to access CAP-1002. Because what we see from the open-label extension data is [ once ] drawn CAP-1002 disease attenuation is almost immediate, but there is no pulling back once the muscle group is lost. It's not recovered. Fibrotic tissue cannot be turned back into muscle. So there is an urgency to initiate therapy. The cardiac benefits has been shown in HOPE-2, I mean HOPE-2 OLE, and we look forward to continuing that trend and hopefully be able to provide the first approved actual therapy for the cardiomyopathy with Duchenne. And obviously, as I've mentioned, the safety profile is very strong with over 200 subjects treated to date and a very clean record. We see CAP-1002 as part of the treatment regimen for Duchenne muscular dystrophy, and I think many of you, physicians, families, advocates, are seeing it the same way. There will be obvious need for dystrophin-modifying therapeutics, gene therapy, exon skipping. There is going to be a continued need for steroids, although I think we all hope to be able to slow that down or wean off as we get other therapeutics approved because of the draconian side effects of steroids. But either way, because of the immunomodulatory implications of CAP-1002, the pro-regenerative opportunity provided making healthy new muscle, CAP-1002 can work in conjunction with these other therapies to be able to provide perhaps the best opportunity for the slowing of the disease process associated with Duchenne. I heard Eric Hoffman speak recently at a conference, and he said it most eloquently, as many of you know he can do -- he said the dystrophin mutation causes Duchenne muscular dystrophy, but actually most of the pathology is caused by inflammation and fibrosis. So, we have to be able to address the inflammatory and fibrotic pathways as well as work to improve dystrophin-modifying therapeutics. So keep that in mind, many opportunities for CAP-1002, they work along with other therapeutics. I just want to briefly review with you HOPE-3. We are still enrolling HOPE-3 both cohort A, which is nearly done, and cohort B, which is just getting started. It's a randomized double-blind placebo-controlled study. Cohort A is 58 patients. The primary efficacy end point is the one that you've just seen in HOPE-2, clinically and statistically significant. And HOPE-2 OLE, which is the performance of the upper limb, 2.0 at 12 months. The secondary endpoint are cardiac and quality of life. We have an interim analysis for futility coming up in the fourth quarter of 2023. We have high hopes that the therapy will not be futile based on all of the previous data that I've shown you, as I've mentioned several times. And I have to say, I'm incredibly excited looking forward to the completion of enrollment of cohort A in the fourth quarter of this year. And that means just a little more than 1 year away we will have top line data. And we're offering open-label extension for all participants in the HOPE-3 clinical trial. So please pay attention to that as an opportunity to get on this therapeutic faster. And so here are the sites that we currently have opened. There are 17 active trial sites. We hope to be adding a few more. We work primarily -- in fact, only with certified Duchenne care centers. Thank you PPMD for making those possible. It makes them fight for life for the work [ with ] and all of the structures are in place to deal with that, not only Duchenne patients, but clinical trials for Duchenne muscular dystrophy. The PIs are -- there needs to be sites that are mentioned here. Please feel free to reach out to either us or through some of these physicians and if you're interested in participating in cohort A or cohort B. So let's talk for a moment about cohort B. There's been a lot of questions. What is cohort B? Why cohort B? Why do you need a placebo group? What is happening? So as I mentioned, FDA usually approves or requires to approve a new site for biologic manufacturing by a clinical trial. That's how they validate that -- in fact, the therapeutic, the medication is working in the way that the original manufacturer product did. Because of our strong safety profile, because of our strong efficacy profile, FDA has said, okay, if we get approval on your small L.A. site, you can start to be able to treat patients from L.A. But if you want to go to your larger scale commercial manufacturing site in San Diego, which we built in order to meet market demand, you have to do a clinical trial to show that. They want a placebo group, and it's funny, because I've been asked many times, why can't you use the placebos from cohort A. We thought that too, but FDA wants a separate placebo group because the performance of the upper limb could have some volitional type of impact, which -- many of you with the disease will counter this and say that's not true. Talk to FDA about that. They believe that there's a volitional component. They want a placebo group for every treated group so that they can do a direct comparison of those that are in the trial to make sure that the clinical effect that we're seeing is, in fact -- are not based on trying harder, but in fact, based on a treatment effect of the medication. So that's okay. We'll be able to scale up our manufacturing from San Diego. Because of FDA working with us and because of our really devoted clinical team led by Mark Awadalla, we are able to go directly into cohort B. So cohort B will start enrolling very soon. Please look to sign up for it, because the faster we get enrolled, the faster that we can file this prior approval supplement. Of course, only FDA would call it prior approval. I like to call it post-approval supplement. After the BLA we could transfer San Diego and then be able to meet the market demand more efficiently. Pat and I have discussed multiple times, and I've discussed at the conference and with many of the subjects and their families, a couple of really important issues. One, can we infuse more frequently? We're going to look into that. Two, why not start earlier, why start with a later stage? we want to expand to younger patients as soon as we possibly can. There's other muscular dystrophies that have a similar pathophysiology. So, we're looking into expanding into those Becker, as well as some of the other muscular dystrophies that are not as severe as Duchenne, but definitely require therapeutic. And then, of course, other diseases of similar sorts with inflammation, and fibrosis being the key pathophysiological manifestations. And so look for us getting across the line with CAP-1002 for later stage, DMD and then expanding our opportunities. I'll close today and open the line for questions. I just want to summarize. We have strong, consistent and compelling clinical and safety data, Phase 1 study and Phase 2 study and open-label extension in Phase 2. We've shown data out to 24 months. Look for the 36-month data coming in the first or second quarter of 2024. Families are going into a fourth year of open-label extension. What I think is really interesting about the OLE study is the families are signing up for the infusion nearly on the day that they are qualified for their next dose, because they're already starting to see a drop-off in folks and want to get right back in there. So I think that's further validation of the efficacy. FDA is working directly with us. Please don't think that they are trying to block us. They're trying to help us. We have RMAT designation which gives us preferred access. We've already got multiple meetings with them this year, and we'll continue to meet with them to get this across the line. We manufacture our own products. We feel like we can do it better than anybody else. We've built an in-house manufacturing facility for commercial demand. We spent under $2 million on that facility, and it's in our footprint. Really just behind the wall that I'm -- of the office that I'm sitting in, and that allows for rapid expansion for commercial use. Nippon Shinyaku, all of you know about Viltepso, an approved product in the U.S. They are going to be doing marketing and distribution of CAP-1002. We take it all the way through approval and sell our product to them post-manufacture. So, we will make the products, make sure we validate its efficacy through our stock potency profile, that allows good financial support for us as we move through approval. It goes without saying that we are lucky to be working with all of the advocacy groups, primarily PPMD, the group that has worked with us, Pat, I think you were one of our very first advisors when we had just pre-clinical data. So thank you for all of your support. And we have a lot coming up. This is going to be a big year. '23 is going to finish and '24 is going to go very fast. So look for a lot of developments in CAP-1002 in DMD. I work directly with a lot of your -- the families, they e-mail me directly, I try and respond to each one individually. I feel your pain for your family and for yourself. I understand that upper limb function is really the predictor of quality of life. And I will do everything in my power and my team. All 100 Capricor people will work to get this therapeutic to your boys and to your families so that hopefully we can attenuate this disease. And it goes without saying that those of you that open your arms and open your hearts to clinical studies allow us to get these therapies tested and done, but it's a huge risk for you. So thank you so much for the trust you place on us. Mark's on the line. Please reach out to him directly if you have any questions. You'll find him really pleasant to deal with. And we'd love to finish enrollment in cohort A and get cohort A enrolled and cohort B fully enrolled as fast as possible. So thank you for that. And of course, we're on clinicaltrials.gov if you have any other questions regarding the clinical trial. And I will stop there and let you ask any questions that you might have. Again, PPMD, thank you for giving us this opportunity. Don't hold back on your questions. It's kind of a complicated story, so I'm happy to answer as best I can.

Linda, thank you for that. That was really amazing. And certainly, it is sometimes a very complicated story, and we all get mixed up on HOPE-1 and HOPE-2 and HOPE-3 and where we're going, but knowing where we're going is to cross line to approval. So, we have a few general questions, and then we'll get into specifics. So one of the questions -- one of the first questions we received was the fact that, if in the middle of a study that you're doing HOPE-3 at this moment, or -- because -- and HOPE-2 and 1 are on extended access, can -- and with the potential approval that we're going to see, I guess, tomorrow and the 26th with the [ more lone ], should there be -- a person in this study, can they switch from their prednisone dose? And keeping in mind the [ more lone ] will not be -- it's not approved tomorrow and then available the next day, probably it would be available in the first quarter of -- or the second quarter of '24, would they be allowed to switch from one to the other within the course and the context of the study?

Mark, will you take that question, please?

Yes. So from a steroid use perspective, as long as they stay on the same similar dosing as far as equivalency of the steroids, and they're both marketed products, yes, they can switch over.

But Mark, you're saying once it's approved, not within the course of the study, just to clear?

Yes. So when it's planned -- whatever steroid out there, has to be an approved product.

So -- and then there is a general question about anxiety, and I'm going to start it. Linda and Mark, and you can certainly chime in here. One of the questions was, is there increased anxiety during the study? And I'll say that anxiety is part and parcel of Duchenne muscular dystrophy and Becker and female carrier. So anxiety is prevalent throughout our community. I think that participating in any study would -- regardless of what it is, it increases the anxiety -- just enthusiasm, anxiety and all those emotions. And then certainly, finding veins on these young men is sometimes really a challenge. But I don't think, in my view that the technology here and the cells that you receive are part and parcel or increased anxiety to any degree. And Linda or Mark, if you want to comment on that, that would be great.

Mark, can you go ahead?

Yes. So, we have not seen treatment-emergent adverse events with regards to anxiety that is related to CAP-1002 to date. So it's -- we just have not seen that.

I appreciate that. I'd like to go back to Slide 16 on cohort B. There seems to be a good bit of confusion about cohort B, and let's sort of take questions one-by-one. So this is a placebo-controlled trial. What is it -- is it a 2:1 placebo? Or what's the ratio?

Yes. We did a 1:1, because -- I would keep the patient number as low as possible. So, we wanted to belt and [ bender ] it and built it for significance. We're hoping, of course, like anybody else, once you're approved, FDA will be a little bit more forgiving if it doesn't quite hit. So that's why it's powered a little bit lighter than cohort A, but they are requiring sort of a full bells and whistles clinical trial at this time.

And it will be a one-to-one -- and in terms of the clinical sites that you're choosing, will HOPE-B follow in the same clinical sites that HOPE-A is in? So those same sites will just morph into cohort B. Is that correct?

Yes.

So, I'll take this one. So yes, it's really important to understand that one of the wins with FDA was that they didn't ask us to wait for data from cohort A, which is often what they do to start cohort B. What they're allowing us to do is roll [ problem ] right from cohort A on Friday -- and days of the week are just exemplary, it's not necessarily Friday to Monday, but then Monday is our cohort B. And that allows us to maintain the same sites, the same infusion protocol. Everything is all the same. So families will get a good chance there.

And this is -- and you're opening more sites and when will you be able to talk about those sites that you're expanding to?

Mark?

Sorry, trying to get off mute. Yes. So we have 17 sites that are up and running. Those are all reflected in clinicaltrials.gov. There are an additional 3 sites that we are working to activate in the near -- there's an additional 3 sites that we're working to activate in the near future. And once they are activated and we can get through that activation process, they will also be listed on clinicaltrials.gov. So, we're targeting about 20 sites that are going to be enrolling into HOPE-3.

And Mark, just when you say you're trying to activate the sites, maybe just shed a little light on what activation means, what you have to go through? Because, as you might imagine, if some of these families have gone to a site that said, we are a candidate for a site, and then are not hearing anything or it's taking long, it just feels like -- what is the process? And is there -- are there ways -- as you might have mentioned, someone mentions where the site -- then you went to site open the next day, if possible. So that gets hard?

Yes. So bringing sites up and running is probably the most challenging thing in doing clinical research. It's a minimum of a 9-month process, and it's a lot of getting the right approvals from their IRBs and contractual executions being completed and various trainings that need to happen in order to be able to participate in the study, where it's trainings to complete the MRIs that we're looking for in a very specific fashion or trainings with regards to administering the pole 2.0, that is our primary endpoint. So there is a laundry list of things that are -- that need to be completed by the sites in order to them to be activated. For those 3 sites, we are in the final stages of getting them activated. So hopefully, we'll be at that 20 site list very soon -- very, very soon.

And one other question that -- in the antisense oligonucleotides studies where children were and are sometimes getting weekly infusions or with newer technologies, perhaps fewer -- less frequent infusions, we all know that it is often incredibly difficult to get into the veins of these young men, because they roll or they just aren't very visible and accessible. So have you thought about -- Linda and Mark, as you expand and now you're doing every 3-month infusions if -- at that rate or even more frequent, would you consider allowing a port or at least parents having the option of a port to deliver?

We haven't really [ approached ] that. That's actually the first time I've heard anything about this. It's certainly something that we'll talk about as we move on in time because, of course, we want them to be as comfortable as possible. There's also, obviously, risk support. So, we'll have to get the advice from the physicians on that one.

Yes. I think at least put it on the table as something to discuss as you move forward once you think about this in the next studies. One of the questions that I think is really relevant here in the world of gene therapies is, if you receive -- if you're a patient receiving CAP-1002 now or once it's over the line, does that prevent or exclude you from receiving any gene therapy product or participating in a gene therapy study?

From our perspective, no, of course.

So -- I mean I think from all of us, in our experience, it might be that if you're on CAP-1002 and lining up for a gene therapy protocol, you may need to wash out of that depending on the frequency of that. But if it's every 3 months, they may just -- it will depend on the physician. It will depend on the product you're accessing or the study you're accessing and the protocol that's involved. Jumping around a little, Linda, you talked about, in quarter 4 you're going to have interim results. Will you be -- we all like dates and times. We'd like to be very specific in this world we live in. You will be releasing those on an investor call, I'm certain. Would you consider another webinar to talk about those? And will that compel you or enable you to have a discussion with FDA about accelerated approval?

Yes. So first, going back to your gene therapy question before, Pat, I want to say that we've done pre-clinical work looking in animals, of course, with the microdystrophin-treated animal and CAP-1002, and we've seen no blocking of the impact of gene therapy. So that's why, from our perspective, they would be holding hands and good players in the sandbox together. In terms of the interim results, it's a futility analysis. FDA has really held our hands very closely on this one, because of -- again, there are concerns of any unblinding or evolutional impact to the performance of the upper limb. So it will be a pure futility analysis, so we won't have any efficacy data. However, what I can say is we'll have a fully enrolled cohort A. We'll have an actively enrolling cohort B. We'll have, hopefully, prevention of futility or suggesting that the study is not futile, and that certainly is a strong package to go to FDA with.

And maybe shed a little light on the futility -- the concept of futility here?

Yes. So in terms of futility, it basically means that placebo and -- would have to do better than CAP-1002 in terms of the opportunity there. So that's unlikely, but of course, we'll be excited to see that the study is not futile.

Well, it's not what you've seen, so it's not what you expect. Can I say that accurately?

Yes.

And the HOPE-B trial that you're going to recruit 44 patients in a one-to-one blind, can you tell us a little bit about those patients? Or is that the same in terms of the inclusion criteria as HOPE-A? And can you elaborate on that?

Yes, Mark, do you want to take that?

Yes. So the patient -- it's the same inclusion/exclusion criteria. So it's the same patient population as cohort A.