Capricor Therapeutics Inc Study result

In just a moment. For this webinar with Capricor Therapeutics, where they're going to be providing an overview of some of the new HOPE-3 two-year open-label extension data, and having an update ahead of the November PDUFA date. Just some general housekeeping: this meeting or webinar is being recorded, so if you have to step away, if you have someone that this would be relevant to, the recording should be up on the website in about a week's time. And at the end of today, we will have an open Q&A, so during the presentation, if you have questions, there's a Q&A box at the bottom of your screen. Please submit questions there. We will try to get through those and the ones that were submitted ahead of time as we can. So we're joined by a few members of the Capricor team, as well as Dr. Craig McDonald and Dr. Chad Villa today. So we'll hopefully be able to answer all of your questions. And I think with that, I'm going to hand it over to Linda Marbán to get us started.

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 Jeremiah Cell for the treatment of Duchenne muscular dystrophy, including our updates on our most recent data presented at the World Muscle Society and 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. Well, 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 Jeremiah Cell, 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 Jeremiah Cell 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, and those treated with Jeremiah Cell 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 Gilman and Anna Mayhew, published in 2025. We, however, we saw statistically significant and clinically meaningful improvement in absolute change from baseline and pulled 2.0. So no matter how you look at it, the data shows a benefit in sustaining upper limb function in those with advanced DMD. I don't have to reiterate this to you. But HOPE-3 represents one of the largest DMD data sets 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 power 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 9, which encompasses a large proportion of those with DMD. Next slide, please. Now, as I just mentioned, the new refined indication is treatment of upper limb impairment in those older than age 9.

Now, 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 data set 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 data set 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 pull 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 the statistical analysis plan version 1.1 that was never meant to be applied to the full data set. In addition, the key secondary endpoint of HOPE-3 was the left ventricular ejection fraction in the ITT population, ITT as 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. So 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 can't 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 most important which is the most important group to assess the benefits of Jeremiah Cell 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 FDA allowed us to submit a major amendment and the data submitted to 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. And so 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. And 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 1-point change in the performance of the upper limb 2.0 in those treated with Jeremiah Cell compared to the placebo group or the natural history cohort. In a few minutes, Dr. McDonald will show you what a 1-point change looks like and many of you on this call can tell us what a 1-point change feels like.

Importantly, one key element of alignment with the FDA has been that a 1-point change in the pull 2.0 is clinically relevant. I would like to take you 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.

And I'm really pleased to be able to present these updated data that really focus on longer-term treatment effects in the HOPE-3 trial participants. And I'll 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'll discuss some HOPE-3 open-label extension skeletal muscle upper limb functional results as well as the cardiac as some cardiac MRI results. And we'll also provide some update with regard to the open-label extension safety data as well. Next slide. And before I get into the data, what I'd really like to emphasize is that a 1-point change in the pull 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 1-point change in the pull 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 1-point change in the pull 2.0 was clinically meaningful and clinically relevant.

And just to illustrate this, this actually demonstrates on the one of the functions of the pull, the bringing hand-to-mouth function, which has been deemed by the DMD community to be one of the most important 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 can click this first image here, this patient actually is bringing their hand the cup fully to the mouth without compensation. They actually have a 200-gram weight in that cup. And they're easily able to bring that cup to the mouth without any compensation. And this would be scored as a score of 2 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. And so as you can see 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. So they would actually be scored as a 1-point score on the bringing hand-to-mouth function.

So the difference between the first image the first video and the second video is essentially a 1-point change in the pull 2.0 assessment going from a score of 2, normal ability to a score of 1 with difficulty in compensation. And I think most of you will agree that the difference is is there are certainly clinically meaningful to a patient with Duchenne. If we can go to the next slide, I'd like to again just bring people up to date with regard to the phase three open-label extension study design. So year one, compared patients who were treated with Jeremiah Cell with placebo in a double-blind fashion, so 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. And then the placebo patients then essentially had a delayed start in beginning Jeremiah Cell. So after 12 months, they actually transitioned to open-label extension treatment where they were actually treated with Jeremiah Cell. And then the other patients that actually were originally treated with Jeremiah Cell continued on Jeremiah Cell. So we can actually see the treatment effects over two years in the Jeremiah Cell 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 Jeremiah Cell. And so 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 the there was an FDA approval with accelerated approval for instance for gene therapy and some 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 and 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. So 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. And if you look in the early start treatment patients versus the delayed start treatment patients, they were 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 Jeremiah Cell early start patients versus 83.7% of the placebo delayed start patients. Their pull entry score the proportion of patients that had pull entry scores of 2 to 3 were quite well balanced between the two groups. And also the proportion of patients that had pull entry scores of 4 to 6. Those scores would be patients that were able to reach up to the shoulder or to the scalp or fully overhead. The proportions of the patients who were very similar across the two groups. And the in fact, the total pull 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 Jeremiah Cell 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 Jeremiah Cell treated patients, 98% of the placebo treated patients were on standard of care steroids. Next slide. So just to remind you, the hope three clinical trial actually did meet its primary pre-specified endpoint, which was a change in the pull 2.0 total score. This study originally was actually when we expanded the cohort to a full 106 patients. The study was actually powered statistically powered to show a 1.1 point change difference in the pull 2.0 score. So 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 pull 2.0. There was some confusion I think in the adcom over a 1.5 point change, but it actually was the study was actually statistically powered to show a 1.1 point change. And 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%.