Evaluating Capricor’s Cardiomyopathy Cell Therapy Deramiocel for DMD

Linda Marbán, PhD

Capricor Therapeutics' Deramiocel, a potentially-adjuvant allogeneic cardiosphere-derived cell therapy intended to treat Duchenne muscular dystrophy (DMD), has previously been evaluated in the HOPE-2 clinical trial (NCT03406780) and is currently being evaluated in HOPE-2’s ongoing open-label extension (OLE) study (HOPE-2-OLE; NCT04428476). Notably, a biolgics license application for the product is currently under review by the FDA.

At the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific conference, held March 16 to 19, in Dallas, Texas, data from HOPE-2-OLE were presented by Capricor. After the close of the conference, CGTLive® interviewed Linda Marbán, PhD, the CEO of Capricor Therapeutics, to learn more about the cell therapy and the clinical results that were announced.

CGTLive: What is Deramiocel?

Linda Marbán, PhD: Deramiocel is an allogeneic cell therapy product. It's primarily a stromal cell that's a rare population found within the heart that is isolated from explanted human hearts that can be used for transplants, but are not for technical reasons. This happens about 40% of the time. As a result of that, we will never have a supply chain issue in terms of accessing the master cell banks. From that, cells are cultured and grown out to a relevant dose of 150 million cells. Those cells are infused by simple intravenous delivery 4 times per year, and the results of that are improvement in skull and cardiac muscle function in DMD.

Deramiocel can be well-described by its antifibrotic and immunomodulatory properties. Let me explain to you briefly how deramiocel works. It's infused into the body, as I mentioned, using a simple intravenous procedure. It's typically lodged in the microvasculature of the lungs, which is not at all a safety concern because there are literally miles of these tiny vessels in the pulmonary beds. Once there, the cells release exosomes. Exosomes track to sites of injury, and they're primarily taken up by the macrophage, where they shift cells from a M1, which is an angry or inflammatory phenotype, to an towards an M2, which is a healing or less inflammatory phenotype. Those exosomes then additionally drive cellular behaviors that are antifibrotic in nature by knocking down collagen I and collagen III. All of those activities have been demonstrated in every lot of cells that are released and are required for our release and our potency criteria as part of our drug product profile.

Can you go over some of the key findings Capricor presented at MDA this year?

The most important clinical study that we've done thus far is the HOPE-2-OLE study because this has tracked the same group of young men with DMD now over 4 years, but the data that we showed at MDA was the 3-year data. So that means we have 3 years of continuous data collection on these boys and young men, and actually we've been tracking them for 5 years, because all of them were part of the initial HOPE-2 clinical study that was published in The Lancet.

What we were able to show are several important takeaway points. One, in this nonambulant patient population, for which very few options exist, we saw stabilization of skeletal muscle function to the point where disease progression was attenuated by 71%. That means a guy on deramiocel had a improvement in his function, or a delay in disease progression, that would be 71% greater than his nontreated colleague, or another guy with DMD. This could be measured by simple activities like hand-to-mouth activities—eating, drinking, combing your hair—some of the advocates like to say hugging your mother—anything that is related to using the upper portion of your body.

Let me also say, since this is a really important point, maintenance of upper limb function is directly correlated to the preservation of quality of life in these boys and young men. By the time most of them go off their feet, their legs are tired. They've been falling, they sometimes have had broken bones. Things have not gone smoothly for them as they ambulate. Once they sit in their chairs, they feel in control of the world again. Upper limb function—arms, hands, and sometimes shoulders—allow them to do these activities of daily living that maintain independence, such as using their phones, eating, drinking, etc.

We are providing a core opportunity for these guys on Deramiocel to maintain the things that really keep them emotionally in a better place. Most of the time people don't realize that while these boys are losing skeletal muscle function, which is visible to the world, what is really taking their lives eventually is the cardiac disease associated with Duchenne. As you know, the heart is a muscle. The muscle in the heart is just as rife with concerns regarding the lack of dystrophin as any other muscle cell. The slow, steady breakdown of cardiac muscle, which is not something we would be anticipating, leads to a fibro-fatty replacement that is leading to a heart that literally becomes like a bag of jello at the end of their lives. If we can slow the progression of the aggregation of the scar, we can slow the decline in cardiac function, and we can help preserve their lives. That's exactly what deramiocel has done. We have seen year over year improvement in cardiac function in these boys and young men, measured by MRI and measured by ejection fraction, which is as you know how the heart meets the needs of the body. Then we have measures of cardiac remodeling, such as volumes, which suggests that we are preserving or maintaining the shape of the heart, which allows normal function to occur. Now what becomes even more interesting in this data set is that as I mentioned we were able to compare it to a natural history data set. This is data that was collected by the Action Network, the Cardiac Consortium in Duchenne, and published in the journal Circulation, Heart Failure, by Jonathan H. Soslow, MD, MSCI, and his colleagues at Vanderbilt. We were then able to have something to benchmark against what's happening to the heart of these guys and normal progression of DMD, and compare that to deramiocel.

What we were able to see is that year over year, again, we are showing improvement in cardiac function compared to natural history. One could argue that the Performance of the Upper Limb or the North Star Ambulatory Assessment, or any of these others are volitional: you know you're getting a drug so you might perform better. You cannot wish your heart better. It just does what it does. And so the fact that we have this objective measure of MRI, both in our treated patients and in the natural history patients, and we see a 6.9% improvement over 24 months in our treated patients compared to the standard of care guys who are getting the best cardiac meds have to offer, as are our patients, we now have a really strong metric of improvement. Skeletal muscle function improvement and cardiac muscle function improvement leads to a really great opportunity with a very safe therapeutic in deramiocel.

This transcript has been edited for clarity.

Read more coverage of the 2025 MDA Conference here.

REFERENCE
1. Capricor Therapeutics Announces FDA Acceptance and Priority Review of its Biologics License Application for Deramiocel to Treat Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. March 4, 2025. Accessed April 28, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/305/capricor-therapeutics-announces-fda-acceptance-and-priority