Rocket Pharmaceuticals, Inc. Common Stock Study update

Thanks, Mike, for having us. Great to be here. Big picture, Rocket Pharma is a gene therapy company. Our renewed and invigorated focus is on cardiovascular genetic medicines. We have three programs in the clinic. One hypertrophic, mostly cardiomyopathy called Danon disease, one arrhythmogenic cardiomyopathy called PKP2, and one dilated cardiomyopathy called BAG3. All are progressing rapidly. We also have a legacy pipeline of hematologic conditions. We just got an approval for severe LAD-I called KRESLADI earlier this year, for which we sold a PRV for $180 million. We're very proud of that. So at this point, we are an integrated company from discovery to commercialization from the beginning to end. Today is a very important day, and I'm very happy to announce here at Morgan Stanley that the FDA has now cleared our path to dosing the rest of the Danon trial.

We were previously on hold last year due to a safety issue, and we were asked to treat three patients with a modified immunomodulation regimen and a recalibrated dose. We treated those three patients safely. The therapy was well-tolerated, and the FDA has now given us a green light to move forward. Interestingly, the green light does not expand the trial at all. We'll continue with the 12-patient single-arm trial. We already treated three, so nine more. Everyone needs to be treated at the recalibrated dose with the revised immunomodulation regimen, which is what we wanted, actually. We anticipate moving that trial forward as soon as possible. This was definitely the upside because there could have been the possibility that the FDA asked for a larger trial, given the safety issues earlier.

Because the safety was so pristine, I believe that they allowed us to continue the trial exactly as it is. We expect to start treatment for the rest of the patients soon and complete dosing by mid-2027. Importantly, we will provide a comprehensive Danon disease program and general portfolio update on October 6th this year at 4:30 P.M. The other important point, very important point that I want to make is about our current cash position and runway. We remain well-capitalized. Our current runway extends into the second quarter of 2028. I also want to remind investors that Danon disease has pediatric designation, so it carries the potential of an additional PRV at approval, which is important when considering the program's overall funding in the future.

We also have an active ATM with Cantor, and honestly, several financing options available to us and a lot of flexibility given the cash runway to select the right capital at the right time. I wanted to make that point. Our focus, in the meanwhile, is really executing the Danon pivotal program and making future capital decisions at the time that they make the most sense.

Yeah. The original dose was 6.7 E13 vector genomes per kilogram. The recalibrated dose, and I don't say new dose, I say recalibrated dose, is 3.8 E13 vector genomes per kilogram. In Danon disease, because of impaired autophagy, we have very good evidence to believe that higher full empties actually lead to a more potent product for a variety of reasons. So having 40% or so more fulls, sorry, more fulls lead to more potent product. Having 40% more fulls, higher full empty ratio, leads to the 6.7 E13 product in phase II having been stronger than we thought, more potent than we thought. So we had to recalibrate it down to 3.8 E13, so the new 3.8 is the old 6.7.

We believe with FDA alignment and expert alignment that the new product in phase II is exactly the product that we treated patients in phase I. So that's the rationale for it. Also, two of the pediatric patients in the phase I trial had been treated at around four E13 with the old product, and even if this full empty calculation doesn't hold 100% true, those two patients did very well. In fact, they had the most profound reductions in LV mass index for at least three years. So we know that this range from about four E13 up to about one E14 is active, and we selected a dose that we believe is on the best side of the benefit risk profile.

Yeah. So we first had a regimen in phase I that was a combination of pretreatment rituximab over two cycles, pretreatment sirolimus and ongoing sirolimus for about a couple of months, and steroids with as rapid taper as possible. With the more potent product, we found a higher incidence of TMA than we were comfortable with. So what we did then is that we added a C3 inhibitor from Apellis. That C3 inhibitor was instituted about a year ago in two patients, and it worked for TMA. It did eradicate TMA, but unfortunately, it came with the paradoxical reaction of capillary leak syndrome for a variety of reasons we can talk about if you'd like. But when we saw the capillary leak syndrome, one of which case was fatal, we had to obviously remove the C3 inhibitor. It's not the C3 inhibitor itself, by the way.

It's the C3 plus the AAV, the torrential rain of AAV. The combination basically de-opsonizes the AAV that would've been opsonized with C3b, and the AAV then attacks endothelial cells. It's not something that we would've predicted, but it's what happened in the real world clinic. So we pulled out the C3 inhibitor, number one. We've now extended the rituximab to be given over three cycles, same total dose, but we believe the extended rituximab further eradicates B cells and prevents classical complement activation. We added eculizumab only as PRN, in other words, as needed, which we have not needed to use. You only use it if there's evidence of TMA, and we have the steroids with the rapid taper. That's the new regimen, and so far it's working very well.