Rocket Pharmaceuticals, Inc. (RCKT) Earnings Call Transcript & Summary

All right. Welcome, everyone. Thanks for joining in. This is Gavin Clark-Gartner from the Evercore ISI Biotech Research Team. Really happy to be here down in sunny Miami for the first day of our healthcare conference. And first up, we have the CEO of Rocket Pharma, Gaurav Shah. Thanks for joining us, Gaurav. I'm going to turn it over to you just for an overview of the company, where things stand today, then we'll get into it.

Thanks for having us, Gavin. Great to be down here and warmer weather in our midst. And so Rocket Pharma, we're a gene therapy company. We have 2 platforms. One is cardiovascular AAV-based therapies. One is Ex Vivo Lenti-Based therapy for hematology. We have 3 disclosed clinical programs in each with proof of concept in the clinic in most of these programs. The last one, BAG3 is just now entering the clinic now. So the 3 hematology programs that we started with included LAD-I, Fanconi Anemia, and Pyruvate Kinase Deficiency. And the 3 cardiovascular programs include Danon disease, PKP2 and BAG3. And our focus is increasingly going to be on the AAV portfolio given the high unmet need, the high patient numbers, the greatest opportunity for value creation there. So one thing we did this year was to pivot more and more toward the AAV programs as a way to be good stewards of capital, extend the cash runway and focus the resources in the company on the most high-value programs. We are in the midst of getting the Danon program started back up again after a safety event last year, and we're in the midst of getting PKP2 and BAG3 further in the clinic as well and very excited about the future.

Awesome. All right. So let's dive right into the AAV side. We'll start off on Danon since you just got the hold lifted, as you noted. Maybe just kind of walk through next steps, timing, cadence of dosing, all of that.

Yes. So the lifting of the hold was -- from a timing viewpoint, was really fast. It was really rapid, one of the most rapid that we've seen. Our focus really has been on structured benefit risk as we open the trial back up again. In terms of dosing, so we had dosed in the Phase II 6 total patients. The goal was 12. Two of these patients had a Capillary Leak Syndrome and associated edema that in one case, did lead to a patient death. So we paused the trial. We were on hold for 3 months. In restarting the trial, we removed the complement inhibitor, which, along with AAV9 was jointly responsible in our total analysis for the Capillary Leak Syndrome. So without the C3 inhibitors, that's 2 patients that we cannot count. So we anticipate likely replacing those 2 patients and still having at least a total of 12 patients treated. We will begin that trial in the first half of 2026, treat 3 patients in a staggered fashion 1 month apart, go to the FDA, get alignment on a full and confirm a path forward. We've heard no indication otherwise that it's anything other than what they've said in the past in terms of a single-arm, 12-patient trial and then move forward pretty rapidly in a non-staggered fashion once we're past the staggered phase. So all of that starts up in first half of '26.

Yes. Like thinking about gene therapies, just given kind of the logistics involved in dosing, I mean, think about the timelines. First half is a fairly broad window to start, and then there's a minimum 1 month, but it's probably hard to sequence exactly for that 1 month given all the start-up activities. So the kind of -- is this going to be rolling through to end of '26 into '27? Or do you think it could be done kind of quicker for the first 3 staggered patients?

Well, our target is first half '26 as fast as possible. We've identified these patients. Patients have not dropped out of the trial. So we have that group of patients that are still eligible. We do have to do a 3-month troponin run-in, which adds some complexity to it. And these patients, some of them also will need vaccines ahead of potential eculizumab. So there is some staggered time period that could extend beyond 1 month, but because the patients are already selected, we know who they are, we're going to try to make it as close to 1 month staggering as possible. Probably won't be perfect, but we'll try to be close.

Looking ahead then, as you're planning to give us the next updates for Danon kind of as you progress, I'm assuming you're not planning to give us updates patient by patient and you kind of look at some of the patients together. Would you plan to give us data at the end or wait for a regulatory meeting also and give that in one update? What are you thinking?

I would say we do the staggered safety run-in, get alignment with FDA. And as folks may recall, last year, when we were going to finish the trial, we were going to do a comprehensive trial and epidemiology and patient finding update as well. So we want to do all of that at once when we have real clarity on both the trial, where the patients are and the full market opportunity to be able to give some wholesome information to the Street at the same time at once.

And do you still have additional claims analyses that you have ongoing in the background or the commercial analysis?

Yes. It's a lot of work ongoing, both from the top-down perspective, really honing in on what the exact epidemiology is based on a variety of different sources and then the bottoms up, which I think is going to be the real setup for the commercial launch.

Great. What -- you mentioned this before. Like what gives you confidence that the FDA is still aligned on the 12-patient, single-arm study, and there's not going to be any changes to that?

So you never know. As we know, the FDA's viewpoints are in flux. And for Rare Pediatric Fatal Diseases, our opinion is that they're moving in a favorable direction in general. All of our interactions with them so far have not been derailing. They haven't questioned things that are in writing already and the agreements that we already have in writing have not been questioned to date. We try to interact frequently and transparently with the FDA. And when we do reference things like pivotal trial and study design, we haven't heard of any specific pushback, right? So every indication right now is that there's general ongoing support. We did design the Danon trial to be pretty robust in terms of stats and the assumptions because, as you know, patients who are not treated with gene therapy who have Danon disease progress pretty rapidly in 2 or 3 years, they're on a heart transplant list or unfortunately passed away, their heart grows pretty fast. And as the NEJM article showed last year, treated patients have the exact opposite trajectory with shrinking of heart size, they're starting to feel better and not just quality of life, but every single biomarker moves in the opposite direction in a positive way. So there's a wide gap between treated and untreated. So the design from an objective viewpoint makes a lot of sense. It continues to make sense. And that's why I don't think there's been pushback. But obviously, we need to pivot. We need to be agile. We need to be humble and we need to learn and listen from the FDA right now.

Yes. And on that point of kind of trial design statistics, I think you were planning to give an update this year on some of that -- those details. Is that planning to be with the next update on the clinical data, regulatory, commercial, all rolled together?

Yes. So all one big update is the plan after the patients are hopefully treated safely and we have the FDA path forward.

And now that I guess the dust has settled a little bit like after the safety events, what are you hearing from the community in terms of where they stand with adoption and if any of their perceptions have changed?

Yes. First of all, our commitment to the patients, the families, the patient advocacy groups, the Danon Foundation is unparalleled in the sense of how much we lean in and rely on them for -- to help us understand the disease and to help them educate us and us educate them when we need to update on trial issues, right, which we have been doing pretty regularly. And in the couple of weeks after this patient death happened, obviously, community was shocked. We were shocked. We went through a mourning phase there for sure. About 2 weeks later, though, we had a webinar with the full patient advocacy group, which included some of the family of the patients who have been treated. And there was almost unanimous understanding and ongoing enthusiasm for the trial, just understanding that this is a fatal disease. We are figuring things out. The reality is that there are no preclinical models that predict safety in AAV for Danon, really in almost all AAV. There's no preclinical models that predict safety. So we're going to have to learn from real live human beings with complex biology that just can't be replicated in preclinical models. And I think these families are brave, courageous, they understand that, and they've stood by our side as we've stood by theirs. So I think there's going to be enthusiasm as the trial opens up again. And if we can replicate some of the data that we saw in the Phase I, I think this community is really going to come behind the gene therapy. And also, there's no alternatives other than transplant. And transplant itself has a 50%, 10-year survival rate with risk of retransplant. And even transplanted patients who "do well" are feeble, frail and have very difficult quality of life. So I think that community is really waiting.

So let's move on from Danon here. Let's go over to PKP2. I guess one place to start, what's the timing of FDA discussions? When do you think you'll have an update on kind of the registrational path to market?

So we started that trial at a dose that we thought would be the final dose, and it is. And we do have FDA agreement that this can be the final dose. So we're in discussions about -- primarily about trial design, and we're open-minded about what that trial design could be. At the end of the day, what you want to do is have a design that wins, right? Not necessarily just the smallest design or the quickest path to market. You want the most robust trial that demonstrates unequivocal benefit risk to regulators and to payers. So that's our focus right now. It's going to take some time just like it did for Danon. PKP2 is a disease that progresses more slowly than Danon. You don't see the rapid changes in months like you do in untreated Danon patients. It takes some time. So we're going to have to be thoughtful and disciplined about how we approach that trial design.

Do you have the preference for what endpoint you would want to pursue? Understanding it's a collaborative discussion. I know you've kind of spoken about composites before because there's heterogeneity and some patients have different manifestations, like some patients have a more acute PBC involvement, there's QT inversions. So like what would you want to do if they were up to you?