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

Welcome back to the next morning session of our second day of the 2026 Leerink Partners Global Healthcare Conference. I am Mani Foroohar, Senior Analyst Genetic Medicines. And for this session, I'll be hosting Gaurav Shah, CEO of Rocket Pharmaceuticals. Welcome to Miami.

Starting to like Miami. Good to see you, Mani.

It's not bad. All are welcome, [ bienvenidos ]. So before we dive into the details, I'm sure we'll talk data positioning. Let's talk about where your interactions are with the FDA, just to level set where in discussions you are on Danon and where in discussions you are on PKP2 because you're engaged across a couple of different -- and then we'll talk across all day. You're engaged across a few different assets simultaneously with them.

Yes. Great question. So good to be here. Thank you to Leerink for having us back year after year. Before I answer, we are a gene therapy company focused mostly on rare cardiac assets. We also have a historical portfolio of lentiviral assets that are more ex vivo oriented and headed toward hematologic conditions such as Fanconi Anemia, LAD-I and PKD. We'll come back to that in a second. Getting straight to the answers on Danon and PKP2. So for Danon disease, we have not interacted on the clinical side since the clinical hold was lifted, at which time we agreed that we would treat 3 patients in a staggered fashion. We're going to do that -- we're going to start that the first half of this year. And at the end of that period, we would go back to the FDA to seek guidance on what the rest of the trial looks like. There's no indication that it would be any different from previously, but we -- that is a discussion that is pending once those 3 patients are treated. For PKP2, we've started a dialogue last year with the FDA at the end of our Phase I. And we got agreement that we have reached the right dose, the correct dose. We are in the process of putting together a study design and discussing it with them. We hope to have some clarity on that this year. So yes, both are in progress. And as far as we know, they're progressing pretty well.

Okay. And with that table setting, let's see. We'll start with the -- let's start with Danon. How should we think about the tempo of communications in terms of dosing 3 patients? When you -- we should expect you guys to be back in touch with the FDA and CIRCA and giving us disclosure around the path forward once you have that data in hand and what that means on the path to pivotal and approval?

So we plan to do a program update for Danon disease that hopefully includes a safety information. Hopefully, there's clearance there. Along with that, we've been talking for a while about an overall epidemiology update that's both top-down and bottom-up. Top-down, we've made a lot of progress in thinking about the cardiomyopathy genetic frequency models and applying them to Danon. We'll be able to talk about that. We've also been out there not in a big commercial setting way yet, but finding patients one by one and we'll be able to marry those 2 streams together along with the safety update and hopefully some FDA guidance in the path forward second half of this year.

That's helpful. While we're doing our sort of around the horn, let's hop over to PKP2 before we dive into individual programs. You guys are engaging with the FDA on potential regulatory path to approval. You're definitely carving a path through the jungle for a number of other companies. You're going to be first to go to the FDA. Talk to us about how you think about what are endpoints that really matter, both from a clinical outcome perspective for patients, but also on something that has a little bit of statistical meat that you can have a regulatory review and discussion. And those 2 things I know are not always the same thing.

It's a great question, and it's a question that many of us are trying to answer. Danon disease, by the way, was a one-off. It was one of the most aggressive cardiomyopathies out there in boys, especially these boys progress rapidly in the course of 1 or 2 years, you can see differences that are clearly well differentiated from a natural history of what happens to patients if they are not treated. Therefore, we were able to design a single-arm trial that was pretty small in size with a potential large benefit, magnitude of benefit, right? I think all the other cardiomyopathies are not going to be like this. They're going to be a little more complicated. There will be potentially more than one endpoint. In Danon, we had LV mass index. I anticipate in PKP2, we would have some combination of arrhythmias, right ventricular function and size and potentially clinical outcomes. I think also, I can't guarantee that we will have a single-arm trial in PKP2 because the natural history of PKP2 is more heterogeneous than what we've seen in Danon disease, for example. Therefore, the jury is out. There are many possibilities here, including a single-arm trial, including an observational crossover and other designs as well. As far as endpoints, people have talked a lot about PVCs, NSVTs and other arrhythmias. I think that cannot be the only endpoint here. I think it will be a combination of one of those types of endpoints, potentially protein expression and potentially even a third composite that might include something around right ventricular function because that's the ultimate marker of progression of disease in PKP2. So I'm laying out the buckets of endpoints without committing to anyone only because we haven't had that dialogue yet.

And remind me, what's the time horizon in which we should expect to hear back?

For PKP2 regulatory clarity, I would say we anticipate an update this year, 2026.

Great. I want to stay here before we hop over to legacy lenti programs. I think one of the conversations we've had, we've had a couple of your -- a couple of other companies looking at these patients. Obviously, PKP2 is a hot target. There's the question of where along the funnel you're supposed to be studying and then treating patients between people who have a genotype and then those who have a phenotype given variable preference was further down the funnel and then further down the funnel, those with meaningful symptoms, those an ICD, those with frequent shocks, you can cut the pie pretty thinly in terms of once you get to very severe patients. At what point where in that funnel should we be dosing patients in a pivotal trial? And what does that mean for who gets gene therapy out in the real physical world of commercial therapies?

Yes. This is always the conundrum in drug development. The highest magnitude of benefit is going to come in patients who are moderately progressed. Now how you define that could -- so that the other side of that conundrum is that how you define that moderately progressed patient could be wide, could be narrow, could narrow your label, could narrow your addressable market, right? So that is the question that we seek to address this year. I would say that without committing to a specific population, PKP2, like Danon, like BAG3, like Fanconi Anemia, you have to find that Goldilocks zone where patients are progressed enough to show real benefit and have a positive trial, but also not so far progressed that they have too much fibrosis or there's a point of no return, right? So that is a zone. It's a great question, Mani. That's what we're figuring out. But it's probably a combination of arrhythmias as well as right for function. There's a moderate zone there that we're going to be targeting.

That makes sense to me. So let's talk about -- I'm going to hop over to the lenti side of the house, if that's okay. So one way or another, we have some clarity on Priority Review Vouchers for approval for pediatric diseases, which give some more clarity and an alternative source of financing for companies that's not dilutive to ownership. That increases the financial benefit of unwinding from your current CRL on the lenti side. Let's talk about the path to getting out from underneath CRL and the path to commercialization, what that means in terms of for you guys financially, balance sheet-wise, but also just in terms of becoming commercial on the lenti side.

So we're -- our PDUFA date for KRESLADI LAD-I is March '28. So we're in a quiet period, I would say. It's tough to talk too much on the actual interactions there. We do think that LAD-I in our trial, we've demonstrated pretty robust -- as robust as possible clinical benefit with 100% survival in the Kaplan-Meier curve and all patients is doing well at an age that they probably would not be doing well. So we feel good about the file, but I can't discuss more at the moment. We will plan to put KRESLADI up for commercial readiness and have accessibility for patients as soon as possible. I think that, that is, first of all, part of the agreement for PRVs that you have to have products be commercially ready. We also believe that the infrastructure and muscle memory that we will develop in the KRESLADI commercial readiness efforts, payer discussions, reimbursement discussions, qualified treatment center discussions, getting a team that's up and ready, thinking about branding for these gene therapies, all of that muscle memory will read forward positively when we launch Danon and other programs. We are not putting a lot of commercial efforts into the lenti pipeline at the moment. We're funneling our resources fully to AAV once KRESLADI is launched. So that's the plan. That was a pivot point last year to reprioritize and focus the company. And I think now we've emerged in 2026 as a rare cardiac genetic enterprise that we're very proud of.

Perfect. Let's talk about as that transition is happening, let's talk a little bit about the state of the company as you sort of rightsize the headcount. Are there any further operational nuances that need to get worked out? Obviously, you have a new manufacturing facility in New Jersey, et cetera. Is there any additional restructuring or operational changes that need to happen? Or do we -- are we in a position to manufacture commercial scale AAV in New Jersey?

Yes. So we -- at this point, we have the right lean team of leadership team as well as leaders of functions and associates around the company. We have around 200 colleagues, we call themselves Rocketeers at Rocket. And we believe at this point, we have the infrastructure operationally to execute on both AAV manufacturing internally. We're also building a commercial force to be able to scale up to Dan and launch and other launches as well. So I would say we're in pretty good shape operationally at this point...

Perfect. As we think about the path forward commercially, I think there's been a lot of discussion independent of regulatory debates back and forth. I think an ocean of ink has been spilled, let's say, the FDA. I'm going to look past that for the moment. For Danon in particular, where are we in terms of quantifying the number of Danon patients that are diagnosed, those who are misdiagnosed given the complexity of the patient journey and scope the population, which I know has been a topic of a lot of debate because this is not a disease that's been historically -- it's not historically well understood like something agent like sickle cell. It's a relatively novel discovery in the modern era.

Yes. So to expand on your point, the Danon gene and clinical syndrome connection was made in 2001, right? So it's a newly understood disease. Awareness is relatively recent. The LAMP2 gene was not even on the cardiomyopathy panel until the mid-2010s. So there are a lot more cases of Danon out there than we know or that we've diagnosed. The ICD-10 code, for example, is something we just put together a couple of years ago. So over time, we're going to see the true frequency of Danon manifest in the real world, and we're just not going to see that until then. Now in terms of how we find those patients, I think that we have to look at both -- you mentioned earlier, a genotypic approach as well as a phenotypic approach. I think you applied it to PKP2. But for Danon, for male Danon, the genotype is mostly the phenotype. So that simplifies things because if you go out and look for LAMP2 and cardiomyopathy panels and their males, they're going to get Danon disease. The penetrance is almost 100%. In females, it's also almost 100%, but the manifestations might be softer or delayed. So the genotype and phenotype match in Danon disease, that's a very unique position of strength that we have as we unleash our medical affairs and genetic diagnostic efforts.

When we think about the opportunity in Danon, we talked about discovering new patients, getting LAMP2 into routine testing. How is that playing out OUS versus U.S.? The evolution and build of novel indications and novel markets can be pretty choppy globally. Talk about where we are in Europe, Japan and elsewhere.

Believe it or not, genetic testing, especially for cardiomyopathies is more widespread in Europe and especially Japan, actually. So in some ways, the physicians there have seen more Danon are more aware of Danon. We are opening up 3 European countries into our pivotal trial. And I think there are lessons to be learned from the European experience of diagnosing genetic cardiomyopathies to apply to the U.S. I think in the U.S. the last time that we've done a survey, only 10% to 20% of patients with cardiomyopathy ever get a genetic test for their cardiomyopathy. That needs to increase. And I think as that does increase, especially earlier in life, we'll be able to diagnose more Danon patients over time.

So I'm going to hop over and keep moving down the cardiac pipeline. Obviously, when you think about PKP2, if we can go back to the clinical data there, what's the right steroid prophylaxis for each of these indications. We'll start with PKP2, but you can run through the whole pipeline. And how do you determine what is the right prophylactic regimen, steroid complement inhibition, et cetera? Is it determined by dose? Is it determined by construct/vector? Sort of what have we learned because now that we've had experience across a few different indications, both at Rocket, a couple of other companies, like as a sector, what have we learned?

First of all, I would say that we have to remain humble. We thought we had cracked the code and we hadn't. So curiosity, humility are paramount as we move all these trials forward. There are lessons to apply across the cardiac indications, whether you're using AAV9 or Rh74 or another capsid. Our approach has to be -- has been to be moderately aggressive in prophylaxis, including pretreatment Rituxan, sirolimus and steroids with hopefully a rapid taper, that combination and eculizumab on a PRN on TAP ready if and when needed for complement activation. We've now canceled the C3 inhibitor approach for reasons that that you know, but primarily because it exacerbated endothelial damage and caused capillary leak syndrome in 2 patients. So we've removed the C3 inhibitor. We remain with rituximab, sirolimus and steroids for all of our indications, whether it's Danon, PKP2, BAG3, et cetera. That's been our approach. It's moderately aggressive. And I think the lessons on dose have more to do with making sure that the total viral capsid dose is capped at a certain point and you're not overdosing these patients with too much viral vector, which can overwhelm the complement system and liver system and others. Those 2 lessons were we had to learn in the clinic. Unfortunately, in the AAV world, there are not strong preclinical predictors or models of safety signals. There are good predictors of efficacy, but not safety. You just don't see complement activation or liver elevations in the same way that you do in the real world in real patients. So we have to learn in the clinic. I think we've learned a lot of lessons. There may be some more to learn. But I think that between the dose between the capsid and this moderately aggressive regimen, we feel pretty good about safety.

I think one of the conversations that I've had is around the importance of dose because we've seen a lot of safety issues across AAV driven by dose. And I found that there's a little bit of misunderstanding around dose versus how much empty capsid you have in terms of what you're actually putting into people. Can you talk to us a little bit about the state of your manufacturing process and where we are in terms of empty capsid rates across the portfolio, what that means in terms of potency and efficacy at any particular headline dose?

This is a hot topic. It has been for years. I think that the industry has applied learnings from the cell therapy world into gene therapy. And I'm not sure it was always well thought through. I'm not sure that a super high full empty ratio is necessarily better than a moderately high full empty ratio. I think we're learning that there might be some advantage to not having a perfect full empty ratio. The higher fulls, at least in Danon disease affect potency in a very big way and can affect safety when you have an enriched product. Now we've improved our full empty from Phase I to Phase II. In the Phase I, it was, I would say, moderately on the lower side, and now we're moderately on the higher side. I don't want to give exact numbers here. But I believe that we are in a pretty good place now that's acceptable to the FDA that allows for appropriate efficacy, better safety and long-term reduced cost of goods and more patients treated per batch as well. So I think we're in that balanced zone with the current full empty ratio.

So let's talk about that. I think there is -- the received wisdom and consensus right now is you should go for as much -- as high a full empty ratio as possible to drive your dose down as low as possible while delivering a defined number of viral genomes per target cell that's not deliver, assuming it's not the indication. That is sort of the state of consensus currently. Talk about specific data points that suggest that's not true and nuances that investors should keep in mind. I think that's about your programs, but also across the space.

So I think you have to look at each program disease by disease. It might be that in a certain indication with a certain capsid with a certain super high full empty ratio, you get that Goldilocks zone of efficacy safety combination. That could be. In our experience, I can tell you about Danon disease when we enriched the product from Phase I to Phase II with a much higher full empty ratio, we ended up with a more potent product. I would say that is specific to Danon because Danon disease is a disease of autophagy. Once you get certain complement factors and interleukins build up in the cell, it's hard to extrude them. So you create this positive cycle of feedback and you can exacerbate the complement activation just by having an enriched product, potentially also subject these patients endothelial damage. We saw that in Danon and what we did in the Phase II -- from the Phase I is we then corrected the total dose for the enriched higher full empty ratio by about 40%. So that's why the new dose is lower than the old dose. It's recalibrated. It's actually the same drug potency, but it looks like a lower calibrated dose, right, [ 3.8.0E13 ]. So that's the application to Danon. I suspect there are other diseases like that, where just blindly improving the full empty may backfire. I don't know what those diseases are, but one has to be careful. I think the current state of consensus is probably appropriate for some diseases and some vectors, but not others. You just can't compare apples to oranges. I would also caution since you asked about the general field and not just Rocket, I would caution against comparing dose for dose from company to company because the way that we measure doses, whether you use area under the curve or ELISA may differ. The FDA tries to standardize the guidance, but it might be different for different companies. So one company's 7E13 is not the same as another company 7E13. It's just not right to compare those. Capsids are different. The way we measure the vector is different, the full-empties are different. The regulatory elements in the vector are different. There's CPG islands might differ. There's a lot of differences. So you just can't compare across. And you have to interpret each program for what it is in the clinic. That would be my consensus statement.

That's helpful. And I think a great summary of a lot of the things that we've learned in the last few years. Let's talk about BAG3, which we always talk about a lot because it's earlier stage, an asset that you guys brought in as part of a small transaction a couple of years ago. All the focus on the late-stage pipeline tends to forget that. Talk to us about where we are in terms of data we have in hand and path to patients and sort of what the future is for that program and how it fits into your broader strategy?

So our preclinical models from BAG3, which we first looked at through the Renovacor acquisition, but we've done our own work in the last couple of years. This is a dilated cardiomyopathy, I come back to that in a second. In dilated cardiomyopathies, there's a more standard trodden path in terms of endpoint selection. You can look at ejection fraction. You can look at cardiac output, you can look at LV strain. There are other ways -- there are ways that are established and sort of paved before we came into this dilated cardiomyopathy space. So we feel that there could be a clinical path here that's more straightforward than something like PKP2. We're going to enter the clinic. The IND is cleared in mid-2026, a small 3 to 6-patient Phase I trial, standard dose escalation. The dose is based on the preclinical models as well as your experience in the other programs. We hope that even the first dose we start with like we did for Danon and PKP2 could be the final dose. That's the intent of the dosing strategy here. Now as far as endpoints, obviously, it's too early to talk about this. We're developing natural history. We're developing a deep understanding. I think one other advantage for BAG3 and why we're super excited about it as a potential hidden gem is that there's much less competition here. We do things the right way. We have a very strong ownership of IP in the U.S. for BAG3. And I would say that the -- this particular acquisition from Renovacor, we're especially proud of. We'll have more to talk about in the months and years to come.

Great. We're winding down to the end of time here. This was tremendously useful and looking forward to seeing more data throughout the year.

Thank you, Mani. Thank you.

Pleasure to have you.