Rocket Pharmaceuticals, Inc. ($RCKT)

All right. Good morning. Let's kick off our next session. It is my pleasure to introduce Gaurav Shah, CEO; and Meg Dodge, Head of IR from Rocket Pharmaceuticals. Welcome. Very exciting to be hosting you again this year. Before I have a lot of questions prepared, but before we get to that, I want to kick it off to Gaurav for opening remarks.

Rich, thanks for having us. It's great to be back. This is a very exciting year for Rocket Pharma. We are a gene therapy company. We are focused, laser-focused on cardiovascular genetic medicines, especially rare diseases where there's a high unmet need and where there are no alternative treatments other than heart transplant, which can be devastating in most cases. So our focus has shifted over the years. We started off as an ex vivo lentiviral-based company with three programs in the clinic, one of which got approved. We're very proud of the first CBER approval this year with KRESLADI for severe LAD-I, but we have since then shifted our resources, finances and focus to be a cardiac gene therapy company. This is an exciting year because while we're laying low and executing, there's a lot of things going on behind the scenes for all three clinical trials that are ongoing right now, one for Danon disease, which is primarily hypertrophic cardiomyopathy; second for PKP2 with -- sorry, which is an arrhythmogenic cardiomyopathy and third for BAG3, which is dilated cardiomyopathy. These three buckets represent three of the biggest buckets of genetic cardiomyopathies: hypertrophic, arrhythmogenic and dilated, and we're taking a big bite out of the apple in terms of finding potential cures to cardiac genetic diseases.

I see fantastic. So we hosted you guys last year at this conference. It was under a very different circumstance. You guys -- it was right after the clinical hold on Danon's, the pivotal study. And then you fast forward to today, a lot changed, right? You guys have the first FDA approval. The CRL was cleared, and you guys are up and running again with that -- with the pivotal study for Danon. And I believe the company is in a much better place given what happened and -- but the stock is still down 10% year-after-year. What is the market missing?

I think this is a show-me story. I think once we -- so we've got the CRL lifted, first of all, we had the clinical hold lifted last year. We got the KRESLADI approval. We got the Danon trial back up and running. We've started treating patients. And I think as we demonstrate more momentum and achievement of milestones, the cardiac gene therapy that Rocket is will come more and more into focus. I'm very confident about that. Several catalysts potentially coming up, including treating these patients with Danon disease safely with the revised regimen, number one. Number two, followed by a regulatory and a market update on Danon, I think the market is looking for those answers actively as we speak. Getting some clarity on the PKP2 pivotal trial design is an important part of expanding beyond Danon. And I think treating some BAG3 patients safely as well will put us back on the map in a very real way.

I see. Okay. That makes sense. I think there's a lot of derisking ahead for the company.

We're in the midst of that. So in addition to everything that Gaurav just mentioned, Rich, I'd also say that beginning in 2025, we made the announcement when we came out with earnings from the prior year. So when we announced our 10-K last year, we said that we're leaning into the cardiovascular genetic medicines company. However, Rocket's origin is -- has a legacy, and that just takes time. So I think that we're in the midst of demonstrating that. And so I wouldn't necessarily say that we are waiting to derisk other things. I think the stock price is -- showed that we're undervalued presently, but we're in the midst of reprioritizing everything that we've already stated that we would.

Yes. And each of these cardiomyopathies represents a potential $1 billion-plus revenue opportunity. So it's there to be unlocked over time.

Got it. Maybe step back a little bit. And how do you find like sort of the investor sentiment towards gene therapy as a class? I'm sure you guys talk to a lot of investors. And then what do you think are the views of just, not just Rocket but gene therapy? And what does it take for this class to, kind of, draw back interest?

Gene therapy is finding its place. It started as a very optimistic space, sort of a blue sky honeymoon period in the -- I would say, in the 2010s for the most part. We had a couple of pretty successful launches and revenue generation opportunities with AveXis and ELEVIDYS. So I think we've demonstrated that gene therapy has a market, it can work. It can be safe in patients with high unmet need and devastating diseases. Gene therapy is not for all diseases. And I think some of the pitfalls on efficacy and not demonstrating efficacy are seen where there's not a clear benefit of something like gene therapy. That's number one. Number two is we've had to overcome a lot of safety hurdles in the last few years. But I think the page is turning. And I think in this new era, developers are finding a safe path forward as I think we are for Danon. And secondly, they're applying gene therapy to diseases where it will actually work and people will take it and there is a market for it. So I think it's going to come back. It's not for everyone. It's not for all diseases. And I think the market is going to reward real drugs with real markets over time.

That makes sense. So there's a lot going on at Rocket at this point. I think you mentioned a couple of these assets. So what's the status for Danon, PKP2, the BAG3? What are some of the key readouts and milestones for the next 12 months?

Sure. So as Gaurav was mentioning, we've got a bunch of key activities for the remainder of 2026, including some type of update from the pivotal study, which we're in the midst of. We announced that in our May earnings. So with this Danon recalibration, we are also going to be giving a more broad program update later in 2026. So that's talking about a few things: one, the regulatory path forward for the Danon registrational study. Two is talking about what the statistical analysis plan is with the agency so that we can better spell out to the street, what to expect in terms of the BLA path forward, folding in an epidemiology update. So a refined way of how we at Rocket are thinking about the top-down, bottoms-up approach to the disease as well as the identified patient population. And for this study, it's focusing on males. We also will be giving an update on PKP2 in terms of announcing where we land with the agency with respect to what a pivotal study looks like for that program. In parallel, we've already announced that we're dosing a few additional patients in the Phase I because we've already disclosed that we found -- we believe that we found the efficacious dose. So that's the dose that we'll be moving forward with in the pivotal Phase II study. But announcing what it is that we've aligned on with the agency is another path forward, and that will really be a differentiator for that indication. And then thirdly is getting the BAG3 study up and going in the clinic and dosing patients there. So those are three catalytic things that we're looking forward to announcing to show our progress this year.

Got it. And then -- so in March, you guys received the first FDA approval for the company, KRESLADI. And that came along with the PRV and so forth. But since then, right, I think we're all waiting to hear about what's the commercial plan. I think you guys mentioned that potentially later this year, you would disclose what that looks like. What's taking so long?

So what's taking so long? We're in line with other ex vivo lenti launches in terms of when the drug was infused into patients. Usually, it takes 6 to 12 months in general. So we're in that range. Setting up the qualified treatment centers, setting up the payer discussions and reimbursement discussions. And really, the supply chain is very complicated here. It's much more complicated than AAV. So making sure that's pristine. We want to make sure that the patient experience is pure, clear and sort of easy to navigate for patients and families. So we're doing it the right way and trying not to rush it and especially because it's not a big market, we haven't put any much -- really any marketing dollars behind it. So we're doing it patiently, the right way, but it's in line with other launches as well.

I see. Okay. And then what's the status for the RP-L102 for Fanconi and then the 301 for PKD. I know back then, you guys put that you guys deprioritized or do a strategic review. What's the -- and I think you mentioned that you guys are exploring other options for how do you develop this potentially out-licensing it. What's the status for these programs?

So we're still in those discussions. And both -- especially Fanconi Anemia. Fanconi Anemia is a program that is near the end goal of being ready for BLA submission. The data have only matured and improved over time on the clinical side. So in the right hands, I think that this can get to patients soon. So we're exploring that. PKD is an earlier-stage program. When gene therapy works, it works. We demonstrated that early on, and hopefully, that sees the light of day for patients as well.

I see. Okay. Why not take Fanconi to the finish line, too, right? I mean there's -- I think there's a PRV that's also that we qualify for. Why not also take that one like you did for [indiscernible]?

You can only do so much. And so when we made the strategic corporate decision last year to reprioritize the pipeline to really demonstrate near- and medium-term value for patients and shareholders alike, you can only do so much and trying to progress six clinical programs at the same pace at the same degree of just perseverance, it can't really be done. And so we decided that the cardiovascular programs is what we were really going to pour all of our effort into. I like to use the analogy that our LV assets are, kind of, like building a custom house where we need to find the right buyer. So we can be patient with that. But as Gaurav said, the data for FA is only matured. And so in the right hands, there's true potential for that program.

Yes. And the cardiac programs are the highest value by far, by perhaps a log or so. And they're also easier to develop in terms of being in vivo. There's no ex vivo cell therapy component. It's just gene therapy. So therefore, the long-term cost of goods are lower, and we can control it in-house. So that's the story that we're building moving forward.

Right. Does it also make sense to license KRESLADI as well so you guys can focus on that cardiovascular?

Potentially, yes. Some of the -- some of my own mentors in the space in biopharma have said even in larger companies, companies need to focus on a few things and do them very, very well, and we're taking that seriously.

I see. Okay. Can you remind us of the cash position now and then after the PRV sale, what's that runway look like? And what does it include and not include?

Sure. So what we announced when we had the KRESLADI approval and then with recent earnings is that our cash runway has been extended with the monetization of that PRV, which we disclosed that we sold it for $180 million, means that our cash runway is into the second quarter of 2028. So what we're really doing is trying to demonstrate the derisking with each one of our programs and unlocking additional capital to apply to each one of those programs as we achieve different milestones with those programs. So as we keep moving forward with each of the programs, we'll unlock more capital and resources to invest in those programs.

I see. So in terms of that runway and that 2028 guidance, what does it include in terms of all these different -- we know that Danon still have that pivotal program ongoing. Does that like cover sort of up to potential BLA filing?

A good way to think about it is we'll need to think about additional resources to really commercialize what will be needed for Danon.

I see. Okay. Got it. Let's dive into Danon. So the FDA lifted the clinical hold and then they allow -- I think, August last year, and then they allow sort of the reinitiation of that pivotal study with a recalibrated dose for three patients. So where are you now with these three patients? Are you on track to align with the FDA on the next step in the second half of the year? And when should we expect to see data?

We have initiated dosing of those -- that cohort, that three patient cohort, and we'll provide further updates on those patients as well as a regulatory path forward and also an overall commercial market opportunity update in the second half as -- and we'll announce that ahead of time.

I see. Okay. So now let's forward to second half of the year when you have these three patients dosed and go back to the FDA. What is that process? What is your base case? What is the best case? What's your worst-case scenario, just looking at what the FDA could request?

There are several processes by which one can go back to the FDA. In this case, they've asked us to come back after that safety cohort has been dosed. So it's expected. It's not something that we're going to sort of chase them down for. I think it will be a pretty straightforward discussion and meeting. I expect that we will treat whatever number of patients that we need to treat at this dose, at the revised recalibrated dose and the revised immunomodulatory regimen. Maybe that's 12 patients. It could be more. I don't know. There's no indication from them that there's any change though to study design or patient numbers. There's -- that wasn't part of any discussion. So I think if things go well, then we anticipate a similar trial as the original one will move forward to as a pivotal trial, but we just don't know yet.

I see. Okay. And I believe you guys now under this new regimen, you guys allow the use of eculizumab, which is a C5 inhibitor in the trial with a lower threshold for intervention instead of the C3 that you guys used before that caused a capillary leak syndrome. Any reason that adding a C5 will not lead to the adverse effect compared to a C3? And then also, I mean, since they both -- they complement system with C3 higher in more upstream and then the C5 in more downstream. How confident are you that the C5 will not lead to the same sort of adverse effect?

Yes. So we've always had the C5. We've always had eculizumab as a rescue dose. If we see signs of complement activation. That's actually not a new thing. That's been there throughout Phase I. We have used it in a couple of patients where we had TMA. We did use eculizumab. It did mitigate the TMA somewhat. And we didn't see the paradoxical reaction that we saw with C3. So therefore, we decided to keep that on as needed. It's not upfront. It's not something that we're going to pretreat patients with like we did the C3 inhibitor. But we've dosed some patients with this because of the TMA. We did not see a paradoxical capillary leak or anything else untoward from the C5. And therefore, we're continuing it, into this trial as well.

I see. Okay. So the...

C3 was -- and I will just point out that the C3 inhibitor, it's not the C3 inhibitor alone, but the combination with this torrential rain of AAV, it mitigates TMA for sure, but it produces this paradoxical late onset capillary leak that none of us and not the FDA either anticipated.

Right, right. Because I think the reason why you selected that particular C3 was that you guys thought it was safe to begin with, right -- it's a combination of it. But then for C5, you guys are comfortable because you have seen the use of combination and hasn't led to any adverse effects. Okay. So the dose that you will use in this sort of recalibrated dose for these three patients is half of what it used to be. And I think this dose was kind of similar to what the lower dose for some pediatric patients that you use, but not in the adults. So is there any concern that this dose may not be sufficient for adults?

So what I would say is that -- so it's not half. It's close to -- I would say it's about 60% or so of the original dose. The potency is meant to be matched. So we have good reason to believe that the higher full empties in a disease like Danon, where autophagy is impaired, leads to a more potent product, even if you have the same transgene dose. And there's various reasons for that, that Jonathan Schwartz and others have presented publicly. But what I can say is that we saw in the Phase I, there were two patients on the pediatric side who were dosed lower. And they were actually dosed at the Phase I around 4E13 dose because their body mass index was too high and they were children. But if you compare that product with the new product, the Phase I to Phase II, the equivalent current Phase II dosing for those pediatric kids would have been around 2.5 to 3E13, right? So it was actually a pretty low dose, even lower than what we're doing now, potency to potency. And those patients 3 years out, still have very robust protein expression, and they had pretty profound improvements in LV mass index and other markers in the first year as well. So we did see all of that.

I see. Okay. And then...

Sorry, I think there's a range of dosing here, and it's better to err on the lower side for the benefit of safety. Or the mid side, right?

Okay. And then of the patients who were previously dosed from that first batch before the CRL, how are those patients doing? I mean, obviously, they were treated and you're still monitoring them. How have they been performing so far? I mean the ones without the...

Capillary leak, yes.

Right, exactly.

Yes. So we treated six patients, two had the capillary leak. The other four, we don't have an official follow-up but they're alive, they're not transplanted. Anecdotally, they're doing well. And those who had TMA, the TMA has resolved completely.

Right. Okay. Got it. And how is the FDA going to look at those patients, right? Those patients probably have to benefit from the treatment. So when you go back to the FDA, are they also part of that package when you go back and present the data?

They will be part of the package. I think it will help with the supportive data package, both for this discussion and for the BLA. I don't know if they'll count for efficacy just given the recalibrated dose, but I think that's an unknown right now.

I see. Okay. And what about outside the U.S., have you -- what's the development status there?

Yes. So we have three centers up and running in Europe and U.K. So we anticipate -- and we've had discussions with EMA along the way, and we anticipate that we'll do the BLA in the U.S. first. The U.S. is the first and most important market here just because it establishes the commercial footprint for us. But Europe is a very big part of it to follow soon after.

I see. Okay. So given what happened, let's say, you go back to the FDA, they request that you do more patients. What's the feedback from the Danon disease community so far? Because there's obviously could be some concern given what happened. How supportive do you think that community still is for this treatment?

Very supportive. I mean we've hosted a number of events with the Danon community through the Danon Foundation and otherwise. And the support is overwhelming to please don't stop this study, please continue to bring this therapy to market because we as Danon patients want to see something. We want to have options. So there's overwhelming support by the Danon community to continue to pursue the program.

I see. Okay. Let's shift gears to the PKP2. I think that's also another very exciting program. Can you give us a quick reminder of the data so far? What let you guys move straight into a pivotal before completing the rest of the Phase I dose escalation study?

Yes. So for that program, we started at a dose, PKP2, that we thought would potentially be the effective dose. So we had a dose escalation, but the intent was like for all our programs that we want to hit it right the first time. It's a traditional design, three patients treated. We treat additional patients if there are DLTs experienced, which we did not have any disease, dose-limiting toxicities. So we just enrolled three. We saw directionally a trend in the right direction for all three. And therefore, we approached the FDA who agreed that this could be the dose for a pivotal trial. We have let the natural history work that we're doing play out a bit this year so that we can approach them with a robust proposal for what a pivotal trial design would look like at this dose. So that's the history of why we're moving quickly with a low number of patients. Having said that, there are patients who are interested in the therapy, and we've kept the Phase I open to treat more patients, both to give them the benefit of treatment while setting up the Phase II, which won't be starting until next year, but also because it gives us some more data long term as a supportive data set for the BLA.

I see. And what's the status for that alignment of the pivotal program with the FDA? And when should we see that design? And then is there any risk that the FDA would want you to collect more and maybe longer patient data before you can proceed with that pivotal study?

Yes. We expect to give an update in terms of what the pivotal study design looks like later this year. So we look forward to being able to disclose that once we complete conversations with the agency. So that's well underway. We may additionally choose to put out additional long-term follow-up data from the Phase I cohort. So that's something else that we're trying to explore and find a way to get that out into the community as well.

Yes. And I don't anticipate an ask for a much longer data set. I only say that because we've already started these discussions, and we would have known that by now.

I see. No, the reason why I asked is that I think your competitor obviously has longer data and they're starting those type of conversations after these data.

Yes. I mean, well, I believe we probably dosed first. So we haven't necessarily put the data out there, but we have pretty long-term data for the three patients at this point that continues to show directionally that there's potential benefit here.

Okay. Great. And can you walk us through the patient prevalence? I know we -- obviously, a lot of people have done work on this, I believe it's fairly large. But in addition to that, but how many of them are actually suitable for treatment and for gene therapy? Maybe help us think through all the different qualifying or just qualifying cuts that based on the overall prevalence down to who are suitable for gene therapy?

So a robust comprehensive analysis of this is something that we will provide as the program moves forward. Right now, we're in discussions regarding what the most eligible population should be, right? Because patient selection is very important for the pivotal trial. And the pivotal trial will determine the answer to your question, right? So my sense is that unlike Danon males, in which gene therapy should be for every Danon male out there, whether they have manifestation of disease or not. I think for PKP2, it's going to be a subset of patients. We do know that 80% of these patients have ICDs. So obviously, a lot of them or most of them are experiencing problematic arrhythmias, which can be fatal. There's a lot of sudden cardiac death or shocks that these patients have. So there is a lot of arrhythmia burden. There's also a lot of right ventricular dysfunction in these patients, especially as they grow older. So I think we need to target a population or a segment of these patients who are moderately progressed, but not so severely progressed that there's too much fibrosis and the gene therapy can't enter the heart. So there's, again, that middle zone. It's not going to be like Danon where it's really for all and we'll define that moderate population over time.

I see. So you're going to, I guess, give the market more guidance in terms of who are going to be eligible and how many patients with that.

Yes. I think getting clarity on the Phase II will help us answer that in a more concrete way.

I see. Okay. And what are some of the endpoints that you guys have been thinking about? I know it was very -- this is very novel in some way. And how long does it take to, kind of, reach those endpoints do you think?

It's an arrhythmogenic cardiomyopathy. So obviously, the name arrhythmia is a logical endpoint. There are several types of arrhythmias in these patients, of course, PBCs and SVTs, but also T-wave inversions which are arrhythmias, but they're EKG findings. We can also look long term at ICD shocks. So there are a variety of arrhythmias, which are predictors of fatal outcomes or progressive disease. We'll also look at heart function, especially the right ventricle. We'll look at protein. And I think we will also look at clinical endpoints, how patients function and feel. This is a disease that causes a lot of anxiety because of the shocks and people just feeling better, being able to exercise with some confidence and reducing the number of shocks are all something that this community values quite a bit. I'll just point out on protein expression, we showed not just protein expression improvements either by western blot or immunofluorescence, which we saw in all patients. We also showed trafficking of PKP2 to the cardiac junction. And I think that combination of events is important for robust protein expression. So that will be part of the story as well.

I see. And usually, like how long do you think for these benefits to manifest?

I think in the cardiac world, I mean, look, in traditional adult cardiomyopathy, it sometimes takes years to see benefit of beta blockers, et cetera. In this setting, because these are especially like for Danon, but also [Audio Gap] starts manifesting, there's pretty rapid symptoms and signs. So we think in 1 to 2 years for these conditions, we can see a change from either natural history or if there's a randomized arm, a randomized arm. I don't think it's longer than that, but I also don't think it's less than 1 year.

I see. Okay.

So it just takes time to remodel a little bit.

Right. So potentially, when you think about a pivotal program, you have to build the sort of time line into like the endpoint observation and on that. I see. Okay. Got it. So your competitor presented interim data for, I think, 10 patients with different doses. It looks pretty encouraging. And I think there's some liver tox increase and some other safety effects that we saw there. How does your data compare to what you saw from your competitor? And what's giving you confidence to go straight into a pivotal program?

So it's not our place necessarily to comment on other data sets. I will say that the rh74 capsid, we have a lot of experience in the clinic with it. And the doses that we're dosing these patients in the mid to upper E13 range, especially with the higher full empties that we're able to generate now are way lower than the total capsid exposure that the Duchenne World has seen with Sarepta and others. So I think we feel pretty good about the experience with rh74 with this type of cardiac disease. There's just a lot of patient experience and regulatory precedent for it. So I think that's a key advantage. But look, it's a big market and there's potential room for more than one, and there's people who have antibodies to different capsids, and let's see how it plays out.

Right. Because they use a different capsid. You use the one that's similar to what's been used in DMD, which has some safety on its own.

At higher doses that are about 2 or 3x the capsid exposure that we have here.

I see...

It's not at these doses, far lower.

I see. Okay. Got it. And how do you think about in terms of the time line for -- into the pivotal? Are you able to leapfrog over Lexeo? Because I think first to market is important because this is a disease that you want to be there first to, kind of, be the one who educate people, be the face of the treatment for these patients.

Yes. I think leapfrog is an interesting term. I think we need to do this the right way. Yes, it is important to be first, but it's also -- it's actually more important to win. So if we have a drug that works, we need to design a trial that shows that it works reliably, consistently, reproducibly. And I think having a very collaborative dialogue with the FDA, which we have been having is important because in our interactions with them, we get a sense that they want this trial to succeed. And with that end in mind, it is important to be first, but it's also important to have a trial that actually works, right? So that's what we're going for.

I'll jump in here for just a second. So there are a couple of other players in the PKP2 space, and it's great for the patient community to have these options out there. But as Gaurav said and what he mentioned earlier is we're most interested in being thoughtful, slowing down and patiently designing our study so that in the long run, it's a safe, efficacious study that will really benefit the PKP2 community, and we're taking our time to do that. So this collaborative engagement to properly design what we feel is going to be a great pivotal study is something that's of the utmost importance to us.

Right. Okay. Makes sense. You guys are also enrolling additional patients besides the three that you guys showed earlier. And -- but also at the same time, you announced that you're -- the intention to go into a pivotal study. So are these patients that you're enrolling from the same dose cohort that you presented earlier? And also based on these patients, are you going to present a longer follow-up on the three patients that you showed before? And also these additional patients that you're dosing now?

We will. We will. We tend to empower our partners in the academic and clinical world to define when they think it's ready to be presented. So I think that will be up and coming at some point.

How many patients should we expect when you finally show that data? I mean the three and then how many additional patients do you expect to do?

I would say we're treating up to three more. So that's -- but again, that's not in the pivotal trial. The pivotal trial, obviously, will have a lot more. So yes, I would say 3 plus 3.

Right. And on those additional data that you're -- additional patients enrolling, is it to more or less help inform the pivotal design? Or is it more just to kind of better understand the treatment than that?

Yes, it's not to inform the design. We're ready to discuss the design already, and we're in that process. There's only so much that you can learn from additional patients. And we've seen, fortunately, the same directional improvements in 3 out of 3 patients consistently long term. So I don't think adding more patients would help that. And I know that just from discussions. It is, however, again, for the patients who want to be treated, provide them the benefit of not having to wait for the Phase II. And also, it provides a longer-term data set when we do file a BLA because you want to have some patients who are out a few years when you file the BLA.

Right. I see. Got it. So we're out of time. I do want to ask you about BAG3. So I'm going to turn it back to you for closing remarks. And if you don't mind, please include something about BAG3 about the status, the plan there, and I'll let you close the meeting.

BAG3 is a very exciting opportunity. I would say prevalence-wise, it's somewhere between Danon and PKP2. We have a Phase I trial that is starting and we'll be treating patients soon. And I think, again, that potentially opens up the third door of access to dilated cardiomyopathies, which is the biggest bucket of cardiomyopathy out there. So I think BAG3 is a big opening for the future of cardiac gene therapies. And we're excited to start soon.

Fantastic. Gaurav, Meg...

Thanks for having us.

Glad to host you guys, and thanks everyone.

Thank you.

Appreciate it.

Wonderful.