Thank you for joining us, this afternoon for our third day of our annual Bank of America Healthcare Conference. My name is Cameron Bozdog, and I'm part of Jason Zemansky's mid-cap biotech team here. I'm pleased to have with me today, Rocket Chief Medical and Gene Therapy Officer, Jonathan Schwartz. Thank you so much for joining us today. It's great to be here. Perfect. Well, maybe let's just dive right into it. You know, to start broadly, could you briefly describe your platform, you know, especially for those who may not be as familiar in the audience? Absolutely. I think it's important to emphasize that Rocket is not a platform-based company. We really consider ourselves more of a disease-focused company with a focus on very high unmet need diseases for which there's a viable means for gene therapy to be either transformative or curative. And so really, the focus is on the disease, and then we have employed both lentiviral as well as adeno-associated viral, AAV, technologies based on the needs of the particular diseases. And really, the focus is much more about finding diseases where there's a very plausible means of correcting with gene therapy. Can you get the gene of interest into the right population of cells at sufficient quantities before there's irreversible damage to effect a very profound reversal of the disease phenotype? Our focus has also been really on trying to sort of be best-in-class, first-in-class, frequently, only in class. And we try to identify indications that allow that to happen, and indications in which there are quantifiable endpoints. So there's a path forward both for health authority approval as well as value demonstration. At present, we have five clinical stage programs, three of which are lentiviral in hematology and immunology diseases, and two AAV clinical stage programs, both in cardiac disorders, as well as one disclosed preclinical program in another cardiac disorder. And just for those that are not familiar with the story, this year, we have a PDUFA date coming up at the end of June for leukocyte adhesion deficiency one, LAD-I. We're on track to submit a BLA in the first half of this year for Fanconi anemia and have already submitted the European equivalent. The Danon and pivotal phase II study is underway, and we are currently activating the pivotal study in pyruvate kinase deficiency, as well as have initiated a phase I study in PKP2 arrhythmogenic cardiomyopathy. So that's Rocket in a nutshell. Perfect. Maybe to kind of focus here on, you know, what differentiates you from other developer, other developers of gene therapies. Is it maybe the indications you're targeting, you know, something else from your platform that, that differentiates you? I think the differentiation has very much been severalfold. In part, it's the sort of platform-agnostic approach, what's going to be best for a given disease, as opposed to, "Here's something that came out of so-and-so's lab or this Nobel laureate's shop, and now let's figure out how to make it work in the clinic." I think that's a very, that's a very important distinguishing feature. It's. It really starts with the diseases and how we can make a difference. I think another really important distinction is that, we have a culture of working leadership. Although we've continued to expand the company, we're now almost 300 employees with any number of people at leadership levels. The three original C-level leaders, Gaurav Shah, our CEO; Kinnari Patel, our COO and president; and myself, have been with the company now, each of us, more than eight years. We continue to get into the weeds on a daily and weekly basis, really trying to set an example for the rest of the team that if you don't do it, if we don't do it, nobody else is going to do it. Although obviously, as any biotech we have to outsource, we try to retain as much activity in-house as possible because no one cares more than us. Obviously, a relentless focus on the patient. That is something that I think probably many companies say. I'd like to think we actually do that and have delivered on it. I spent a long part of my career taking care of people with horrific diseases before coming to industry. So those are most of the distinguishing features. Great, and then, you know, perfect segue into my next question. You know, could you maybe comment on, you know, your, your manufacturing capabilities and why this has become such a critical piece for gene therapy developers? Yeah, well, it's critical because it's hard. There's a lot of ways to go wrong, and you can burn through a lot of money and resources very quickly without necessarily getting what you need. That's probably another distinguishing feature of Rocket, is that we've been pretty judicious stewards of both human as well as financial capital, and I think that's enabled us to survive some very rough waters with respect to the past several years when the XBI has been taking a beating. But with respect to the manufacturing, we've had a very thoughtful, staged approach to manufacturing, which combines both external, carefully chosen partners, especially for lentiviral work, as well as then building up an in-house capability for our own AAV manufacturing. We understood at a very early stage that manufacturing could easily make or break even the most well-thought-out clinical program, and so we put significant investment into it. That started with lenti, where we for each of the three late-stage lenti programs that we have, we started off with commercial-grade vector, commercial-grade cell processing, even as we just did first in human trials, so that we wouldn't have to worry about a potential transition later on. On the AAV side with Danon, we started with some very really terrific contract partners. But as we recognized clinical proof of concept, we realized that we wanted to develop our own capabilities, and so we made the commitment, once we had sufficient proof of concept, to build the facility that we have in Cranbury, New Jersey, which has 50,000 sq ft of AAV manufacturing capability. We're using product from Cranbury, both in the phase I PKP2 study as well as the pivotal Danon study. And the metrics of that product in the Danon program have been superior to what we were able to use in phase I, which will hopefully translate as the trial progresses into enhanced safety as well as ultimately lower cost of goods. Perfect. You're currently advancing programs specifically in cardiology and hematology. You know, what makes these specific indications attractive when you're looking at them from a mechanistic standpoint and maybe from a commercial standpoint as well? Yeah. So, I mean, we've tried to find indications where gene therapy could make a profound difference, and as I said a few minutes ago, where we could be first, best, or only in class. And that's true for the existing late-stage programs, as well as some of the preclinical programs that we're working on behind the scenes. Across the spectrum, we select indications where we and our partners have a profound understanding of the underlying biology. There's a strong scientific rationale, and endpoints that are quantifiable and achievable and likely to resonate with health authorities and payers. Very, very importantly, our indications, whether they be on the hem or immunology side or on the cardiac side, are ones where gene therapy is not a nice-to-have. It's essential, and transformative, and I think that segues into a very good position as we approach commercial stage. Because we want to be developing therapies where the importance of the therapy filling a high unmet need, the magnitude of benefit is relatively easily explainable, and really then justifies a strong commercial proposition. Great. Maybe shifting gears here to your commercial stage. We're coming up on your first PDUFA, June 30th. Can you talk about your pre-commercial efforts and, you know, what elements you're hoping to have in place at this time? Sure. So, you know, the Kresladi PDUFA is June 30th, and that's for leukocyte adhesion deficiency one, LAD-I. The plans are to launch the product as soon as possible after an approval, and we'll be able to provide more specifics on that over the coming weeks. I think it's important to emphasize that LAD is an ultra-rare disease. Newly diagnosed patients are gonna get referred to expert centers, and most of our commercial preparation activities have really been about establishing site readiness for our qualified treatment centers. This is the kind of disease where there's limited need for a large number of MSLs or a sales force or any sort of extensive commercial infrastructure. Most of the primary immunodeficiency expert community is aware of our data and aware of the differences relative to allogeneic transplant and are excited to be able to refer patients. You know, as far as the commercial opportunity, this approval and launch is gonna be able to enable us to show a validation of our CMC and regulatory capabilities and enable us to kind of demonstrate execution at a relatively modest scale. You know, we'll have a limited number of qualified centers, probably on both ends of the country. And then, and then that launch will hopefully then enable us to further scale up as we get into the bigger indications with approvals in Fanconi anemia, and then the successively larger one, in Danon disease to follow. So hopefully we'll be able to demonstrate the ability to execute on a sort of mature commercial level. And obviously, having a PRV as well is added upside, both for LAD-I and then subsequently for Fanconi. And then kind of focusing here on what you think investors should expect as far as, you know, the initial pace of uptake, any chance you can start this process immediately? And then, more broadly, kind of what do you expect the biggest near-term hurdles to be? Near-term? Hurdles, challenges. You know, I think the near-term challenges in LAD-I are gonna be relatively modest. You know, we haven't really disclosed any projections in terms of, you know, patient numbers or sales numbers. I think it's important to emphasize that the pricing conversations that we've had with payers are underway. Those conversations have been positive and productive so far, in part, you know, because this first one is a relatively rare disease, but predominantly because, from a value-based perspective, this is an appealing high-value proposition. You're talking about severe variants of LAD-I, which is uniformly fatal in childhood, predominantly in early childhood. Allogeneic transplant is effective and potentially curative, but even in the most recent series, with all the different improvements in the allogeneic field, because of the complexities of this disease, comes with significant complications: high rates of graft failure, high rates of graft-versus-host disease, not complete, incomplete survival. And really, we're able to take kids with this brutally lethal immunodeficiency and give them what looks like potentially a full, a full ride, a full lease on life. If you could briefly just touch on your expectations for what the label could look like. So, we anticipate that the label will be for the more severe forms of LAD-I. It's hard to be too specific until we've had the labeling discussions with FDA. For those of you who are not versed in FDA inside baseball, those discussions typically happen at the very, very end of the late-stage review cycle, right before the PDUFA. So, can't say too much, but it's likely that the label would be more expansive than the eligibility for the pivotal study. Specifically in terms of— I don't think the label would stipulate that patients can't have an HLA-matched sibling donor, but there may also be some other areas in terms of integrin expression, where things go beyond what the study requirements were. Perfect. Then moving ahead to Fanconi anemia, is the BLA still on track for 1H 2024? And then what elements are still left to do? Yeah. So, the BLA is on track, and we have ongoing discussions with the agency regarding the strongest possible package for submission. And I think this is an area where having a good collaborative relationship with the FDA, with the CBER division across multiple programs is really helpful. You know, we're able to sort of get their input as to, "Okay, here's what needs to go in. Here's what you might want to do slightly differently than in the MAA," which we submitted several weeks ago in Europe. And, you know, I think again, from a launch perspective, there's a lot of synergies with LAD-I. The commercial team is in place, both for LAD-I and with FA, so we'll have had the benefit of an initial launch in a rare disease with LAD-I, as we get closer to the Fanconi launch. And it's fortuitous that, you know, this—the first launch is the smallest indication. And then we get progressively larger from there, so we can continue to apply any lessons learned from the predecessor launches to streamline the larger and more commercially intense act launch activities. Yeah, you make a great point there. You know, do you think this initial launch could be an approval to just get your foot in the door? You know, how de-risking is that first approval for the overall platform? Yeah. So I think, you know, I think it is de-risking, and it does give us a foot in the door. It is obviously a PRV, which is always helpful. It's always nice to have an extra $100 million or so in the wallet, and hopefully a second one to follow. I think very importantly, it's an opportunity to garner trust of our treatment partners, patients, the overall rare disease community, and the broader medical field, and demonstrate that gene therapy can be curative, without many of the transplant-related complications that are still really problematic for both LAD-I and Fanconi anemia. You know, gene therapy for a lot of these diseases is still very much a new paradigm. A lot of the broader medical community and broader investment community still thinks of it as something for the future, not the present. And, so any sort of approvals and successful launches will go a long way to help with that. I'm old enough to have lived through the sort of first generation of monoclonal antibody development in cancers and autoimmune and inflammatory diseases, and was, in fact, a clinical investigator when I was at Mount Sinai for both Avastin as well as Erbitux, at a time when a really, really large portion of people still were saying: "Oh, my God, you think you're going to treat these complicated diseases with antibodies? You know, you stupid kid, get—y ou know, like, "Okay, knock yourself out." And, you know, obviously, in this day and age, you, you couldn't imagine, those fields without a huge number of, of highly, effective and, and meaningful antibodies. And I think so that, that's kind of where we are with gene therapy, and, and that's where we're really excited about these approvals and launches, because it goes well beyond just LAD-I and Fanconi anemia. Great. Great. Yeah, well, maybe turning now to Danon, you know, based on your research, you know, what levels of expression of LAMP2 do you think are necessary to be clinically relevant here? Yeah. So I think what we learned from the preclinical work, and also from our phase I experience, is that when you turn on the switch, the results are pretty profound. And even patients who have relatively modest grade 1 expression, you see histologically, that all this, the built-up autophagic vacuoles really, really reduce down to more normal levels. The myocardium normalizes and the profound disarray that's characteristic of Danon disease disappears, but way more importantly, that there's a clinical benefit, and that, you know, that clinical benefit is measured both in terms of blood-based biomarkers, really profound improvements in the hypertrophy on echo— as well as improved and mostly normalized NYHA Class with very large bumps in quality of life across multiple different instruments. And that's sustained now out to three years or beyond. So a little appears to go a long way. Obviously, you know, I think some of the immunohistochemistry data that we've presented so far, you know, may actually be underestimating the amount of LAMP2, but it's what we've been able to measure to date. And it certainly seems to be adequate, even with relatively modest levels, and more on that to follow. And then when you're thinking about your pivotal trial design, you know, was there one specific element the FDA was focused on in agreeing to it? Or do you think it was more so the totality of data and, and just was the overall flexibility, you know, potentially due to the fact that, you know, you're a rare disease with, with limited options? Yeah, I think for the FDA, a bunch of different factors went into it. You know, Danon disease is one of the most aggressive cardiomyopathies ever described, and it's uniformly fatal, typically earlier for the men and boys, but also very much so for the females. And you know, from the FDA perspective, you know, I think absolutely the totality of data was really important. The fact that we saw improvement across everything that we were really able to measure, you know, whether it was markedly elevated troponin levels or natriuretic peptides normalizing, whether it was extensive hypertrophy improving, you know, by double-digit percentages or the other sort of more clinical quality of life things. That, that was really helpful, and that was helpful also, in terms of FDA, really you know, accepting the fact that all of the secondary endpoints on top of the primary, the co-primary endpoint, would be helpful both for accelerated approval as well as for ultimately, full approval, which, which would require really just longer follow-up of the phase II patients, not, not some separate trial in, in a separate population, which, which is important. So it was the, I think, the total magnitude of benefits seen in phase I, as well as the fact that, as I mentioned, you know, Danon is a really aggressive cardiomyopathy, and it's also not only one of the most aggressive, but it's one of the most hypertrophic. And that hypertrophy contributes to all of the clinical elements and, and the, the pathophysiology. So, you know, the hypertrophy really directly results in diminished function, feel, and survival. And that resonated with the FDA, which was why they were willing to accept the co-primary endpoint of one year LAMP2 expression by at least grade one in the myocardium, as well as an at least 10% reduction in hypertrophy as measured by left ventricular mass index. Perfect. And can you briefly touch on the enrollment progress here? Are we still on track to see interim data in 2024? And then ultimately, you know, what should investors be looking for in the update? And yeah, what would you constitute, I guess, a good, a good readout here? Yeah. So the study is active and enrolling as anticipated, very much on track. We have avoided precise guidance, as we're really more focused on enrollment, treatment, and execution, with the goal of also, you know, preserving data integrity, not providing, you know, a whole bunch of interim looks at efficacy as we did in phase I. That was really important for phase I, but the goal for phase II is to make sure that we're doing our utmost, to you know, treat the patients and follow them properly, enabling health authority approval and other good launch outcomes. I think you can anticipate some updates regarding the study status this year, and we'll provide more granularity on that later in the year. Perfect. Well, it looks like we're out of time here, but thank you so much for such a, a great, exciting conversation, and I'm looking forward to what Rocket has in store in the next couple of months. Thank you so much. It's a pleasure to be here, and we'll look forward to more. Thank you.