Morning, ladies and gentlemen, and thank you for standing by. Welcome to the Rocket Pharma Clinical Update conference call. At this time, all participants are in a listen-only mode. This call is scheduled for approximately 30 minutes. Following the company's prepared remarks, we will open the line for a question-and-answer session. To ensure we hear from as many participants as possible, we kindly ask that you limit yourself to one question. I would now like to turn the conference over to your speaker host today, Meg Dodge, Vice President of Investor Relations and Corporate Affairs. Thank you, and welcome to Rocket's RP-A501 Clinical Update conference call. I'm joined on the call today by Dr. Gaurav Shah, our CEO, and with us available to answer questions will be Dr. Kinnari Patel, COO and President of R&D, and Dr. Jonathan Schwartz, Chief Medical and Gene Therapy Officer. Before I turn the call over to Gaurav, I would like to remind you that today's call may include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Rocket's filings with the SEC, which are available from the SEC or on the Rocket Pharma website for information concerning risk factors that could affect the company. I will now turn the call over to Gaurav. Thank you, Meg, and thank you to those joining today's call. Earlier today, we issued a press release providing an important update on RP-A501, which is Rocket's investigational gene therapy for Danon disease. A patient enrolled in our phase II pivotal trial experienced an unexpected serious adverse event and clinical complications related to capillary leak syndrome. Rocket is conducting a comprehensive root cause analysis and remains in active dialogue with the FDA and other key stakeholders, with the current focus being on the recent introduction of a novel immune suppression agent to the pretreatment regimen that has been implemented to mitigate complement activation. Now, this novel agent was specific to the Danon program and not for PKP2, BAG3, or other programs. Following this initial SAE, Rocket proactively and voluntarily paused further dosing in the study out of an abundance of caution. We immediately notified the U.S. FDA, and the FDA on May 23rd placed the trial on clinical hold to allow for additional evaluation. Subsequently, the patient experienced additional medical and procedural complications during his hospital course and unfortunately passed away after a systemic infection. First and foremost, our thoughts are with the patient's family, caregivers, and the treating clinical team. This is a deeply tragic loss, and we are committed to fully understanding the circumstances surrounding it objectively and neutrally. We are also immensely grateful to the family for their contribution to this important clinical research and their commitment to helping advance science for the broader Danon community. Now, as was shared in our press release and just now, there is an ongoing and objective review to assess the root cause of the initial SAE. As I mentioned, an area of focus is a recent protocol amendment that introduced a novel immunomodulatory agent to the pretreatment regimen. This change was implemented proactively to further enhance patient safety and was informed by the occurrence of complement activation earlier. Rocket is carefully evaluating whether a mechanism related to the new agent may have influenced immune responses in an unexpected or paradoxical way. Again, this agent is specific to the Danon program and has not been used in PKP2, BAG3, or other programs. Also, these programs are not impacted by this clinical hold. We are working now with sites, external scientific experts, and the FDA. While the clinical hold remains in place, we are unable to provide guidance on the exact timing of completion of the phase II trial. We believe that transparency and responsibility are absolutely critical during times like this, so we are working together with the FDA to define the next steps. We are confident that there is a path forward, and we remain committed to advancing RP-A501 with the highest standards of safety, science, and care. We want to recognize the Danon community especially. Rocket remains dedicated to open communication with patients, families, and advocates, and will continue to work closely with the Danon Foundation to keep the community informed as we move through this process together. We will continue to move with care, clarity, and deep respect for the patients and families who make this work possible at all. Shifting gears separately, let me emphasize also and importantly that the company is prioritizing investments into its AAV platform while conducting an internal strategic review to optimize value for the rest of the pipeline. The PKP2 and BAG3 programs are on track, and we continue to move toward completion of the CRL response for LAD as soon as possible. With these changes, Rocket now expects its existing resources will be sufficient to fund operations into 2027, exclusive of any potential proceeds from the sale of PRVs that could follow the anticipated approval of therapies from the hematology portfolio. We will provide further updates on the program and cash guidance as additional information becomes available. Thank you for joining the call, and with that, Operator, we are ready to take questions. Thank you. At this time, we will be conducting a question-and-answer session. As a reminder, to ensure we hear from as many participants as possible, we kindly ask that you limit yourself to one question. If you have any questions or comments, please press star one on your phone at this time. We ask that while posing your question, you please pick up your handset, if listening on speakerphone, to provide optimum sound quality. Once again, that is star one if you wish to ask a question. Please hold while we pull for questions. The first question today is coming from Josh Schimmer from Cantor. Josh, your line is live. Thanks for taking the question. Condolences to the family of the patient. I guess, are you able to provide any additional details around this event in terms of when it occurred? Number one, what the specific immune or novel agent was that was added? I guess this is incremental to the steroids, sirolimus, and rituximab. Are you able to provide any comments in terms of the number of patients treated in the program to date? If the answer to any of those is no, when might we expect to hear? Yeah, so the patient was treated in early May, and the agent that was used was a C3 inhibitor. It was introduced into this trial because there was ongoing evidence of complement activation in Danon disease, and we aimed to try to completely eliminate any TMA risk altogether. At that time, this particular agent was coming into the market, and also we had some experience in pediatric patients, so the timing was right to try to eradicate the risk of TMA altogether, not just for Danon, but potentially as a read-through to other AAV programs across our portfolio and others. It was with that in mind that we introduced this novel agent. Now, I will say that we are considering that as one option, one thought, one idea for root cause. We're doing a comprehensive root cause analysis pretty neutrally and objectively, and this is one idea, so current focus, but just one idea. In terms of the number of patients, we're not quite ready to comment on that, but as the protocol, it goes through the FDA, and we have discussions with them to resolve the hold. We'll be able to provide further guidance. Okay, thank you very much. Thank you. The next question is coming from Mani Foroohar from Leerink. Mani, your line is live. Hey guys, thanks for taking the question. I would add my condolences to the family of this patient. I want to follow up a little bit on Josh's question, which seemed to be the most important. Can you give us a sense of when the decision was made to add this C3 inhibitor potentially to the protocol? Was this the only patient to receive this agent? I have a quick follow-up. Yeah, the decision was made earlier, several months ago, to add this. There was one more additional patient who did receive this agent as well after this patient that we are talking about. The second patient has had a much reduced course, has had evidence of capillary, but has had a reduced course. What we were able to do here is learn from the first case and intervene so that we did not see the same events happening in the second patient. There are two cases like this now. I will say that both of these cases are cases where the only difference really was the introduction of this agent, so that is why that is one hypothesis that we are working with. Okay. When you're talking, is the right interpretation of that that you had some number of patients, at least these two, who have had capillary leak syndrome after dosing with the AAV, after receiving the other three agents in the immunomodulatory regimen that Josh helped to list, and then after that, at some point, they had capillary leak syndrome, and then this novel agent was given, and then they had an acute infection, or did the acute infection come prior to the capillary leak syndrome, and the novel agent was given after? Can you clarify the order of events there? Sure. So yeah, let's walk through the timeline here in some granularity. These are the only two patients that have seen what we're calling a capillary leak syndrome, the ones that we're talking about here. Now, this agent is given before the infusion. It's given a few doses after infusion as well. It's given in conjunction with the other standard immunomodulatory regimen, including rituximab, sirolimus, and steroids with hopefully a rapid taper. All of that is given together. It was a full package that was intended to eradicate complement activation as well as any later T-cell responses to really focus on the safety profile of these patients in the days and weeks after therapy. Safety is, of course, our first priority here while we develop a full benefit risk profile. In terms of the occurrence of the medical events, we did not see TMA. We did not see other gene therapy effects like myocarditis. About a week after the infusion, that's when we started seeing some evidence of capillary leak. There were other medical complications and procedural complications in the week or so afterwards. Actually, the patient was at that time stable and doing potentially well enough that we were cautiously optimistic of recovery. The capillary leak was improving. Unfortunately, over the weekend, over this past weekend, he developed an acute systemic infection that accelerated his demise. That's the full sequence of events. The clinical hold was placed on Friday. The clinical hold was placed Friday just before this demise. All of these, the most severe events unfolded literally in the last three or four days. Okay. Thanks for letting me know. That's helpful. I know there's a lot of other questions on the line, so I'll hop off. Thank you. Once again, as a reminder, in the interest of time, please limit yourself to one question on today's call. The next question is coming from Mike Oates from Morgan Stanley. Mike, your line is live. Hi, good morning. It's Avraham Novick [guess] on the line for Mike. Thank you for taking our questions. I guess, are there any patients that have been enrolled in the study that have still not been infused with RP-A501? I guess just as a quick follow-up, were there any previously dosed patients who have had complement-mediated adverse events? Thanks. Yes, so there are patients who are still waiting to be treated. Our plan and the timeline was such that we would have finished the treatment of these patients by mid-year, which is when we were going to have the program update as we've guided to previously. There were more patients left to be treated, all ready to go, and were lined up to be treated shortly. Unfortunately, we had this setback that we're talking about today, so that's going to be paused. Earlier in the trial, we did see complement activation and TMA. It was a gene therapy associated effect that's part of trial safety benefit that we usually read out at the end of the trial. Those patients are actually now doing well from a safety and potentially even an efficacy viewpoint. Because it was part of routine explained side effects of gene therapy, we continued with the program. There was no clinical hold, and we modified the protocol in the way that I described earlier to continue to further mitigate the risk. Thank you for taking our questions. Thank you. The next question will be from Andrew Tai from Jefferies. Andrew, your line is live. Hey, good morning. Sorry about the news. Quick question would be that as we think about the timelines for your Danon program, is there a way to topline the data without all 12 patients needing to be followed up to 12 months at this juncture? Thanks. That's a great question. We're unable to comment on that at the moment. I think we could have more clarity as we get more information in alignment with FDA. Thank you. Thank you. The next question will be from Tyler Van Buren from TD Cowen. Tyler, your line is live. Hey guys, thanks for taking the question. Since you discussed that this agent was introduced to reduce the incidence of TMAs, can you give more color on the incidence of TMAs that have been observed to date, or any additional color in what you've seen so far in the trial? Yeah, so there was an initial episode of TMA that was linked to an additional gene mutation that confers complement sensitivity in some patients. We modified the protocol with a 14-panel test to reduce or to eliminate those patients from enrolling who would have those sorts of gene mutations that exacerbate complement. There was another one that persisted. There was another TMA that we saw also. And TMA is a known risk of this therapy. We do not think that the risk is ever going to be zero. In order to try to make it as close to zero as possible, we introduced this new inhibitor, and we are going to evaluate what finally happened here. I should also say that those patients who did have those early complement activations have completely recovered from the sequelae and are doing well right now. Thank you. The next question will be from Corey Jubenville from LifeSci Capital. Corey, your line is live. Hi, this is Thibaut Pardo for Corey Jubenville. My condolences to the families of the patients. We had up to five years of AAV data that were going pretty well. The phase I program, we had everything pretty controlled with once the update to include rituximab, sirolimus, and prednisone combo. Why take that risk of introducing a novel agent? We always aim to provide the optimal experience for patients and really lean in on the benefit risk. At the time, we did not know how rapidly these complement issues would and could resolve. We worked with an abundance of caution, putting patient safety first to make sure that other patients did not necessarily have those experiences. Since then, those patients, as I mentioned, have recovered fully from the complement activation issues. I think that we were trying to be extra careful with safety and trying to eliminate all risk altogether. Thank you. The next question will be from Sami Corwin from William Blair. Sami, your line is live. Hey there. Thanks for taking my question. I was curious what dose of the C3 inhibitor was used and if that agent had been studied previously in combination with those other immunosuppressant agents. Can we still expect the mid-year Danon update to be on track? Thanks. We're unable to provide the exact details of the inhibitor dose at the moment, but it was based on preclinical data as well as some preclinical proof of concept. We have some evidence of utility of the agent in the setting of similar programs that we extrapolated from. I think that we're going through a root cause analysis. This is just one idea that we're exploring neutrally and objectively. Thank you. The next question will be from Kostas Biliouris from BMO Capital Markets. Kostas, your line is live. Thanks for taking our question and sorry to hear the news about the patient. Can you maybe discuss the dose that was used for the patients that had the adverse events, maybe the two latest patients? What drug dose was used? Was it higher than previous patients? Any particular characteristics of these two patients that may have contributed to these adverse events? Their age, maybe their weight was different than others? Any color around the characteristics would be helpful. Thank you. Thank you. No, the dose was the same. It was 6.7 E13 vector genomes per kilogram. We have gone through a drug comparability from phase I to phase II product and within batches of phase II product. To date, the drug has been comparable up to phase I. Just clarify, the dose amount, the weight of these patients was similar to others, or maybe it was higher, and the dose amount was higher? No, the weight was mid-range, and certainly the dose was within range of prior patients as well. Certainly not higher. Thank you. Thank you. The next question will be from Gavin Clark- Gartner from Evercore ISI. Gavin, your line is live. Hey, guys. Sorry to hear about this outcome. I was just wondering, is there a possibility that regulators may want you to enroll additional patients in the study now to gain more clarity on the overall safety profile and risk-benefit? Yeah, we don't know. This will provide further clarity when we have more information for sure. I will say that we have a large number of patients. We actually over-enrolled the trial, and we believe that if that's the case, we'll be able to find and enroll the rest of the patients. We don't know right now. Are you able to say how much you over-enrolled the trial by? No, we can't say that at the moment. We'll have more information when we have more data from the FDA. Got it. Thanks. Thank you. The next question will be from Richard Law from Goldman Sachs. Richard, your line is live. Hey, guys. This is Paxton Al [guess] for Richard. I know you guys discussed that this was an issue specifically related to the Danon program, but acknowledging that PKP2 is using a different vector, could you talk a little bit about the read-through to this program? Are the safety risks here just as high, and will there be any additional adjustments to the protocol, or how do you think about using this agent in those patients? Thanks. Yeah, so first of all, we do not think that there is a read-through to PKP2 or back read. They are different in vector design, transgene, the population, the disease itself. We will, of course, take these learnings to other programs. We have not implemented any changes to the immunomodulatory elements for those programs. For RH74, complement activation historically has been less of a risk, and the current immunomodulation for these programs remains the same, and we feel confident that it is the right one for those programs. Thank you. The next question will be from Greg Harrison from Scotiabank. Greg, your line is live. Good morning. This is Teraesa Vitelli. I'm for Greg. Thanks for taking our question. Just wanted to see if one possible path forward is to remove the use of the C3 inhibitor in the remaining patients, given that the patients who were dosed without the inhibitor did not have the same serious adverse events as the two patients who did receive it. I do not want to comment on exactly what the path forward would be, but there are various ways to move forward, including revising the immunomodulatory regimen, perhaps to a simpler one. We, of course, will continue to screen out patients who have predisposition for complement activation based on genetic testing. There may be other changes that we come up with together with FDA, for example, leaning in a little bit more to the existing complement inhibitors that have been demonstrated to be safe already. There are ways to do this, and we do feel confident that we will find a path forward as expeditiously as possible. Thank you. The next question will be from Gil Blum from Needham & Company. Gil, your line is live. Thank you for taking our question this morning, and allow me to add my condolences. Just to be perfectly, perfectly clear, the only events of capillary leak syndrome that were seen were only when this agent was used. There was no evidence in any of the other patients. That's correct. Thank you. Thank you. The next question will be from Yun Zhong from Wedbush. Yun, your line is live. Hi, good morning. Thank you very much for taking the question. This is a follow-up question to your previous comment on existing complement inhibitor with probably better safety profile. What was the reason that you chose the new agent over those existing agents that could potentially be safer, please? It's been shown in other trials, in other programs, to potentially be more efficacious at complement inhibition and safe in other programs. We felt that in order to mitigate the risk of complement activation in Danon patients, it was a better choice and sort of moving the field in the right direction to mitigate safety. That was the reason for it. Also, there was pediatric data that was available that we could potentially apply to Danon. We leveraged some of that information to move it into the Danon program. Sometimes drug development is never linear. We are, of course, going back to the drawing board, but we're confident that there is a path forward with a simplified regimen here. Great. Thank you very much. Thank you. The next question will be from Eric Joseph from JP Morgan. Eric, your line is live. Hi. Thank you. Let me add my condolences on a setback here. The C3 inhibitor that you're using here, is that a licensed product? Secondly, can you just talk about any other instance of opportunistic infection that has been managed in the phase I study or otherwise? Thank you. It is a licensed product, yes. In terms of other opportunistic infections, there was in the phase I an episode of sepsis that resulted from a skin injury in a patient who was on immunomodulation, but he recovered fully. Thanks for taking the questions. Thank you. The final question today will be from Jason Zemansky from Bank of America. Jason, your line is live. Good morning. Thanks for squeezing me in, and let me echo my condolences for all involved here. Look, I appreciate the timing forward is somewhat opaque here, but could you just maybe articulate in some granularity what next steps would entail just to give us a sense here of what needs to transpire before we get any clarity here? Yeah. Good question. We're already in deep dialogue with FDA back and forth and doing a neutral, objective root cause analysis. We're discussing with them a potential revised immunomodulatory regimen and potentially other changes. We'll get a formal list of questions from them shortly and be able to respond to them. I can't give you a timeline on exactly when we'll come out of that process, but as expeditiously as possible is the goal, is the target. Meanwhile, the patients continue to be on the docket to be enrolled and treated as soon as possible. The program overall has demonstrated great benefit-risk in the phase I with the NEJM publication last year with six of six patients performing well. This is a drug. This is an active program. We're committed to it. It is going to move forward. We've had this very sad and unfortunate roadblock at the moment, but it does not stop the Danon program from moving forward. I just don't want to give timelines right now, but we will get back on track as soon as possible. I apologize for the follow-up here, but has sort of new FDA been any more or less responsive or challenging in terms of your dealing with them? I have to say in our dealings, if anything, they've been more responsive and more collaborative and faster. Of course, that's my experience here and us here at Rocket. Got it. Appreciate the color, guys. Thanks. Thank you. This does conclude today's conference. You may disconnect your lines at this time and have a wonderful day. Thank you again for your participation.