Welcome to the Rocket Pharmaceuticals, Incorporated Investor Conference Call. My name is Vanessa, and I will be your operator for today's call. At this time all participants are in listen-only mode. Later, we will conduct a question-and-answer session. I will now turn the call over to your host, Mayur Kasetty, Director of Business Development and Operations.

Thank you, Vanessa. Good afternoon, everyone. This is Mayur Kasetty, Director of Business Development and Operations and Investor Relations lead at Rocket Pharmaceuticals. Thank you for joining us. The purpose of this call is to share and discuss key updates on our clinical programs. Before we begin, I would like to briefly discuss the use of forward-looking statements on this conference call. Statements we make on this call may include statements which are not historical facts, and are considered forward-looking within the meaning of the Securities Laws, and which are usually identified by the use of words such as anticipates, believes, estimates, expects, intends, may, plans, projects, seeks, should, will and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the Safe Harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act, and are making these statements for the purposes of complying with those Safe Harbor Provisions. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected and/or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements, and will be affected by a variety of risks and factors that are beyond our control, including without limitation, those set forth in our earnings release issued earlier today and in Item 1A Risk Factors of our annual report on Form 10-K for the year ended December 31, 2020, and as updated by our subsequently filed quarterly reports on Form 10-Q and our other SEC filings. We assume no obligation to publicly update any forward-looking statements whether as a result of new information, future events, or otherwise. Participating on today's call on behalf of Rocket are Dr. Gaurav Shah, Chief Executive Officer, Dr. Jonathan Schwartz, Chief Medical Officer and Clinical Development, Senior Vice President, Dr. Gayatri Rao, Chief Development Officer and Head of Regulatory Policy, Carlos Garcia, Chief Financial Officer, and Claudine Prowse, Senior Vice President of Strategy and Corporate Development. There will be a question-and-answer session at the end of this call, in which we will all participate. I will now turn the call over to Gaurav.

Thank you, Mayur, and thank you, everyone for joining us today. We have several updates to take you through. Let me highlight four key take-home points for today. First, regarding the Danon clinical trial, we are reiterating our previous guidance that based on our most recent FDA interactions, and exercising the best of our judgment and estimation, we continue to anticipate resuming the trial this quarter Q3. Second, for Danon, the low dose is demonstrating increasing and durable benefit. We'll go over key data points including some new ones in MS. Third, for Danon we are removing the high dose from future dosing plans. Fourth, Fanconi Anemia LAD-1 and PKD remains on track, and we will provide further clinical updates in Q4. Those are the key takeaways. We will now get to some more details. Starting with Danon, we've been working very closely with the FDA over the last several weeks, and through our discussions, we have agreed to modify our immune-suppression and component inhibition protocols to bolster safety guardrails. In addition to these protocol updates, we've had a chance to review updated low dose datasets with the FDA that Rocket believes is supportive of its potential as a viable Phase 2 dose. Notably, photographic evidence for all three low dose patients showed improvements being a decrease in our basic vacuoles, a hallmark of Danon disease pathology, as assessed by electron microscopy of cardiac tissue via endomyocardial biopsy. Additionally, two of the three low dose patients were closely monitored immunosuppressive regimen compliance demonstrated improvements in class from two to one, which translates to no impairment of function. These patients also demonstrated substantial improvement of a key marker of heart failure BNP, which decreased by 75% and 79% versus baseline levels, as well as improvements in cardiac output by 35% to 62% compared to baseline, as measured by invasive hemodynamics. All three treated low dose patients continue to demonstrate stabilization or improvements in the six minute walk test as well as New York heart association class. Given the activity observed in the patients in the low dose cohort, and importantly, to mitigate associated safety concerns in the 14 range, we have decided to forego pursuit of the higher doses, meaning 1.1 to 14 factor genomes per kilogram or higher. This decision was made in agreement with the FDA and allows us to focus fully on the low dose moving forward. The 6.7e13 dose also reduces the total number of patients needed in our Phase 1 study, and potentially allows for more rapid progression to Phase 2. Now as disclosed in December of 2021, a patient in the high dose cohort who is the heaviest patient treated day and a half, highly advanced disease, developed complement mediated thrombotic microangiopathy, which resulted in more dialysis. This patient continued to have progressive disease considered unrelated to gene therapy by the trial investigator as well as his transplant cardiologist and successfully went on to receive a heart transplant. The patient is currently doing well clinically and of course resolution of this baseline biography that was present prior to treatment. Analysis of the explanted heart demonstrates fibrosis that was consistent with end stage Danon disease. Our belief has always been that the onset of fibrosis in the year or so prior to transplant could diminish the efficacy of gene therapy. This patient exemplifies the importance of early intervention in this disorder. We at Rocket do not consider this a safety issue and it is not considered related to the whole. We believe it does highlight the importance of the right timing in order for gene therapy to be fully effective. In discussions with the FDA, on this case, we have refined our eligibility criteria to focus on patients earlier in disease. Now, importantly, as of this past week, we have submitted all requested changes to the FDA and have confirmation that we have agreement on the updated protocol. As mentioned, we expect that we can resume the trial in Q3 with the revised eligibility criteria in place and refined safety measures in place. Moving forward, we have inbound interest from more than 20 patients for participation in the trial and we look forward to progressing rapidly towards Phase 1 completion and the Phase 2 registration trial. One final point on Danon, throughout the duration of this hold, we've had an exceptionally collaborative discussion and dialogue with the agency. With our confidence in the low dose and the modifications to our clinical trial protocol, we are truly excited about the prospects for the Danon program and look forward to presenting longer-term data for both the low and higher dose patients in the fourth quarter of this year. Now turning to our lentiviral programs, we've provided updates at ASGCT for our Fanconi Anemia, LAD-1 and PKD programs and continue our momentum for regulatory filings. For the final line program, we are deeply saddened that the first patient treated in our infantile malignant osteopetrosis Phase I trial had passed away from likely non-gene therapy-related pulmonary complications with autopsy-confirmed evidence of pulmonary hemorrhage that was very likely related to thrombocytopenia following conditioning therapy and also related to underlying osteopetrosis. Of note, pulmonary complications occur more commonly in osteopetrosis patients relative to many other non-malignant immunologic diseases, especially in those patients who are undergoing transplant. Consistent with the protocol, we have paused enrollment, pending a comprehensive evaluation in collaboration with an independent data monitoring committee. We look forward to providing updates in all our programs in the fourth quarter of 2021. Finally, as many of you may know, Claudine Kraus will be transitioning out of Rocket to take on a CFO role at another company. Claudine has been with us Rocket for 3.5 years and has been an integral part of our growth story from the days of Inotek for those who were there then, to a progressed to a mid-cap public company. While we are and I personally am sad to see Claudine leave us, we are tremendously excited for her and sincerely thank her for her contributions here at Rocket. Now I'll pass it to Claudine.

Thank you, Gaurav. Looking back, Rocket has had extraordinary growth. Since going public, the company has already delivered a lot of value to shareholders. I look forward to seeing Rocket's continued success in the future over the long term. I am truly grateful to be a part of this journey. Mayur?

Thank you, Claudine. This concludes our prepared remarks. The Rocket executive team is now happy to address any questions on this update. I'll turn the call back over to the operator for Q&A.

Hey, guys. This is Ashwin on for Greg. Thanks for the questions. So it seems like you're pretty much aligned with FDA at this point for resuming Danon. Is there anything else that needs to be done before getting that study started? And just kind of tacked on to that a little bit, with this upcoming AV gene therapy icon with. Is any chance that's a gating factor? If not just what are your general expectations for that outcome? Thank you.

Thanks for your question. So as of last week, we have confirmation of no further clinical contacts in the protocol. We respect the FDA process, and we're waiting for the FDA to complete their full review. That's what we can say at the moment. With regard to the upcoming Advisory Committee Meeting, I will actually pass this over to Dr. Gayatri Rao, who is one of the Rocket executive team members and who, as you may know, was the Head of the Office of Orphan Drug Products for seven years at the FDA and now working on this. Gayatri?

Thanks. Hi, everybody, this is Gayatri Rao. To answer this specific question related to the advisory committee meeting, as far as we know, we really have no reason to believe that there's any sort of relationship between this clinical hold and the timing for the Advisory Committee Meeting. It's certainly inconsistent with all the communications that we've had with the agency to date. With respect to the meeting itself, we're looking forward to engaging in the meeting and listening and learning from the discussion there.

Good afternoon. Thank you for taking our questions. Regarding the thrombotic microangiopathy, could you provide details about the reclassification of SAE? Has this been taken into account in the mitigation strategy you submitted last week? Additionally, as a follow-up to your May call where you discussed two main areas related to the resumption of the trial—risk mitigation and eligibility criteria—has there been any change in your perspective or any updates to that proposal since the May discussion? Thank you.

Absolutely. So the SAE reclassification was based on recent guidance that we've gotten from the agency. It is reflected in certain protocol changes that will define such events as SAE in the future design. So it's really part of a tightening of protocol measures and safety monitoring. With regard to what we have said in May, it's the same thing. We have defined these monitoring parameters more closely. We define handling of SAE. We timed some of the safety guardrails around depression and inhibition and slightly refined eligibility criteria to focus slightly earlier on end-stage disease patients. Those are the same points that we had anticipated in May, based on the initial FDA call, and they remain the exact same.

Good afternoon, and thank you for taking our question. Just about the deaths that happened on the IMO study. Is there really any significant differences between the conditioning regimen seeing and transplants in these patients versus the gene therapy?

Okay, you mean versus other gene therapies?

No, just versus hematopoietic stem cell transplant, which is sometimes known as the standard of care.

Got it. Is there any difference between the deconditioning used in osteopetrosis gene therapy versus osteopetrosis transplant? That's what you're asking.

Hi, this is Jonathan Schwartz. The conditioning regimen that's used in the osteopetrosis gene therapy study is an amyloidosis B cell tran governed by pharmacokinetic guidance or TDM therapeutic drug monitoring. In general, this is a less extensive, mild suppressive and less extensive immunomodulatory regimen compared to what would be utilized in an allogeneic transplant for this condition. Typically, your allogeneic transplant regimens utilize combinations of amyloidosis therapy, sometimes cycloquesoc and cyclophosphamide, total body irradiation and different chemotherapy regimens and also utilize immunosuppressive or lympho-suppressive therapies as well. So this is a less extensive, but nonetheless, an amyloidosis conditioning regimen that's part of our gene therapy program.

Did that answer your question? Sir? Do you have a follow-up?

No, I do not have a follow-up. That does answer my question. Thank you.

Great, thanks for taking my question. Gaurav, maybe two questions. The first one is when you did your echoes, did you see any left ventricular ejection fraction benefits? Or were patients essentially sort of normal at baseline? And what about stroke volume because it's obviously related to cardiac output? And then any updates on six-minute walk testing with longer follow-up? And with all of that in mind, based on what you're seeing, what do you think might be a primary endpoint for the pivotal?

Hi, Yaron. On the echo ejection fraction, many patients—most patients have preserved ejection fraction until they reach a stage disease. This is true for most of the patients that have been enrolled in the trial. We have disclosed previously that the last patient who did, as I mentioned earlier, move on to have a transplant. That patient was starting to lose cardiac function. More on that as we update our criteria. Sorry, you have to ask the second one again; a couple in there.

Yeah, the second one, what about stroke volume, because it's obviously a determinant of cardiac output. And then six-minute walk testing?

Stroke volume, and then we'll get to the six-minute walk. On cardiac output, the data that was revealed in December, there is the current data set that we're working on that we've also shared with the agency. Some of these patients do start having worsening cardiac output even before there's a loss of ejection fraction. In two of the three patients we have mentioned, we have started to see increases in cardiac output as measured by the basic dynamics. In terms of six-minute walk tests, we have now—this is new information from before—demonstrated six-minute walk test stabilization or improvement in all three of the low dose patients. So that's the law of site stabilization, or improvements in BNP as well as your consultation class. So that's the information. On the endpoints, we have cast a wide net in terms of capturing appropriate endpoints to help us guide towards phase two. These include biomarkers and the kind that we've discussed, BNP, clearance, as well as imaging endpoints such as injection fraction, clinical functional endpoints, such as six-minute walk test, or even quality of life endpoints such as NYHA class. So any of these could be part of the endpoints; we can't speculate on what those will be until we have an end of Phase 1 discussion with the FDA. I think there's been about a quarter delay here on the trial right now. At the same time, we've had a collaborative discussion with the FDA. Sometimes you don't have these discussions about endpoints until later in development. We're hopeful that potentially we can expedite the trial based on the conversations we're having right now.

And to make sure I got that right, the six-minute walk test, I'm sorry, if I missed it. You mentioned you saw an improvement in the six-minute walk and in NYHA class, and I'm sorry, in BNP and New York art class. But did you also say the six-minute walk was stabilized or improved?

Yeah, so I'll go into detail. All three patients have stabilization or improvements in BNP, six-minute walk test and cardiac output—sorry, BNP, six-minute walk test and heart lung. All three patients have stabilization or improvement. The two patients who have monitored immune suppression regiment and were closely monitored, those two patients specifically had drops in BNP from 75% to 79% versus baseline. They also had improvements in New York Heart Association class. Those are the two patients who had the larger immune suppression. But all three patients had stabilization across all parameters. Six-minute walk test specifically, we haven't revealed that data. We will in the fourth quarter, but patients have been stable or improved in all three of those patients as well at this point.

Hey, thanks for taking the question. My first question is are there any changes to the protocol for Danon disease that can potentially change the proportion of patients that would be eligible for the trial and follow-up?

Hi, Mani. We are identifying patients that we would consider end-stage disease. We've always said that in the last year or so prior to transplant, the onset of fibrosis is such that gene therapy probably would not be affected. Those patients were never considered to be part of the treatable population. So overall, the answer is it does not change the treatable or addressable market.

Great. You said you're looking forward to meeting and listening and learning at the September ADCOM. Can you confirm whether or not you're invited or will be participating in the proceedings yourself?

Yeah, we have had no discussions with the FDA about the ADCOM. Today, we have not been invited, but we'll certainly be listening.

Thanks for taking the question. With the agreement from the FDA not to proceed with the high dose, what should we expect for the clinical progression of this program? Is it the lower dose with more adult patients, and then going into a pediatric population, or do you plan on kind of advancing in the pediatric population once you can re-enroll patients into the trial? And then I had a question on the special regimen?

Hi, thanks for the question, Raju. Our intent is to move forward right away with the pediatric population logos and we'll have an update as that happens.

Okay, great. And maybe can you just clarify the changes that were made to the immunosuppression regimen as far as complement activation goes? That would be helpful. Thanks.

We will definitely update as the trial progresses and certainly in the fourth quarter. I don't want to provide too many specifics during an active FDA dialogue. But yes, we will definitely update. There's nothing in there that we would consider major. It's refinements, revisions, tightening of the protocol. And nothing that really affects the types of patients that we can treat other than the eligibility points made or affects the trial conduct in any way.

Hey, thank you for taking my question. I have just a couple. One is on the patients with fibrosis. You've defined the market as about 33,000 patients across the U.S. and the EU. Is that 30,000 patients with fibrosis that are in advanced stages, or how are you whittling down from there to your enrollment criteria?

Yeah, that's a good question. We think that the number of patients with fibrosis is probably about the impact of gene therapy is very small. It's really going to be boys in the months and maybe a year or so leading up to the actual heart transplant, or unfortunate cases of death. Females, which is a population we haven't really talked about yet, and certainly very liable as we move the program forward, have different sorts of heart disease, and certainly would not be affected in the same way. So I think that if you're looking for exact numbers within those 30,000, those numbers are general there. We think if anything, they're going to get validated by a third party. As we capture even more types of mutations, there's a possibility that those numbers could expand. So I don't think that sliver of sort of patient baseline characteristics that will eliminate end-stage diseases is going to get into that progress number too much.

Yes, thank you. And you've mentioned females consistently since the start of the trial. What exactly do you need to see in the current patients that are enrolled to move forward with girls?

With females? We don't really need to see that much. I think we want to get a little bit closer, further into the Phase 1 and start thinking about what Phase 2 design will look like in boys first, but there's nothing more we really need to see to start a trial on females. We have not given any guidance on when that trial will start, but it's certainly in the near to medium term plans.

Got it. Okay. And just to clarify, the Phase 2 trial you're planning will be only in boys then?

The current Phase 2—not the current, the upcoming Phase 2 will be based on the current Phase 1, and we would want to extrapolate what we learned in Phase 1 to Phase 2. So that first trial, which we hope will be registration in nature, wouldn't be limited to boys. In parallel, we would start exploring a trial in females that would support a separate trial.

Great, thanks for taking the question. Just continuing on the topic of the Phase 2 registration study for Danon, what kind of data are you looking to capture from the pediatric patients enrolled in that Phase 1 study? And how do you think that will ultimately inform the design of the Phase 2? What are the different parameters here you're considering that are still not yet determined that will be informed by Phase 1? And then separately for the unfortunate patient who passed away in the IMO study, are there any unique features about that patient that might have explained the unfortunate outcome whether they were older or more advanced disease than patients who might have otherwise gone for a traditional stem cell transplant?

Right, thanks, Josh. So in terms of what we would need to see in the pediatric Phase 1 path to start Phase 2, I think that's the discussion that obviously we'll have with the agency at the end of the Phase 1 meeting. If we see more of what we saw in the low dose adults and confirmation of the potential prospect of direct benefit of pediatrics, if we can confirm that, then, we'll be moving toward Phase 2 relatively rapidly. In terms of how to define the final endpoint for the Phase 2 trial, I think that's still under discussion that will be had as soon as possible. I think the dialogue we've been having over the last several weeks hopefully primes the end of Phase 1 dialogue and accelerates Phase 2 development plans for pediatrics, as well as adults potentially. On the osteopetrosis patient, I will defer to Jonathan, whether there were any differences in that patient versus other osteopetrosis patients that might have predisposed.

Can you repeat the question with respect to the osteopetrosis patient?

Yeah, Jonathan, just wondering if there are any clinical features that might have portended the outcome that they had whether it was a more advanced disease or an older patient who maybe had not been eligible for an earlier stem cell transplant, that might explain why they had that death.

Yeah, so we'll provide more comprehensive information regarding that specific individual as we disclose clinical data at relevant conferences later this year. I don't think that there was necessarily anything that we would identify in this patient as either low or high risk. One thing that we're very much aware of is that in osteopetrosis, many of these patients do have chronic lung compromise, that's related to the bone abnormalities that the ribs cause a restricted lung pattern. Some of the sinus abnormalities create sort of a chronic inflammation in the bronchitis and pulmonary parenchyma, which is probably why these patients do have a high degree of pulmonary complications in allogeneic transplant settings. Obviously, our intent is to provide a therapy that is less overall chemo than you'd have in a transplant. But nonetheless, you're still talking about many of these patients having fairly complex lung environments. I don't think we can comment right now that there was anything specific about this patient that we'd be able to say made him or her different from a typical osteopetrosis patient. All these kids have pretty severe underlying disorders.

Okay, may I ask one quick follow-up on the Danon pediatric patients and next phase of the trial? If they are younger, are they unlikely then to have baseline abnormalities that would be amenable to improvement? And I guess for older patients, you could see the improvement in BNP and performance and heart failure if you're enrolling younger patients. Are you unlikely to see that just because they have not deteriorated to a degree that they would have meaningful baseline abnormalities?

Hi, Josh, Gaurav here. We are treating several pediatric patients who are experiencing the onset of cardiac disease even before adolescence. The cutoff age for young adults is 15, and anyone below that is categorized as pediatric. Although the disease inevitably results in heart failure at some point, it varies widely among individuals. Many pediatric patients exhibit some signs or symptoms of cardiac disease, and those are the ones who will be included in the pediatric Phase 1 trial. The goal is to potentially move to therapy even before cardiac disease begins as a preventative approach, but that isn't the primary focus of this trial. All pediatric patients will show some sign or symptom of class 2 heart failure or higher. And before we move to the next question, Josh, I also wanted to add that in terms of the protocol, we have defined measures by which we apply for trial. We have shared this information with the FDA, and we have not been asked to put the trial on hold. It's a self-mandated pause based on the protocol, just to be clear.

Also, Josh, I know we're spending a lot of time. You had asked about what other information could help us move the trial, the pediatric trial forward into Phase 2. We're also developing a final version of our natural history output. We're learning a lot about how patients decline, especially in the early teenage years. We hope that side by side with the activity that we're starting to see in the low dose can justify a trial that could potentially be a single-arm trial. So that's the idea here, moving to Phase 2.

Hi, thanks for taking the questions. So I want to ask about the decision to discontinue the high dose. I mean, clearly, it makes sense for all the reasons we talked about. But I remember you had pursued it, in part, because you thought there may be some extra cardiac benefits. So without capturing dose now that you have the option of the high dose, do you think that impacts the overall value proposition of the gene therapy to any significant degree?

So Danon disease is multi-organ, as you say. It would be nice to treat the full spectrum of disease if possible. However, the mortality in this disease is cardiac. We were able to address the cardiac aspects of the disease. Extending life is, in our estimation, the ultimate value proposition, especially if we can confirm normal longevity on these patients who would otherwise pass away or be in a heart transplant by age 19, or 20. So it was a strategy that we had in place, but I think we go with what works and what works in a very major way.

Understood, thank you for that. Can you clarify what the appropriate endpoint for Phase 2 in Danon is? Is your baseline assumption that the approval you anticipate will be expedited? Or do you believe you will be able to secure full approval and then use that to conduct additional clinical work after the initial approval?

Yeah, it's hard to speculate at this point. I think that we have a range of biomarkers that could support an accelerated approval plan. At the same time, we also recognize that a mortality benefit is the ultimate marker of clinical success here. So, at the moment, we can't really speculate. But we hope to have answers as we start having the Phase 1 biological agency. I will also ask Jonathan to weigh in here, and also comment on some of the other extra credit manifestation points that were there.

Thank you, Gaurav. Jonathan Schwartz here. Again, I think it's important to emphasize that although obviously the cardiac disease is fatal in essentially all male Danon disease patients, and that's where we'll build the endpoint around, I don't think we can yet discount whether the low dose can or can't affect the non-cardiac manifestations. Importantly, if you look at them in female patients, they don't have substantive extra cardiac manifestations. So we may well see benefit in neuromuscular or neurocognitive aspects of the disease in these male Danon patients with the levels of transaction that has protein expression that has been seen in the low dose adults treated to date. Likely, that will take a little bit longer to determine than the cardiac benefits that we believe we have seen to date. But certainly is possible that we may also substantively affect those non-cardiac elements in these patients, just as the females who have likely 30% to 50% of normal lab-to-expression that has been seen.

Hi, thanks for taking my questions. As it relates to the patient that underwent heart transplant, you mentioned fibrosis was apparent. However, was there any worsening myocarditis observed in the expanded heart, or evidence that an immune response contributed to the need for heart transplant? And if so, has there been anything similar observed in biopsies from patients?

Hi, Patrick, no, no myocarditis, no inflammatory changes. We also didn't see any of those technologies on the other low dose patients that we've looked at.

Hi, good evening. Thanks for taking the question. I joined late, so sorry if the questions already being addressed. But maybe just a clarification question as it relates to the potential pivotal Phase 2 for Danon? Should we be—are you contemplating a single program that addresses both adolescence and pediatrics? Or would they be programs run in parallel? And I guess to the extent it's the latter, can you just maybe articulate what some of the gating factors would be to an end Phase 1 meeting? The data that you have so far, in terms of patient numbers in the follow-up sufficient? Or would you need to see incremental data with the revised protocol, or new patient data with the revised protocol?

Yeah. So with regard to the start of Phase 2, what we need to see is, number one, some data in pediatrics, for sure. We need to see the output from a natural history so that we can define the protocol design and also figure out what the right endpoints are going to be in cooperation with the FDA. Those are the things that are engaging. We don't think that we need to add more patients to get there. If anything, actually, since we've cut out the high dose now, the number of patients needed to the end of Phase 1 meeting is likely going to be smaller. For your first question, we anticipate one trial for pediatrics and adolescence. We don't anticipate two separate ones there. So right now, the gating factors are the ones you described, and we hope to do… Thank you, everyone, for participating in today's call, and we look forward to updating you again soon.

Thank you, ladies and gentlemen. This concludes our conference and we thank you for your participation. You may now disconnect.