Rocket Pharmaceuticals, Inc. (RCKT) Earnings

Management highlights

- Danon clinical trial: Reiterating Q3 resumption plan based on FDA interactions; low dose showing increasing and durable benefit with improvements in cardiac tissue, BNP, and cardiac output; removing high dose from future dosing plans. - Fanconi Anemia LAD-1 and PKD: On track with Q4 clinical updates. - Infantile Malignant Osteopetrosis (IMO) trial: First patient passed away due to non-gene therapy related pulmonary complications, enrollment paused pending evaluation. - Claudine Prowse's transition: Leaving Rocket to take CFO role at another company.

Guidance

- Reiterated expectation to resume Danon clinical trial in Q3. - For Danon, low dose demonstrating benefit, high dose removed from future plans. - Fanconi Anemia LAD-1 and PKD on track with Q4 updates.

Segment performance

No detailed financial performance by product segments provided in the transcript.

Risks & headwinds

- Uncertainty regarding realization of forward-looking statements. - Risks associated with clinical trial outcomes, including safety and patient-specific factors. - Pulmonary complications risk in IMO trial patients.

Analyst Q&A

• Q: Hey, guys. This is Ashwin on for Greg. So it seems like you're pretty much aligned with FDA at this point for resuming Danon. And I guess 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 [indiscernible]. Is any chance that's a gating factor? And if not just what are your general expectations for that outcome?

  A: 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. And 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? Gayatri: Thanks. Hi, everybody, this is Gayatri Rao through how 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. And 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.

• Q: Great. Good afternoon. Thanks for taking our questions. On the thrombotic microangiopathy, are you able to discuss the details behind the reclassification of SAE [ph]? And I guess, does that have anything to do with -- or has that been reflected in the mitigation strategy as you submitted it last week? And I guess a follow up to that is, in the May call, you talked about two buckets as it pertains to the resumption of the trial, that being risk mitigation and eligibility criteria. So has anything changed in your view or anything in that proposal changed since that May update?

  A: Absolutely. So the SAE, reclassification was based on recent guidance that we've gotten from the agency. And it is reflected in certain protocol changes that will in the future design such events as SAE, I think that's the bottom line. So it's really part of a tightening of protocol measures and safety monitoring. And 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.

• Q: 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?

  A: Okay, you mean versus other gene therapies?

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

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

• Q: Yeah.

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

• Q: Hey, guys. I have just a couple. One is on the patients with the fibrosis. You've kind of defined the market as about 33,000 patients across the U.S. and the EU. And is that 30,000 patients with fibrosis that are in advanced stages, or how are you kind of whittling down from there to your enrollment criteria?

  A: Yeah, that's a good question. We think that the number of patients with fibrosis, that's 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 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. Now. 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 state diseases is going to get into that progress number too much.

• Q: Great, thanks for taking the question. With the agreement the FDA cannot go into 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?

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

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

  A: Yeah, that's a good question. We think that the number of patients with fibrosis, that's 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 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. Now. 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 state diseases is going to get into that progress number too much.

• Q: Great, thanks for taking the question. Just continuing on the topic of the Phase 2 registration study for Danon, what kind of data is that that you are looking to capture from the pediatric patients enrolled in that -- in the 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 -- with IMO who passed away, are there any unique features about that patient that 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?

  A: Right Thanks, Josh. So in terms of what we would need to see in the pediatric Phase 1 LOTOS [ph] to start Phase 2. I think that's the discussion that obviously we'll have with the agency at the end of Phase 1 meeting. I think 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. Jonathan: Can you repeat the question with respect to the osteopetrosis patient?

• Q: 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 I guess maybe capturing dose now that you have the option of the high dose, do you think that that impacts the overall value proposition of the gene therapy to any significant degree.

  A: 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. So we were able to address the cardiac aspects of disease. Extending life is in our estimation, the ultimate value proposition, and especially if we can confirm normal longevity on these patients who would otherwise pass away or being 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.

• Q: 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 I guess maybe capturing dose now that you have the option of the high dose, do you think that that impacts the overall value proposition of the gene therapy to any significant degree.

  A: 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. So we were able to address the cardiac aspects of disease. Extending life is in our estimation, the ultimate value proposition, and especially if we can confirm normal longevity on these patients who would otherwise pass away or being 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.

• Q: Hi, thanks for taking the 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 and biopsies from patients [ph].

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

• Q: 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 when in parallel? And I guess to the extent it's the latter, can you just maybe just articulate what some of the gating factors would be to an end to 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?

  A: Yeah. So with regard to 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. And 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 ne meeting is likely going to be smaller. So that's one point I want to make. 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...