Rocket Pharmaceuticals, Inc.

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 a listen-only mode. Later, we will conduct a question-and-answer session. If you have a question, you can enter the queue by pressing star, then 1 on your touch-tone phone. I will now turn the call over to your host, Mayura Cassetti, Director of Business Development and Operations.

Thank you, Vanessa. Good afternoon, everyone. This is Meir Cassetti, 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 State 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 this statement for 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 in 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 31st, 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 Shyam, Chief Executive Officer, Dr. Jonathan Schwartz, Chief Medical Officer and Clinical Development Senior Vice President, Dr. Gayathri 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 the four key take-homes for today. First, regarding the Danube clinical home. 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 acutely. Second, again, the low dose is demonstrating increasing and durable benefits. We will go over key data points, including some new ones in a minute. Third, For Dannon, we are removing the high dose from future dosing plans. Four, panconi anemia, LAD-1, and PKD remain on track, and we will provide further clinical updates in Q4. Those are the key takeaways. We'll now get into some more details, starting with Dannon. 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 complement inhibition protocols to bolster safety guardrails. In addition to these protocol updates, we've had a chance to review updated low-dose data sets with the FDA that Rocket believes is supportive of its potential as a viable phase 2 dose. Notably, photographing evidence for all three low-dose patients showed improvements, meaning decrease in autophagic vacuoles, a hallmark of Danden disease pathology, as assessed by electron microscopy of cardiac tissue via endomyocardial biopsy. Additionally, two of the three low-dose patients with closely monitored immunosuppressive regimen compliance demonstrated improvements in New York Heart Association class from 2 to 1, which translates to no impairment of function. These patients also demonstrated substantial improvement of a key marker of heart failure, BMP, 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 BMP six-minute walk test, as well as New York Heart Association class. Given the activity observed in patients in the low-dose cohort, and importantly to mitigate associated safety concerns in the E14 range, we have decided to forego pursuit of the higher doses, meaning 1.1 E14 vector genomes per kilogram or higher. This is a decision that was made in agreement with the FDA and allows us to focus fully on the low-dose moving forward, the 6.7 to 13, also reduces the total number of patients needed in our phase one study, and potentially allows for more rapid progression to phase two. Now, as disclosed in December of 2020, one patient in the high-dose cohort who was the heaviest patient treated to date and had highly advanced disease developed complement mediated thrombotic microangiopathy which resolved fully with transient hemodialysis. 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 reports resolution of his baseline biopsy that was present prior to treatment. Analysis of the explanted heart demonstrates fibrosis that was consistent with end-stage data 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, and this patient exemplifies the importance of earlier 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 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 toward Phase 1 completion and the Phase 2 registration trial. One final point on damage. Throughout the duration of this hold, we have had an exceptionally collaborative discussion and dialogue with the agency. And with our confidence in the low dose and the modifications to our clinical trial protocol, we are truly excited about the prospects of our DANID program and look forward to presenting longer term data on both the low and higher dose patients in the fourth quarter of this year. Now turning to our lentiviral programs. We've provided updates to ASGCT for our Fanconi anemia, LAD1, and PKD programs continue our momentum toward regulatory violence. For our final LENTI program, we are deeply saddened that the first patient treated in our infantile malignant osteocatrosis phase one trial has 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. It 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 on all of our programs in the fourth quarter of 2021. And finally, as many of you may know, Claudine Krause will be transitioning out of Rocket to take on a CFO role at another company. Claudine has been with Rocket for three and a half years and has been an integral part of our growth story from the days of Inateck for those who were there then, who were private 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. And 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. And I look forward to seeing Rocket's continued success in the future over the long term. I am so truly grateful to be a part of this journey. Mayor?

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.

And thank you. We will now begin our question and answer session. With your question, please press star, then 1 on your touch-tone phone to enter the queue. If you wish to be removed from the queue, you can press the pound sign or the hash key. If you're using a speakerphone, please pick up the handset first before pressing the numbers. In the interest of time, we ask that you please limit yourselves to one question and one follow-up question, and we thank you. Our first question is from Greg Harrison with Bank of America. Please go ahead.

Hey, guys. This is Aspen on for Greg. Thanks for the questions. So, it seems like you're pretty much aligned with FDA at this point for resuming Gannon. I guess, is there anything else that needs to be done before getting that study started? And just to kind of tack on to that a little bit, with this upcoming AAV gene therapy adcom that FDA is running, is there any chance that's a gating factor? And if not, just what are your general expectations for that adcom? Thank you.

Hi. Gaurav here. Thanks for the question. So as of last week, we have confirmation of no further clinical comments to the protocol. We respect the FDA process and we're waiting for the FDA to complete this 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. Guy P. Rao, who is one of the rocket executive team members and who, as you may know, I was head of the Office of Orphan Drug Products for seven years at the FDA and now working with this.

Thank you. Thanks for us. Hi, everybody. This is Gayathri Rao. To answer the 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 or the advisory committee meeting. And it's certainly inconsistent with all of the communications that we've had with the agency to date. With respect to the meeting itself, you know, we're looking forward to engaging in the meeting and listening and learning from the discussion there.

Okay. Thank you.

And thank you. Our next question is from Dagan Ha with Stifel.

Great. Good afternoon. Thanks for taking our questions. On the thrombotic microangiopathy, are you able to discuss the details behind the reclassification as SUSAR? And I guess, does that have anything to do with, you know, or has that been reflected in the mitigation strategy as you submitted it last week? And I guess a follow-up to that is, you know, 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? Thanks, Gaurav.

Absolutely. So the SUSAR re-classification 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, define such events as SUSARs. I think that's the bottom line. So it's really part of the timing of protocol measures and safety monitoring. And with regard to what we had said in May, it's the same thing. We have defined these monitoring parameters More closely, we've defined handling of SAEs. We've tightened some of the safety guardrails around immune suppression and complement inhibition and slightly refined the eligibility criteria to focus slightly earlier on treatments that avoid 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.

Thank you very much.

And thank you. Our next question is from Gil Bloom with Needham & Company.

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

You mean versus other gene therapies?

No, just versus the medical edX stem cell transplant, which is sometimes used as standard of care.

Got it. Is there any difference between the conditioning used in osteopetrosis gene therapy versus osteopetrosis transplant? That's what you're asking, correct? Yep, correct. I'll pass that over to Dr. Jonathan Schwartz.

Hi, this is Jonathan Schwartz. The conditioning regimen that's used in the osteopetrosis gene therapy study is myeloablative busulfan that's governed by pharmacokinetic guidance or TBM, therapeutic drug monitoring. In general, this is a less extensive treatment myelosuppressive 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 myeloablative therapy. Sometimes that's usulfan and cyclophosphamide or total body irradiation and different chemotherapy regimens. And then they also utilize immunosuppressive or lymphosuppressive therapies as well. So this is a less extensive but nonetheless myeloablative conditioning regimen that's part of our gene therapy program.

That did 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.

Thank you very much. Our next question is from Jeroen Werber with Cowan.

Great. Thanks for taking my question. Gaurav, I have maybe two questions. The first one is when you did your ECHOs, 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 a pivotal? Thank you.

So on the injection fraction, on the echo for injection fraction, many patients, if not most patients, have preserved injection fraction until they reach end-stage disease. This was true for most of the patients that have been enrolled in the trials. We have disclosed previously that the exception here was that 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. And, sorry, you have to ask the second one again. There's a couple in there.

Yeah, the second one, what about stroke volume? Because that's obviously a determinant of cardiac output. Yeah, and it's a six-minute walkback.

stroke volume, and then we'll get to six minute walk at end points. So 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. And in two of the three patients I've mentioned, we have started to see increases in cardiac output as measured by the basic tumor dynamics. In terms of six-minute walk tests, we now, and this is new information from before, have demonstrated six-minute walk test stabilization or improvement in all three of the low-dose patients, and that's alongside stabilization or improvement in BMP as well as New York Heart Association class. So that's new information. And the endpoints We have cast a wide net in terms of capturing appropriate endpoints to help us guide toward phase two. These include biomarkers of the kind that we've discussed, ESP, even vacuole clearance, as well as imaging endpoints such as ejection fraction, clinical functional endpoints such as six minute walk test, or even quality of life endpoints such as NYHA class. 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 one discussion with the FDA. I think the, you know, 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

And 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 six-minute walk in New York Heart class, and I'm sorry, in BNP in New York Heart class. But did you also say six-minute walk, it was stabilized or improved?

Yeah. So I'll go through the details. All three patients have stabilization or improvement in BNP, six-minute walk test, and cardiac output. And sorry, BNP six-minute walk test, and heart blast. All three patients had stabilization or improvement. The two patients who had monitored immune suppression regimen that was closely monitored, those two patients specifically had drops in BMP from 75% to 79% versus baseline. And also they had improvements in New York Heart Association class. Those are the two patients who had the monitored immune suppression regimen. But all three patients have stabilization across all parameters. Six-minute walk test specifically, we haven't revealed those data. We will in four quarters, but it's been stable or improved in all three of those patients as well at this point.

Great. Thank you.

And thank you. Our next question is from Manny Forohar with SPV Lyric. Please go ahead.

Okay, thanks for taking the question. My first question is, are there any changes to the protocol for Danden disease that could potentially change the proportion of patients that would be eligible for the trial? I have a follow-up.

Hi, Mike. 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 effective. 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 here.

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

Yeah, we have had no discussions with the FDA about the ATCOM. To date, we have not been invited, but we'll certainly be listening. Thanks. That's helpful, guys.

And thank you. Our next question is from Raju Prasad with William Blair.

Thanks for taking the question. With the agreement of the FDA to not 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 into the pediatric population once you can re-enroll patients into the trial? And I have a question on the immunosuppression regimen.

All right. Thanks for the question, Roger. Our intent is to move forward right away with the pediatric population blood dose, and we'll update as that happens.

Okay, great. And maybe if you just clarify the changes that were made to the immunosuppression regimen as far as complement activation goes, that'd 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 point we made or affects the trial conduct at any rate.

Great. Thank you.

And we have our next question from Esther Regevalu with UBS. 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 US and EU. And, you know, does that 32,000 exclude the patients with fibrosis that are in advanced stages? Or how are you kind of whittling down from there to your enrollment criteria?

Yeah, that's a good question. We think that the number of patients with fibrosis that's prevalent enough to prevent impact of gene therapy is very small. It's really going to be boys in the month and maybe year or so leading up to the actual heart transplant or in unfortunate cases, death. Females, which is a population we haven't really talked about yet and certainly very viable 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 the, you know, if you're looking for exact numbers within those 30,000, those numbers are general. We think, if anything, they've been validated by a third party now. And as we capture even more tactile mutations, there's a possibility that those numbers could expand. So I don't think that that sliver of sort of baseline characteristics that would eliminate end-stage disease is going to be, is going to, you know, get into that problem number too much at this point.

Yeah, thank you. And we kind of, you know, you kind of mentioned females consistently since the start of the trial. What are, you know, what exactly do you need to see in the current patients that are enrolled to, you know, to move forward with girls? With females?

With females. Yeah. Sorry. No, no. We don't really need to see that much. I think we want to get a little bit further into the phase one and start thinking about what phase two design would look like in boys first. But there's nothing more we really need to see to start a trial in females. We have not given any guidance of when that trial will start, but it's certainly in the near to medium term plan.

Got it. Okay. And just to clarify, the phase two trial you're planning will be only in voice then?

The current phase two would, you know, not the current, the upcoming phase two would be based on the current phase one. And we would want to extrapolate what we've learned with phase one to apply to phase two. So that first trial, which we hope will be registration in nature, would be limited to voice. And in parallel, we would start exploring a trial in email. that would support a separate trial that's registration . Okay.

Thank you. That's very helpful. Thank you. Our next question is from Josh Zimmer with Evercore.

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

Great. Thanks, Josh. So in terms of what we would need to see in the pediatric phase one low dose to start a phase two, I think that's a discussion that obviously we'll have with the agency at the end of phase one meetings. I think if we see more of what we saw in the low-dose adults and confirmation of potential prospect of direct benefit in pediatrics, if we can confirm that, then we'll be moving towards Phase II relatively rapidly. And in terms of how to define the final endpoint for the Phase II trial, I think that's still a discussion that will be had as soon as possible. I think the dialogue that we've been having over the last several weeks hopefully primes the end of phase one dialogue and accelerates phase two development plans for pediatrics as well as adult protection. On the osteopetrosis patient, I will defer to Jonathan if 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 patients?

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

Yeah, so we'll provide more comprehensive information regarding the 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 and some of the sinus abnormalities create sort of a chronic inflammation in the bronchi 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's less overall chemo than you would have in an allotransplant. But nonetheless, you're still talking about many of these patients having fairly complex lung environment. 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 of these kids have pretty severe underlying disorder.

May I ask one quick follow-up on the Dana and pediatric patients in the next phase of the trial? If they are younger, are they unlikely then to have baseline abnormalities that would be amenable to improvement? I guess, you know, for older patients, you could see the improvement in BMP and performance status and heart failure. But 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.

There are a number of pediatric patients who have onset of cardiac disease even earlier than the adolescents that we've been treating. And remember the cutoff here is age 15 for young adults, such as adolescent, and below that is considered pediatric. And the disease is, although inexorably leads to heart failure around the age of 19 or 20, on average, it is heterogeneous. So there are many pediatric patients who do have some signs or symptoms of cardiac disease, Those are the ones that would be enrolled in the pediatric phase one. Ultimately, we may want to move the therapy even before onset of cardiac disease as a preventative measure, but that's not what this trial is about. All pediatric patients will have some signs or symptoms. Class two heart failure or higher is the impact. Okay, got it. Thanks very much. And before we move to the next question, Josh, I also wanted to add an IMO that the protocol has defined measures by which we have paused the 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. And 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 two. We're also developing a final version of our natural history output. And we're learning a lot about how patients decline, especially in the early teenage years. And we hope that that side by side with activity that we're starting to see in a low dose can justify a trial that could potentially even be a single arm trial. So, that's the idea here moving . Got it. Thanks, .

And thank you. Our next question is from David Hong with SMBC.

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

So, dengue disease is multi-organ, as you say. It would be nice to treat the full spectrum of disease if possible. the mortality in this disease is cardiac in origin. So if we're able to address the cardiac aspects of the 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 early to 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. Thanks for that. And then I was wondering with the, you know, as you tease out what's the appropriate endpoints for a phase two in Gannon, do you, is your baseline assumption that the approval that you'll get, would that be accelerated approval? Or do you think, you know, you'd be able to get a full approval Basically, do you anticipate 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 Immortality 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 them in the phase one dialogue with the agency. And I will also ask Jonathan to weigh in here and also comment on some of the other extracardiac manifestation points that were just asked.

Thank you, Gaurav. Jonathan Schwartz here again. I think it's important to to emphasize that although obviously the cardiac disease is what is fatal in essentially all of the male denon 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 Danone female patients, they don't have substantive extracardiac manifestations. So we may well see benefit in neuromuscular or neurocognitive aspects of the disease in these male Danone patients with the levels of transduction and protein expression that have 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 it is possible that we may also substantively affect the non-cardiac elements in these patients just as the females who have likely 30 to 50% of normal LAMP2 expression largely are unaffected by those aspects of this disorder.

Okay. Thanks so much for taking the question.

And thank you. Our next question is from Patrick Dozal with LifeSci Capital.

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 explanted 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 at the low dose? Thanks.

Hi, Patrick. No, no myocarditis, no inflammatory changes in the explanted heart. And we also didn't see any of those pathologies on the other low-dose patients that we've looked at.

Got it. Thanks.

And thank you. Our next question is from Eric Joseph with JPMorgan.

Hi. Good evening. Thanks for taking the question. I joined late, so sorry if the question's already been addressed, but maybe just a clarification question as it relates to the uh potential pivotal phase two for dannon's should we be are you contemplating a single program that addresses both adolescents and pediatrics or would they be programs when in parallel and i guess to the extent it's the latter um can just maybe just um articulate what some of the gating factors would be to um an end of phase one meeting are the data that you have so far in terms of patient numbers and follow-ups efficient, or would you need to see incremental data with the revised protocol, or new patient data with the revised protocol? Thanks.

Yeah, so with regard to the start of phase two, what we need to see is, number one, some data in pediatrics, for sure. And we need to see the output from our natural history so that we can define the protocol design and also figure out what the right endpoints are going to be in collaboration 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 end a Phase I 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 adolescents. We don't anticipate two separate ones there. So right now the gating factors are the ones used. Thank you everyone for participating in today's call and we look forward to updating you again soon.

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