Lexeo Therapeutics, Inc. (LXEO) Earnings Call Transcript & Summary

Good morning, and welcome to Lexeo Therapeutics webcast presentation. [Operator Instructions] As a reminder, this call is being recorded. I would now like to turn the conference call over to Ashley Kaplowitz, Head of Capital Markets at Lexeo Therapeutics. Ashley, please go ahead.

Thank you, and good morning. Earlier today, we issued a press release announcing the finalized registrational trial design for LX2006 for the treatment of Friedreich's ataxia or FA. A copy of the press release and slides related to today's call can be found on our website at lexeotx.com. Joining us in today's call will be Nolan Townsend, Chief Executive Officer; and Nani Bhalla, Chief Medical Officer. Louis Tamayo, Chief Financial Officer, will also be available for Q&A. Before we begin, I would like to remind you that this call will contain forward-looking statements regarding Lexeo's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our filings with the SEC. With that, I would like to turn the call over to our CEO, Nolan.

Thanks, Ashley, and thank you all for joining us today. At Lexeo, we are committed to pioneering meaningful genetic medicines for individuals living with rare and serious diseases, particularly where treatment options remain limited. Today, we're excited to share important progress on our LX2006 program, which we believe has the potential to make a meaningful difference for individuals living with Friedreich's ataxia. As announced in our press release this morning, we have now finalized the pivotal study protocol and statistical analysis plan in support of an accelerated approval pathway for LX2006, establishing a clear framework for execution as we advance the program. SUNRISE-FA 2 is an open-label trial in which at least 13 participants aged 16 and older will receive a single IV administration of LX2006 compared with an untreated control group of at least 13 participants who will not receive LX2006. There will be no placebo or sham procedures for participants in the untreated control group. The inclusion of a concurrent untreated control arm was in response to feedback from the FDA aimed at reducing potential source of bias in the study. We designed this control arm to essentially mirror an external natural history control while being implemented prospectively within the same protocol. This will ensure consistency in study assessments and evaluation methods across both arms. And, importantly, it does not impact key study parameters, including size and duration of the study. In fact, we will now enroll fewer patients in total than the previously guided pivotal study in external natural history control combined. The primary endpoint is LVMI, which will be used to power the study. We are also evaluating several important secondary endpoints, including mFARS, KCCQ, high-sensitivity troponin I, and lateral wall thickness to provide a more comprehensive view of both cardiac and neurologic benefits of LX2006. We believe this study design best positions us to demonstrate meaningful impact on cardiac disease while also aiming to capture broader functional benefit, supporting the potential overall value of LX2006 for Friedreich's ataxia patients. We also continue to engage with the FDA on a confirmatory evidence strategy. To date, discussions have focused on the potential use of certain secondary endpoints at the 12-month time point to support a full approval. After we complete those discussions with the agency, we will provide an update. Turning to CLARITY-FA. Our ongoing natural history study will be used to provide supportive evidence on the untreated disease course for both accelerated and full approval. Enrollment is progressing well with a double-digit number of participants enrolled or imminently enrolling into the study to date. The patients enrolled in CLARITY-FA are eligible to participate in SUNRISE-FA 2 as both studies have identical inclusion criteria. As a result, we have made a strong start identifying potential participants for the pivotal study while finalizing its study design over the past several months. And as noted in our press release this morning, we expect the first patient to enroll from CLARITY-FA into the SUNRISE-FA 2 study by the end of the month. With the protocol in support of accelerated approval in place, we are confident in the trajectory of enrollment going forward. And we have seen acceleration more recently as we've activated additional sites for CLARITY-FA, with greater than 60% of participants coming in over the last 2 months. We currently have 19 sites active across 8 countries with more than half of those sites activated in the last 6 months. We know these are the right centers as they represent leading institutions in FA care and also bring deep experience in gene therapy. Further, as we think about the broader potential of LX2006, we are establishing multidisciplinary teams across these centers, integrating both cardiac and neurologic expertise to ensure we are well positioned to address the full spectrum of disease even as our initial focus remains on the cardiac component. Overall, we are very pleased with the progress to date, and we'll provide enrollment updates at key future milestones. Turning to Slide 5, we are excited to initiate the study later this month. We are targeting a top line data readout in the second half of 2027 and a BLA submission in the first half of 2028. Given the significant urgent unmet need in this patient population, we are taking every possible step to pursue the most expedited path to approval. Overall, this regulatory update reflects many years of work behind LX2006, and we're focused on executing the next phase of development to advance this program forward, including building the commercial foundation needed to support a successful launch. With that, let me now turn it over to our Chief Medical Officer, Nani Bhalla, who will begin by highlighting the significant unmet need in FA, summarize the latest safety and efficacy data for LX2006 and then provide more detail around the finalized study design and statistical plan for the SUNRISE-FA 2 pivotal study.

Thank you, Nolan, and good morning, everyone. Friedreich's ataxia is a rare progressive multisystem disorder affecting approximately 5,000 people in the United States and about 15,000 globally. While it is often thought of as a neurologic condition, cardiac complications are the most common cause of mortality in FA, and there are currently no approved treatments focused on the cardiac aspects of this disease. Nearly all people with FA will develop some degree of cardiac complications over time and up to 40% have left ventricular hypertrophy as defined by an abnormal left ventricular mass index or LVMI. This population represents the key target group for the LX2006 pivotal study, although a broader population has been studied in the Phase I/II trials. Individuals with FA have very low levels of frataxin protein. That deficiency disrupts normal mitochondrial function in the heart and in other tissues involved in the disease. LX2006 has been designed to address the root cause of disease by restoring frataxin. It delivers a functional full-length copy of the frataxin gene using an AAVrh10 vector. This vector has a natural affinity for cardiomyocytes, which allows us to efficiently target the heart and use relatively lower doses, which we believe is differentiating from both an efficacy and safety standpoint. We also designed LX2006 with a CAG promoter, a strong and clinically validated promoter that could drive expression more broadly. While the heart is our primary focus, given its role in mortality, this approach allows for frataxin expression beyond the heart, including in skeletal muscle and potentially in the dorsal root ganglia. On Slide 9, you'll see a snapshot of the data that has been generated to date. I'll start with the cardiac MRI data, focusing on the 6 participants with abnormal LVMI at baseline, which aligns directly with the inclusion criteria for our pivotal study. On average, these patients achieved an 18% reduction in LVMI at 6 months and 23% reduction in 12 months. And looking at the higher dose cohorts 2 and 3, we saw even greater reductions of 28% and 33% at 6 and 12 months, respectively. We are advancing the dose used in cohort 3 into the pivotal study. Just as important, these improvements are durable and, in many cases, deepen over time. A majority of participants reach or remain within the normal LVMI range at their most recent visit with some patients maintaining this benefit out to 3 years post treatment, which we believe is a strong evidence of sustained disease modification. Looking at supportive biomarkers, 16 of 17 participants show reduced or stable troponin I levels, supporting a favorable effect on cardiac injury. And importantly, from a safety perspective, LX2006 continues to be generally well tolerated with no new signals of concern. Overall, these data demonstrate durable, clinically meaningful improvements in cardiac structure and biomarkers, providing strong support for our pivotal study design and the broader development strategy for LX2006. I want to highlight recent data that we shared at ACC on one patient with more advanced cardiomyopathy. While the majority of participants had normal baseline left ventricular ejection fraction and remained stable post therapy, this patient started with significantly impaired cardiac function with a left ventricular ejection fraction of 35%. Following LX2006 treatment, we observed substantial improvements across multiple measures, including an 83% reduction in troponin, a 48% reduction in left ventricular mass index and an increase in left ventricular ejection fraction from 35% to 74% at 18 months. While this is a single patient, it illustrates the potential for LX2006 to meaningfully improve cardiac function even in later-stage disease. Lastly, we also recently shared interim clinical data for LX2006 at ASGCT, where we showed statistically significant improvements in mean mFARS scores for LX2006-treated participants in the Phase I/II studies compared to a propensity-matched control cohort from the UNIFAI natural history study. Relative to baseline, the majority of LX2006 treated participants demonstrate statistically significant mFARS improvement or stabilization at their most recent visit with an annualized difference in progression of 2.3 points per year. These are compelling findings showing that LX2006 may benefit frataxin deficiency in tissues beyond the heart, supported by nonhuman primate data showing expression in the peripheral nervous system and the dorsal root ganglia. The separation from natural history, especially a propensity matched natural history control cohort represents clinically meaningful improvement in this measure of neurologic function specific to FA. Treatment benefit was observed in participants regardless of background use of SKYCLARYS. We believe LX2006 provides a benefit with an effect size that is similar to what SKYCLARYS has demonstrated in its registrational study, albeit run differently. And while a 1- to 2-point improvement on the mFARS scale may sound modest, it has the potential to translate into meaningful functional gains, such as greater ease of daily activities like brushing teeth, handling utensils or dressing. We are very encouraged by this data, particularly as they support the potential for broader utility and a more comprehensive label, including possible use as a confirmatory endpoint. Turning to Slide 12, here, you will see the finalized pivotal protocol details. The study design we shared today builds on our discussions to date with the FDA and incorporates refinements to strengthen scientific rigor while maintaining the same overall study size, duration and open-label framework. Within the SUNRISE-FA 2 pivotal study, each group will have at least 13 participants aged 16 years and older. Participants in the LX2006 treatment group will receive a single intravenous administration of high-dose LX2006 of 1.2E12 vectors per kilogram. The untreated control group will not receive LX2006 or any placebo or sham procedure, and both groups will be followed for 6 months. Participants that are eligible and enroll for CLARITY-FA into SUNRISE-FA 2 will be randomly allocated to LX2006 treatment or the untreated control arm. Random allocation is an important element of this pivotal study design. It is intended to minimize physician selection bias, such as providers selecting patients with certain criteria for LX2006 intervention. It ensures baseline characteristics are balanced and strengthens statistical rigor. We have incorporated specific measures within the statistical analysis plan to ensure the treated and untreated control groups are appropriately balanced, in particular, stratifying the 2 groups so that average baseline LVMI is comparable. The top-line efficacy and safety readout is expected after the last patient has completed the 6-month follow-up. After that, participants in the untreated control will have the option to cross over and receive LX2006 and will then be followed as part of the long-term follow-up for over 4 years. So, we will ultimately generate safety and durability data for a sample of over 25 patients with moderate to severe FA cardiomyopathy. Turning to the next slide. The primary endpoint for SUNRISE-FA 2 is LVMI assessed by cardiac MRI. LVMI is a well-established objective endpoint in FA cardiomyopathy and is clearly linked to cardiac outcomes. Published literature demonstrates a strong link between increased LVMI and an increased risk of mortality in FA, with every 10-unit increase in LVMI associated with a 20% higher risk of death. Importantly, LVMI has also not been shown to have a placebo effect or vary significantly over a 12-month period in FA cardiomyopathy. This study will include participants with abnormal LVMI at baseline, defined as at least 2 standard deviations above the normal mean and is powered to detect an LVMI effect size of 15% or greater. As a reminder, across the 2 Phase I/II studies for LX2006, -- we saw an 18% mean LVMI reduction at 6 months in patients with an abnormal LVMI treated with LX2006 and a 28% mean LVMI reduction at the same time point in participants with abnormal baseline LVMI treated with higher doses of LX2006, which is what we plan to advance into the pivotal study. This reinforces confidence in our ability to meet the endpoint. The FDA also recommended removing cardiac frataxin protein expression as a co-primary endpoint. While frataxin expression played an important role historically and prior data clearly demonstrated a plausible mechanism for LX2006, LVMI remains the most relevant and clinically meaningful cardiac endpoint in this disease. Importantly, removal of this endpoint reduces burden for study participants by eliminating the need for invasive cardiac biopsies, which we believe will meaningfully support enrollment and interest in the study. Although pediatric cohorts will not be included in the top line efficacy analysis, there is significant unmet need among adolescents and younger patients with FA cardiomyopathy. As such, we plan to evaluate the potential of LX2006 in individuals aged 6 to 16 following the establishment of safety in adults. Turning to our final slides. We're pleased with the finalized open-label study design and statistical analysis plan for SUNRISE-FA 2 evaluating LVMI at 6 months. We believe we have landed on a study design that positions us well in generating clinical evidence for accelerated approval. From a manufacturing standpoint, we're in a strong position. The FDA has confirmed that no additional nonclinical murine bridging studies are required and that we are able to use our optimized high-yield SF9-baculovirus manufacturing process to initiate dosing in the SUNRISE-FA 2 pivotal study. Importantly, clinical drug products have already been manufactured at commercial scale and is immediately available for patient dosing, supporting a timely and efficient study start. Looking ahead, we also anticipate some flexibility in PPQ as previously shared, which will support faster timelines for us to reach a BLA filing. I will now turn it back to Nolan.

Thank you, Nani. We believe LX2006 has a clear and compelling path forward with multiple value inflection points in the near, mid and long term. We remain on track to initiate the pivotal study by the end of the month, an important milestone as we advance the program forward. We are proactively and thoughtfully building the commercial foundation needed to support a successful launch. This includes targeted and disciplined investments in launch planning and core commercial capabilities that we believe are critical to long-term success. From an execution standpoint, we are confident in our ability to advance this program. We bring together a leading cardiac genetic medicines platform with proven clinical and commercial experience and a differentiated approach to development and manufacturing. Importantly, these capabilities are built to translate our scientific progress into meaningful outcomes for patients while creating long-term value for shareholders. Thank you for joining today. Those impacted by FA are central to our mission, and we are committed to advancing the development of LX2006 given the urgent need for new treatment options. I will turn it over to the operator to help facilitate the Q&A portion of today's call.

[Operator Instructions] Our first question comes from Mani Foroohar with Leerink Partners.

That looks better if I unmute the line. Congratulations on a great update. Can you walk us through nuances of how a potential label could be influenced by characteristics of the patients enrolled? Is there any possibility that the label could be confined specifically to patients based upon baseline characteristics of severity, et cetera? And I have a quick follow-up.

Yes. Thanks, Mani, for joining this morning, and thank you for the question. I would first say, in general, the improvement in left ventricular mass index corresponded to other important biomarkers that we observed in the Phase I study, including reductions in troponin, improvements in lateral wall thickness. The reductions in troponin and lateral wall thickness are in some ways, independent of the left ventricular mass index starting status. So, we'll have this data from the Phase I/II study to support a future label discussion, which we think will not restrict the label to only these patients that have more than 2 standard deviations of left ventricular mass index at baseline. I don't know, Nani, if you have any other thoughts, you'd like to share related to that.

No, I think you've covered everything, Nolan. I think the fact that we've seen that elevated troponin level in those patients even who had relatively just mildly LVMI in our Phase I, Phase II data suggests that that data is going to contribute to show that these patients benefit regardless.

Yes. And remember, troponin is an important secondary endpoint, lateral wall thickness is an important secondary endpoint. mFARS is an important secondary endpoint. All of these are independent of the left ventricular mass index level at baseline.

You guys anticipated my next question by ending on that mFARS comment. When we think about metrics that apply outside of just cardiac benefit, how do we think about the commercial relevance of mFARS benefit, et cetera? And broadly, how should we interpret that? Obviously, the study is not powered for some specific mFARS benefit. But how should we think about the commercial relevance of that potential incremental benefit above and beyond the direct cardiac implications for survival and cardiomyopathy?

I'll say a few words. I mean I think we're focused primarily on patients that have some form of cardiac involvement. But obviously, given this has obviously a clear neurologic component to the disease, it's important to show benefit there, especially if we want to engage neurologists. But I don't know, Nani, if you have any other thoughts, you'd like to share related to that.

No. I think the fact that when we've seen in our studies, when they were -- when we had SKYCLARYS on board, for example, there was really no particular effect from that where they were on it or not. So, it seems that we are showing a similar benefit that we've seen that's out in the market currently. So -- and the fact that we play well with SKYCLARYS from what we've seen in our Phase I/II data, we feel that commercially, if you're having a drug that shows that similar benefit and also gets you cardiac improvement, that should be a favorable profile overall.

I would go further and just say this would be the best-in-class treatment. So, to see this degree of cardiovascular improvement, we have all of the abnormal patients in the normal range from an LVMI perspective. We have the late -- the patient with the 35% ejection fraction improving, and we're seeing a similar mFARS benefit to the commercially approved therapy. I think these things together would make this from a commercial perspective at the moment, the best-in-class treatment out there. But we look forward to advancing this study and being able to demonstrate that degree of treatment effect across a broader number of patients.

Our next question comes from Kristen Kluska with Cantor Fitzgerald.

This is Ian on the line for Kristen. Just following up on the last question. I just wanted to clarify. So, based on the secondary endpoints, have you had discussions about the possibility of this to fully encompass FA and not just cardiomyopathy?

Yes. In short, the secondary endpoint includes mFARS, which is the neurologic scale for the disease, if that was the question. So, it does include aspects of the disease beyond just cardiac and the secondary endpoint. Hopefully, I answered the question.

Yes. Yes, it did. And then just if I could sneak in a second question. What percent of the patients do you expect will have the abnormal LVMI at baseline that you will -- that will meet the criteria that you're looking for to enroll?

100% of them. All will have 2 standard deviations above normal from a baseline characteristic standpoint for left ventricular mass index.

Our next question comes from Brian Skorney with Baird.

Congratulations on finalizing the design. I guess 2 questions. Just on the LVMI change, I just wanted to talk through what your expectations would be around what the concurrent control arm would look like? Would the expectation just be that it would be unchanged in the control arm? Or is there an expectation for worsening? And just how did you arrive at that 15% powering? I think in the past, you talked about 10% change as the endpoint. Just trying to think is this just to do -- because now you're including the concurrent control, that threshold moves up a little bit. And just maybe clarifying on the last question on the mFARS secondary question, would the understanding be that the initial label would look like an accelerated approval in cardiac in FA cardiomyopathy. And then if you hit on mFARS as a secondary, that label would expand to be a full approval that would just be in FA, not -- without sort of the cardiomyopathy specification?

Okay. Thanks, Brian, for the question. It's a multipart. So, let me just kind of break it down into pieces here. So, the first question you asked was about the concurrent control, the untreated control and our expectations for that. Maybe, Nani, you could say a few words in what we would expect to see in 6 months from that group.

Yes. Thanks for that question. So, we do not expect to see any dramatic change at all, actually, barely any change in that 6-month period in that control group. So, your comment that we don't -- that you just said, hey, we don't expect to see much change and that you will really just see the change in the treatment group, that's correct. That's what the expectation is given the published data that we have out there right now in looking at these patients with that level of LVMI abnormality.

The next question was about the 15%. As we've discussed previously, a 10% reduction in LVMI is linked to a 20% reduction in the risk of mortality. That concept remains the same here. 15% was a powering assumption to give us some cushion relative to that 10%. And as you're also aware, at our higher doses in our Phase I/II study, we've gotten a 28% reduction in left ventricular mass at the same time point. So, we believe we have sufficient cushion above the 10% from a powering assumption perspective, but we believe the 28% effect size that we've seen in LVMI in the Phase I would obviously have us clearing that 15% pretty credibly. So, I think we landed in a good place with respect to the combination of size, length and so on of the study against that 15% powering assumption. And then the last question you had was about the label, the initial label, or our assumptions of that. I would agree, I think the -- while we've not had detailed label discussions at the moment, obviously, so all of this would be some form of speculation, but I think our view would be that the initial label would include patients with some form of cardiac involvement. Exactly what profile of patients that is would be subject to a discussion. But I would note that troponin is an important endpoint here. The existence of troponin, we saw this across a number of patients in our Phase I/II -- sorry, elevated troponin. We saw this in our Phase I/II study for a number of patients that did not yet have elevated LVMI. So, to the extent we continue to see that degree of treatment benefit across patients with troponin, and we can see that those results also correspond to our Phase I/II study, I think troponin may be a good biomarker to look at to consider for a patient that has some cardiac involvement. And so that's the direction of travel from our perspective that maybe troponin would be a good biomarker to consider for a future label and identification of patients that would ultimately benefit from a therapy like LX2006. Over the long term, obviously, we'd love to have a possibility to treat patients even earlier in the disease. But I think we need to also consider what effect we're having on mFARS and at what stage of the disease. And so, I think that's a future discussion and probably one that's relevant for the full approval of FDA dialogue.

Our next question comes from Paul Matteis with Stifel.

This is Matthew on for Paul. And congrats on all the progress so far. I guess I wanted to follow up a bit more on the powering that you mentioned before. Maybe I heard incorrectly, but I think, Nolan, you said that the 15% was a cushion on top of the 10% bar originally. Could you clarify that? And then also, the power is only for the 15%. We wanted to double check if the FDA is -- the bar for the FDA approval, is that still 10%? And then separately, another quick question. Maybe on the 6-month endpoint versus a 12-month endpoint. I guess from the phase -- from the earlier data, the curves continue to kind of -- or the benefit continues to deepen over time. Maybe how would you be able to show that if the untreated arm crosses over at the 6-month endpoint? Do you have other ways to show that?

So, the first question on powering. So, the bar has not changed. The 10% reduction remains the clinically meaningful threshold. So, that -- nothing has changed with respect to that. The 15% is the powering assumption. Obviously, the effect size combined with the variability of effect is what leads to the size of the study. So, we chose 15%, which we believe to be a conservative number, especially relative to the 28% that we've achieved at the same dose. In the same time frame, and yet it also credibly clears the 10% threshold from a powering assumption standpoint. So, that's what we designed the study around a 15% observed effect. And that was -- that's the -- what led to the size of the study that you're -- that we're discussing today. In terms of 6 months versus 12 months, while the effect does deepen between 6 and 12, it's not a substantial deepening. So, we're at 28% at 6 months, and I think we're -- we're at 33% at 12 months. All of those clear 10% very significantly by almost double. So, the idea of waiting for 12 months, there's a trade-off of getting the file into the FDA sooner so we can get to an accelerated approval sooner. And we look at 12 months across a range of endpoints as possibility for a discussion around full approval. But that's sort of our thinking around 6 versus 12 that we're seeing a very significant effect size at 6 months. So, why wait for 12 in order to move forward for the top line readout and submit the BLA.

Our next question comes from Christopher Raymond with Raymond James.

Just want to dig in a little bit more to the mechanism, I guess, to cross over from CLARITY to SUNRISE. I think I heard you say that you've got double-digit patients enrolled or identified now for CLARITY. What is the bar? Like, how long do patients need to be followed? I'm sorry if you already answered this in CLARITY and then to be able to cross over into SUNRISE?

I'll ask Nani, our CMO, to take this one.

Yes. Thanks. [indiscernible] Chris. So basically, the patients who are in CLARITY can come into FA at any point. Right now, as Nolan said, we've identified double-digit patients that are being enrolled into CLARITY-FA. And once we get the trial up and going on the SUNRISE-FA 2 and get that first patient in later this month, we will then start to just transition folks as they arrive into CLARITY-FA into the trial. And some of this will just depend on where the sites are, how long it's taking for the sites to get activated and then also whether the sites in the U.S. or Europe. So, all of that is going to impact the transition time from CLARITY-FA into SUNRISE. So -- but there's going to be -- once the trials are up and running, there's not going to be a particular amount of time that you have to spend in CLARITY-FA to get into SUNRISE. But nonetheless, whatever time you do spend in CLARITY-FA will contribute towards the total evidence that we use because that will still serve as a somewhat of a natural history for these patients before they come into the study. So, it's still an important data set to mine from that perspective. And then regarding -- and then it just depends on whether they -- whether they consent to get in, neutralizing antibody titers are met, those criteria, but those are the only things that we would be considering at that point.

Yes. It's a very good feeder for SUNRISE-FA 2, the identical inclusion criteria. The only thing that would potentially prevent a patient from crossing over would be the existence of neutralizing antibodies that emerge. And we have to go through and do those tests for neutralizing antibodies and then those patients are eligible to cross over into SUNRISE-FA. So, it's a pretty nice bolus of patients that we're starting with here.

Our next question comes from Tessa Romero with JPMorgan.

This is Caroline Pocher on for Tessa Romero at JPMorgan. Just 2 from us. So, how much safety data did the FDA express they would like to see included in the BLA filing, both in terms of number of patients and duration? And then what are the other relevant enrollment criteria outside of abnormal LVMI? What changes, if any, did you make from the Phase I/II to the pivotal trial? And are you permitting patients to be on SKYCLARYS in the pivotal?

Okay. So, just to break -- how much safety data -- the second question was.

Change from any new criteria in the LVMI, any additional.

Okay. For enrollment and then -- okay. So just on safety, I mean, the study design reflects the safety database that would be relevant for the accelerated approval. So, the safety data that would come out of this study combined with the Phase I/II is viewed to be sufficient to support the accelerated approval path. So, the study fully reflects a combination of the sort of efficacy bar that we've discussed with the FDA, combined with the requirements on safety data. That's fully reflected in the numbers that you see here. On the next one, enrollment criteria beyond LVMI.

Yes. So there's -- the primary criteria still remain the LVMI, more greater than 2 standard deviations from the mean. So, there's no real change other than that. And then the neutralizing antibodies exclusion inclusion still remains. So, there's really no other major change from Phase I, Phase II other than that LVMI cutoff. And the secondary endpoints that we're looking at are pretty much the same. We were measuring them in Phase I, Phase II and measuring them as we go forward. So, really no major difference.

Well, the one -- we have an ejection fraction cutoff, which we had in the Phase I.

Well, we had one in the Phase I as well, Phase I, Phase II as well. They were just different from what Lexeo had versus Weill. There was a 5% difference there. But basically, we have a cutoff of 35%, which has now been put into the criteria because it was 35% at Weill, 40% at Lexeo. We've just aligned at 35%.

Okay. Great. And then just really quick, are you permitting patients to be on SKYCLARYS in the pivotal?

Yes. They are -- they can be on SKYCLARYS. We're going to have certain criteria for SKYCLARYS. They can be on SKYCLARYS on a stable dose prior to coming in, but we will -- they will not be able to start SKYCLARYS once they are in the study, but they will need to be on a stable dose coming in.

Our next question comes from Leland Gershell with Oppenheimer.

Looks like a strong update here. I just wanted to ask in terms of the pediatric approval plan. So, it looks like with the SUNRISE-FA will be enrolling adults, but you mentioned that there'll be 6 patients evaluated for safety in the pediatric cohort. So, should we expect, the accelerated approval will be adults only and then full approval would contain an expansion down to younger ages? How should we think about the younger age [indiscernible]?

Well, so the pediatric patients are being evaluated for safety. Maybe you want to say a few words about that.

Yes. So, you're correct. The initial trial is patients 16 and over, and then there will be 6 patients between ages 12 and 16 that will be recruited afterwards for just a safety evaluation. And so, the pediatric filing will include those patients, but it will come after the adult database will be submitted first. And then as we start to align on the pediatric plan with the agency along with some of the other discussions we're having with them. And the same thing outside the U.S. So those are -- but for now, the plan is to come in with the adult indication first. But -- and then come in very soon thereafter because we'll have that data coming in very quickly right after we have the adult population. So, there won't be a huge time difference between coming in with the pediatric side.

Not that the duration is substantial to wait. And just to clarify, it's between 6 and 16, so it's 3, 16 and 12 and then 3 at 12 and 16.

Okay. So, we could see allowance for the younger patients even under the accelerated approval just sometime after the initial approval.

Correct. Yes. A label expansion at that point.

Our next question comes from Moritz Reiterer with Guggenheim.

This is on for Debjit. Congrats on the progress. Most of my questions have actually already been answered. So, just a quick one for me. Just to clarify, the primary endpoint is measured after 6 months with the n of 13 or after all 26 patients have completed the 6-month treatment post crossover?

The former. So, 6 months with an n of 13 relative to the untreated concurrent control.

Thank you. I'm showing no further questions at this time. This does conclude today's question-and-answer session. You may now disconnect. Thank you for your participation. Good day.