Sarepta Therapeutics - Q2 2023

Transcript

Operator (participant)

As a reminder, today's program is being recorded. At this time, I'll turn the call over to Francesca Nolan, Executive Director, Investor Relations and Corporate Communications. Please go ahead.

Francesca Nolan (Executive Director of Corporate Affairs)

Thank you, Jonathan. Thank you all for joining today's call. Earlier this afternoon, we released our financial results for the second quarter 2023. The press release is available on our website at Sarepta.com, and our 10-Q was filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, and Dr. Louise Rodino-Klapac.

After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements. Please take a moment to review our slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control.

Actual results can materially differ from these forward-looking statements, any such risks can materially and adversely affect the business, the results of operations, and trading prices for Sarepta's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q filed with the SEC, as well as the company's other SEC filings.

The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today, based on subsequent events or circumstances. Now I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

Doug Ingram (CEO and Member of Board)

Thank you, Fran. Good afternoon, thank you for joining our Second Quarter 2023 Financial Results Conference Call. The second quarter of this year was perhaps the most consequential period in the long, consequential history of Sarepta. For families living with Duchenne, it was far more than that still. Buddy Cassidy, living with Duchenne and an ELEVIDYS Advisory Committee member, shared the collective view of the Duchenne community on the June approval in words far more eloquent than I could possibly muster.

As Buddy said, and I quote, "There is more to do, but now let us pause and bask in the glow of our achievement. Let us bask in gratitude. Let us pause in celebration. Let us watch as dawn rises and brings in the day." Close quote.In May of this year, the FDA held an advisory committee meeting on our gene therapy, SRP-9001, now called ELEVIDYS. With a majority vote, the advisory committee recommended the approval of ELEVIDYS for the treatment of ambulatory patients with Duchenne muscular dystrophy.

On June 22, the FDA granted an accelerated approval for ELEVIDYS to treat Duchenne muscular dystrophy, currently labeled for four and five-year-old patients. At the time of the approval, FDA leadership informed Sarepta and the patient community that if our confirmatory trial, EMBARK, meets its objectives, the FDA will, in the words of Dr. Peter Marks, "Move with maximum speed following submission of the data to the agency, minimizing any impediments to review results rapidly and broadening the label by removing any age restrictions." We have our path.

Our confirmatory trial is well-designed and powered to show a statistically significant benefit in the studied population. For the avoidance of doubt, we have powered this study to show a benefit in the studied population, that's 4-7 years old, and with that, we will have confirmed the mechanism of action in Duchenne patients applicable to all age ranges. We will have the top line for EMBARK in the fourth quarter of this year.

We will announce top-line results as we submit them to the division, followed shortly by a label supplement. If successful, we should be able to expand our label in the first half of 2024 to include the majority of Duchenne patients. Additionally, we have already commenced our non-ambulatory trial, ENVISION, or Study 303, and we intend to commence two trials with alternative approaches to cleaving or clearing preexisting antibodies.

Our goal is to expand our label for ELEVIDYS to cover as much as 95% of the Duchenne patients. In a moment, our Chief Customer Officer, Dallan Murray, will provide details on the early days of the ELEVIDYS launch. ELEVIDYS is our fourth approved Duchenne therapy, and we have been very successful with all of our prior launches. Consistent with our track record, the ELEVIDYS launch is going well.

A significant number of sites are now initiated and ready to infuse. Payer discussions and negotiations have been more positive than our prior successful therapies, and there is a significant amount of enthusiasm from physicians and families as we have a substantial number of start forms and more coming weekly. In fact, I am pleased to announce that the first reimbursed ELEVIDYS infusion occurred earlier today.That is faster than we projected and speaks to the team's ability to execute.

Now, as positive as this is, please bear in mind that the significant ramp in infusions will begin later this year. This is primarily due to payer logistics and to the release protocol for ELEVIDYS, which requires that both we and the FDA release each lot.

Shortly, our Head of Research and Development and Chief Scientific Officer, Dr. Louise Rodino-Klapac, will provide an overview of our development activities, including progress with our next-generation PPMO, SRP-5051, and on the gene therapy side, with our LGMD portfolio. To remind you, in addition to ELEVIDYS-... We have a deep pipeline and are advancing a number of therapies in 2023. In fact, we have 24 ongoing human clinical trials by the end of this year.

We continue to advance our next generation viral capsid, myoAAV, which in early animal models, looks to be as much as 10-fold more tropic than current AAVs. From a manufacturing perspective, our technical operations professionals, more than 400 in all, are focused with our partner, Catalent, on producing and releasing lots to support our launch. Looking to the midterm, we will also continue to work to establish comparability at our Thermo Fisher plant for ELEVIDYS.

Looking to the future, we are advancing our approach to manufacturing to support our entire pipeline. In fact, we have made great progress in next-generation suspension technology, which we will use across our gene therapy portfolio, including the LGMD programs and even potentially for ELEVIDYS.In fact, we have largely completed our suspension-based process development for ELEVIDYS, and we have made three runs at 250 L with a fourth run to occur later this year, with the goal of scaling to 1,000 L in the near term.

We have seen yields that are multiples greater than the current standard. As the leader in gene therapy for rare diseases, we will continue to focus on improving the science and the delivery of our therapies. Moving finally to quarterly performance, we have had another strong quarter with our three approved PMOs, EXONDYS, AMONDYS, and VYONDYS.

I am pleased to announce that second quarter total revenue came in at $261.2 million, and net product revenue from our PMOs came in at $239 million, exceeding internal estimates and analyst consensus.In the second quarter, we saw no negative impact on the approved PMOs from any warehousing related to the ELEVIDYS approval and do not anticipate substantial impact over the course of the year.

We remain comfortable with our full-year guidance of $925 million for total PMO net product revenue, with a current bias to modestly exceeding that guidance. It is too early in the launch to provide an accurate guidance for ELEVIDYS, but we will continue to evaluate that. At Sarepta, we have a distinct culture. It is easy to say one is patient-focused, but our words are backed by action. We put the welfare of our patients above all other considerations, and when necessary, we fight for them.

The tools we use for that fight include our commitment to scientific excellence and the courage to represent the patients who depend upon us.Our fight may not always be easy, but it is paying off. We have four approved therapies and a wealth of potentially life-enhancing programs in our pipeline. We will achieve $925 million on the first three of our four approved therapies this year, and far more next year when our newest approval is considered.

We have a near-term, high probability of success plan to broaden the label of the first and only gene therapy for Duchenne, and if our plans are successful, we could be profitable in the next few quarters. We have done a lot already, but with our plans, our pipeline, and our commitment to dogged execution, we have only just begun. With that, I will turn the call over to Dr. Louise Rodino-Klapac, who will provide an update on our research and development progress. Louise?

Louise Rodino-Klapac (President of Research & Development and Technical Operations)

Thanks, Doug. The accomplishments within R&D over the last quarter are many, and highlighted by the approval of ELEVIDYS on June 22nd, 2023. The approval of ELEVIDYS via the accelerated approval pathway represents a win for the Duchenne community and an important step towards the broad approval for individuals living with Duchenne, regardless of age or ambulatory status.

As we look forward to the weeks and months ahead, we remain firmly committed to our values to follow the science and present objective evidence that supports ELEVIDYS's ability to change the trajectory of Duchenne muscular dystrophy. Since 2018, and across multiple studies, we've dosed the largest number of Duchenne patients, more than any other gene therapy in development for this disease. To remind you, we've shown consistent results across three clinical studies with respect to both biomarker expression and functional results.

In clinical trials, ELEVIDYS demonstrated positive results at multiple time points, including one, two, and four years after treatment, in addition to a consistent safety profile. The BLA for ELEVIDYS included efficacy and safety data from studies 101, 102, and 103, or ENDEAVOUR, as well as an integrated analysis across these three clinical studies, comparing functional results to propensity-score-matched external control.

Importantly, the functional data reinforced the consistency of NSAA improvement across these three independent trials and show mean improvements across key secondary functional endpoints, such as time to rise and 10 m walk/run. The data from studies 101, 102, and 103, cohort 1, which is ages 4-7, have now been either published or accepted for publication in peer-reviewed journals.

When compared to appropriate control populations, ELEVIDYS has consistently shown a treatment effect as measured by change in NSAA score at one year. We've applied the learnings from studies 101, 102, and 103 in the design, the execution, and statistical analysis plan for our Phase III EMBARK study. To remind you, EMBARK is a double-blind, randomized, placebo-controlled trial of ELEVIDYS in Duchenne patients ages 4-7. We completed enrollment in the fall of 2022.

The trial will be considered successful if the entire treated population shows a statistically significant positive difference in NSAA scores at one year compared to placebo.Our conviction around EMBARK is founded in data and was designed based on our experience with studies 101, 102, and 103, along with our propensity-weighted external controls and natural history data sources. We took extensive measures to ensure success, which include the following:

The EMBARK study design improves on study 102, with measures to increase homogeneity, including a floor and a ceiling on baseline NSAA and a requirement for rise from floor to be less than five seconds at screening. We also ensured a balanced distribution between treatment arms by including a stratification factor for baseline NSAA score. We also increased the target sample size to 120 to increase power and enrolled 125 patients. All of these measures result in a study powered well over 90%.

As discussed at the advisory committee in May, with an assumed standard deviation of 3.5 points in 120 patients, EMBARK was powered greater than 90% to see a 2.2 point difference on NSAA. Thus, we've always been confident in the powering of the study. We've also done extensive analysis and modeling that provides additional confidence in the success of EMBARK.

First, when the integrated summary of efficacy population included in the BLA, which was an N of 52, is narrowed to those who meet 301 entry criteria for an N of 33, the standard deviation goes down, confirming increased homogeneity. We also performed simulation models of four scenarios drawn from existing program data that have all yielded greater than 90% power. Given the entire protocol, we're able to detect an even lower treatment effect.

For example, with an assumed standard deviation of 3.5 points, our analysis would predict statistical significance at observed treatment effects in the overall intent to treat population as low as 1.3 points. Taken together, we have strong confidence in the Part One readout of EMBARK. With regards to additional ELEVIDYS studies, we've commenced dosing on ENVISION, our placebo-controlled Phase III study in nonambulant and older ambulant patients with Duchenne.

We are also on track to commence an apheresis study as well as an imlifidase study in AAV-RH74 antibody-positive Duchenne patients this year. This is all with the goal of serving the entire Duchenne population. Now moving to limb-girdle muscular dystrophy, or LGMD. We remain committed to advancing our LGMD portfolio across a variety of subtypes and look forward to providing updates on these important programs in the months ahead.

We're pleased to report that we have fully enrolled JOURNEY, our LGMD natural history study. 126 patients with sarcoglycanopathy have been enrolled and will be followed for 36 months. We've also made excellent progress enrolling VOYAGING, our Phase I study evaluating SRP-9003 for the treatment of limb-girdle muscular dystrophy Type 2E in ambulant adult patients and nonambulant patients using clinical process SRP-9003 material.

Combined with positive expression and functional data shared from our initial study, SRP-9003-101, we believe the data from VOYAGING will give us insights into a broader patient population. Our next milestones for VOYAGING include completing enrollment in Q3 of this year and initiating our Phase III study using commercially representative process material later in the year.

Finally, we've commenced dosing of a systemic pilot study, NAVIGATING, for our SRP-6004 dual vector Rh74-mediated gene therapy to treat LGMD 2B, characterized by the absence of the protein dysferlin. The innovative dual vector strategy allows us to deliver the full-length dysferlin gene, the sole cause of LGMD 2B. We also continue to make progress in manufacturing for all LGMD candidates in our pipeline and look forward to initiating clinical studies as rapidly as possible.

Turning now to the progress we've made with our RNA platform. We were pleased to complete enrollment in the first quarter of 2023 for a momentum study for SRP-5051, and we remain on track to announce data from the study in the back half of 2023.

In regards to our post-marketing studies for the PMOs, as mentioned last quarter, we completed enrollment in the ESSENCE trial, our post-marketing requirement for golodirsen and casimersen, and continue to make good progress with our MISSION study, which is on track to be fully enrolled this year. The accomplishments of 2023 and the opportunities before us speak to the promise of science to fundamentally impact and change the lives of patients around the world.

On the research side, we continue to make excellent progress on the MyoAAV platform, along with an exciting pipeline of genetic medicine candidates. My deepest gratitude to our R&D colleagues across RNA, gene therapy, and gene editing for their extraordinary work to get us where we are today. Finally, to the patient community, we understand the urgency, and we're working tirelessly to bring forth transformative genetic medicines as rapidly as science will allow.

We are doing everything we can to expedite the EMBARK study readout so that we can expand the ELEVIDIS label. We expect the data will be available in the next 3-4 months. I will now turn the call over to Dallan for an update on our commercial activities. Dallan?

Dallan Murray (EVP and Chief Customer Officer)

Thank you, Louise, and good afternoon. We were thrilled to receive approval for ELEVIDYS on June 22nd, and we owe a tremendous debt of gratitude to the patients who participated in the trials, the KOLs, and our R&D colleagues for getting us to this point. As Doug and Louise have said, we are deeply committed to broadening the label at the earliest time point that is feasible. During this time, the team is diligently working day and night to expedite access to this potentially transformative therapy for all eligible 4-5 year-old Duchenne patients.

Their dedication is focused on ensuring swift and seamless access for those who can benefit from ELEVIDYS. In these early stages, much of our focus is on supporting those sites who have boys turning six years old.At the same time, we are also rapidly preparing the sites to treat all of the patients who are eligible today and laying the groundwork to be ready for a broader patient population when the time comes.

The team's remarkable progress and unwavering sense of urgency in executing our now four Duchenne launches are truly commendable and reflect our commitment to providing timely access to potentially transformative patients, therapies for patients. The commercial and medical teams began educating the centers within 24 hours of approval, as we've done in our previous three launches. Right from day one, our case managers were fully prepared to assist patients in navigating the intricate aspects of the gene therapy treatment journey.

Doug has previously highlighted the unique components of a gene therapy launch, which we must get right in order to serve the community.The three areas of focus are site readiness, payer engagement, and building the capabilities for antibody testing. In terms of gene therapy site readiness, as of today, we have over 50 sites trained, activated, and ready to receive product. We have achieved this ahead of our own aggressive timelines.

On the payer front, since approval, the team has engaged both commercial and Medicaid payers, representing approximately 250 million lives. Continued progress has been made in educating and informing them on the clinical data to support policy formation to our approved FDA label. As an example, United Healthcare, one of the largest commercial insurers in the United States, published their coverage policy for ELEVIDYS yesterday, aligning the therapy to its FDA-approved label.

Finally, to touch on antibody testing. Over 700 kits were in the hands of our key sites within a day or two of approval.Testing is currently underway, and the process is working smoothly. We've seen very strong demand for ELEVIDYS and are encouraged by the discussions with KOLs, payers, and the broader community. We began receiving enrollment forms within hours of approval, and we continue to see them come in on a daily basis. Since June 22nd, the team has had over 500 interactions with both treating and referring sites.

In these early discussions, our focus has been first and foremost on patient safety, eligibility, procurement, dosing and preparation, and reimbursement. Launching the first gene therapy for Duchenne patients requires a multifaceted approach with a high level of communication, not only with HCPs and sites, but also patients, families, and payers to ensure patients have timely access to this groundbreaking therapy.

As a result of our preparation and diligent efforts, we are now at the point where patients can begin receiving ELEVIDYS with confidence. As I previously highlighted, our engagement with payers has been constructive. The team is optimistic in making progress towards our goal of ensuring timely access. Of note, we are seeing states reach out to their local KOLs and experts to inform policies. We expect to have payer policies in place within 3-6 months, depending on the plan.

In the interim, we are working with payers on a case-by-case basis to obtain access for patients. To that end, we have received multiple authorizations, and as Doug mentioned, we were thrilled to announce that the first patient was dosed today.Over the course of the next week and a half, we have a handful of additional infusions across the country scheduled, with patients representing a combination of commercial and Medicaid insurance coverage. We are gratified by the tremendous work being done across the country to support patients.

In particular, there has been a concerted effort since approval to rally around those patients who are approaching their sixth birthday. The incredible efforts to support those patients from all involved has been truly humbling. While we are encouraged by our progress and accomplishments to date, it's important to reiterate that we are not providing revenue guidance in the early stages of this one-of-a-kind launch.

As Doug made clear on the approval call, we expect this to take some time in the early stages before dosing can begin in earnest to generate the launch ramp we are confident will come.I want to take a moment prior to reflecting on our PMO business, to thank everyone within Sarepta and our key partners who have worked so hard to make this launch a reality and allowed us to be ready to serve these patients right from day one.

Now, regarding our PMO business, it's critical to highlight the fact that we have not lost a step supporting our PMO patient community, while we've risen to the challenge of the first Duchenne gene therapy launch. As Doug mentioned, we delivered $239 million in net product revenue in the second quarter, representing 13.1% growth over the second quarter of 2022. Exondys 51 totaled $134.7 million, representing 6.6% growth over Q2 of 2022.

For Vyondys 53, sales were $32.6 million, growing roughly 8.2% over the second quarter of 2022. For AMONDYS 45, sales totaled $71.7 million, representing more than 31% growth versus Q2 of 2022. Total ex-US net product revenue in the second quarter was roughly $35 million. This represented an increase over the prior quarter, which was expected and fully reflected in our annual guidance and forecast.

As discussed on last quarter's call, we expect to see even more quarter-to-quarter fluctuations in the overall net product revenue as the ex-US becomes a bigger percentage of the overall PMO mix. Importantly, these quarter-to-quarter fluctuations, along with the shifting mix of the PMO revenue base, have all been anticipated and fully reflected in our annual guidance.

Overall, the fundamentals of the PMO business coming out of Q2 are completely in line with what we expected at this point in the year, and we reiterate our full year guidance of $925 million in net product revenue for our PMO therapies. In closing, our teams are fully engaged and executing today to support patients with all four of our approved therapies.

I'm particularly pleased to see the continued success of our PMO business in the second quarter. In fact, looking back on the execution of all three of our PMO launches should provide a high level of confidence in the future of Sarepta and our potential to transform the Duchenne space with Elevidis and pave the way for precision genetic medicines for other rare patient populations, such as limb-girdle muscular dystrophy.With that, I'll turn the call over to Ian Estepan for an update on our financials. Ian?

Ian Estepan (President and COO)

Thanks, Dallan, good afternoon, everyone. This afternoon's financial results press release provided details for the second quarter of 2023 on a non-GAAP basis as well as a GAAP basis. Please refer to the press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results.

For the three months ended June 30th, 2023, the company recorded total revenues of $261.2 million, which consists of net product revenues and collaboration revenues, compared to revenues of $233.5 million for the same period of 2022, an increase of $27.7 million. Net product revenue for the second quarter of 2023 from our PMO exon skipping franchise was $239 million, compared to $211.2 million for the same period of 2022.

The increase in net product revenue primarily reflects increasing demand for our PMO products. In each of the quarters ended June 30th, 2023 and 2022, we recognized $22.3 million of collaboration revenues, which relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $28.2 million for the second quarter of 2023, compared to $26.4 million for the same period of 2022.

On a GAAP basis, we reported a net loss of $23.9 million, or $0.27 per basic and diluted share, and $231.5 million, or $2.65 per basic and diluted share for the second quarter of 2023 and 2022, respectively.We reported a non-GAAP net loss of $75.2 million, or $0.85 per basic and diluted share in the second quarter of 2023, compared to a non-GAAP net loss of $103 million, or $1.18 per basic and diluted share in the second quarter of 2022.

In the second quarter of 2023, we recorded approximately $34.1 million in cost of sales, compared to $37.8 million in the same period of 2022.The decrease in cost of sales primarily reflects a decrease in our royalty payments during the three months ended June 30th, 2023, due to changes in the BioMarin royalty terms and a decrease in write-off of certain batches of our products not meeting our quality specifications for the three months ended June 30th, 2023, as compared to the same period of 2022, partially offset by an increase in demand for our PMO products.

On a GAAP basis, we recorded $241.9 million and $252.3 million in R&D expenses for the second quarter of 2023 and 2022, respectively, a year-over-year decrease of $10.4 million. The decrease is primarily due to a decrease in manufacturing expenses, partially offset by increase in clinical trial expenses and compensation and other personnel expenses.On a non-GAAP basis, R&D expenses were $212.2 million for the second quarter of 2023, compared to $230.4 million for the same period of 2022, a decrease of $18.2 million.

Now, turning to SG&A. On a GAAP basis, we recorded approximately $118.6 million and $154.3 million of expenses for the second quarters of 2023 and 2022, respectively, a decrease of $35.7 million. The decrease was driven primarily by a decrease in stock-based compensation expense. On a non-GAAP basis, SG&A expenses were $90.3 million for the second quarter of 2023, compared to $63.7 million for the same period of 2022, an increase of $26.6 million.

On a GAAP basis, we recorded $16.9 million in other income net for the second quarter of 2023, compared to $17 million in other expense net for the same period of 2022. The change is primarily due to an increase in interest income and accretion of investment discount through the investment mix of our investment portfolio, as well as a reduction of interest expense incurred as a result of the repayment of our December 2019 term loan during 2022.

In the second quarter, we entered into an agreement to sell the rare pediatric disease priority review voucher received from the FDA in connection with the approval of Olevidus for a consideration of $102 million, with no commission cost.The net proceeds were recorded as a gain from the sale of the PRV, as Olevidus did not have a carrying value at the time of the sale. Finally, we had approximately $1.9 billion in cash, cash equivalents, investments, and long-term restricted cash as of June 30, 2023.

In closing, I'd just like to reiterate how exciting a time it is for Sarepta and the patients we serve. Seeing the first patient dose today brought true joy to all of our hearts. Then from a financial perspective, we're looking forward to being one of the rare biotech companies to actually make the transition to profitability. In fact, we anticipate becoming non-GAAP EPF positive in the upcoming quarters.

This has truly been quite an accomplishment on all fronts for us, and we're particularly proud of what we've been, what we've been able to do. With that, I'll turn the call over back to Doug, to start the Q&A.

Doug Ingram (CEO and Member of Board)

Thank you very much, Ian, and hear, hear to those last comments. Jonathan, let's open the call for questions.

Operator (participant)

Certainly. Ladies and gentlemen, we ask that you please limit yourselves to one question each. You may get back in the queue as time allows. One moment for our first question. Our first question comes from the line of Colin Bristow from UBS. Your question, please.

Colin Bristow (Managing Director of Biotechnology Equity Research)

Hey, good afternoon, and congrats on another milestone with the, the first patient dosed. I, I guess a sort of two-part question around the comments you made around EMBARK, hitting with as low as a 1.3 point delta. I'm curious, what is the powering that the 1.3 delta is at? Have there been any discussion with FDA whether this would be considered clinically meaningful?

Just as a sort of follow-up from that, I think the most common question we're getting is that if EMBARK misses the primary in the overall population, but shows a directional benefit in 4-5 year-olds, given there's no multiplicity strategy, has FDA given any indication on whether this would be sufficient to maintain the approval status? Thank you.

Doug Ingram (CEO and Member of Board)

I'm gonna turn the question over to Louise on the powering issue, but real quickly, just to on the latter question. We haven't had discussions with the agency directly about, you know, clinically meaningfulness of a particular number, but I wanna remind you that the effect one sees at 52 weeks isn't the effect, it's a signal of the long-term effect. You know, as using a, you know, an artful metaphor, if we took off from Los Angeles and we were one degree off trying to get to Tokyo, by the time we hit Catalina Island, we wouldn't be that far off.

If we continued with that one degree, we'd be, you know, 500, 600, 700 miles away from Tokyo. That's what we're dealing with here. This is a disease that is degenerate over, degenerative over time.If we can see a statistically significant benefit in a mere 52 weeks, we have clearly changed the trajectory of this disease in a very positive way. With that said, let me turn the technical question on the powering calculations over to Dr. Louise Rodino-Klapac.

Louise Rodino-Klapac (President of Research & Development and Technical Operations)

Thanks, Doug. Based on the modeling that we did, this isn't a traditional power calculation. This was a simulation model in order to determine the lowest effect size that we could see in order to hit stat sig. We put the following assumptions into our model, which was 125 patients, which is the number of patients we enrolled, no dropouts, because we've not seen any dropouts in Embark. We assumed a standard deviation of 3.5 across the entire 4-7 year-old population.

Then we varied the effect size in order to see how low we could go in order to still hit statistical significance. That's how we arrived at the equal to or greater than 1.3 as the, as the lowest number. This isn't the assumed effect size.This is as low as, the modeling will show us to still see statistical significance.

Doug Ingram (CEO and Member of Board)

One, one final thing. Colin, you had asked about the way the agency would look at the data. Again, we are powered for success in Embark, and our goal is to see statistically significant, meaningful benefit from the therapy in 52 weeks. At the end of the day, the agency's standard is to look at the totality of evidence across the primary and the secondary. Sort of statistical significance, we'd look at presumably, look at the totality of evidence to justify the mechanism of action and expand the label to the broader population.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Brian Abrahams from RBC Capital Markets. Your question, please?

Brian Abrahams (Managing Director and Global Head of Healthcare Research)

Hey, guys. Good afternoon, thanks for taking my question. In the back half of this year, we're going to see data from several late-stage DMD gene therapies. I guess I'm curious, based on what you're seeing on the ground so far, if you have a sense as to what physicians and patients are going to be looking for as they potentially choose a gene therapy to take, assuming there's multiple therapies available?What are your views on the potential approval paths based on an interim functional analysis? Is that something that you guys ever contemplated or explored with the FDA? Thanks.

Doug Ingram (CEO and Member of Board)

We have, there's one therapy that's approved for Duchenne muscular dystrophy, that's a gene therapy. To be honest, we think very little about other organizations right now. We have a path in front of us. We have to serve the patients that are available to benefit from our therapy today, and we need to broaden that label, and that's what we're focused on right now. Of the things that we worry about right now, those are the, the, you know, all of the top priorities, and worrying about other organizations and their plans is tertiary or less than tertiary to us.

Operator (participant)

Thank you.

Doug Ingram (CEO and Member of Board)

Is to prioritize children and ensure they can get access, if at all possible, before they age out of the label. You saw that, poignantly today with a boy who received access today, one day before his sixth birthday. Dallan, do you have any other, thoughts on that?

Dallan Murray (EVP and Chief Customer Officer)

Yeah, Brian, thank you for the question. In the short term, we've been focused on, on those boys that are, that are turning six in the, in the next while. As Doug said in the earnings call, we, there's an incident population in Duchenne of, of 400 patients born each year. Now, not all of those patients are diagnosed by the age of their, their sixth birthday. There's actually a pretty, you know, good percentage that don't get diagnosed by their sixth birthday.

There is a, you know, a, a good number of patients sitting in, in the sites that are, that are turning six, and a big focus in terms of our execution. As, as Doug also said, and as we've said before, we aren't, we aren't guiding around patient numbers.we're gonna, we're gonna focus on net revenue as we've done with the other launches.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your question, please.

Salveen Richter (Managing Director and Lead Analyst for the U.S. Biotechnology Sector)

Good afternoon. Thanks for taking my question, and congrats as well on, on treating the first patient here. With regard to the 3.5 standard deviation assumption, you know, recognize that that's what you saw, I believe, in, in Study 103. You know, I guess, is there anything else that you're using to support that assumption? You know, in the context of heterogeneity and even with stratification, what would be, you know, how you're thinking about the impact here if it's higher? Thank you.

Doug Ingram (CEO and Member of Board)

Actually, one would actually presume potentially the opposite. The 3.5 standard deviation was the original powering for EMBARK. That considered the historical trials, but didn't take into consideration the various tightening of the protocol that occurred with respect to Study 303, 301, or EMBARK, to reduce heterogeneity and make, you know, create more homogeneity. You'll recall, we have a very strong ceiling and floor in that trial.

You'll recall that we have stratified not only on the basis of NSAA baselines, but also on age, on the 4-5 and 6-7 year-old range. You'll recall that we have restricted all of the patients to rise time under five seconds. All of that should, should theoretically at least, reduce heterogeneity, create more homogeneity across the population, and reduce standard deviation.

The 3.5 points that Louise mentioned was considered before those, and didn't take those into consideration. Indeed, when Louise's team did their modeling, they didn't change the standard deviation, so they didn't actually amend that for, for their modeling purposes. We feel very good about where we are right now. Then to remind you, you know, the study was powered off of 120 patients with a presumption of some dropouts.

We sit here today, the study was over-enrolled. It's now 125 patients, and we've had absolutely zero dropouts, and frankly, don't anticipate any dropouts before the last patient, last visit, which will occur in mid-September. We feel very good about where we are right now.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Gil Blum from Needham & Company. Your question, please.

Gil Blum (Senior Analyst)

Good afternoon, everyone, and thanks for taking our question. Maybe a bit of a rephrasing on an earlier question here. Is there a situation in which you think the data from EMBARK will be broken out based on age, given, you know, potential different feedback from the agency? Thank you.

Doug Ingram (CEO and Member of Board)

No, no, we don't. The study has been powered to see a treatment effect in the studied population, which is four to seven. It's very... It's very well powered to see that. We've had conversations with the FDA and FDA leadership, which has, has confirmed that if we're successful in our trial, they will move rapidly once we've submitted data to them to review that data and to remove the age limitations.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Yanan Wang from Mizuho. Your question, please.

Yanan Wang (Director and Equity Research Analyst)

Hey, guys. Yeah, congrats on the dosing the first patients. My question is just referring to what Doug said in the prepared remark. You said you're going to expand the label in the first half to the majority of patients. Can you kind of elaborate by what you mean by that? Will the older patients and the non-ambulatory patients, will those be included, or will that come much later, where I think your goal is to reach 95% of the patients? Thanks.

Doug Ingram (CEO and Member of Board)

Yeah, thank you very much for your question. Let's go, there's sort of two steps to this. As we stand here today, we have a label for four and five-year-old patients. When EMBARK is successful, and, you know, we have a lot of conviction around EMBARK and the success of EMBARK, we will immediately submit that data to the agency before we've even submitted a BLA supplement, with the goal of them beginning the review as soon as they receive that data.

Assuming that EMBARK's successful, we would assume that all age limitations will be removed from the label, and that gets us to the majority of patients, both ambulatory, non-ambulatory, and all age ranges. As we've said, we've had conversations with the agency about removing all of the age ranges.

There would be no logical basis to assume that, you know, ambulation status would be a reason to limit access. It's not as if this protein is aware that a patient's in a wheelchair or not. We're, we feel very confident about that. There is one additional thing we'll do, which is we'll take a cut from our current non-ambulatory study to have additional safety data that supplements the safety data we already have on the older and non-ambulatory patients as well.

That's our goal first, early next year to have a broad label that covers all patients. There will still remain two limitations in the ability to receive that therapy.One of them is this, 5% or so of mutations that are, that, that cover exon 8 or, and, and/or 9, that are contraindicated for those mutations. That will remain for some time. We're gonna continue to do work on that and hopefully narrow that, but for the time being, that will be in the label. Then the second one is preexisting antibodies.

About 13.9%, based on, based on our seroprevalence study, represent patients that have some environmental exposure to something that looks like an antibody for RH74. Those patients cannot currently be dosed, but as Dr. Louise Rodino-Klapac mentioned in her prepared remarks, we're starting two different alternative approaches to clear those antibodies. One, Imlifidase to cleave them, and apheresis is a second alternative to clear antibodies.

If one or both of those are successful, then in the near term, we could start presumably empowering physicians to safely and effectively dose even patients that have preexisting antibodies. That would get us to more than just the majority of patients, to potentially as much as 95% of patients. That's our goal.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Michael Yee from Morgan Stanley. Your question, please.

Michael Yee (BioTech Analyst)

Hey, guys. Thanks for taking the question. Maybe just another one on the ELEVIDYS launch. In your prepared remarks, you mentioned greater than 50 sites are trained and activated currently. Just curious if you can give us the total number of sites expected? Just trying to get a sense of whether that represents a majority currently or where you're at in that process. Thanks.

Doug Ingram (CEO and Member of Board)

50 sites is a tremendous number of sites. We are, I am completely thrilled with the team's ability. About 80% of all Duchenne patients are covered by about 50 centers of care in the United States. 50 sites is an enormous number of sites to, to infuse ELEVIDYS. Our goal is to get to as many as 70 sites over time, and we're significantly ahead of schedule in our, our goal to do that. We're, we're in really, really great shape from a site perspective, and Dallin and his team deserve an enormous amount of kudos for where we've gotten right now.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Danielle Brill from Raymond James. Your question, please.

Danielle Brill (Biotechnology Research Analyst)

Hi, guys. Good afternoon. Thanks for the question. I have a quick follow-up to Salveen's question on the standard deviation. I guess I'm, I'm curious, are you able to see blinded SD data or any other blinded data from EMBARK that allows you to stress test your powering assumptions? Just kind of hoping you can elaborate further on, on your confidence in the assumptions. Thanks.

Doug Ingram (CEO and Member of Board)

We do not have access to. Looking at the blinded data wouldn't be very insightful, and we don't have access to the unblinded data. We feel very. What we feel very comfortable with is that our initial study was powered with the standard deviation that we were seeing in studies that did not have the homogenizing restrictions that EMBARK has in it.

Yet, when we did the simulations, when Louise and her team and our stats group did the simulations to test the powering assumptions and the like, they did not actually take into account the homogenizing aspects of the change in protocol. Things like, as I mentioned before, stratifying on age and, you know, making sure that all kids had a rise time under five seconds and having strong floors and ceilings and the like.

You know, we feel very good about the powering of the study, and we feel good as we sit here today on the standard deviation. We, we haven't had access to unblinded data to, to test those assumptions.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Ritu Baral from TD Cowen. Your question, please.

Ritu Baral (Managing Director and Senior Biotechnology Analyst)

Good afternoon, guys. Thanks for taking the question. Just back to the centers for a second. Doug, can you say if the handful of patients that you were referencing in the next, in, in the next couple of weeks, will they be at five different centers and of the 50? Can you talk a little bit about, are there centers that you expect to move faster than others, maybe given their history with Zolgensma and how comfortable they are? If I can squeak another one in, do you know how many antibody tests have been run, and can you release that?

Doug Ingram (CEO and Member of Board)

I don't know the last answer for you. I can answer the first two. All of them are all of the handful are different sites. They're broadly across different sites. I, if any sites are faster. Oh, the, the good news on these first of all, the amount of passion from the physicians is really wonderful, and everyone's trying to move as fast as possible to get kids infused and benefit these kids, particularly kids that might otherwise age out.

We have really benefited, and the team has really benefited from the fact that these, most of these sites, the majority of these sites, have had experience with Zolgensma and know how to infuse gene therapy.They were well prepared before we went in and got the process of initiating them and getting them site ready. I would say, broadly speaking, there's a lot of enthusiasm to move as fast as reasonably possible to get patients benefiting from Elevidys.

Operator (participant)

Thank you. One moment for-

Dallan Murray (EVP and Chief Customer Officer)

Yeah, and, and in terms of, in terms of the, the, the, antibody testing, it's going smoothly, and, and functioning well, and we aren't disclosing the, the numbers right now, but it is working well and, and, and going smoothly. We're happy with the demand.

Operator (participant)

Thank you. Our next question comes from the line of Anupam Rama from JP Morgan. Your question, please.

Anupam Rama (Managing Director and Senior Equity Analyst)

Hey, guys. Thanks so much for taking the question. Just a clarification point, sorry if I missed this. What are the gating factors to starting that SRP9003 pivotal study later this year? Thanks so much.

Doug Ingram (CEO and Member of Board)

I'll turn this over to Louise, if I'm getting any of it wrong. I think it's all just CMC and manufacturing, if I'm not mistaken. Louise, you tell me if I, if I'm missing a nuance.

Louise Rodino-Klapac (President of Research & Development and Technical Operations)

No, that's accurate. Just all the, making sure the release assays are in place and we're set. We, as we mentioned, we fully enrolled Journey and have a great deal of patients lined up, and most of them having natural history data as well.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Joseph Schwartz from Leerink Partners. Your question, please.

Will Wood (Director and Equity Research Analyst)

Hi, all. This is Will on for Joe today. Thanks for taking our questions, and I'll add my congrats on the progress this quarter. One for us, wondering what the opportunity is for SRP-5051 relative to the PMOs that you currently market. Is this a potential franchise expander, and are there any reasons why a patient is not currently on a PMO but would be a candidate for a PPMO? Thank you.

Doug Ingram (CEO and Member of Board)

Not on it. The, you know, I think, broadly speaking, if it were successful, we'll see the data later this year, and then we'll, if we're successful with the data later this year and the risk-benefit justifies it, we're going to seek an NDA for 5051 next year. The goal then would be. There's a couple things. The first goal is that it would be, a more convenient and, and potentially much more powerful version of our PMOs. For patients already on the therapy, it would, you know, would be a great transition to this therapy for them and benefit them.

You could envision in the United States that we might have even we've had a great success record with access.We might have even greater success with access if we were making, you know, 3%, 4%, 5%, which would be multiple four-folds more.... dystrophin than the PMOs. It does always offer the theoretical opportunity to move outside of the United States, which is something we're very excited to do, which is bringing our RNA technology more broadly around the world to benefit patients.

There, there's a lot of potential opportunity with the PPMOs, if successful. We're looking forward to looking at the Part B of MOMENTUM later this year, and then making some decisions across the portfolio and aggressively bringing things forward if, if we see success with 5051.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Kristen Kluska from Cantor Fitzgerald. Your question, please.

Kristen Kluska (Managing Director and Biotechnology Equity Research Analyst)

Hi, everyone. Congrats on today's milestone. Given that you're taking all these steps now across sites, payers, and antibody testing, is it your expectation that if you end up getting a broader label in the first half of next year, that the 3-4 month timeline you've communicated to us in terms of patients getting on therapy could be shortened? Thank you.

Doug Ingram (CEO and Member of Board)

Yeah, the answer is, generally speaking, yes. This really is an initiation issue with the launch of the therapy. Policies have to be in place. In some places, codes have to be in place, and the like. Then, of course, we have this current release process, so we ought to be in a position to move faster over time. As, as I said before, we've had a lot of very fantastic early success, but we should assume that the, the real ramp begins later this year.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Tim Lugo from William Blair. Your question, please.

John Boyle (Senior Analyst)

Hi, team. This is John on for Tim. Thanks so much for taking our question. I was just wondering, beyond the effort that the team is making to get access to patients approaching six years of age, just wondering if you could talk a little about any higher demand you're seeing from the patients approaching that age cutoff, and if you're seeing more patient starts from those patients?

Doug Ingram (CEO and Member of Board)

I'll turn this over to Dallan.

Dallan Murray (EVP and Chief Customer Officer)

Yeah, thanks for the question. We're seeing demand broadly in both the four and five-year-old age group. In terms of access, early on, it is skewing heavily to those patients that are that have the birthdays. Just be more so maybe because of the urgency and the dialogue that's happening between KOLs, payers, and the teams right now.

Early on, yes, we are seeing it skew toward towards six year, the people with birthdays turning six, but we expect that to normalize very quickly as we start to work towards all of the patients that are eligible in that four to five age group.We're seeing, we're seeing demand in start forms across the ages.

Doug Ingram (CEO and Member of Board)

Yeah.

Dallan Murray (EVP and Chief Customer Officer)

We'll likely get access skewing to the older kids in that age range for the obvious reason that we wanna get them dosed before there's an issue with the label.

Doug Ingram (CEO and Member of Board)

Yep.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Brian Skorney from Baird. Your question, please.

Luke Herrmann (Equity Research Analyst)

Hey, this is Luke on for Brian. Thanks for taking our question. Regarding the pace of progress getting the ENVISION trial up and running, have you seen any signals that the availability of commercial product might be a headwind to enrollment in the ambulatory population?

Doug Ingram (CEO and Member of Board)

The answer to that's gonna be no. We were very thoughtful about the protocol for ENVISION. In fact, we've significantly limited the, the number of patients that are gonna come out of the United States to ensure that we don't have an issue with the, the progress of that therapy as we broaden the label. Now, that does mean that the enrollment for ENVISION will move slower than, for instance, EMBARK, which rapidly enrolled, as everyone may recall.

Ultimately, we're not seeing an impact from this approval on that basis, and, and part of it's because we're, we're going to, enroll the majority of, of, subjects outside of the United States.

Operator (participant)

Thank you. One moment for our final question for today. Our final question for today comes from the line of Dibjit Chattopadhyay from Guggenheim. Your question, please.

Dibjit Chattopadhyay (Senior Managing Director and Senior Biotech Analyst)

Hey, good afternoon, and thanks for taking me, getting my question in. What is the current gross margin for ELEVIDYS, and where do you think it'll migrate, either on peak capacity or if you could successfully migrate to the 1,000 L scale?

Doug Ingram (CEO and Member of Board)

Sure. I'll turn this over to Ian.

Ian Estepan (President and COO)

Sure. We've said that we would expect the margins to be like high quality, targeted agents, kind of in that 80% range, you know, similar to what we're seeing with our PMOs. Now, obviously, it's gonna be higher when the, the earlier patients are being dosed, and then as heavier patients and we expand the label, it'll trend down, but basically into, you know, kind of that, that 80% range. Then obviously, to your good point, we could see a big change.

We're not in a position to quantify that from where we are from a manufacturing perspective, on our suspension process, but obviously, it has, you know, to Doug's point, a big impact on our, on our yield.We could see that driving that number higher, but obviously, we're not willing to commit to that just yet.

Operator (participant)

Thank you. This does conclude the question and answer session of today's program. I'd like to hand the program back to management for any further remarks.

Doug Ingram (CEO and Member of Board)

Thank you, Jonathan, thank you everyone for joining us this evening and for your, your questions. I appreciate it. We've obviously made, from my perspective, great progress so far this year, both with the approval of ELEVIDYS and then serving patients, both with ELEVIDYS and with our existing PMOs. I will remind us that the team has done a brilliant job of continuing to serve the community with our PMOs, we're, we feel very confident about our current guidance on the PMOs.

We have a lot to do for the rest of the year, both serving these patients, continuing to serve the patients with the PMOs, getting the EMBARK readout, about which we have an enormous amount of conviction, then we will share that with you at essentially the same time that we share it with our colleagues at the FDA.

Our goal, of course, is to broaden this label as soon as reasonably possible and bring ELEVIDYS to the vast majority of patients living with Duchenne and their families. With that, I look forward to updating everyone over the course of the quarter, and I would ask everyone to have a lovely evening.

Operator (participant)

Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.