Sarepta Therapeutics Inc

NASDAQ:SRPT

Earnings Call Analysis

Revenue Growth and R&D Reduction Highlight Earnings

The company's PMO business saw net product revenues of $240 million in Q3, a 16% rise compared to the previous year, with steady growth across its products. Annual guidance was reaffirmed, anticipating over $925 million in PMO net product revenue for 2023. On the innovation front, the NAVIGENE study for LGMD2B therapy completed dosing, with results expected in the first half of 2024. Cost-wise, R&D expenses fell by $29.8 million to $163.9 million, indicating efficiency gains. Meanwhile, their financial position remains robust with $1.8 billion in cash and equivalents as of September 30, 2023.

Robust Revenue and Earnings Performance

The company demonstrated strong financial performance with total revenues reaching $331.8 million, marking a notable increase of $101.5 million over the same period last year. The net product revenue from the company's PMO business in Q3 was $240 million, representing a 16% increase compared to Q3 of 2022. Additionally, the company achieved non-GAAP profitability which, assuming an expansion to the label to the broader Duchenne population, should lead to sustained profitability.

Product Pipeline Progress and Clinical Studies

The company has completed enrollment and is progressing with several key clinical studies. Voyagene is set to initiate a phase 3 study later this year, with results expected in the first half of 2024. The momentum study for SRP-5051 has also completed enrollment in Q1 2023, with results anticipated within the same year. The ESSANCE trial, a post-marketing requirement for golodirsen and casimersen, was completed, too, and will read out in early 2026. The company's MIS51ON study for EXONDYS has fully enrolled 160 patients and is moving forward with its phase 3 component.

Guiding Towards Sustained Profitability

With a combination of a net loss of $40.9 million or $0.46 per share and a non-GAAP net income of $37.7 million or $0.37 per share, the company is able to navigate its transition towards sustained profitability, foreshadowed by a successful EXONDYS launch and possible label expansions.

Research and Development, and SG&A Expenses

The company observed a decrease in non-GAAP R&D expenses to $163.9 million in the third quarter of 2023, a $29.8 million reduction from the same period in 2022. However, there was an uptick in GAAP SG&A expenses, driven primarily by increases in professional services and employee compensations.

Strong Cash Position Amidst Turbulent Markets

Amid unpredictable market conditions, the company holds a strong cash position with approximately $1.8 billion in cash, cash equivalents, investments, and long-term restricted cash, earmarking these resources to build inventory to serve the DMD population, highlighting the strategic use of capital within the company.

Commitment to Rapid Regulatory Approvals

The organization is on the verge of submitting a BLA efficacy supplement, with a commitment from the reviewing agency to expedite the process as much as possible, which could significantly impact the timeline for bringing its treatments to market and expanding their use.

Earnings Call Transcript 2023-Q3

[Operator]

Good afternoon, and welcome to the Sarepta Therapeutics Third Quarter 2023 Earnings Call. [Operator Instructions] Please be advised that today's conference 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]

Thank you, Michelle, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the third quarter of 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 could materially differ from these forward-looking statements and 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.

And now I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

[Douglas Ingram, executive]

Thank you, Fran. Good afternoon, and thank you for joining Sarepta Therapeutics' Third Quarter 2023 Financial Results Conference Call. It was only 2 days ago that we announced the results of our double-blind, placebo-controlled trial EMBARK. Therefore, I will not linger on the result here, but I will begin by summarizing Sarepta's perspective.

First, taken as a whole, the results of EMBARK confirm that ELEVIDYS stabilizes, slows are entirely arrest decline, does across the ages and does so with a laudable safety profile not shared by other programs for Duchenne. Second, the EMBARK results have not only satisfied the confirmed environments for our June approval, but have shown that ELEVIDYS benefits patients across age consistent with its mechanism of action.

Hence, we will soon be submitting a BLA supplement to broaden the ELEVIDYS label to remove age and ambulation restrictions. And finally, we have already engaged in productive and encouraging discussions with FDA and they have confirmed that they are committed to reviewing an application to broaden the label and are committed to doing so rapidly. Now let me comment on quarterly performance. The third quarter was a defining moment for Sarepta. We launched our fourth therapy in the first gene therapy for with Duchenne muscular dystrophy. We continue to drive great performance with our 3 PMOs and importantly, on a non-GAAP basis, we achieved profitability placing us an ever more rarified biotech territory.

As you will have seen in our release, led by an exceptional launch of ELEVIDYS and continuing performance of our 3 approved PMOs, EXONDYS, VYONDYS and AMONDYS. The quarter total revenue came in at $332 million, and total net product revenue stands at $309.32 million growing 49% over the same quarter last year, reflecting the team's ability to execute and serve Duchenne patients, ELEVIDYS net product revenue came in at $69.11 million merely triple mean external consensus.

Likewise, our PMOs achieved $240.21 million in net product revenue growing 16% over the same quarter prior year, and non-GAAP earnings stood at $38 million in the quarter, a major milestone for Sarepta as we transition to a profitable and in the near term, cash flow positive organization.

The team has done a tremendous job working with families, physicians and payers in the quarter, and it shows in these results. Dallan Murray, our Chief Customer Officer, will walk you through what has been nothing short of a remarkable launch of ELEVIDYS. And looking to the near future, we will take our proven track record of execution and move forward rapidly to expand the label of ELEVIDYS. So this team can employ that level of execution to make ELEVIDYS available to the majority of Duchenne patients in the United States.

Following Dallan's discussion, Dr. Rodino-Klapac will provide an update on our pipeline progress. Now as you would expect, we are not providing updated guidance this early in the launch, but also, obviously, across our 4 approved therapies, we are going to substantially exceed $1 billion this year, another important milestone to be sure. And with that, let me turn the call to Dallan for a commercial update. Dallan?

[Dallan Murray, executive]

Thank you, Doug, and good afternoon. The launch of ELEVIDYS in the third quarter was Sarepta's fourth Duchenne launch. It was by far the most complex and challenging to date. And I'm proud to say the team was ready on day 1, and they have knocked it out of the park thus far. As Doug has mentioned, we generated just over $69 million in net product revenues in the third quarter for ELEVIDYS. .

Notably, the team exceeded our own lofty site readiness expectations with nearly 70 sites ready to dose today. This helps us support the patients at risk of aging out today and also sets us up for longer-term success going forward. We approached this launch by building organically upon what was already best-in-class Duchenne commercial and medical teams.

We put additional responsibility on everyone across the board rather than building out separate gene therapy teams, and they have stepped up magnificently to meet this important moment. Our early success was achieved in 3 ways: first, flawless execution with our external stakeholders. That is the neuromuscular KOLs gene therapy sites of care and the eligible patients they serve. Secondly, proactive payer engagement to expedite access for those patients who are eligible on the label; and third, establishing a well funding flexible distribution model supported by the Sarepta SiPs team to get each patient's customized kit to the site of care at the right time, just in time for the infusion.

I would like to take a moment now to recognize the Duchenne community and how they came together to expedite access for patients who are eligible for ELEVIDYS, led by our doctors, nurses and other HCPs, all stakeholders were ready for this important moment, and it was humbling to see the whole community come together to support eligible patients in their treatment journey.

This launch also demonstrated the progress our teams and the experts have made in the past several years educating the payers about Duchenne. We were gratified by the urgency of payers and expediting policies that allowed access for eligible patients.

Additionally and importantly, the payers played a key role in supporting patients who are at risk of aging out. Saying all of that, we still have much more work to do with some of the payers to achieve our goal of securing access and treatment for all eligible patients across the country regardless of plan.

The team is working diligently as we speak, educating the payers on the robustness of the newly available EMBARK data. We're confident that this data sets the stage nicely for access to align with our label today as well as when we gain a broader label. The fast start in Q3 was a function of the team's efforts in the quarter itself. And just as importantly, their efforts over the past 7 years, building the model which we have established to support all of the Duchenne patients eligible for our therapies. Had this been Sarepta's launch, our trajectory in the third quarter would have been very different and much slower.

We've gained deep knowledge and expertise through 3 PMO launches, and I'm glad to say we were able to apply these learnings to the launch of ELEVIDYS. So to summarize ELEVIDYS, it was a great first quarter for the launch because our team and our key stakeholders were prepared and they executed flawlessly to support the patients we serve, driven in large part by the robust ELEVIDYS revenue in the third quarter. We grew overall net product revenue by roughly 30% over the prior quarter.

Net product revenue in Q3 of 2023 was $309.3 million. Importantly, as Doug said, in addition to our success with ELEVIDYS, we also had our most successful quarter ever serving patients with our established PMO franchise. We see continued opportunities in the U.S. and globally for our PMO business in spite of the fact that we also expect cannibalization from ELEVIDYS over time. Since the [ 4 to 5 ] population represents far less than 10% of the PMO business in the U.S., this cannibalization will not have a material impact on our 2023 net product revenue.

I'd like to take a moment here to thank all of those who are relentlessly supporting our PMO patients. So as a result of the whole team's effort, the net product revenue from our PMO business in Q3 was $240 million, representing a roughly 16% increase over the same quarter in 2022.

Looking now at each of our PMOs individually, net product revenue for EXONDYS 51 was $142.3 million in Q3, which was over 16% above the same quarter in 2022. VYONDYS 53 net product revenue was $31.7 million, 3.4% above Q3 of 2022. And AMONDYS 45 generated net product revenue of $66.3 million in Q3 of 2023. This represents roughly 21% growth over Q3 of 2022.

As we mentioned in previous calls, we are in the mature phase of the market now for all 3 of our approved PMOs. As a result, while we expect the U.S. growth to continue to flatten and the ex U.S. revenues, while still in the growth phase to remain lumpy from quarter-to-quarter and thus difficult to project on a quarterly basis. Taken together, we can reiterate our annual guidance of greater than $925 million in net product revenue for our PMO business in 2023.

I'll end by saying that I've been continually amazed and impressed by the resilience, commitment and execution of our Sarepta teams over the years. And while the success over those years has been impressive, what the teams have achieved in the third quarter of 2023 stands above and beyond anything I've seen in my 10 years working to serve the Duchenne community.

The future is bright for Sarepta and for the Duchenne community who have been waiting for and very much deserve this progress. Words can't adequately express just how proud I am of our whole team. The individual stories from across the country are too numerous to mention here. Nor can we as a team put in towards the joy we feel when we celebrate each and every patient who gains access to any of our dystrophin restoration therapies.

And so with that, I'll turn the call over to Dr. Louise Rodino-Klapac. Louise?

[Louise Rodino-Klapac, executive]

Thanks, Dallan. Our commitment to the science remains steadfast and our goal to change the lives of patients with rare diseases unwavering. Our opportunity to do good is limitless for those living with Duchenne, limb-girdle and many other diseases for which therapies are either inadequate or nonexistent.

As Doug has already detailed the EMBARK results, I will focus my comments on the progress of our gene therapy and RNA programs. First, limb-girdle muscular dystrophy or LGMD. We remain committed to advancing our LGMD portfolio across a variety of subtypes and look forward to providing continuous updates on these important programs in the months ahead.

We presented on our LGMD pipeline this past weekend at the Speak Foundation's 2023 International LGMD Conference and shared our urgency with the community to bring forward genetic medicines for LGMD. To begin, we made excellent progress for, 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.

We are pleased to report that we completed enrollment in VOYAGE and we remain on track to initiate our Phase III study using commercially representative process material later this year. Combined with positive expression and functional data shared from our initial study, SRP-9001-101. We believe the data from will give us insights into a broader patient population. We are also excited to report that we completed dosing in our systemic pilot study, for SRP-6004 dual vector Rh74 mediated gene therapy to treat individuals with LGMD2B.

LGMD2B is characterized by the absence of the protein deterlin. The innovative dual vector strategy allows us to deliver the full length dystrophin gene, the sole cause of LGMD2B. We look forward to reporting results from the study in the first half of 2024. As mentioned last quarter, our LGMD natural history study of the sarcoglycanopathy LGMD2E, 2C and 2D, all Journey has been fully enrolled, and we will follow patients for 36 months.

We continue to make progress in scalable manufacturing for all of our LGMD candidates in our pipeline and look forward to initiating clinical studies as 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're targeting readout of the study in 2023. Regarding our post-marketing studies for the PMOs as mentioned last quarter, we completed enrollment in the ESSENCE trial, a post-marketing requirement for golodirsen and casimersen.

As a reminder, ESSENCE is a 2-year study and is due to read out in early 2026. Finally, we are pleased to have completed enrollment in our MISSION Study, our dose post marketing commitment for EXONDYS. Mission is a randomized double-blind safety and efficacy dose finding study comparing the approved dosage of eteplirsen, a 30 mg per kg weekly to a dosage that provides significantly higher exposure up to 200 mg per kg weekly.

Patient is a 2-part Phase III study that was fully enrolled in October 2023 with 160 patients enrolled. We remain committed to rapidly and diligently advancing mission and sharing data as soon as it becomes available. We look forward to reporting continued progress with our RNA programs in the coming months.

On a personal note, my passion for science and its promise to help others begin early in life. These many years later, as I reflect on my career and where we are today in realizing the promise of genetic medicine. I'm grateful and I'm humbled, and yet we have so much more to do.

We move forward from here today toward a more promising future for individuals around the world living with rare disease. In closing, I'd like to take a moment to thank the team for their continued dedication and passion to patients, the science and our mission.

I'll now turn the call over to Ian for an update on our financial results. Ian?

[Ian Estepan, executive]

Well said, Louise. Good afternoon, everyone. This afternoon's financial results press release provided details for the third quarter of 2023 on a non-GAAP basis as well as a GAAP basis. Please refer to our press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results. .

We're obviously quite pleased with the financial results for this quarter on the back of a tremendous start or the EXONDYS launch. We actually achieved non-GAAP profitability. And assuming an expansion to the label to the broader Duchenne population, we should achieve sustained profitability.

We're quite thrilled to achieve this milestone just in the first quarter of the launch. For the 3 months ended September 30, 2023, the company recorded total revenues of $331.8 million, which consists of net product revenues and collaboration revenues compared to revenues of $230.3 million for the same period of 2022, an increase of $101.5 million.

Net product revenue for the third quarter of 2023 from ELEVIDYS was $69.1 million. Net product revenue for the same period from our franchise was $240.2 million compared to $207.8 million for the same period of 2022. For the quarter, individual net product sales were $142.3 million for EXONDYS 51, $66.3 million for AMONDYS 45 and $31.7 million for VYONDYS 53.

The increase in net product revenue primarily reflects increasing demand for our PMO products as well as net product revenue associated with the sales of ELEVIDYS. In each of the quarters ended September 30, 2023, and 2022, we recognized $22.5 million of collaboration revenue, which relates to our collaboration arrangement with Roche. The reimbursement of co-development costs under the Roche agreement totaled $34.9 million for third quarter of 2023 compared to $22 million for the same period of 2022.

On a GAAP basis, we reported a net loss of $40.9 million or $0.46 per basic and diluted share and $257.7 million or $2.94 per basic and diluted share for the third quarter of 2023 and 2022, respectively. We reported non-GAAP net income of $37.7 million or $0.37 per diluted share in the third quarter of 2023 compared to a non-GAAP net loss of $70 million or $0.80 per diluted share in the third quarter of 2022.

In the third quarter of 2023, we recorded approximately $37 million in the cost of sales compared to $40 million for the same period of 2022. The decrease in cost of sales primarily reflects write-offs of certain batches of our PMO products, not meeting our quality specifications in the 3 months ended September 30, 2022, with no similar activity for the same period of 2023, partially offset by increasing demand for our PMO products.

On a GAAP basis, we recorded $194.3 million and $216.7 million in R&D expenses for the third quarter of 2023 and 2022, respectively, a year-over-year decrease of $22.4 million. The decrease is primarily due to a decrease in our manufacturing expenses partially offset by increases in clinical trial expenses.

On a non-GAAP basis, R&D expenses were $163.9 million for the third quarter of 2023 compared to $193.7 million for the same period of 2022, a decrease of $29.8 million. Now turning to SG&A. On a GAAP basis, we recorded approximately $120.9 million and $104.8 million of expenses for the third quarter of 2023 and 2022, respectively, an increase of $16.1 million. The increase was driven primarily by an increase in professional services and compensation and other personnel expenses, partially offset by a decrease in stock-based compensation.

On a non-GAAP basis, the SG&A expenses were $92.8 million for the third quarter of 2023 compared to $66.8 million for the same period of 2022, an increase of $26 million. On a GAAP basis, we recorded $12.3 million in other expense net for the third quarter of 2023 compared to $400,000 in other income net for the same period of 2022. The change is primarily due to the impairment of our investment and loss on contingent consideration, that partially offset by increases in accretion of an investment discount, net and increases in interest income due to the investment mix of our investment portfolio as well as reductions of interest expense incurred as a result of the repayment of our December 2019 term loan during 2022.

We had approximately $1.8 billion in cash, cash equivalents, investments and long-term restricted cash as of September 30, 2023. We're obviously pleased with the amount of capital on our balance sheet, but in turbulent markets, we know cash becomes even more valuable. We continually evaluate our expenses. That said, based on the EMBARK results and the information we have today, there's no better use of our cash than to build inventory to serve those with DMD. So with that, I'll turn the call over to Doug to start Q&A. Doug?

[Douglas Ingram, executive]

Thank you very much, Ian. Michelle, let's open the call for questions.

[Operator]

[Operator Instructions] The first question comes from Anupam Rama with JP Morgan.

[Anupam Rama, analyst]

Just going back to the EMBARK results, we've gotten this question. If you guys adjust for multiplicity on your key functional secondary endpoints, would you still have statistically significant outcomes on these key measures?

[Douglas Ingram, executive]

Yes. Thank you for that question, Anupam. I will turn this call over to Louise. .

[Louise Rodino-Klapac, executive]

Thank you. We actually performed a global statistical test, and we did this to do just that to test from multiplicity and show that the secondary is do not hit significant just by chance. So we essentially tested NSAA combined with the secondaries and show that they were, in fact, statistically significant.

So this is a quantitative way to test the totality of evidence in respect. So if you think of the forest pot that we showed on our call, that's essentially a statistical test to show that together, we see that these are statistically significant.

[Operator]

The next question comes from Tazeen Ahmad with Bank of America Securities.

[Tazeen Ahmad, analyst]

For me, I think one of the most popular inbounds I've been getting in the last 2 days is just try to triangulate timing. So Doug, to the extent that you can provide us color with what steps are involved next in order to complete your filing? And is there any kind of precedent for a filing like this on the time it would take the agency to review an application? Could it be this calendar year that this could all be complete? Or would it be something more traditional like a 6-month review, for example?

[Douglas Ingram, executive]

Tazeen, thank you for your question, and then let me preface my question by saying I'm probably going to frustrate you by not giving hard and fast time lines other than we're going to move rapidly and we have a commitment from the division to move rapidly as well. .

Our goal is to file a BLA supplement. I believe it's an efficacy supplement and we're going to do that very soon. The team is working on it right now. I don't want to commit to the exact date, but very, very soon that will be submitted. I think traditionally, the agency may have 6 months to review, I do not believe -- I believe the agency is committed to moving as fast as is reasonably possible to review this.

And there is precedent for this. You see this in other areas like oncology, all the time where you can get for something like this, very fast turnaround. And of course, remember, this isn't a BLA, but a BLA supplement. So the inquiry will extraordinarily important is focused, and that focus is on the fundamental question, does the totality of the evidence, justify conclusion that ELEVIDYS is bringing a better life to these patients. And of course, we believe that it does.

The standard for this is quite clear. It's substantial evidence looking at the totality of evidence, the statute on this is quite clear. I apologize. I don't know if that music is I promise I'm not playing a guitar right now.

The statute says it's very clear. Can 1 fairly responsibly conclude that the therapy we'll have the effective reports to have and the regulations are also particularly clear that for life-threatening and severely debilitating, ones like used, Duchenne, especially when no satisfactory alternative therapy exists.

The FDA has determined that it is appropriate to exercise the broadest flexibility in applying the statutory standards. And as Louise just pointed out to everybody, -- not only are the evidence on whole, very compelling that ELEVIDYS is arresting the decline in these patients. But if you do the actual statistics, and look across the primary and our functional secondaries, you can see statistically adjusting for any risk of a false positive adjusting for multiplicity, that is powerfully statistically significant.

So all of which is to say winding back to the original question Tazeen, that we're going to submit a BLA supplement very soon. the agency is committed to working with us very rapidly. And while I won't give an exact time line, I am confident that we're going to move quickly to review this and a successful broaden this label.

[Operator]

The next question comes from Gena Wang with Barclays.

[Huidong Wang, analyst]

Maybe just follow this comments. Doug, will you announce when BLA efficacy supplement was accepted. And in the data package, can you lay out what kind of data will be included in addition to what you share with us? Would that also be like, say, the protein correlation of the protein level versus function will -- these data also will be included in the package?

[Dallan Murray, executive]

There will be certainly more in the package and then the top line, we're still evaluating other information, including for instance, protein and other things, CK and the like. But obviously, the focus of the review is going to be, first and foremost, the efficacy and the safety for this therapy. And then, of course, it's all going to be evaluated in relation to our request to road this label by removing age limitations and emulation. -- limitations on that. We -- I don't think we've made any final decisions about what we're announcing during this process. But obviously, generally speaking, we tend to be pretty transparent with folks.

[Operator]

The next question comes from Colin Bristow with UBS.

[Colin Bristow, analyst]

And congrats from the impressive and ELEVIDYS. Maybe another 1 on the EMBARK data. Can you speak to the interpatient variability you saw in ELEVIDYS-treated patients? Sort of a question we've been getting is, were the positive results driven by a small group of high responders. And maybe if you could just talk a bit on how this variability compared to the Phase II experience, that would be helpful.

[Douglas Ingram, executive]

Sure. I'm going to flip this over to Louise to answer specifically, but I would generally not that the positive results, the p-value on these positive results are they're not close on the time to rise, it's 0.002 on the 10-meter walk around at 0.004. On the global statistical analysis, when 1 looks at the primary and all the secondaries together, it's 0.004. So it's very, very powerful. But Louise, perhaps you want to answer more specifically on some of the variability issues.

[Louise Rodino-Klapac, executive]

. .

Yes. Generally, we did not see variability -- high variability amongst the patients with standard deviation was either at or below what we anticipated from our previous studies that we use to power and Parker we did not see any high variability.

[Operator]

The next question comes from Reed Forsyth with Guggenheim.

[Unknown Analyst]

Did the top line data provided to the FDA from EMBARK include information on...

[Douglas Ingram, executive]

I am very sorry, but I was unable to hear that question. Can you ask it again, perhaps?

[Unknown Analyst]

Yes. This is Ray on for Debjit. Did the top line data provided to the FDA on EMBARK include information on...

[Douglas Ingram, executive]

Goodness. I'm so sorry, right? I heard the beginning, but I don't hear the question itself.

[Unknown Executive]

I think he asked the aspect included data on microdystrophin expression.

[Douglas Ingram, executive]

Well, with the -- I imagine that we'll have that data available during the review process with the FDA. As Louise said, the expression we're seeing is in the hunt in range of what we've normally seen. So there's nothing unusual about it. In fact, the P value on it is 0.0, many 0s, very strongly. Robustly as you would expect, a limited robustly. That's the question part. Apologies I couldn't hear you on sight about that.

[Operator]

The next question comes from Brian Skorney with Baird.

[Brian Skorney, analyst]

I guess it wasn't something we looked at very closely before, but I'm sorry you want to tell, I think, had a nonsignificant difference in favor in treatment, but not that different in terms of magnitude, I think, maybe just under half a second differences. Maybe tell me if that's right or not. So I know you've talked extensively about the baseline imbalance issue here and it seems particularly acute in case of baseline time to rise with the active arm was 5.1 at Phase and placebo was So I was just wondering if you've gone back and looked at making adjustments for baseline imbalances to evaluate the tons to rise differences in Study 102. And in particular, if the 4- to 5-year-old subgroup looks the same in?

[Douglas Ingram, executive]

Yes. Thank you for that question, Brian. I'll turn this to Louise to respond.

[Louise Rodino-Klapac, executive]

I'm going to speak generally because what we did was take the inclusion criteria that we've generated for Embark and applied it to our previous data when we compared it to the external control -- and what we found there is a difference when you exclude those patients that would have been excluded by that criteria 102, where you had those rapid decliners. So in that case, we saw a more significant difference. But -- the specific numbers are escaping right now, but we did do that analysis where we kind of applied the same exclusion criteria and did see a difference.

[Ian Estepan, executive]

Yes. Maybe just 1 thing to add in that analysis to Les' point, we saw a really good consistency between what we observed in 102 and what we've observed in 301.

[Operator]

The next question comes from Salveen Richter with Goldman Sachs.

[Salveen Richter, analyst]

With regard to the regulatory submission, are there formal or regulatory procedures involved with revisiting an accelerated approval after the primary endpoint fails in a confirmatory trial here? And then just any preliminary feedback on your data from payers and how that might impact the existing label or from physicians with regard to how they think about use in patients here?

[Douglas Ingram, executive]

Yes. Again, on the first question, I'm not confident I understand the question, may be very clear, the standard for confirmation of an accelerated approval is looking at the totality of evidence in determining whether the benefits of that therapy have been confirmed by the entire data set, not just the confirmatory data, but all of the surrounding evidence that would exist, including other studies. And I would strongly argue that not only embarked, but all of the supporting evidence as well as strongly confirm the benefits of this therapy.

So I think we're in very good shape there. The focus of our review with this division is going to be on the breadth of the expansion of this label. That I am quite confident is going to be the review focus -- and as it relates to that, as you know, our strong view is that having confirmed these results and then confirmed them across patients and looking at the totality of this evidence and looking at the forest plot as an example of looking at the statistical analysis of the forest plot adjusted for multiplicity, it is quite clear that this therapy is arresting the decline in these patients and deserves to be made available to patients were now a limitation to age or artificial restriction around angulation.

As it relates to payers, this is additional evidence in our armamentarium with payers. Things have gone very well. Dallan and his team, medical affairs, our commercial, our field force, access to reimbursement and the like. have just done a fabulous job supporting the launch of elevates and I hope everyone will agree with me that it shows in our performance this quarter and this bolsters the discussions that the team can have.

Now we can give as an example. We now have a really powerful metric that it's compelling on the speed with which 1 you put a kit on on therapy. So as I will remind you on the time to rise, not only is the P value, I think, 0.002, if I am not mistaken -- but in time to rise is the single greatest prognosticator of loss of ambulation and a rise time above 5 seconds, as we've talked about often and is in the literature robustly is the single greatest predictor of early loss of ambulation. And EMBARK has shown that using ELEVIDYS reduces the odds of that occurring in a 52-week period. by over 90%.

So this provides an additional compelling point with payers who, frankly, so far, have done a really good job of providing access. This provides additional evidence that it really is important to get kids on this therapy as soon as possible. And I would argue looking forward to label expansion and is a compelling argument for why this therapy should be -- this label should be expanded as soon as possible as well. So everyone has access to it as well.

[Operator]

The next question comes from Uy Ear with Mizuho.

[Uy Ear, analyst]

Congrats on the great quarter for El -- so I guess my first question is, were those -- the patients with dose were they primarily those who were pretty much anticipated the approval the accelerated approval, and they get them more like the bolus. And like how many would you be able to share how many patients are waiting to be dosed in the coming quarter? And just continue on this theme. Now that the Embark data has read out, do you have any sense of any shift in patients receptivity to the product at all? I know it's early days.

[Douglas Ingram, executive]

Yes. Let me answer those questions quickly. First, I don't think there will be any shift in the desire for this therapy. I think except for patients that are not in the parents of patients that are not in the 4- to 5-year-old range I think are probably even more compelled to want this start and are going to wait impatiently as they should be in patient to have this label broadened.

We don't share patient numbers. We're going to use as our metric for success and the measure of our success on net product revenue. As we said, on the issue of sort of bolus or warehousing of patients, there were certainly some number of patients that physicians were getting together and gathering to ensure that they could preferentially get dosed before they aged out because the label, obviously, as you know, restricts the dosing to 6 and below 6% and 5%.

But we've had a steady stream of new start forms since the approval. And so looking forward, we have a steady stream of start forms that are working through the process. And 1 other thing people have been asked, but I'll say it done the team, all and others has done a brilliant job on site activation. I think our goal, as you know, our goal and aspirationally been to have 50 sites ready to infuse at launch. And then very aspirationally, we thought perhaps by the end of the year, sometime next year, we can get all the way to 70 sites, but we're at 70 today. So the team has just done a brilliant jump making -- getting sites ready and up and running and there is a steady stream of start forms to work through.

[Operator]

The next question comes from Danielle Brill with Raymond James.

[Danielle Brill, analyst]

Doug, so we spent a lot of time discussing EMBARK efficacy at data I'd like to switch over to safety. I recall myocardis events being discussed at the AdCom, including 1 event that had occurred in EMBARK at the time. Just curious if there are any additional safety events of this nature that occurred in the study or any other SAEs leading to hospitalization?

[Tim Lugo, analyst]

Thank you for your question, Danielle. I will turn the call over to Louis to respond.

[Louise Rodino-Klapac, executive]

Yes, we did not see any differences in the types of SAEs or the frequency of the SAES that was 1 of the most reassuring things about bark was the continued safety profile and now taken together all of the previous trials, we have a large safety data base that's consistent on those trials.

[Operator]

The next question comes from Ritu Baral with Cowen.

[Ritu Baral, analyst]

Doug, could you -- and maybe, Dallan, walk us through how you see patient numbers for the different scenarios that are regulatory experts suggest could are in play essentially for label expansion. You mentioned 10% of your hemo sales are for 45 -- those are covered -- but how would you segment it by maybe 6- to 7-year-olds if FDA wants to go down that route again? And how that number would change you do got the full ambulatory population, which per my calls now extends to like 12 years of age.

[Douglas Ingram, executive]

For ambulatory?

[Ritu Baral, analyst]

Yes. Like that's the average age of loss of ambulation now 12 13.

[Douglas Ingram, executive]

That may be correct. I'll Dallan confirm that in a second. Broadly speaking, I mean, look, first of all, I want to be very clear, we're not looking for a label expansion to go from 4.5 to 4 to 7, and we don't think there's any reason scientifically 1 would be limited to 4 to 7, given the data.

And we've never seen that before. once -- you've never seen in any other label for Duchenne therapy, these sorts of age-related restrictions. But answering modest question, the all ambulatory versus all ambulatory and nonambulatory is about 50%. So there's -- so the ambulatory population is about half of all patients and the nonambulatory the other half, of course, -- and so that, to our mind, is the big cut. But Dale, is there anything else you'd like to say on this topic.

[Dallan Murray, executive]

No, I think you covered it, Doug. Our goal is to target all the patients that we can get in the entire population, read you to your question about average age of loss of ambulation. I think you're in the right range. But the KOLs have been talking a lot about the definition of loss of ambulation too because, as you know, there's heterogeneity. So you have some patients walking at much older ages, and we have a whole cohort of patients who've been treated with the PMOs for years now that are going to, we believe, have older ages of loss of ambulation as well.

So it won't be -- we believe the ambulatory population won't be defined by age. But as Doug said, our aspiration is a broad label and targeting all of the patients who will be eligible.

[Ritu Baral, analyst]

And is that 50% of your PMO sales too?

[Douglas Ingram, executive]

Yes. The ambulatory versus nonambulatory split, I think it's in that range of 50%. I think the access is more difficult in the older patients. So on average, we've got a higher penetration in the younger given population.

[Operator]

The next question comes from as with Morgan Stanley.

[Unknown Analyst]

You mentioned now that you have about 70 sites are active. Can you give us a sense of what percentage of those sites have actually prescribed elevates so far? .

[Douglas Ingram, executive]

We are going to -- apologies I'm going to frustrate you. We're going to resist that level of detail either on numbers of sites are infused or probably more specifically number of patients infused at any 1 time. As we have done for the last 7 years, and I think we've done generally over time to good success with folks. We use net product revenue is the marker for success and uptake and the like. .

[Unknown Analyst]

So apologies for that, Mike.

[Operator]

[Operator Instructions] The next question comes from Tim Lugo with William Blair.

[Tim Lugo, analyst]

You mentioned earlier in the week that you didn't expect an additional advisory committee for broadening the label. But we can all remember when we did expect 1 for the accelerated approval discussion. I guess why not request an AdCom? It seems like listening to the AdCom, the participants were much more amenable to non-age-restricted approval than the agency was.

[Douglas Ingram, executive]

Yes. Okay. So it's a good question, and I'm not surprised by the comment. There are those that might say that I have a poor historical track record of predicting ad coms notwithstanding the factor the last time I said we were going to have to have that in writing. The reason that we don't believe we're going to have an outcome is that we don't believe that we will need one. And I think that -- I believe, as we sit here today, that, that is a view that would be shared by us and FDA leadership.

As we've said before, -- we had a very productive and encouraging discussion with the FDA leadership on the data and on the possibility of submitting it for a broad label. And I would also note that the agency has changed the division, in particular, has gone through some pretty significant changes over the course of this year. There's been a reorganization just to remind you where OTAT has been replaced by the super office.

And not too long ago, a new leader, Dr. Nicole Verdun, took the helm as the Head of. So I would say were not to remember that the division is evolving. Obviously, in the event that there was an advisory committee, we would be well prepared for it. And I believe we would perform exceptionally well there. I think Dr. Louise Rodino-Klapac and his team just did a fabulous job representing us. And as 1 may recall, we did ultimately win that outcome. But as we sit here today, we feel pretty confident that we can get a little expansion without an advisory committee.

[Operator]

The next question comes from Gil Blum with Needham & Company.

[Gil Blum, analyst]

Congratulations on all the progress. Going back to a question, a follow-up on Alan's earlier questions about any questions ago. So if you are on Study 102. Is there -- any chance that there would be some follow-up, especially on the patients that were older and were crossed over in part 2 of Study 102 regarding time to rise. It will be interesting to see how that data looks in comparison to the EMBARK data.

[Tim Lugo, analyst]

Sure. Louis, any thoughts on that?

[Louise Rodino-Klapac, executive]

Okay . all the 102 patients are continued to fall for up to 5 years. So that's certainly something that we can look at over time. We don't have that they didn't have, so we can look at that.

[Operator]

The next question comes from Brian with RBC Capital.

[Brian Abrahams, analyst]

Congrats on the strong first full quarter of the ELEVIDYS launch. Can you remind us of the protocols in place in Embark to protect against functional unblinding -- was this a topic that ever came up with the FDA in your recent discussions? And might you expect any differences in the effect functional and blinding, if there was any, it might have on time tests versus on NSAA?

[Douglas Ingram, executive]

Yes. I can allow Luis to discuss the protocol aspects of the blinding process, which was exceptionally rigorous we can generally assume that if that these very objective time test would be less subject to any kind of influence in the event there wasn't unblinding. But I would say also that I think the protocol was very good about the blinding process and the study itself, 1 should remember, was actually very well run. I want to be clear about that. .

[Tim Lugo, analyst]

Luis, any thoughts on the blinding process? .

[Mary Jenkins, executive]

Yes.

[Louise Rodino-Klapac, executive]

Just specifically to the patients and caregivers obviously blinded the PIs as well as the physical therapist doing the functional tests are all completely slide. So the studies maintain blinded steady staff disrupt is blinded. It's maintained by a third party. So there is a rigorous process in place to make sure that the blind remains intact. .

[Operator]

The next question comes from Kristen Kluska with Cantor Fitzgerald.

[Unknown Analyst]

This is Jason Bouvier on for Kristen Kluska. Congrats on the strong quarter for ELEVIDYS. One question from us, the cadence treating patients is going faster than the original time lines you laid out. So we're just wondering what the biggest drivers are there? And how might this also impact the potentially broader launch next year?

[Douglas Ingram, executive]

Well, I'm going to take the question even know Dallan wants to because I want to brag about our team. I mean I think there's 2 significant reasons why the cadence of this launch is going exceptionally well and why this launch is it, from my perspective, an unprecedented success in gene therapy, the first of which, of course, is the therapy itself.

ELEVIDYS is an extraordinarily needed therapy that patients who have been on it and families that share their experience with strongly of the belief that they need this therapy, and these kids have been stabilizing or doing things age-specific that untreated kids haven't been able to do.

And then if you don't mind me bragging a little bit about the team. I mean this is an example of exceptionally great execution by the Sarepta folks led by Dallan, Customer Officer, by going beyond that, this is our manufacturing and distribution folks as well, just a large team effort to execute on this. And this isn't new for us. I want to remind everyone now that we have now 4 therapies that we have launched. Every 1 of those therapies and their launches have gone exceptionally well.

I mean if we look at the P&L, it's just digress for a moment. I mean we are now from our first PMO that was approved in late 2016. We're still growing. We grew at 16% quarter over the same quarter last year, even as we're launching evidence is doing brilliantly there. So I think there's a combination both of the great therapy as all of our 4 therapies, I believe, have been and exceptional focused, granular, well-informed execution. And what does this mean for the future, it means that we know how to serve the Duchenne community and one of the things that excites us about a broader label is we'll be able to bring ELEVIDYS to the majority of children and young men in the United States that are living with and generating irreparably from this ferocious disease. And so I'm really excited about the opportunity to bring this therapy to more patients even as we're doing really well with the launch right now. Thank you very much for your question.

[Operator]

The last question comes from Joseph Schwartz with Leerink Partners.

[Joseph Schwartz, analyst]

Great. I was wondering how are you thinking about upcoming clinical data for a different gene therapy candidate, which will have an interim look soon. Is there anything that you'll be focused on in particular? And how do you see the trade-off between safety and efficacy. If it were able to produce a greater impact on FAA, how would that impact your relative value proposition for ELEVIDYS?

[Douglas Ingram, executive]

Thank you for the question. Look, as I've said many times before, we have in front of us an exceptionally for Roche's competitor and that Duchenne muscular dystrophy and all of our focus and all of our energy is in beating the damn disease. And I think this team is doing a brilliant job of that. We're exceptionally pleased with the performance of ELEVIDYS. There were some -- many years ago, people made decisions about constructs and capsids and the like. And with the benefit of many years of experience, we are exceptionally proud of.

And frankly, nothing less than thrilled with the particular capsid and construct that we have. It's shown not only, but it is able to intervene protect these muscles of these children and arrested decline that it can do that with a particularly lonable safety profile given the amount of therapy required here and the fact that it's full body infusions. rh74 has been a standout. And we're quite confident that anyone who is rational who had an opportunity to make a decision today about what capsid they would use and what construct they would develop. I'm sure they would do their best to try to copy us. So we're -- we're not focused on any competitor besides Duchenne muscle dystrophy, and we are ferociously committed to beating this disease. So that's our focus right now. But thank you very much for your questions.

[Operator]

I would now like to turn the call back over to Doug for closing remarks.

[Douglas Ingram, executive]

Well, thank you very much, Michelle. And thanks, everyone, for attending tonight, and thank you for your very thoughtful questions. Let me summarize. This quarter has been an extraordinarily important one. With our fourth approval, we launched elevates and in my opinion, we launched it brilliantly. We've continued to serve the community with our PMOs, which continue robust growth even in the face of an ELEVIDYS launch. And on a non-GAAP basis, we are now profitable, and we are marching toward a cash flow positive in the very near future. We have built a strong enduring organization that is focused on 2 major things. The first is serving our patient community through brilliant science and the second is executing and getting things done. And that is precisely what we will be doing over the coming months. We intend to continue our strong performance and commitment to serving this community. We intend to move with speed to submit our efficacy supplement and conclude the review on the broadening of the ELEVIDYS label.

And

when our label has been updated to remove age and ambulation restrictions, we intend to bring this therapy to the majority of patients living with Duchenne in the United States. And with that, I look forward to updating all of you on our progress along the way and have a lovely evening. Thank you.

[Operator]

This concludes today's conference call. Thank you for participating. You may now disconnect.