Sarepta Therapeutics (SRPT) This fall 2024 Earnings Name Transcript

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Sarepta Therapeutics (NASDAQ: SRPT)
This fall 2024 Earnings Name
Feb 26, 2025, 4:30 p.m. ET

Contents:

• Ready Remarks
• Questions and Solutions
• Name Members

Ready Remarks:

Operator

Good afternoon, and welcome to the Sarepta Therapeutics fourth quarter and full 12 months 2024 monetary outcomes convention name. As a reminder, immediately’s program is being recorded. Presently, I would like to show the decision over to Mary Jenkins, affiliate director, investor relations and company communications. Please go forward.

Mary Jenkins — Affiliate Director, Investor Relations and Company Communications

Thanks, Lisa, and thanks all for becoming a member of immediately’s name. Earlier this afternoon, we launched our monetary outcomes for the fourth quarter and full 12 months 2024. The press launch, slides, and supplementary data can be found on the Buyers part of our web site at sarepta.com. Our 10-Okay might be filed with the SEC later this week.

Becoming a member of us on the decision immediately are Doug Ingram, Ian Estepan, Dallan Murray, and Dr. Louise Rodino-Klapac. After our formal remarks, we’ll open the decision for Q&A. I would like to notice that in this name, we might be making various forward-looking statements.

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Please confer with Slide 2 on the webcast, which comprises our forward-looking statements. These forward-looking statements contain dangers and uncertainties, a lot of that are past Sarepta’s management. Precise outcomes may materially differ from these forward-looking statements, and any such dangers can materially and adversely have an effect on the enterprise, the outcomes of operations, and buying and selling costs for Sarepta’s frequent inventory. For an in depth description of relevant dangers and uncertainties, we encourage you to evaluation the corporate’s most up-to-date SEC filings.

The corporate doesn’t undertake any obligation to publicly replace its forward-looking statements, together with any monetary projections offered immediately, based mostly on subsequent occasions or circumstances. As famous on Slide 3, we are going to talk about non-GAAP monetary measures on this webcast. Descriptions of those non-GAAP monetary measures and reconciliations of GAAP to non-GAAP are included in immediately’s press launch and the slide presentation out there on the Buyers part of our web site. And now I will flip the decision over to our president and CEO, Doug Ingram, who will present an summary of our latest progress.

Doug?

Douglas Ingram — President and Chief Government Officer

Thanks, Mary. Good afternoon, everybody, and thanks for becoming a member of Sarepta Therapeutics’ fourth quarter and full 12 months 2024 monetary outcomes convention name. As you could know, again in late 2017, we created an expansive strategic plan that we name Mission Moonshot, one that may require that we elevate billions of {dollars}, constitution course via the unknown and overcome a number of unexpected obstacles, obstacles that may have deterred a much less dedicated staff, but in addition a strategic plan, if achieved, which might guarantee a greater life for hundreds of Duchenne sufferers and cement the sturdy way forward for Sarepta. After years of labor and reams of recent perception into the remedy of Duchenne, in 2024, we achieved all the objectives specified by Mission Moonshot.

We obtained approval for the broadest doable label for ELEVIDYS, attaining our aim of a transformative remedy that might serve the overwhelming majority of Duchenne sufferers. We labored with the FDA to reframe the method to the event of uncommon and ultra-rare illnesses in order that therapies beforehand rendered unviable by FDA necessities now have the potential to assist sufferers. And consequently, our LGMD franchise is shifting with renewed velocity towards three potential approvals over the following three years. We broadly launched ELEVIDYS in 2024 and achieved outcomes higher than all different in vivo gene therapies mixed.

On the similar time, we proceed to serve the group with our PMOs, which grew even within the face of a strong gene remedy launch. We turned sustainably worthwhile and money movement constructive in 2024. Certainly, by the tip of 2030, we are going to do over $16 billion cumulatively in working revenue and over $13 billion in free money movement, and that is after we’ve closed and made our preliminary funding within the Arrowhead transaction. And we’ve secured sturdy and much more diversified future via our Arrowhead collaboration, pursuant to which we now add to our gene remedy pipeline a broad platform of siRNA together with 4 scientific applications, three preclinical applications, and 6 analysis applications throughout neuromuscular, CNS, cardiomyopathy, and pulmonary.

Along with a number of gene remedy launches within the coming few years, we could have a number of potential blockbuster siRNA launches earlier than the tip of this decade. Now, talking extra particularly of efficiency. We had an exceptionally sturdy fourth-quarter and full-year efficiency with our 4 permitted therapies. For the fourth quarter, our web product income stood at $638 million, rising at 75% over the identical quarter prior 12 months.

This represents greater than $60 million in overperformance to our prior steerage. Our full-year web product income stood at $1.8 billion, representing year-over-year progress of 56%, and this overperformed to our steerage by over $100 million. Turning to ELEVIDYS. In 2024, we had, by a large margin, essentially the most profitable launch of a gene remedy but in historical past.

For the fourth quarter, ELEVIDYS gross sales stood at 385 — $384 million, representing a 112% enhance over the prior sequential quarter. And whereas we’ve already achieved over $1 billion in gross sales since our preliminary approval in 2023, this represents lower than 5% of the on-label addressable alternative. So, clearly, that is just the start. Our three PMOs, EXONDYS 51, AMONDYS 45, and VYONDYS 53, achieved $254 million within the fourth quarter and $967 million for the total 12 months.

We have been worthwhile on a GAAP and a non-GAAP foundation within the fourth quarter, and we have been money movement constructive. Dallan Murray, our chief buyer officer, will present extra colour on industrial efficiency in a second. After which to spherical out the decision, our CFO, Ian Estepan, will talk about our financials in additional element. Trying ahead, in 2025, we are going to capitalize on the successes of 2024.

As you recognize, our web product income steerage for 2025, excluding royalties from Roche, is between $2.9 billion and $3.1 billion, roughly one-third of which is able to come from the PMOs and a bit over two-thirds of which is able to come from ELEVIDYS. This represents year-over-year progress of 70% for whole web product income, and all through ELEVIDYS, this represents over 160% year-over-year progress. On the R&D and tech ops facet, we’ve extra upcoming milestones this 12 months than every other time in our historical past. As you recognize, we already met our vital ELEVIDYS milestone in late January.

We reported the two-year and one-year crossover outcomes for ELEVIDYS from our pivotal trial EMBARK. And in all prespecified measures that features all useful measures, muscle well being, and biomarkers, these on ELEVIDYS did strongly statistically, considerably higher than untreated pure historical past would have predicted. We’ve got handed 600 sufferers now on remedy throughout a broad vary of ages and weights. These information are additional proof of the transformative potential of ELEVIDYS to alter for — the long run course of this illness for sufferers.

To proceed to serve theglobal marketand enhance COGS, we’re planning for a transfer to suspension manufacturing. And after finishing our GMP runs, we intend to start our suspension manufacturing bridging research this 12 months. As famous, we are actually shifting quickly with our LGMD platform. We’re persevering with to dose our research for SRP-9004 to deal with LGMD Kind 2D, and we’ve initiated our registration research for SRP-9005 to deal with LGMD Kind 2C.

We’ve got accomplished dosing in our pivotal trial for SRP-9003 to deal with LGMD Kind 2E, and we might be submitting our BLA for approval later this 12 months. We additionally intend to file our IND for SRP-9010 to deal with LGMD Kind 2A later this 12 months. If profitable, we are going to launch SRP-9003 subsequent 12 months. We’ll launch SRP-9004 the next 12 months, and SRP-9005 might be launched the 12 months after that.

As you recognize, we’ve closed our transaction with Arrowhead this month. And already, there might be a number of very vital milestones in 2025. This 12 months, we could have our preliminary readout for cohorts for ARO-DUX4 to deal with FSHD kind 1. Once more, this might be a really vital proof of biology.

We might be taking a look at muscle focus, downstream gene correction, and security. We’re additionally very excited concerning the potential to straight measure knockdown of the aberrant protein of curiosity, DUX4. No different program to this point has been in a position to obtain this, and this is able to be a really highly effective outcome if profitable. Likewise, we could have a readout of our preliminary cohorts for ARO-DM1 to deal with DM1, the place we may get hold of proof of biology taking a look at muscle focus, knockdown, gene splicing, and security.

If profitable, we may launch our remedy for DM1 in 2029. Our scientific applications for MMP7 and SCA2 are progressing properly as properly. We intend to provoke our first-in-human scientific research earlier than the tip of this 12 months for ARO-HTT, which is meant to deal with Huntington’s illness. And at last, we’ve a major variety of siRNA and gene remedy pipeline applications underway.

And so, we intend to schedule an R&D Day later this 12 months to debate all of them in additional element. Our head of R&D and chief scientific officer, Dr. Louise Rodino-Klapac, will talk about our pipeline progress in a second. With grit and operational excellence, we achieved all of our multiyear aims in 2024.

In 2025, we are going to proceed to execute. We’ll construct on our basis as one of many only a few absolutely built-in worthwhile and money flow-positive biotechs on the planet immediately. And we are going to obtain our subsequent ambition, which is to develop into the following globally related large biotech centered on enhancing the lives of these amongst us with life-limiting uncommon illness. And with that, I’ll flip the decision to Dallan Murray for extra element on industrial efficiency and plans.

Dallan?

Dallan Murray — Vice President, Advertising

Thanks, Doug, and good afternoon. I am delighted by the distinctive efficiency the staff delivered within the fourth quarter and for the total 12 months 2024. As we preannounced in January, web product income for 2024 totaled $1.79 billion, consisting of roughly $967 million from our PMO franchise and roughly $821 million for ELEVIDYS. 2024 marked the eighth 12 months of our PMO franchise, which continued to carry out properly and grew modestly 12 months over 12 months, even within the face of the transformation introduced out by ELEVIDYS.

As in prior years, the staff delivered this progress organically with out taking worth will increase on any of our permitted PMO merchandise. As such, this progress speaks to the rise in sufferers we’re serving within the Duchenne group. For 2025, the PMOs stay an integral a part of our steerage. And even within the face of sturdy ELEVIDYS efficiency, we’re solely seeing modest U.S.

web cannibalization. We’re comfy with the present consensus estimates as they stand immediately for the PMOs. For the fourth quarter, web product revenues for the PMOs totaled roughly $254 million, rising at roughly 9% in comparison with the fourth quarter of 2023. Particular person PMO web product revenues have been $137.6 million for EXONDYS 51, $40.2 million for VYONDYS 53, and $76.2 million for AMONDYS 45.

Now, turning to the ELEVIDYS launch and efficiency. This fall was our second full quarter with an expanded label, and we couldn’t be extra happy with the launch execution. Specifically, for the fourth quarter, ELEVIDYS income totaled $384.2 million, exceeding our quarterly steerage by over $60 million. And please keep in mind, even with this spectacular progress, at this level within the launch, we’ve handled roughly 5% of the on-label addressable affected person inhabitants for ELEVIDYS.

So, the chance forward of us stays vital, and we’ve the wind in our sails in the meanwhile. The latest findings from the Half 2 of the EMBARK research provides to the prevailing strong physique of scientific proof. It will undoubtedly assist the staff with their efforts going ahead. Because the launch progresses, we stay assured in our understanding of the launch dynamics and the important thing drivers, which proceed to be strong affected person demand for each the ambulant and non-ambulant populations, ample website capability for each the infusion and follow-up, constructive traits in entry and reimbursement for each ambulatory and non-ambulatory sufferers and constant conversion charges as we proceed to see sufferers gaining entry inside the three- to five-month conversion timeline.

Doug took a while on the latest JPMorgan assembly to offer extra element on that conversion timeline. Understanding this course of is important to understanding our enterprise mannequin and the boldness we’ve in our success and talent to execute each quarter to quarter and within the coming years. 5 launches in a decade of working in partnership with the important thing neuromuscular establishments provides us a deep line of sight into the cadence of dosing every affected person in every heart, in every area, and throughout the nation. For every gene remedy affected person, roughly 20 to 25 folks inside every establishment play an vital half in making that dose occur.

And people people are throughout every establishment, from the chief staff to the pharmacy division in addition to the medical finance and numerous administrative groups. And that is solely the folks inside the establishment. We additionally depend on extra folks from our distribution and manufacturing companions, together with others from numerous inside Sarepta groups. All must do their particular person components with perfection and below tight timelines to efficiently dose every affected person.

Why is that this vital? There are two causes. The primary and most important is that we have now proven as a staff, we are able to do that reliably and efficiently for over six quarters now since our preliminary launch. We have constructed the mannequin and proven we are able to reliably execute, which has been difficult for others to perform. Secondly, it provides us an excessive amount of confidence in our income projections, that are pushed by our understanding of the affected person journey.

There are a number of elements that contribute to the cadence of sufferers being handled, and we’ve line of sight into every of those elements. With over eight years of economic expertise comes understanding of the place the sufferers are and their pathway to remedy. We’re additionally happy with the continued progress in getting broad protection for ELEVIDYS and proceed to see sufferers gaining entry who’re in plans with extra restrictive insurance policies. So far, not a single affected person has been completely denied protection.

And as you’ll be able to see from our efficiency, it is a illness state that we perceive extraordinarily properly. We’re very assured in our progress trajectory, and I would prefer to reiterate a degree that Doug made in January that places our efficiency into broader context. We challenge that within the first 30 months of our ELEVIDYS launch, ELEVIDYS web product income will outperform each different in vivo gene remedy mixed over that very same time frame. Our success of ELEVIDYS exhibits that onetime gene remedy might be commercially viable, offering hope for these with Duchenne and for all these with genetic circumstances with unmet want.

As a reminder, our 2025 web product income steerage is $2.9 billion to $3.1 billion, which represents roughly 70% progress over 2024. Up to now, the launch has performed out according to our projections, and we stay comfy with this steerage given our sturdy end to 2024 and our lengthy monitor document of precisely predicting our efficiency. In abstract, we’re comfy with our steerage for the 12 months and with Q1 consensus. We anticipate to ship sequential progress quarter over quarter all through 2025.

And now I hand the decision over to Dr. Louise Rodino-Klapac for the R&D replace. Louise?

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Thanks, Dallan. Constructing on the accomplishments of 2024, I am thrilled with the promise earlier than us and the huge alternatives there are to proceed to make a distinction in sufferers’ lives. Firstly, ELEVIDYS. Late final month, we introduced constructive follow-up information from EMBARK or Examine SRP-9001-301, our world randomized, double-blind, placebo-controlled, Section 3 scientific research of ELEVIDYS.

Particularly, we shared crossover outcomes from those that obtain remedy in Half 2 of the research. And we additionally shared the two-year outcomes of these handled in Half 1 of the research as in comparison with an exterior management. Given what we learn about ELEVIDYS that the science and information have proven us and what we’ve noticed in a big inhabitants of sufferers which were handled with ELEVIDYS, we weren’t shocked by such overwhelmingly constructive information from the research, which demonstrated that ELEVIDYS impacts the trajectory of Duchenne and gives an early remedy possibility supposed to keep away from pointless and unavoidable muscle injury. Talking to the remedy’s sturdiness, the info are clear.

These not on remedy decline of their useful skills sooner than these on remedy, who keep more healthy longer versus the pure historical past would predict. Intervention is crucial in sustaining treasured muscle earlier than it is misplaced. With that, I would prefer to pause for a second and reiterate the importance of the MRI muscle information. As talked about on final month’s name, these information assist long-term perform and more healthy muscle.

Particularly, we noticed modest to no enhance in fats fraction from baseline to 2 years, and ranges at two years have been properly beneath what we have seen at one 12 months within the placebo sufferers. That is constant throughout muscle teams. We look ahead to publishing information from EMBARK at forthcoming scientific conferences and in peer-reviewed journals. In abstract, as evidenced by the info, ELEVIDYS demonstrated a clinically significant response throughout all of Sarepta research with rising divergence from pure historical past over time that helps the sturdiness of the remedy.

Towards our aim of offering ELEVIDYS to all eligible sufferers, we’re advancing the ENVISION research or Examine SRP-9001-303, a worldwide randomized, double-blind, placebo-controlled, two-part trial evaluating the protection and efficacy of ELEVIDYS in non-ambulatory and older ambulatory people with Duchenne. ENVISION is progressing properly, and as beforehand talked about, enrollment in the USA is full. And our final affected person final go to is predicted in 2027 following an 18-month placebo-controlled interval. As well as, for the roughly 15% of sufferers who’re screened out for preexisting anti-AAVrh74 antibodies, we have commenced two research, one with imlifidase or Examine 104 to cleave antibodies and a second with plasmapheresis or Examine 105 to take away antibodies.

We anticipate to have expression information from each of those research within the second half of 2025. Shifting now to our applications for the limb-girdle muscular dystrophies or LGMDs. We have been thrilled to announce in December 2024 that we accomplished enrollment and dosing of EMERGENE or Examine SRP-9003-301, our Section 3 scientific trial of SRP-9003 to deal with LGMD Kind 2E or beta-sarcoglycanopathy. EMERGENE is a worldwide research, and the first endpoint is biomarker expression of the protein, the absence of which is the only reason behind LGMD2E.

Information from EMERGENE are anticipated within the first half of 2025. Additional, we have been happy with the outcomes of our pre-Biologics License Software assembly with FDA, together with endorsement for a rolling BLA submission. We’re on monitor to submit our BLA filings looking for accelerated approval for SRP-9003 within the second half of 2025. We’re additionally inspired by the progress of our different LGMD applications.

On the finish of 2024, we initiated Section 1 of SRP-9004 in growth to deal with LGMD2D. And in early 2025, we are going to provoke our Section 1/3 seamless design scientific trial for SRP-9005, which is in growth for the remedy of LGMD2C. This March, we look ahead to sharing with you welcome information from our Duchenne and LGMD applications on the MDA Scientific and Scientific Convention happening March sixteenth via the nineteenth in Dallas, Texas. And we additionally look ahead to highlighting our spectacular pipeline at an upcoming R&D Day in 2025.

As a preview, we’ve quite a few applications in numerous phases of growth throughout neuromuscular, central nervous system, cardiac, and pulmonary indications, a lot of that are nearing INDs. Of observe, for neurotrophin 3 or NT-3, we’ve optimized the assemble for Charcot-Marie-Tooth kind 1A or CMT1A utilizing AAVrh74 and are actually quickly advancing to the clinic following thrilling preclinical information. As a reminder, we’re utilizing a surrogate method for supply of the NT-3 gene to enhance myelination and nerve regeneration in CMT1A. This pipeline and a product method has applicability to different CMTs in addition to different demyelinating indications.

On the analysis facet, we have continued to innovate throughout platforms. We have optimized, developed, and characterised new AAV capsids that may change the panorama for neuromuscular gene remedy and unlock potential in cardiac and CNS illness areas. We’re additionally driving innovation in gene modifying, enhanced supply for RNA and are pioneering new mechanisms to up-regulate gene expression. The long run can’t be brighter for genetic medication.

Additional, we look ahead to sharing information with you later this 12 months round our FSHD1 and DM1 applications. As a reminder, SRP-1001, previously generally known as ARO-DUX4, is at present in scientific growth to deal with FSHD1, an autosomal dominant illness related to the failure to take care of full epigenetic suppression of DUX4 expression and differentiated skeletal muscle, resulting in over-expression of DUX4, which is myotoxic and might result in muscle degeneration. We’re inspired by the nonclinical information generated up to now and look ahead to the info readout later this 12 months. Turning to myotonic dystrophy kind 1 or DM1.

DM1 is pushed by an expanded CUG trinucleotide repeat within the three-prime untranslated area of DMPK transcripts. These irregular transcripts trigger misregulated splicing generally known as spliceopathy for sure messenger RNAs, that are straight linked to the scientific manifestations of DM1. We imagine that silencing the apparently transcribed DMPK mRNA utilizing SRP-1003, previously generally known as ARO-DM1, might assist CUG expansion-related splice defects in sufferers with DM1 and thereby enhance muscle power and performance. We look ahead to sharing the info from the SAD research later this 12 months as properly.

Now, to debate our RNA PMO platform. The ESSENCE trial, our post-marketing requirement for golodirsen and casimersen, in addition to MISSION, our or post-marketing dedication for EXONDYS, are each absolutely enrolled and stay on monitor. We look ahead to sharing information as quickly because the research are accomplished. In abstract, I would prefer to take the chance to thank the affected person group, investigators, and my Sarepta colleagues.

All this progress wouldn’t be doable with out you. And at last, I would like to acknowledge this Friday is Uncommon Illness Day. There are greater than 7,000 uncommon illnesses, solely a small % of which have any remedy. As an organization devoted to bringing forth new therapies for uncommon illness, it is an vital day for our staff and the sufferers we serve.

It is a day to replicate on the impression of uncommon illness on the affected people and their households and to acknowledge all of the work that also must be carried out and to have a good time the progress that we have made. With that, I will flip the decision over to Ian for an replace on the financials. Ian?

Ian Estepan — Government Vice President, Chief Monetary Officer

Thanks, LRK. Properly mentioned. Good afternoon, everybody. This afternoon’s monetary outcomes press launch offered particulars for the fourth quarter of 2024 on a GAAP in addition to a non-GAAP foundation.

Please confer with the press launch and slide deck out there on Sarepta’s web site for a full reconciliation of GAAP to non-GAAP monetary outcomes. For the three months ended December 31, 2024, the corporate recorded whole revenues of $658.4 million, which consists of web product revenues and collaboration and different revenues in comparison with revenues of $396.8 million for a similar interval of 2023, a rise of $261.6 million. Internet product income for the fourth quarter of 2024 from ELEVIDYS was $384.2 million in comparison with $131.2 million for a similar interval of 2023. Internet product income for the fourth quarter of 2024 from our PMO exon-skipping franchise was $254 million in comparison with $233.8 million for a similar interval of 2023.

The rise in web product income primarily displays the online product income from gross sales of ELEVIDYS. Within the quarter ended December 31, 2024, we acknowledged $20.3 million of collaboration and different revenues in comparison with $31.7 million for a similar interval of 2023. This income primarily pertains to our industrial ELEVIDYS provide delivered to Roche, royalty income, and our collaboration association with Roche. The reimbursable co-development prices below the Roche settlement totaled $26 million for the fourth quarter of 2024 in comparison with $23.5 million for a similar interval of 2023.

As a reminder, these Roche reimbursable co-development prices are an offset to working bills. On a GAAP foundation, we reported web revenue of $159 million or $1.65 per fundamental share and $1.50 per diluted share and a web revenue of $45.7 million or $0.49 per fundamental share and $0.47 per diluted share for the fourth quarter of 2024 and 2023, respectively. We reported a non-GAAP web revenue of $206 million or $1.90 per diluted share within the fourth quarter of 2024 in comparison with a non-GAAP web revenue of $86.6 million or $0.82 per diluted share within the fourth quarter of 2023. Within the fourth quarter of 2024, we recorded roughly $132.3 million in price of gross sales in comparison with $44.2 million in the identical interval of 2023.

The rise primarily displays price of gross sales associated to ELEVIDYS in the course of the three months ended December 31, 2024, following the label growth in June of 2024. On a GAAP foundation, we recorded $200 million and $195.5 million in R&D bills for the fourth quarter of 2024 and 2023, respectively, a year-over-year enhance of $4.5 million. The rise is primarily as a consequence of a rise in our manufacturing bills associated to the ramp-up of batches produced for our limb-girdle program, partially offset by a lower in scientific trial bills associated to the discontinuation of the PPMO program. On a non-GAAP foundation, R&D bills have been $172.7 million for the fourth quarter of 2024 in comparison with $165.1 million for a similar interval of 2023, a rise of $7.6 million.

Now, turning to SG&A. On a GAAP foundation, we recorded roughly $163.9 million and $131.7 million of bills for the fourth quarter of 2024 and 2023, respectively, a rise of $32.2 million. The rise was pushed primarily by a rise in skilled providers used to assist the continued efforts to commercialize ELEVIDYS and ongoing litigation issues and a rise in compensation and different personnel bills primarily associated to adjustments in headcount. On a GAAP foundation, SG&A bills have been $131.6 million for the fourth quarter of 2024 in comparison with $105.7 million for a similar interval of 2022, a rise of $25.9 million.

On a GAAP foundation, we recorded $10.1 million in different revenue web for the fourth quarter 2024 in comparison with $15.7 million for a similar interval of 2023. The change was primarily as a consequence of a lower in curiosity revenue and accretion of funding low cost web on account of decrease rates of interest and the combo of our funding portfolio. As talked about earlier, we’re sustaining our 2025 whole product income steerage, which displays a 68% progress from 2024 on the midpoint. We are also introducing expense steerage for 2025.

We anticipate mixed 2025 non-GAAP R&D and SG&A bills to be within the vary of $1.2 billion to $1.3 billion. The incremental expense is nearly completely associated to Arrowhead growth applications. Excluding these prices, our bills can be basically flat in comparison with the prior 12 months. And to conclude, we had roughly $1.5 billion in money, money equivalents, investments, and restricted money as of December 31, 2024.

As Doug mentioned, now that the Arrowhead transaction is now closed, which was absolutely funded by our present money reserves, we challenge returning to related money ranges by year-end of 2025, pushed by the sturdy ELEVIDYS launch. Additional bolstering our monetary place, we secured a $600 million revolving credit score facility. The mixture of a constructive enterprise outlook and our sturdy monetary place us very well to execute on our 2030 strategic aim. And with that, I will flip the decision again over to Doug for Q&A.

Doug?

Douglas Ingram — President and Chief Government Officer

Thanks very a lot for that, Ian. And Lisa, let’s open the decision for questions.

Questions & Solutions:

Operator

Thanks. [Operator instructions] One second whereas we compile the Q&A roster. And our first query for immediately might be coming from the road of Tazeen Ahmad of Financial institution of America Securities. Your line is open.

Tazeen Ahmad — Analyst

OK, nice. Thanks for taking my query. I wished to ask Doug concerning the cadence of what you are seeing in 1Q to this point close to the sufferers which might be being onboarded. You’ve got talked extensively about sure issues that can not be modified, and also you reiterated your confidence about steerage for 2025.

However are you able to give us a bit bit extra granularity on, once more, what you are seeing in 1Q and the way we needs to be interested by the cadence of uptake for the remainder of the quarters this 12 months? Thanks.

Douglas Ingram — President and Chief Government Officer

Yeah. Thanks very a lot to your query, Tazeen. A few issues. First, let me reiterate my confidence on the steerage for the 12 months.

We really feel superb concerning the steerage that we’ve. And I’d remind everybody, we’ve an excellent monitor document of setting affordable steerage and assembly or fairly often exceeding that steerage. The one factor I will say about quarters going ahead is that we are going to proceed to see progress quarter over quarter as we ramp this launch. Issues clearly are going very properly for this launch via 2024.

And I feel our steerage ought to suggest it is going very properly in ’25 as properly. There’s a sure cadence to all of this, every part from the beginning kind, the only case contracts that I’ve talked about earlier than, the infusions, the necessity for preexisting neutralizing antibody assays and the like that describes the cadence. But it surely’s going very properly. And what we’ll see over the course of this 12 months is progress quarter over quarter over quarter to realize our steerage for the total 12 months, which, after all, is $3 billion in whole.

Slightly over two-thirds of that might be coming from ELEVIDYS and the rest from our three PMOs. So, thanks for that.

Operator

Thanks. And one second for the following query. Our subsequent query might be coming from the road of Ellie Merle of UBS. Your line is open.

Ellie Merle — Analyst

Hey, guys, thanks a lot for taking the query. For limb-girdle, simply out of your work within the area, what is the newest on what you see for the prevalence of 2E and what number of within the U.S. are recognized immediately, and the combo of ambulatory versus non-ambulatory sufferers? Principally, if you may be launching right here subsequent 12 months, how ought to we be interested by the contribution doubtlessly to income? And what number of sufferers there is likely to be type of ready for remedy? Thanks.

Douglas Ingram — President and Chief Government Officer

I will provide the broadest strokes, after which I’ll flip the decision over to Louise, if she has any data on the break up between ambulatory and non-ambulatory. Clearly, Kind 2E is a really uncommon illness. It is an ultra-rare illness. In truth, all the three sarcoglycan launches that we’ll have over the following three years are individually very uncommon.

However collectively, they are going to signify about 25% of the Duchenne ELEVIDYS alternative. So, they are going to be vital contributors, initially, to be clear. They’re going to be huge contributors within the lives of sufferers dwelling with and being degenerated from these actually devastating muscular dystrophies. After which they are going to be vital for the group as properly.

However they will be modest. They’re going to be about 25% of Duchenne. So, they will be vital however modest. With that mentioned, extra query that had been requested was the break up of ambulatory and non-ambulatory particularly because it pertains to Kind 2E.

And I do not know, Louise, if in case you have any data on that.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. There’s typically a fair break up. I’d say as genetic analysis, particularly for limb-girdle, has come alongside. We’re seeing extra of the ambulatory inhabitants.

I feel traditionally, you’d have mentioned it will be geared towards the ambulatory, however now it is typically a 50-50 break up.

Operator

Thanks. One second for the following query. And our subsequent query might be coming from the road of Gena Wang of Barclays. Your line is open.

Gena Wang — Analyst

Thanks for taking my questions. I’ve one query concerning the info replace later this 12 months for each FSHD and DM1. If I hear appropriately, DM1 can be the SAD information. Is FSHD additionally SAD information? And if there are SAD information, what number of cohorts and the way lengthy follow-up, and how much information you’ll share with us?

Douglas Ingram — President and Chief Government Officer

Yeah. I’ll flip this to Dr. Rodino-Klapac to offer some colour on that.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Sure. So, for each FSHD1 and DM1, it will likely be the SAD information. So, we’ll be — early, we’ll be specializing in single ascending dose research information, which might be centered on security, some early alerts of biomarker efficacy, which might be muscle focus, knockdown, basically splicing restoration as properly. So, it will likely be early information, however we look ahead to exhibiting that within the second half of the 12 months for each.

Douglas Ingram — President and Chief Government Officer

Additionally actually excited with FSHD as properly that our hope, and naturally, we’ll solely know when the info is available in, is that we’ll be capable of present via an assay the precise direct knockdown of DUX4, which, after all, is the aim of the remedy for FHSD. If we are able to try this, that could be a actually vital proof of biology as a result of no program earlier than has been in a position but to realize that aim. So, we’re very excited to see that as properly.

Operator

Thanks. And our subsequent query might be coming from the road of Brian Abrahams of RBC. Your line is open.

Unknown speaker — RBC Capital Markets — Analyst

Hello. That is Kevin on for Brian. Thanks for taking our questions. So, possibly simply on limb-girdle Kind 2E.

Are you able to possibly inform us a bit bit about what you suppose the bar is to your upcoming 2E information? After which possibly how do you suppose that bar interprets to different LGMD subtypes that we’ll finally see information from? Thanks a lot.

Douglas Ingram — President and Chief Government Officer

We have carried out — I will touch upon it, after which, Louise, you replace with any extra precision. Broadly talking, we’ve been working with the company over a really lengthy time frame in essence to assist educate the company on the bar that ought to exist for these kinds of ultra-rare illnesses, significantly illnesses and therapies like SRP-9003 for limb-girdle Kind 2E, the place you are coping with the alternative of the native protein unaltered, which the absence of that protein is the only and unique reason behind the illness. So, I am very proud to say we’ve very small finish research, they’re single-arm research. They give the impression of being to expression and security.

So, within the broadest of strokes, the bar might be that we’re getting good expression, I’d hope, largely per the expression that we have seen up to now as a result of bear in mind, we have truly dosed SRP-9003 in prior cohorts, and naturally, security profile. We’ve got plenty of conviction round this, as you’ll be able to properly think about, first, as a result of we have already truly dosed sufferers with SRP-9003 but in addition as a result of SRP-9003 stands on the shoulders of all the work that we have carried out with 9001, now ELEVIDYS. We’ve got dosed lots of and lots of and lots of of sufferers with ELEVIDYS. We perceive the legislation of the protection profile, and we perceive the facility of our constructs and our promoter to get actually good expression and get it safely.

So, that is kind of the bar, and we’re very assured about the place we’ll go together with that. And in your different query, this might be related throughout the limb-girdle applications that we’ve already aligned with the company on the method that we’re taking for 9003 and 9004, and 9005. And we’re assured that this impacts a modernization in the best way the company is taking a look at transformative therapies for ultra-rare illnesses. Louise, is there any extra element that I’ve omitted?

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. You summarized it properly. Perhaps I will simply linger on one level, in the truth that for the sarcoglycans, LGMD2E being the primary, these are the full-length genes. So, on this case, beta-sarcoglycan is each the gene remedy.

It is also the biomarker. We have demonstrated extensively preclinically how the biomarker expression results in useful enchancment. After which that translated in our research clinically, and we noticed two totally different doses. We noticed enhancements in each expression that led to useful enhancements over time.

These sufferers — we’ll be sharing five-year security follow-up information for these sufferers persevering with to do properly. So, that might be our first research, after which the opposite sarcoglycans will observe go well with. We’re all utilizing — we’re utilizing rh74 throughout that platform. So, not solely are we leveraging the 9001 information however then additionally the opposite sarcoglycans.

So, we’re in good place by way of the outcomes of those research and the result of the BLA.

Operator

Thanks. One second for the following query. And our subsequent query is coming from the road of Andrew Tsai of Jefferies. Your line is open.

Andrew Tsai — Analyst

Thanks. I recognize the replace. Congrats on all of the progress. Perhaps another query on the DM1, FSHD information you may be sharing later this 12 months.

Do you suppose the preliminary SAD, S-A-D, information might be conclusive to the purpose the place traders can decide whether or not these applications are trying superior or not? Or do you want MAD information? And the way would you outline superiority in these two applications? Thanks.

Douglas Ingram — President and Chief Government Officer

I’ll flip this over broadly to Louise to speak about it. Let me say on the inception — to start with, I do not wish to do what different small biotech corporations typically do, which is oversell early information. The info has to evolve. These are, nonetheless, very, essential proofs of biology.

So, I wish to be very clear, each from a security perspective, a muscle focus perspective, a knockdown perspective, a downstream gene-splicing perspective, and because it pertains to FSHD, the place you’ll be able to truly straight see the knockdown of DUX4. So, whereas there’ll nonetheless be numerous work to do from there and we do not wish to oversell the info, it is a actually, actually vital second. And it ought to give not less than alerts of potential future product profile versus different potential approaches to FSHD and DM1. However Louise, should you can present extra element.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. Simply so as to add to that, I’d say that what we all know from the Arrowhead platform, what we have seen of their different applications, and from the preclinical information is the interpretation from preclinical to scientific. And so, we have been excited to see that, and that is what we’ll be in search of, is that translation into the clinic. So, it’s going to definitely be indicator by way of the knockdown that we’re seeing, the muscle focus.

These are the issues we’ll be in search of. As strong scientific builders, we’re clearly seeking to the MAD information to return following that. However definitely, we’re excited to see the SAD information and the interpretation from preclinical and simply an extension of their already promising information throughout the platform for Arrowhead.

Operator

Thanks. One second for the following query. And our subsequent query is coming from the road of Kostas Biliouris of BMO Capital Markets. Please go forward.

Konstantinos Biliouris — Analyst

Thanks for taking our query, and congrats on the progress. A query on ELEVIDYS from us. Provided that it has been about eight months now because the label growth, are you able to touch upon whether or not you will have seen any reinvestments for PMOs in ELEVIDYS-treated sufferers? And if not, are you listening to something from payers round their willingness to reinvest PMOs following ELEVIDYS remedy? Thanks.

Douglas Ingram — President and Chief Government Officer

Yeah. So, let me say, Kostas, thanks to your query. In broad strokes, I’ll nonetheless observe that it is nonetheless very early days. And so, making an attempt to attract broad conclusions is difficult.

As we have famous, one of the fascinating, I feel, information factors we should always linger on for a second is whereas we have had all this success, we nonetheless solely handled lower than 5% of the addressable on-label affected person inhabitants for ELEVIDYS. And so, you bought to each have — to essentially check this concern, you have to have ELEVIDYS after which you must have the truth that ELEVIDYS is treating a affected person beforehand on PMO. However we do have situations of reimbursement of each. So, we have already seen that.

I do not wish to oversell it proper now. And I am positive we even have situations the place that wasn’t doable. But it surely’s not black or white or binary proper now. What I’ll reiterate, one of many issues that we’re very enthusiastic about is that to this point, we have not seen vital web cannibalization.

We’ll see some cannibalization within the U.S. We’re seeing superb progress of our PMOs ex-U.S. After all, the overlap is modest on condition that we solely deal with 29% of sufferers with Duchenne muscular dystrophy with our PMOs. And it is good to see that we’ve seen some payers and keen to place youngsters on sequential remedy publish gene remedy.

But it surely’s nonetheless very early days, and I would not overread that. Dallan, am I —

Dallan Murray — Vice President, Advertising

No. That is completely proper. That is completely proper, yeah.

Operator

Thanks. The subsequent query might be coming from the road of Mike Ulz of Morgan Stanley. Your line is open.

Mike Ulz — Analyst

Hey, guys, thanks for taking the query. Perhaps only a fast one on the $500 million share repurchase program. Are you able to simply remind us what the timeframe is there after which a few of the concerns as you resolve once you would possibly deploy that? Thanks.

Douglas Ingram — President and Chief Government Officer

Certain. I will flip this to Ian for his ideas.

Ian Estepan — Government Vice President, Chief Monetary Officer

Certain. So, the time interval is eighteen months. Like I mentioned, clearly, we simply accomplished the Arrowhead transaction. And so, we’ll be rapidly constructing again our money reserves over the course of the 12 months.

Like I mentioned in our ready remarks, we’ll be again to the identical stage on the finish of ’25 as the place we began — the place we led to ’24. So, it simply talks to the power of the launch. And so, as we proceed to construct our money reserves, we’ll look to be opportunistic round doubtlessly deploying that capital and shopping for shares. So, clearly, we’re not going to telegraph once we might be doing it particularly, however we definitely have it at our disposal, and we’re trying on the proper time to execute.

Operator

Thanks. One second for the following query. And the following query is coming from the road of Joe Schwartz of Leerink Companions. Your line is open.

Joe Schwartz — Analyst

Nice. Thanks very a lot. So, since approval in ’23, it looks like the ELEVIDYS launches had a couple of totally different phases with nice progress early on following accelerated approval, then a few flat to down quarters in early ’24, adopted by a pleasant — very nice return to progress following the expanded label in mid-’24. So, since your ’25 steerage appears to suggest that progress this 12 months needs to be extra average, I am simply questioning should you can provide us your view concerning the stage of the launch that we’re in now and the way you see it evolving this 12 months.

Are there any vital constraints to progress that we should always consider this 12 months?

Douglas Ingram — President and Chief Government Officer

So, Joe, thanks to your query. And I’ll say with due respect, I don’t characterize our launch precisely the best way you do. I’d say we had a superb launch in ’23 with a really skinny label. Then we had — we achieved one thing that I — achieved, which is a really, very broad label.

However after all, the cadence for that broader launch requires the pure cadence of children getting on remedy, which, to remind everybody, regardless that we had carried out a superb job on website readiness and entry and reimbursement already, there’s only a cadence to getting the children on remedy that takes about 4 months. And there is actually no magic to fixing that as a result of it is the cadence of the only case contract and the scheduling and the infusion beds and the quantity of follow-up and the assay work and the like. So, there is a sure cadence. We had anticipated precisely what we noticed in ’24, which was we might see this hockey stick ramp towards the again half of the 12 months, which is strictly what we noticed.

And as you recognize, we grew within the fourth quarter by 112%. After which I’d observe for this 12 months, I imply, with respect in opposition to the assertion that the expansion is modest this 12 months, we’ll develop with ELEVIDYS over 160% 12 months over 12 months. And I’d put that up — properly, first, I can not put it up in opposition to every other gene remedy, let’s be clear, as a result of we’ve blown away each different gene remedy cumulatively. But in addition, I feel for launches, that is nearly as a profitable launch as one may have imagined.

And we’re nonetheless within the strong, strong progress section of this launch.

Operator

Thanks. And our subsequent query might be coming from the road of Gil Blum of Needham and Firm. Your line is open.

Gil Blum — Analyst

Hello. Good afternoon, everybody, and once more, congrats on all of the progress. So, possibly a query right here on the transfer to suspension manufacturing with the bridging research later this 12 months. Simply are you able to remind us what are the potential related price financial savings? And in addition, how broadly relevant is that this? I imply, you guys use plenty of totally different applications for the gene remedy.

Is that this translatable simply outdoors of DMD, or is that this very slender? Thanks.

Douglas Ingram — President and Chief Government Officer

Yeah. So, let me reply the final query first. So, our aim, if profitable, is to evolve virtually all of our gene remedy applications to suspension. In truth, if I am not mistaken, Louise, you may right me if I’m the one program that may stay in adherent, it is simply the timing of it and we did not wish to decelerate the approval as youngsters are ready for it, is 9003.

Even all the opposite sarcoglycans might be in suspension. And broadly talking, after all, it is very harmful to kind of to attempt to estimate the COGS impression. We have got extra work to do, however it will likely be very, very vital. We’re seeing upwards of 5x to even higher instances extra yield efficiencies.

So, you would envision margins considerably over 90% finally with this and likewise the power to essentially deliver this remedy to the far reaches of the world. And that is, after all, considered one of our large objectives. So, to remind everybody, we mentioned it already within the — in our ready remarks. However our aim is to compete our GMP runs and to begin our bridging research earlier than the tip of this 12 months, definitely.

After which the aim, after all, is that if all goes properly and we’re profitable, to evolve to suspension in 2027, which might be actually, actually a chic timing for us as we take into consideration our world plans.

Operator

Thanks. And the following query might be coming from the road of Ritu Baral of TD Cowen. Your line is open.

Ritu Baral — Analyst

Hello, guys. Thanks for taking the query. Doug and Louise, I wished to ask your present ideas as you perceive the panorama on the potential for splicing biomarker-based accelerated approval to your FSHD and DM1 applications. I do know it is sooner or later, however clearly, it is a scorching subject of the area.

After which truly, if I may observe up on Gil’s query. He requested concerning the bridging research. Are you able to describe what that bridging research is? It seems like it should go quick.

Douglas Ingram — President and Chief Government Officer

Yeah. On the bridging research, it is a comparatively — I do not know if we have given the precise land. It is a comparatively small research taking a look at — empirically taking a look at expression and security to substantiate that it is considerably just like the adherent method. So, it ought to go comparatively quick.

Every little thing’s work, however it ought to go comparatively quick, and we intend to begin that bridging research later this 12 months. After which with that, I will flip it over to Louise. You probably have any ideas or feedback on the potential for an accelerated approval method with both FSHD or DM1.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. We’re within the early phases, I’d say, for FSHD. Doug alluded to it, however we’re in a novel place with FSHD, the place we’ve an assay that really can quantify the knockdown of the first defect within the indication, which is DUX4. And so, that provides us a novel alternative by way of potential biomarkers as properly.

In these early research, we’re taking a look at a number of biomarkers and useful outcomes. And that is actually what these Section 1 research are supposed to take action then you’ll be able to optimize and decide the perfect path ahead. I feel it is a chance to guage so far as splicing. I feel it’s considered one of many biomarkers.

So, whether or not it will be the only biomarker is one thing left to be explored.

Douglas Ingram — President and Chief Government Officer

And naturally, we acknowledge — yeah. We all know, amongst others, there may be plenty of open dialogue and dialogue and even some variations of opinion concerning the pathway for approval. That is considered one of these actually uncommon moments possibly in my time at Sarepta, the primary time the place we get to be told by others. And so, we’ll get knowledgeable by not solely our direct conversations with the FDA however what others are seeing once they’re trying with the FDA, and that may assist inform our path ahead.

So, it is an fascinating and — fascinating place to be once we get to be told by others versus with most of our different therapies having been the one to tell the world and chart the trail ahead.

Operator

Thanks. And our subsequent query might be coming from the road of Brian Skorney of Baird. Your line is open.

Brian Skorney — Analyst

Hey, good afternoon. Thanks for taking my query. I hoped you would type of stroll via what you kind of understand as the present order of potential rate-limiting steps to industrial ELEVIDYS income suggest — recognition. I am simply making an attempt to know.

It does not seem to be it is demand in any sense proper now. So, what’s kind of the step-throughs which might be type of creating blocks from realizing the total demand? Is it like would one be like an insurance coverage authorization? Would two be heart capability? May you want type of rank order these?

Douglas Ingram — President and Chief Government Officer

Yeah. Rank ordering is difficult. Let me flip this over to Dallan and power him into rank order. However let me say a few issues.

I do not wish to name them blocks as a result of it is only a cadence concern. It would be like saying — Dallan typically makes use of a metaphor that that is typically like — consider this greater than — this isn’t like prescribing a drug. That is virtually extra like organ transplant. There’s simply plenty of steps that need to undergo to get from right here to a child dose.

That is why it is a couple of four-month course of. And I will offer you some information on that. There are one thing like 25 people at website of care that contact this remedy shifting from the beginning kind to the infusion. And that goes via numerous totally different departments, not simply the interior pharmacy and the establishments which might be — and the nurses and the doctor.

It is also all the best way again into the monetary space and the CFO of the group and the like. And so, there’s only a cadence. I imply, offer you an instance, Brian, that there’s — it is a couple of — it may be as a lot as a four-week or an extended course of to do the only case contract. Virtually each time a affected person will get dosed, the positioning and the payer enter into a particular website contract.

It is an administrative step. It must be carried out. It’s carried out. It is carried out very properly.

We perceive the method exceptionally properly. I am fairly assured now. I can say that with out concern of being boastful. There is no group on the planet that understands this course of in addition to we do.

However there’s only a cadence to this. And it’s all the belongings you’re mentioning. It is the very means of getting the primary assembly after which attending to the assay after which getting the infusion website prepared. On the similar time, it is the beginning kind within the single case contract.

It is negotiating with the payers if you must. It is, when mandatory, negotiating with the payers round it. Bear in mind, I’ll touch upon this. There’s been externally some misunderstanding concerning payers and a few comparatively superficial surveys that have been carried out.

Look, we’re doing actually nice with payers proper now. We’re doing higher with payers with ELEVIDYS than we did with the PMOs. And I’d observe, we have carried out actually, very well with the PMOs over the time, I feel, as anybody would agree. The insurance policies actually set themselves into three buckets.

Insurance policies — there’s plenty of insurance policies which might be simply dosed to label, give entry to label greater than there have been with the PMO. So, we’re actually enthusiastic about that. A few of our greater payers are in that camp. There are some payers which have restrictions, and there are some payers which have plenty of restrictions.

The fascinating factor is that — these totally different insurance policies won’t have an effect on immediately the final word child getting on the remedy. What they do is internally, they outline the period of time to get a child on remedy and the quantity of labor that must be carried out to get a child on remedy, however they get on remedy. So, I simply wish to get everybody’s head round that concept. And our PMOs, with eight years of battle-hardened expertise, our win fee, if we — a payer goes to be very resistant and take us to an inside/exterior enchantment, is over 90%.

With ELEVIDYS proper now, we’re sitting proper now at 100%. So, no child has been completely denied remedy up to now. So, in any occasion, all of these items describe this broad cadence that’s a couple of four-month course of. However Dallan, if you wish to rank order then for —

Dallan Murray — Vice President, Advertising

Yeah. Properly, Brian, I feel you’ll be able to summarize every part that Doug is saying with one phrase, which is time, proper? Every little thing right here takes time. And so, you actually, due to this fact, can’t level to at least one factor. As I mentioned in my ready remarks, we’ve strong affected person demand.

We’ve got extra demand than may be handled immediately. We’ve got ample website capability. We’ve got sufficient website capability to deal with our peak forecast. We have got constructive traits in entry and reimbursement that we’re permitting to transform sufferers inside that constant three- to five-month time-frame.

So, these collectively, then once you layer in what Doug mentioned, it is only a recreation of time to get these sufferers on remedy. And that’s all truth. As a result of we have got a deep and really detailed line of sight into all of this, that is what informs our quarter-to-quarter progress and our steerage for the 12 months.

Douglas Ingram — President and Chief Government Officer

And I’ll say it is in all probability two issues. It is time and it is being attentive to element, which Sarepta is admittedly good at. We’re — I’m sitting right here, I’ll inform you, at our nationwide coaching assembly immediately with all of our people centered on this. They usually — the quantity and a spotlight, obsession to element and the eagerness to ensure a child by no means slips via the cracks however can get on this remedy and profit from ELEVIDYS is insane.

And that explains why we have been so profitable. And it explains why we’re so comfy with our steerage for 2025, which — I’d say it is very strong steerage, $3 billion. It is a 70% progress total for the 12 months. And because it pertains to ELEVIDYS, over 160% progress 12 months over 12 months, which speaks to the execution capability of this staff out right here at Scottsdale.

Operator

Thanks. And our subsequent query might be coming from the road of David Hoang of Deutsche Financial institution. Your line is open.

David Hoang — Analyst

Hello there. Thanks for taking my query. So, I simply had one on if in case you have any ideas on a latest information set that was generated by a next-generation DMD gene remedy competitor. And do you will have any insights out of your subject power on how households, sufferers would possibly take into consideration receiving remedy with industrial ELEVIDYS versus enrolling in a scientific trial for considered one of these different merchandise? Thanks.

Douglas Ingram — President and Chief Government Officer

Properly, first, there are not any next-generation gene remedy applications. So, I’ll right the document on that. That is a misstatement. However look, a few ideas on it.

We do perceive that Stable put out some very, very early first-in-human information. A few ideas. First, unbelievable. We’re thrilled that various organizations are taking a look at researching new therapies for youths with Duchenne muscular dystrophy.

And to be sincere, we take plenty of delight in it as a result of I feel — however for the success that we have had with our PMOs and with ELEVIDYS, they would not have this strong deal with discovering new therapies for youths. So, we’re very enthusiastic about that. I do wish to observe that we’ve to do not forget that households with Duchenne muscular dystrophy need to make troublesome selections immediately, and so they want correct data to make them. That is for the households to make.

Clearly, there may be one absolute overarching truth, which is there may be one permitted remedy that’s transformative in nature, that could be a disease-modifying gene remedy, and that’s ELEVIDYS. And that may deal with 80% of kids with Duchenne muscular dystrophy and younger males and sometimes girls with Duchenne muscular dystrophy. And our aim is to make sure that households have the correct data to allow them to make the correct selections, which is commonly a really troublesome resolution. Do you get the present remedy? Do you have a look at a scientific trial and take a remedy that is been examined much less and the like? However I simply wish to ensure that the one factor I — I am very thrilled with the others specializing in this.

I feel it is a actually constructive for the Duchenne group, and everyone ought to applaud it. However I do wish to ensure that persons are offering the correct, balanced, affordable data so folks could make clever selections and never make the incorrect selections. And the precise resolution that folks make between getting into right into a scientific trial for a brand new experimental remedy versus getting on an permitted remedy that is been proven to be secure in purposes is a troublesome resolution that is going to be made between the households and their healthcare supplier hopefully correctly knowledgeable with all the present information.

Ian Estepan — Government Vice President, Chief Monetary Officer

And only one factor so as to add to that, and I will flip it to Louise to enter extra depth. However I do suppose it is vital for folks to acknowledge. And definitely, Louise has carried out plenty of work, empirical work for over a few years, taking a look at assemble and seeing their performance. And definitely, as we have seen with different growth applications that totally different constructs have totally different efficacy and security profiles.

And due to this fact, when Louise examined all of those applications, to essentially transfer ahead with the optimized assemble from a useful perspective, and that is why we’re in a position to see information based mostly on our expression result in useful outcomes. And so, that is actually vital when sufferers are interested by therapies that it isn’t simply solely expression however truly the performance of the assemble. And to Doug’s level, we have been in a position to present that in scientific research. However Louise, since you probably did the work, you in all probability have the perfect standpoint on that.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. Thanks for that. Yeah, I feel it is vital in the truth that the dystrophin area is exclusive for gene remedy and that within the small dystrophin area, you are taking a look at totally different useful contributions from these constructs. And so, the standard of the dystrophin that you simply’re producing is extraordinarily vital.

Simply one of many issues that we famous in our research once we examine it to different constructs was the inclusion of spectrin repeat three for stability of the assemble, and we discovered that over time that this was crucial to the performance of our assemble and the corresponding useful enchancment that we noticed that corresponded from preclinical work to scientific work. And so, it was — as you all know, you have been on this journey with us lots of of sufferers over a few years in a number of scientific research exhibiting the identical factor by way of the expression resulting in useful profit and clearly with a standard approval now and over 600 sufferers handled each clinically and commercially. So, definitely, the standard of the assemble and the useful information that is demonstrated within the clinic is crucial to creating a call concerning the remedy {that a} affected person chooses with their households.

Operator

Thanks. And the following query might be coming from the road of Ry Forseth of Guggenheim Securities. Your line is open.

Ry Forseth — Guggenheim Securities — Analyst

Hello. That is Ry from Debjit’s staff. We’ve got two questions. Primary, how is Sarepta modeling the impression of aggressive gene therapies in DMD, particularly on the annual incidence inhabitants below the idea that the prevalence pool is saturated? And quantity two, for the 2E program, ought to we anticipate larger vector genomes per nucleus relative to historic Sarepta information and protein expression above 50%? And is there a threshold for regulatory submission?

Douglas Ingram — President and Chief Government Officer

I feel I’ve answered the edge query. Thanks for that. And I feel if we get expression per what we have seen earlier than with 9003 and earlier than that with 9001 — I’d remind you, we received actual extraordinary vector genome copies for nucleus. And we do it with a really rigorous method, pretty unassailable method when taking a look at issues like vector genome copies and expression, ones that we labored on for years and years with enter from the FDA.

We’d need to be very cautious about that as a result of it is very straightforward to do these items in ways in which give false data. But when we get these ranges of vector genome copies per nucleus and we get the type of expression that we have seen each in 9003 and 9001, we’re very assured that we’ll get an approval, assuming that security is there, and we’re very assured about that. So far as modeling, it is manner too early to be modeling competitors from those who have one, two, and three sufferers in these early experimental therapies. In all probability have not even found out manufacturing at that time.

Actually, we would not be modeling something this decade in any occasion. It is one thing we are able to look to if folks will truly begin progressing.

Dallan Murray — Vice President, Advertising

Though I’d say — thanks for the query as a result of the scale of that incident inhabitants is admittedly underappreciated. It is actually double the scale of the ZOLGENSMA market at present. We’ll be prepared for any competitors when it comes. As Doug mentioned, it should be a very long time coming.

And we actually are enthusiastic about the opportunity of treating sufferers earlier and preserving perform earlier in that affected person journey. So, it is a terrific query from the attitude of a really underappreciated a part of the Duchenne market alternative.

Operator

Thanks. And the following query might be coming from the road of Anupam of JPMorgan. Your line is open.

Unknown speaker — RBC Capital Markets — Analyst

Hello, guys. That is Priyanka on for Anupam. Thanks for taking our fast query. Because the R&D Day is within the second half of the 12 months, can we assume potential new information might be offered there from Arrowhead or different non-Arrowhead pipeline applications? Thanks.

Douglas Ingram — President and Chief Government Officer

I will flip that to Louise to remark.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

I do not suppose we mentioned precisely the timing of once we will current the Arrowhead information. All of it is determined by the timing of the info launch and the way that strains up with R&D Day. We’re excited to speak concerning the platform typically, I’d say that, as a part of R&D Day and our deep pipeline that we have not actually been in a position to share intimately. So, we look ahead to that.

As we’ve extra timing, we’ll share with you.

Operator

Thanks. And the following query might be coming from the road of Biren Amin of Piper Sandler. Your line is open.

Biren Amin — Analyst

Yeah. Hello, guys. Thanks for taking my questions. For the EMERGENE trial, I feel you are enrolling each ambulatory and non-ambulatory sufferers whereas the Section 1 enrolled ambulatory.

So, ought to we anticipate expression can be related non-ambulatory sufferers to what was noticed within the Section 1 ambulatory information? After which once you report these information, will you be evaluating these to the NCH, pure historical past cohort?

Douglas Ingram — President and Chief Government Officer

Louise?

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. A few issues in there. So, we have handled each ambulatory and non-ambulatory sufferers since we see related ranges of expression. So, the EMERGENE — the evaluation will analyze these two populations separate from a useful perspective.

That would be the follow-on research, the confirmatory research. However from an expression stage, sure, we are going to consider each. By way of what we’re evaluating it to, we’ve our personal JOURNEY pure historical past research, and that would be the comparator for the confirmatory research.

Douglas Ingram — President and Chief Government Officer

Yeah. And simply our historical past has proven that we get nice expression throughout the continuum of illness from very younger to very superior.

Operator

Thanks. And our subsequent query might be coming from the road of Gavin Clark-Gartner of Evercore. Your line is open.

Gavin Clark-Gartner — Evercore ISI — Analyst

Thanks for taking the query. I simply wished to deal with terminal worth. So, if I have a look at the outer 12 months of consensus estimates, take 2033, I see about $2.2 billion in U.S. ELEVIDYS gross sales.

So, that suggests about 850 to 900 handled sufferers yearly. Perhaps, Dallan, you would simply remind us like particularly what you are seeing on U.S. incidents. However extra broadly, do you imagine this consensus estimate is believable? And possibly clarify what has to occur for ELEVIDYS to achieve and keep into that vary into the following decade.

Thanks.

Dallan Murray — Vice President, Advertising

That is the — the incident inhabitants, you are kind of taking a look at what the terminal incident inhabitants can be. Within the U.S., the incident inhabitants might be someplace within the low 400s, 420, 430. So, you are able to do the mathematics on that. After which, after all, we’ll have the PMOs on high of it as a result of the PMOs are enduring as properly.

After which by that time, though this is likely to be speculative till we solved it, we are going to probably have solved the redosing concern by the 2030s as properly. So, you’ll be able to — you may have so as to add to that that idea as properly. And naturally, should you’re speaking — that is the terminal worth on ELEVIDYS. It isn’t the terminal worth on the corporate.

As you recognize, if all goes properly, we’ll be launching three limb-girdle applications within the subsequent actually yearly for the following few years. We’ve got new ones coming. We’ve got new INDs. And if all goes properly, we’ll be launching FSHD in 2028.

We’ll be launching DM1 in 2029. Each of these are multibillion-dollar peak U.S. gross sales alternative. So, clearly, the terminal worth might be vital on the group as an entire.

Operator

Thanks. One second for the following query. And the following query is coming from the road of Sami Corwin of William Blair. Your line is open.

Sami Corwin — Analyst

Nice. Thanks. Congrats on the progress. I used to be curious the way you’re interested by the evolution of your gross margins in 2025 and 2026 as ELEVIDYS begins to compromise a bigger proportion of your income.

After which a fast query on our FSHD program. Is that this DUX4 assay new? Or was it developed in-house? And will you simply elaborate on it a bit extra? Thanks.

Douglas Ingram — President and Chief Government Officer

Certain. I will flip the evolution query to Ian, after which Louise can contact on the DUX4 assay concern.

Ian Estepan — Government Vice President, Chief Monetary Officer

Yeah. So, from a margin perspective, what we mentioned is that clearly, we have already expensed the stock already. And so, that is beginning to come off. After which over time, as we proceed to deal with heavier sufferers, you are going to see the margin go down.

We anticipate it to be within the type of excessive 70s as we proceed to penetrate into the non-ambulant affected person inhabitants. However as Doug mentioned, as we proceed to work on our suspension manufacturing course of, we anticipate that to begin getting a lot — considerably larger, trending towards 90%. So, as we’re treating the heavy inhabitants, we anticipate the margins to enhance within the ’27 time-frame.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. And simply on the DUX4 assay, it is a quantitative assay developed by Arrowhead. As we have talked about, DUX4 is expressed at low ranges, someplace across the occasion of 1 in 1,000 nuclei. So, it is troublesome to measure, however Arrowhead has efficiently carried out that.

And so, that is an assay that we’ll be onboarding as properly. However we’re excited to see it as a result of it isn’t one thing that is been in a position to be achieved within the subject.

Operator

Thanks. The subsequent query might be coming from the road of Mitchell Kapoor of H.C. Wainwright. Your line is open.

Unknown speaker — RBC Capital Markets — Analyst

Good afternoon. That is Dan on for Mitch. Thanks for taking our query, and congratulations on the constructive money movement for the 12 months. So, payers we have spoken with have mentioned that they’ve had sufferers expertise two rounds of appeals and have been in the end denied.

Would an IRO denial not depend as everlasting denial? And if not, what qualifies as everlasting denial? Thanks.

Douglas Ingram — President and Chief Government Officer

I am unsure. I do know that — I am unsure who you spoke to. I do know you probably did a survey. One was truly not a payer.

It was PBM. And I feel you might need talked to at least one payer. We’ve got no youngsters which were completely denied remedy. I am not suggesting that it’s going to all the time be 100%.

Our PMOs pattern above 90% over the past eight years, however we’re seeing even a greater response than the PMOs of ELEVIDYS. So, we’re doing fairly properly. We haven’t any child that is been completely denied remedy. Some are nonetheless in course of, however no child has been completely denied remedy.

Dallan Murray — Vice President, Advertising

Yeah. Dan, we have dosed sufferers within the plan that you simply’re speaking about. We’re not going to offer you any extra particulars aside from that.

Operator

Thanks. And the following query might be coming from the road of Uy Ear of Mizuho. Your line is open.

Unknown speaker — RBC Capital Markets — Analyst

Hello, guys. That is Leo on for Uy. Thanks for taking our query. May you present some element on the learnings from the pre-BLA assembly with the FDA on 9003 and the way these learnings is likely to be utilized to the follow-on limb-girdle applications? After which additionally based mostly on the latest adjustments inside the company, how do you suppose FDA interactions would possibly change going ahead? Thanks.

Douglas Ingram — President and Chief Government Officer

So, Louise, do you wish to contact on the kind of pre-BLA discussions broadly?

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. Broadly, it was an especially constructive assembly, I feel, throughout all the various things that you’d communicate to by way of the nonclinical information, the scientific plan for the scientific trial was endorsed, CMC by way of our plan. So, that was endorsed. Utilizing beta-sarcoglycan as a surrogate biomarker for accelerated approval was endorsed.

So, it was a really constructive assembly. The company definitely understands in ultra-rare illnesses, the challenges which might be confronted with that by way of trial design, by way of manufacturing. So, we have already set the stage for the opposite follow-on sarcoglycans. So, I feel it bodes properly for the complete platform, and we’re definitely inspired by it and definitely seen a change within the company over the past two years and actually promising.

And that is one thing we look ahead to as we full the opposite two sarcoglycans as properly.

Douglas Ingram — President and Chief Government Officer

I do wish to say we’re very happy with — I’m very happy with the work that Louise and her staff have carried out, working with the company to evolve and modernize the method to ultra-rare illness. And it is paid dividends for the limb-girdle applications, not solely 9003 B and past. However I additionally wish to give credit score to the division itself. I’ve to say the middle director, Dr.

Marks, has had a imaginative and prescient for being considerate and modernizing the division and comporting with trendy science and never creating limitations that make it unviable to deal with ultra-rare illness sufferers. And I feel that Dr. Verdun, the top of OTP, has carried out actually an distinctive job of taking that imaginative and prescient and operationalizing it in ways in which we’re seeing and I feel others are seeing as properly, which as we take into consideration Uncommon Illness Day arising on Friday and I feel we mentioned some actually good ideas on that, I imply, it is simply poignant that I feel we’re shifting in the correct route as a folks to have the ability to deliver a greater life to sufferers with ultra-rare illness. And I give huge kudos to OTP for enjoying their half in that.

Operator

Thanks. And our subsequent query might be coming from the road of Salveen Richter of Goldman Sachs. Your line is open.

Unknown speaker — RBC Capital Markets — Analyst

Thanks for taking our questions. That is Tommie on for Salveen. Simply total, what do you see is Arrowhead’s differentiation by way of type of their chemistry or construction versus another RNA approaches in DM1 and FSHD? And on ELEVIDYS, is there flexibility to increase upon present infusion heart capability, together with, as an example, staffing wants? Thanks.

Dallan Murray — Vice President, Advertising

I’ll flip the primary a part of the query to Louise. Let me briefly speak about ELEVIDYS. So, what we actually want to know is that it is a very detailed cadence from starting to get a child dose. So, website capability is not alone the problem.

Folks typically say, properly, what should you discovered a method to have extra infusion days? That might be nice. However then you definitely want infusion nurses. Then you definitely want follow-up. Then you definitely want extra single-case contracts.

Then you’ll want to take into consideration, again within the finance perform, what are the credit score limits related to all of that. So, it truly is simply sure cadence. The factor that I am enthusiastic about is that this staff has unlocked this chance and actually develop into consultants in that cadence, and that is why we’re in a position to present steerage of $3 billion for the 12 months as a result of the staff has found out. However that’s — the cadence is the cadence.

And I do not suppose the chance for dramatically altering that exists. And with that, I will flip the primary a part of the query over to Louise.

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Yeah. On Arrowhead, I feel the great reply is that Arrowhead is targeted on each facet of the assemble. And so, we just like the diligence of their method. I want to name out their focusing on ligands as being a differentiator as a result of attending to the correct tissue within the case of muscle for FSHD and DM1 utilizing the alpha — the beta focusing on ligand that we use the identical one with MyoAAV, for instance.

We all know that it really works properly in muscle. So, that is a differentiator. However they deal with the design from the siRNA, from the focusing on ligands, from each facet of the assemble. And so, we similar to their complete diligent method.

It is one thing that we mannequin with gene remedy, for instance. And so, I feel it is all the above, however we definitely recognize their focusing on ligands for the assorted tissues.

Operator

Thanks. And that concludes immediately’s Q&A session. I want to flip the decision again over to Doug Ingram for closing remarks. Please go forward.

Douglas Ingram — President and Chief Government Officer

Properly, thanks, everybody, to your questions this night. Admire them. We have had a extremely super 2024 and a terrific This fall of 2024. And as we monitor into 2025, issues are going very properly.

A few issues. We’re clearly going to proceed to drive this launch of ELEVIDYS, and the staff has carried out a extremely nice job on that. And I feel they are going to proceed to do this. We’ll proceed to deal with our PMOs and making certain that sufferers are benefiting from our PMOs over this 12 months.

After which we’ve extra milestones to learn out in 2025 than every other time in our historical past. And so, I look ahead to updating people throughout this 12 months as we transfer ahead with our limb-girdle for instance, and we get the FSHD information, and we get the DM1 information after which we maintain driving as a company. So, thanks all very a lot, and have a beautiful night.

Operator

[Operator signoff]

Period: 0 minutes

Name individuals:

Mary Jenkins — Affiliate Director, Investor Relations and Company Communications

Douglas Ingram — President and Chief Government Officer

Dallan Murray — Vice President, Advertising

Louise Rodino-Klapac — Government Vice President, Head of Analysis and Improvement, and Chief Scientific Officer

Ian Estepan — Government Vice President, Chief Monetary Officer

Doug Ingram — President and Chief Government Officer

Tazeen Ahmad — Analyst

Ellie Merle — Analyst

Gena Wang — Analyst

Unknown speaker — RBC Capital Markets — Analyst

Andrew Tsai — Analyst

Konstantinos Biliouris — Analyst

Mike Ulz — Analyst

Joe Schwartz — Analyst

Gil Blum — Analyst

Ritu Baral — Analyst

Brian Skorney — Analyst

David Hoang — Analyst

Ry Forseth — Guggenheim Securities — Analyst

Biren Amin — Analyst

Gavin Clark-Gartner — Evercore ISI — Analyst

Sami Corwin — Analyst

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