Sarepta Therapeutics, Inc. Price & Performance (SRPT)

The results of operations and trading prices for SREPTA's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review 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, As noted on Slide three, we will discuss non GAAP financial measures on this webcast. Descriptions of these non GAAP financial measures and reconciliations of GAAP to non GAAP are included in today's press release and the slide presentation available on the Investors section of our website. And now, I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. [indiscernible] Thank you, Mary. Good afternoon, everyone.

And thank you for joining Sarepta Therapeutics fourth quarter and full year twenty twenty four financial results conference call.

As you may know, back in late twenty seventeen, we created an expansive strategic plan that we called Project Moonshot. One that would require that we raise billions of dollars chart a course through the unknown and overcome multiple unforeseen obstacles, obstacles that would have deterred a less committed team, but also a strategic plan if achieved, which would ensure a better life for thousands of Duchenne patients and cement the durable future of Sarepta. After years of work and reams of new insight into the treatment of Duchenne in 2024, we achieved all of the goals laid out in Project Moonshot. We obtained approval for the broadest possible label for ELEVITUS achieving our goal of a transformative therapy could serve the vast majority of Duchenne patients. We worked with the FDA to reframe the approach to the development of rare and ultra rare diseases so that therapies previously rendered unviable by FDA requirements now have the potential to help patients. And as a result, our LGMD franchise is moving with renewed speed, towards three potential approvals over the next three years. We broadly launched the Levittis in 2024 and achieved results greater than all other in vivo gene therapies combined.

At the same time, continue to serve the community with our PMOs, which grew even in the face of a robust gene therapy launch. We became sustainably profitable and cash flow positive in 2024. Indeed, by the February, we will do over $6,000,000,000 cumulatively in operating income and over $13,000,000,000 in free cash flow and this is after we have closed and made our initial investment in the Arrowhead transaction. And we have secured a durable and even more diversified futures through our Arrowhead collaboration pursuant to which we now add to our gene therapy pipeline a broad platform of siRNA including four clinical programs, three preclinical programs and six research [indiscernible] across neuromuscular CNS, cardiomyopathy and pulmonary. In addition to multiple gene therapy launches in the coming few years, we will have multiple potential blockbuster siRNA launches before the end of this decade. Now speaking more specifically of performance, we had an exceptionally strong fourth quarter and full year performance with our Fluorapride therapies for the fourth quarter Our net product revenues stood at $638,000,000 growing at 75% over the same quarter prior year. This represents more than $60,000,000 in over performance to our prior guidance. Our full year net product revenue stood at $1,800,000,000 representing year over year growth of 56% and this overperformed to our guidance by over $100,000,000 Turning to Eleventis, in 2024, we had by a wide margin the most successful launch of a gene therapy yet in history.

For the fourth quarter, EleVenus sales stood at $385,000,000 representing a 112% increase over the prior sequential quarter. And while we have already achieved over $1,000,000,000 in sales since our initial approval in 2023, This represents less than 5% of the on label addressable opportunity So clearly, this is just the beginning. Our three PMOs, 51, AMONTA 45 and VIONDYS 53 achieved $254,000,000 in the fourth quarter and $967,000,000 for the full year. We were profitable on a GAAP and a non GAAP basis in the fourth quarter and we were caught cash flow positive. Dalen Murray, our Chief Customer Officer, will provide more color on commercial performance in a moment, And then to round out the call, our CFO, Ian Esteban, will discuss our financials. In more detail. Looking forward, in 2025, we will capitalize on the successes of 2024. As you know, our net product revenue guidance for 2025 Excluding royalties from Roche, is between $2,900,000,000 and $3,100,000,000 approximately one third of which will come from the PMOs and a bit over two thirds of which will come from Alevidis. This represents year over year growth of 70% for total net product revenue and for Alevitus Sarepta represents over 160% year over year growth.

On the R and D and tech ops side, we have more upcoming milestones this year than any other time in our history. As you know, already met our important ELEVADIS milestone in late January. We reported the two year and one year crossover results for ELEVITIS from our pivotal trial in MARC and in all pre specified measures that includes functional measures muscle health and biomarkers, those on EleVenus did strongly to than untreated natural history would have predicted. We have passed 600 patients now on therapy across the broad range of ages and weights, These data are further proof of the transformative potential of Alevidis to change the future course of this disease. For patients. To continue to serve the global market and improve COGS, we are planning for a move to suspension manufacturing and after completing our GMP runs, we intend to commence our suspension manufacturing bridging study this year. As noted, we are now moving rapidly with our LGMD platform. We are continuing to dose our study for SRP-nine hundred four to treat LGMD type two d and we have initiated our registration study for SRP-nine thousand and five We have completed dosing in our pivotal trial for SRP-nine thousand and three to treat LGMD Type 2E, we will be submitting our BLA for approval later this year.

We also intend to file our IND for 10 to treat LGMD type IIa later this year. If successful, we will launch SRP-nine thousand and three next year will launch SRP-nine thousand and four the following year and SRP-nine thousand and five will be launched the year after that. As you know, we have closed our transaction with Arrowhead this month and already there will be several very significant milestones in 2025. This year, we will have our initial readout for cohorts for ARO DUX4 to treat FSHD Type one. Again, this could be a very significant proof of biology. We will be looking at muscle concentration, downstream gene correction and safety. We're also very excited about the potential to directly measure knockdown of the aberrant protein of interest DUX4. No other program to date has been able to achieve this this would be a very powerful result if successful. Likewise, we will have a readout of our initial cohorts for ARO DM1 to treat DM1, where we could obtain proof of biology looking at muscle concentration, knockdown, gene splicing and safety. If successful, we could launch our therapy for DM1 in 2029. Our clinical programs for MMP7 and SCOTT2 are progressing well as well.

We intend to initiate our first in human clinical study before the end of this year for ARO HTT Finally, we have a significant number of siRNA and gene therapy pipeline programs underway and so we intend to schedule an R and D day later this year to discuss all of them in more more detail. Our Head of R and D and Chief Scientific Officer, Doctor. Luis Rodina Klaypak, will discuss our pipeline progress. In a moment. With grid and operational excellence, we achieved all of our multi year objectives in 2024. In 2025, we will continue to execute We will build on our foundation as one of the very few fully integrated profitable cash flow positive biotechs in the world today we will achieve our next ambition, which is to become the next globally relevant big biotech focused on improving the lives of those among us with life limiting rare disease. And with that, will turn the call to Dalen Murray, for more detail on commercial performance and plans. Dalen? Thank you, Doug, and good afternoon. I'm delighted by the exceptional performance the team delivered in the fourth quarter and for the full year 2024. As we pre announced in January, net product revenue for 2024 totaled $1,790,000,000 consisting of roughly $967,000,000 from our PMO franchise, and approximately $821,000,000 for Eleventis. 2024 marked the eighth year of our PMO franchise, which continues to perform well and grew modestly year over year Even in the face of the transformation brought about by Alevitas, As in prior years, the team delivered this growth organically without taking price increases on any of our approved PMO products.

As such, this growth speaks to the increase in patients we are serving in the Duchenne community. For 2025, the PMOs remain an integral part of our guidance and even in the face of strong elevitas performance, we are only seeing modest U. S. Net cannibalization We are comfortable with the current consensus estimates as they stand today for the PMOs For the fourth quarter, net product revenues for the PMOs totaled roughly $254,000,000 growing at approximately 9% compared to the fourth quarter of twenty twenty three. Individual PMO net product revenues were $137,600,000 for AxonTA's $51.40200000.0 dollars for Vyondas $53 and $76,200,000 for AmandYS 45. Now turning to the Alevitus launch in performance. Q4 was our second full quarter with an expanded label and we could not be more pleased with the launch execution. In particular, for the fourth quarter, 11is revenue totaled $384,200,000 exceeding our quarterly guidance by over 60,000,000 Please bear in mind, even with this impressive growth, at this point in the launch, we have treated approximately 5% of the on label addressable patient population for ELEVITUS. So the opportunity ahead of us remains significant. And we have the wind in our sails at the moment.

The recent findings from the Part two of the Embark study adds to the existing robust body of clinical evidence. This will undoubtedly help the team with our efforts going forward. As the launch progress as we remain confident in our understanding of the launch dynamics, and the key drivers which continue to be robust patient demand for both the ambulant and non ambulant populations, ample site capacity for both the infusion and follow-up positive trends in access and reimburse for both ambulatory and non ambulatory patients and consistent conversion rates as we continue to see patients gaining access [indiscernible] the three to five month conversion timeline. Doug took some time at the recent JPMorgan meeting to give more detail on that conversion timeline. Understanding this process is essential to understanding our business model and the confidence we have in our success, ability to execute both quarter to quarter and in the coming years. Five launches in a decade of working in partnership with the key neuromuscular institutions gives us a deep line of sight into the cadence of dosing each patient in each center in each region, and across the country. For each and every gene therapy patient, roughly 20 to 25 people within each institution play an important part in making that dose happen.

Those folks are across each institution from the executive team to the pharmacy department as well as the medical finance and various administrative teams. And that's only the people within the institution We also rely on additional people from our distribution and manufacturing partners along with others from various internal Seraptines. All need to do their individual parts with perfection and under tight timelines to successfully dose each patient.

Why is this important? There are two reasons. The first and most critical is that we've now shown as a team we can do this reliably and successfully for over six quarters now since our initial launch. We've built the model and shown we can reliably execute which has been challenging for others to accomplish. Secondly, it gives us a great deal of confidence in our revenue projections which are driven by our understanding of the patient journey. There are several factors that contribute to the cadence of patients being treated and we have a good line of sight into each of these factors. With over eight years of commercial experience comes a good understanding of where the patients are and their pathway to treatment. We are also pleased with the continued progress in getting broad coverage for Alevitas and continue to see patients gaining access who are in plans with more restrictive policies. To date, not a single patient has been permanently denied coverage. And as you can see from our performance, this is a disease state that we understand extremely well. We are very confident in our growth trajectory and I'd like to reiterate a point that Doug made in January that puts our performance into broader context.

We project that in the first thirty months of our ELEVITUS launch, Alevitiv's net product revenue will outperform every other in vivo gene therapy combined over that same period of time. Our success of the Levittis shows that one time gene therapy could be commercially viable, providing hope for those with Duchenne and for all those with genetic conditions with unmet need. As a reminder, our 2025 net product revenue guidance is $2.9 to $3,100,000,000 which represents approximately 70% growth over 2024. Thus far, the launch has played out in line with our projections and we remain comfortable with this guidance given our strong finish to 2024, and our long track record of accurately predicting our performance, In summary, we are comfortable with our guidance for the year and with Q1 consensus. We expect to deliver sequential growth quarter over quarter throughout 2025, And now I hand the call over to Doctor. Louise Rodino, Playpack, for the R and D update. [indiscernible] Thanks, Don.

Building on the accomplishments of 2024, I'm thrilled with the promise before us and the vast opportunities there are to continue to make a difference in patients' lives. Placebo controlled Phase three clinical study of Eluvedis. Specifically, we shared crossover results from those who received therapy in Part two of the study. And we also shared the two year results of those treated in Part one of the study compared to an external control. Given what we know about ELEVADIS, what the science and data have shown us, and what we have observed in the large population of patients that have been treated with the levitus We were not surprised by such overwhelmingly positive data from the study. Which demonstrated that elovidus impacts the trajectory of Duchenne and offers an early treatment option intended to avoid unnecessary and unavoidable muscle damage. Speaking to the therapy's durability, the data are clear. Those not on therapy decline in their functional abilities faster than those on therapy. Who stay healthier longer versus the natural history would project. Intervention is critical in maintaining precious muscle before it's lost. With that, I'd like to pause for a moment and reiterate the significance of the MRI muscle data.

As mentioned on last month's call, these data support long term function and healthier muscle. Specifically, we saw modest to no increase in fat fraction from baseline to [indiscernible] And levels at two years were well below what we've seen at one year the placebo patients. This is consistent across muscle groups. We look forward to publishing data from ENBARK at forthcoming scientific meetings and in peer reviewed journals. In summary, as evidenced by the data, ELEVITUS demonstrated a clinically meaningful response across all of SREUPTA studies with increasing divergence from natural history over time. That supports the durability of the therapy. Toward our goal of providing ellevitist to all eligible patients, we are advancing the ENVISION study, study SRP-nine thousand and one a global randomized double blind placebo controlled two part trial evaluating the safety and efficacy of individuals with Duchenne. Envision's progressing well, And as previously mentioned, enrollment in The United States is complete. And our last patient last visit is expected in 2027. Following an eighteen month placebo controlled period. In addition, for the approximately fifteen percent of patients who are screened out for pre existing anti AAV Rh74 antibodies, We've commenced two studies. One with amyloidase or Study 104 to cleave antibodies and a second with plasmapheresis for Study 105, to remove antibodies.

We expect to have expression data from both of these studies in the second half of twenty Moving now to our programs to the limb girdle muscular dystrophy We were thrilled to announce in December 2024 that we completed enrollment and dosing of Emregene, for study SRP-nine thousand and three-three zero one. Our Phase three clinical trial of SRP-nine thousand and three to treat LGMD Type 2E for beta sarcoglycanopathy. Emregene is a global study The primary endpoint is biomarker expression of the beta circle glycan protein. The absence of which is the sole cause of LGMD2E. Data from Emregene are expected in the first half of twenty twenty five. Further, we were pleased with the outcomes of our pre biologics license application meeting with [indiscernible] Including endorsement for a rolling BLA submission. We are on track to submit our BLA filings to King accelerated approval for SRP-nine thousand and three the second half of twenty twenty five. We're also encouraged by the progress of our other LGMD programs. At the end of twenty twenty four, we initiated Phase one of SRP-nine thousand and four, and development to treat LGMD2D. And in early twenty twenty five, we will initiate our Phase onethree seamless design clinical trial for SRP-nine thousand and five, which is in development for the treatment of LGMD2C.

This March, we look forward to sharing with you a wealth of data from our Duchenne and LGMD programs at the MDA Clinical and Scientific Conference taking place March 6, '16 through the nineteenth in Dallas, Texas. And we also look forward to highlighting our impressive pipeline at an upcoming R and D Day in 2025. As a preview, we have numerous programs in various stages of development across neuromuscular, central nervous system, cardiac and pulmonary indications. Many of which are nearing INDs. Of note, for Neurontrophin-three or NT3, have optimized the construct for Charcot Marie2 Type 1a or CMT1a in using AAV RH74. And are now rapidly advancing to the clinic following exciting preclinical data. As a reminder, we are using a surrogate approach for delivery of the NT3 gene to improve myelination and nerve regeneration in CMT1a. This pipeline and the product approach has applicability to other CMTs as well as other demyelinating indications. On the research side, we've continued to innovate across platforms. We've optimized, developed and characterized new AAV capsids that will change the landscape for neuromuscular gene therapy. And unlock potential in cardiac and CNS disease areas. We are also driving innovation in gene editing, enhanced delivery for RNA, and our pioneering new mechanisms to operate delayed gene expression.

The future cannot be brighter for genetic medicine. Further, we look forward to sharing data with you later this year around our FSHD1 and DM1 programs. As a reminder SRP-one thousand and one formerly known as ARODEX IV, is currently in clinical development to treat FSHD1, an autosomal dominant disease associated with the failure to maintain complete epigenetic suppression of DEX-four expression and differentiated skeletal muscle leading to overexpression of DUC4, which is myotoxic can lead to muscle degeneration. We are encouraged by the non clinical data generated Turning to myotonic dystrophy type one or DM1. DM1 is driven by an expanded CUG trinucleotide repeat in the three prime untranslated region of DMPK transcripts. These abnormal transcripts cause misregulated splicing known as splice off certain messenger RNAs which are directly linked to the clinical manifestations of DM1. We believe that silencing the inherently transcribed DM-one GMPK mRNA using FRP-one thousand and three formerly known as ARO DM1, may halt CUG expansion related splice defects in patients with DM1. And thereby improve muscle strength and function. We look forward to sharing the data from the SAD study later this year as well. Now to discuss [indiscernible] The Essence trial, our post marketing requirement, for golodirsen and casimersen as well as MISSION, our post marketing commitment for EXONDYS, are both fully enrolled and remain on track.

We look forward to sharing data as soon as the studies are completed. In summary, I'd like to take the opportunity to thank the patient community investigators and my Sarepta colleagues all this progress would not be possible without you. And finally, I'd like to recognize this Friday is Rare Disease Day. There are more than 7,000 rare diseases only a small percent of which have any treatment. As a company dedicated to bringing forth new treatments for rare disease, it's an important day for our employees, the patients we serve. It's a data reflect on the impact of rare disease on the affected individuals and their [indiscernible] and to acknowledge all the work that's needs to be done. And to celebrate the progress that we've made. With that, I'll turn the call over to Ian for an update on the financials. Ian? Thanks, Ira K. Well said. Good afternoon, everyone. This afternoon's financial results press release provided details for the fourth quarter of twenty twenty four on a GAAP as well as a non GAAP basis Please refer to the press release and slide deck available on Sarepta's website for a full reconciliation of GAAP to non GAAP financial results.

For the three months ended 12/31/2024, the company recorded total revenues of $658,400,000 which consists of net product revenues and collaboration and other revenues compared to revenues of $396,800,000 for the same period of 2023 an increase of $22,601,600,000.0 dollars Net product revenue for the fourth quarter of twenty twenty four from Alevitus was $384,200,000.0 compared to $131,200,000 for the same period 2023. Net product revenue for the fourth quarter of twenty twenty four from our PMO Axon skipping franchise was $254,000,000 compared to $233,800,000 for the same period of 2023 The increase in net product revenue primarily reflects the net product revenue from sales of Alevitus. In the quarter ended 12/31/2024, we recognized $20,300,000 of collaboration and other revenues compared to $31,700,000 for the same period of 2023. This revenue primarily relates to our commercial levodys supply delivered to Roche royalty revenue and our collaboration arrangement with Roche, The reimbursable co development costs under the Roche agreement $26,000,000 for the fourth quarter of twenty twenty four compared to $23,500,000 for the same period of 2023. As a reminder, these Roche reimbursable co development costs are an offset to operating On a GAAP basis, we reported net income of $159,000,000 or $1.65 per basic share and $1.5 per diluted share and a net income of $45,700,000 or $0.49 per basic share and $0.47 per diluted share for the fourth quarter of twenty twenty four and 2023 respectively.

We reported a non GAAP net income of $2.00 $6,000,000 or $1.9 per diluted share in the fourth quarter of twenty twenty four, compared to a non GAAP net income of $86,600,000 or $0.82 per diluted share in the fourth quarter of twenty twenty three. In the fourth quarter of twenty twenty four, we were recorded approximately $132,300,000 in cost of sales, compared to $44,200,000 in the same period of 2023. The increase primarily reflects cost of sales related to Alevitus, during the three months ended 12/31/2024, following the label expansion in June of twenty twenty four. On a GAAP basis, we recorded $200,000,000 and $19,095,500,000.0 dollars in R and D expenses for the fourth quarter twenty twenty four and 2023 respectively a year over year increase of $4,500,000 The increase is primarily due to an increase in our manufacturing expenses related to a ramp up of batches produced for our lymph girdle program partially offset by a decrease in clinical trial expenses related to the discontinuation of the PPML program. On a non GAAP basis, R and D expenses were $172,700,000 for the fourth quarter of twenty twenty four compared to $165,100,000 for the same period of 2023 an increase of $7,600,000 turning to SG and A. On a GAAP basis, we recorded approximately $163,900,000 and $131,700,000 of expenses for the fourth quarter of twenty twenty four and 2023 respectively.

An increase of $32,200,000 The increase was driven primarily by an increase in professional services, use support the continued efforts to commercialize Alevidis and ongoing litigation matters and an increase in compensation and other personnel expenses primarily related to changes in headcount On a GAAP basis, SG and A expenses were $131,600,000 for the fourth quarter of twenty twenty four compared to $105,700,000 for the same period of 2022. An increase of $25,900,000 On a GAAP basis, we recorded $10,100,000 in other income net for the fourth quarter twenty twenty four compared to $15,700,000 for the same period of 2023, The change was primarily due to a decrease in interest income and accretion [indiscernible] Net as a result of lower interest rates, and a mix of our investment portfolio. As mentioned earlier, we're maintaining our 2025 total product revenue guidance which reflects a 6868% growth from 2024 at the midpoint. We also are introducing expense guidance for 2025 We anticipate combined 2025 non GAAP R and D and SG and A expenses to be in the range of $1,200,000,000 to $1,300,000,000 The incremental expense is almost exclusively related to Arrowhead development programs, Excluding these costs, our expenses would be essentially flat compared to the prior year.

And to conclude, we had approximately $1,500,000,000 of cash cash equivalents, investments and restricted cash as of 12/31/2020 as Doug said, now that the Arrowhead transaction is now closed, which was pulled funded by our existing cash reserves, we project returning to similar cash levels by year end of twenty twenty five. Driven by the strong ELEVITUS launch. Further bolstering our financial position, we secured a $600,000,000 revolving credit facility The combination of a positive business outlook and our strong financial position us really well to execute on our 02/1930 strategic goal. And with that, I'll turn the call back over to Doug for Q and A. Thank you very much for that, Ian. Lisa, let's open the call for questions. And our first question for the day will be coming from the line of Tazeen Ahmad of Bank of America Securities. Your line is open. Okay, great. Thank you for taking my question. I wanted to ask Doug about the cadence of what you're seeing in 1Q so so far with regards to the patients that are being onboarded You've talked extensively about certain things that cannot be changed and you reiterated your confidence about guidance for 2025. Can you give us a little bit more granularity on again what you're seeing in 1Q and how we should be thinking about the cadence of uptake the rest of the quarters this year.

Thank you very much for your question, Tazeen. A couple of things. First, let me reiterate my confidence on the guidance for the year. We're still very good about the guidance that we have and I would remind everyone, we have a very good track record. Of setting reasonable guidance and meeting or very often exceeding that guidance. The only thing I'll say about quarters going forward is that we will continue to see growth quarter over quarter This launch, things obviously are going very well. For this launch through 2024. And I think our guidance should imply it's going very well in 2025 as well. There is a certain cadence to all of this everything from the the start form, the single case contracts that I've talked about in the [indiscernible] the infusions, the need for pre existing antibody assays and the like that describes their cadence. But it's going very well. And what we'll see over the course of this year is growth quarter over quarter over quarter to achieve our guidance for full year, which of course is $3,000,000,000 in total, a little over two thirds of that will be coming from Alevis and the remainder from our three PMOs.

So thank you for that.

Thank you. And one moment for the next question. Our next question will be coming from the line of Ellie Merl of UBS. Your line is open. Hey, guys. Thanks so much for taking the question. For Limb Girdle, just from your work in the space, what's the latest on what you see for the prevalence of 2E and how many in The U. S. Are diagnosed today? And the mix of ambulatory versus non ambulatory patients. Basically, if you will be launching here next year, should we be thinking about the contribution potentially to revenue? And how many patients there might be kind of waiting for therapy? Thanks.

I'll give you the broadest strokes, then I'm going to turn the call over to Luis if she has any information on the split between ambulatory, non ambulatory. Obviously, Type 2E is a very rare disease. It's an ultra rare disease. In fact, all of the three, sarcoglycan launches that we'll have over the next three years are individually very rare. But collectively, they will represent about twenty five percent of the Duchenne ELEVITUS opportunity. So they will be important contributors first and foremost, to be clear, there'll be enormous contributors in the lives of patients living with and being degenerated from these really devastating muscular dystrophy's. And then they will be important for the organization as well. But they'll be modest. They'll be about twenty five percent of Duchenne. So they'll be important to modest. With that said, additional question had been asked was, the split of ambulatory and non ambulatory specifically as to Type 2E. And I don't know, Luis, if you have any information on that Yes.

There's generally even split. I would say as genetic diagnosis, especially for limb girdles has come along, we were seeing more of the ambulatory population. I think historically, you would said it would be geared to the words that ambulatory, but now it's generally a fifty-fifty split.

Thank you. One moment for the next question. And our next question will be coming from the line of Jenna Wang of Barclays. Your line is open.

You for taking my questions. I have one question regarding the data update later this year for both SSD and the DM-one. If I hear correctly, DM-one will be be the sat data? Is FSHD also SAD data? And if there are the SAD data, how many cohorts and how long follow-up and what kind of data you will share with us?

Yes, I will turn this to Doctor. Rodino Claypack to provide some color on that.

Yes. For both FSHD1 and DM1, [indiscernible] the SAD data. So we'll be be early we'll be focusing on single dose single ascending dose study data which will be focused on safety. So some early signals of biomarker efficacy efficacy, which will be [indiscernible] knockdown, essentially splicing, restoration as well. So it'll be early data, but we look forward to showing that in the second half of the year for both We're also really excited with FSHD as well that our hope and of course we'll only know when the data comes in is that we'll be able to show through an assay the actual direct knockdown of DUX4, which of course is the goal of the therapy for FSHD. If we can do that, that is a really significant proof of biology because no program before has been able yet to achieve that goal. So we're very excited to see that as well.

Thank you. And our next question will be coming from the line of Brian Abrams of RBC. Your line is open.

Hi. This is Kevin on for Brian. Thanks for taking our questions. So maybe just on limb girl type 2E, can you maybe what you think the bar is for your upcoming 2E data? And then maybe how do you think that bar translates to other LGMD subtypes that we'll eventually see data from. We've done I'll comment on it and then Luis you update with any more precision. Broadly speaking, we have been working with the agency over a very long period of time in essence to help educate the agency on the bar that should these sorts of ultra rare diseases, particularly diseases and therapies like SRP-nine thousand and three for limb girdle type 2e where you're dealing with the replacement of the native protein unaltered which the absence of that protein is the sole and exclusive cause of the disease. So I'm very proud to say we have very small end studies. They're single arm studies. They look to expression and safety. So in the broadest of strokes, the bar will be that we're getting nice expression I would hope largely consistent with the expression that we've seen in the past. As remember, we've actually dosed SRP-nine thousand and three in prior cohorts and of course a good safety profile We have a lot of conviction around this as you can well imagine First, because we've already actually dosed patients with SRP-nine thousand and three, but also because SRP-nine thousand and three stands on the shoulders.

Of all of the work that we've done with nine thousand and one now elevitas. We have dosed hundreds and hundreds and hundreds of patients Alevudis. We understand the laudable safety profile we understand the power of our constructs and our promoter to get really good expression and get it safely. So that's sort of the bar and we're very confident about where we're going to go with that. And on your other question, this will be similar across the Lidngerdal programs that we have already aligned with the agency on the approach that we're taking for 09/2003 and 09/2004 and nine a modernization in the way the agency is looking at transformative therapies for ultra rare diseases. Luis, is there any more detail that I have omitted?

And you summarized it well. Maybe I'll just linger on one point in the fact that for the sarcoglycans, LGMD2E being the first, these are the full length genes So in this case, beta cyclical glycan is both the gene therapy, it's also the biomarker. We've demonstrated extensively pre clinically how the biomarker expression leads to functional improvement. And then that translated in our studies clinically and we saw two different doses. We saw improvements in both expression that led to functional improvements over time. Those patients will be sharing five year safety follow-up data for those patients continuing to do well. So that will be our first study and then the other cycloglycans will follow suit We're all using we're using 9,001 data, but then also the other sarcoglycan. So we're in good position in terms of the outcomes of these studies and the outcome of the BLA.

And our next question is coming from the line of Andrew Tsai of Jefferies.

Your line is open.

Thanks. I appreciate the update. Congrats on all the progress Maybe one more question on the DM1 FSHD data. You'll be sharing later this year. Do you think the initial SAD FAD data will be conclusive to the point where investors can determine whether these programs are looking superior or not or do you need MAD data? And how would you define superiority in these two programs?

I'm going to turn this over broadly to Luis to talk about it. Let me say at the inception. First of all, I don't want to do what other small biotech companies often do, which is oversell early data. The data has to evolve. These are however Very, very important proofs of biology. So I want to be very clear both from a safety perspective, a muscle concentration perspective, a knockdown perspective, downstream gene splicing perspective and as it relates to FSHD, whether you can actually directly see the knockdown of DUX4. So while there'll still be lots of work to do from there and we don't want to oversell the data, this is a really, really important moment. And it should give at least signals of potential future [indiscernible] other potential approaches to FSHD and DM1. But Luis, you can provide more detail.

Yes. Just to add to that, I would say that what we know from the Arrowhead platform, what we've seen in their other programs and from the preclinical data is the translation from preclinical to clinical. And so we've been excited to see that and that's what we'll be looking for is that translation into the clinic. So it will certainly be a good indicator in terms of the knockdown that we're seeing, the muscle concentration, those are the things we'll be looking for. As robust clinical developers. We're obviously looking to the MAD data to come following that. But certainly, we're excited to see the SAD data and we'll translation from preclinical and just an extension of their already promising data across the platform. Arrowhead.

Thank you. One moment for the next question. A question on ELEVITIES from us. Given that it's been about eight months now since the label expansion, Can you comment on whether you have seen any reinvestments for PMOs in elevated patients? And if not, are you hearing anything from payers around their willingness to reinvest PMOs following [indiscernible] Yes.

So let me say it Kostas, thank you for your question. In broad strokes, I will still note that it's still very early days. And so so trying to draw broad conclusions is challenging. As we've noted, one of the most interesting, I think data points we should linger on for second is while we've met all this success, we're still only treated less than 5% of the addressable on label patient population for Lebitis. And so you got to both have to really test this issue. You've got to have Levittis and then you have to have the fact that Levittis is treating a patient previously on a PMO. But we do have instances of reimbursement of both. So we've already seen that. I don't want to oversell it right now. And I'm sure we also have instances where that was impossible. But it's not black or white or binary right now. I will reiterate one of the things that that is we're very excited about is that so far we haven't seen significant net cannibalization. We'll see some cannibalization in The U. S. We're seeing very good growth of [indiscernible] Ex U. S, of course, the overlap is modest given that we only treat twenty nine percent of patients with Duchenne muscular dystrophy with our PMOs.

And it's nice to see that we have seen some payers interested and willing to put kids on sequential therapy gene therapy. But it's still very early days and I wouldn't over read that. Dalen, if I No, that's absolutely right. That's absolutely right.

Yes.

Thank you, [indiscernible] The next question will be coming from the line of Mike Ults of Morgan Stanley.

Your line is open.

Hey guys, thanks for taking the question. Maybe just a quick one on $500,000,000 share repurchase program. Can you just remind us what the timeframe is there? Then some of the considerations as you decide when you might deploy that? Thanks. Sure. I'll turn this to Ian.

For his thoughts. Sure. So the time period is eighteen months.

Like I said, obviously, we just completed the Arrowhead transaction. And so we're going to be quickly building back our cash reserves over the course of the year. Like I said, in our prepared remarks, we're going to be back to the same level at the end of twenty twenty five as where we started where we ended in 2024. So [indiscernible] to the strength of the launch. And so as we continue to build our cash reserves, we're going to look to be opportunistic around potentially deploying that capital and buying shares. So obviously, we're not going to telegraph when we will be doing it specifically, but we certainly have it at our disposal and we're looking at the right time to do tax accrual.

Thank you.

And our next question comes from the line of Joe Schwartz of Leerink Partners.

Your line is open.

Great. Thanks very much. So since approval in 2023, it's seems like the Levittis launch has had a few different stages with great growth or early on following accelerated approval, then a couple of flat to down quarters in early twenty four followed by nice the expanded label in mid-twenty four. So since your 2025 guidance seems to imply that growth this year should be more moderate, I'm just wondering if you can give us your view about the stage of the launch that we're in now and how you see it evolving this year? Are there any important constraints to growth that we should keep in mind this year? So Joe, thank you for your question. And I will say with due respect, I do not characterize our launch exactly the way you do. I would say we had a brilliant launch in 2023 with a very thin label. Then we had we achieved something that I achieved, which is a very, very broad label. But of course, the cadence for that broader launch requires the natural cadence of kids getting on therapy, which to remind everyone even though we had done a brilliant job in site readiness and accident reimbursement were all ready, There's just a cadence to getting the kids on therapy.

It takes about four months and there's really no magic to fixing that because it's the cadence of the single case contract and the scheduling and the infusion beds and the amount of follow-up and the assay work and the like. So there's a certain cadence We had anticipated exactly what we saw in 2024, which was we would see this hockey stick ramp towards the back half of the year, which is exactly what we saw. And as you know, we grew in the fourth quarter by 112%. And then I would note for this year, I mean, with respect against the statement that the growth is modest this year, we're going to grow with the levittis over 160% year over year. And I would put that up well, first, I can't put it up against any other gene therapy. Be clear because we have blown away every other gene therapy cumulatively But also I think for launches, this is just about as successful a launch one could have imagined and we're still in the robust, robust growth phase of this launch.

Thank you. And our next question will be coming from the line of Gil Blum Needham and Company. Your line is open.

Hi, good afternoon everyone and again congrats on all the progress. So maybe a question here on the move to suspension manufacturing with the bridging study later this year. Just Can you remind us are the potential associated cost savings? And also how broadly applicable is this? I mean, you guys use a lot of different programs for the gene therapy.

Is this translatable just outside of the MD or is this very narrow? Yes. So let me answer the last question first. Our goal if successful, is to evolve almost all of our gene therapy programs to suspension. In fact, if I'm not mistaken, Luis, you'll correct me if I am, the only program that will remain in adhering is just the timing of it and we didn't want to slow down the approval as kids are waiting for it, is 09/2003 All of the even all the other charcolic cans will be in suspension. And broadly speaking, of course, it's very dangerous to sort of to try to estimate COGS impact. We've got more work to do, but it will be very, very significant. We're seeing upwards of five times to even greater times more yield efficiency. So you could envision margins significantly over 90%. Eventually with this. And also the ability to really bring this therapy the far reaches of the world. And that's, of course, one of our big goals. So to remind everyone, we said it already in the in our prepared remarks, but our goal is to complete our GMP runs and to start our bridging study before the end of this year certainly.

And then the goal of course is if all goes well and we're successful to evolve to elegant timing for us as we think about our global plates.

Thank you. And the next question will be coming from the line of Richard Barrow of TD Cowen. Your line is open.

Hi, guys. Thanks for taking the question. Doug and Louise, I wanted to ask your current thoughts as you understand the landscape on the potential for splicing biomarker based accelerated approval for your FSHD and DM1 programs. I know it's far in the future but obviously this is a hot topic of the space. And then actually, if I could follow-up on Gil's question. He asked about the bridging study. You describe what that bridging study is? It sounds like it's going to go fast.

Yes. On the bridging study, it's a relatively if you've given the actual length, it's a relatively small study looking at empirically looking at expression and safety to confirm that it's substantially similar to the adherent approach. So it should go relatively fast. Everything Everything's work, but it should go relatively fast and we intend to start the averaging study later this year. And then with that, I'll turn it over to Luis if you have any thoughts or comments on the potential for an accelerated approval approach with either FSHD or DM1.

We're in the early stages, I would say for FSHD, Doug alluded to it, but in we're in a unique position with FSHD where we have an assay that actually can quantify the knockdown of the primary defects in the indication, which is DUX4 so that gives us unique opportunity in terms of potential biomarkers as well. In these early studies, we are looking at multiple biomarkers and functional outcomes and that's really what these Phase one studies are intended to do so that you can optimize and pick the best path forward. I think it's an [indiscernible] [indiscernible] I think it is one of many biomarkers, but whether it would be the sole biomarker is is something left to be explored.

And of course, we recognize, yes, there we know amongst others there is a lot of open discussion and dialogue and even some differences of opinion regarding the pathway for approval. This is one of these really rare moments, maybe in my time, it's for up to the first time where we get to be informed by others. And so we're going to get informed by not only our direct conversations with the FDA, but what others are seeing when they're with the FDA. And that will help inform our path forward. So it's an interesting and interesting place to be where we get to be informed by others as opposed to most of our other therapies having been the one to inform the world and chart the path.

Thank you. And our next question will be coming from the line of Brian Sworny of Baird. Your line is open.

Hey, good afternoon. Thanks for taking my question.

I was hoping you could kind of walk through what you sort of perceive as the current Order of potential rate limiting steps to commercial levodys revenue recognition. I'm just trying to understand what it doesn't seem like it's demand in any sense right now. So what's sort of the step throughs that are kind of creating blocks from realizing full demand is alike? Would one be like insurance authorization? Would two be central capacity? Could you like kind of rank order [indiscernible] Yes.

Rank ordering is hard. Let me turn this over to Dow and force him to rank order. But let me say a couple of things. I don't want to call them blocks because it's just a cadence issue. It'd be like saying, Balen often uses a metaphor that this is often like think of this more than this is not like prescribing a drug. This is almost more like ordering transplant. There's just a lot of steps that have to go through to get from here to a kid dose. That's why it's about a four month process. And I'll give you some data on that. There are something like 25 individuals at site of care that touch this therapy moving from the the start form to the infusion. And that goes through lots of different departments, not just the internal pharmacy and the infusion center and the nurses, [indiscernible] it's also all the way back into the financial area and the CFO of the organization like. And so there's just a cadence. I mean, to give you an example, [indiscernible] there is it's about a can be as much as a four week or longer process to do the single case contract, every almost every time a patient gets dosed, the site and the payer enter into a specific site contract.

It's an administrative step that has to be done. It is done. It's done very well. We understand the process. Exceptionally well. I'm quite confident now. I can say that without fear of being arrogant, there's no organization in the world that understands this process as well as we do.

But there's just a cadence to this. And it is all the things you're mentioning. It's the very process of getting the first meeting and then getting to the assay and then getting the infusion site ready at the same time it's the start form and the the single case contract it's negotiating with the payers if you have to, It's when necessary negotiating with the payers around it. Remember, I will comment on this There's been externally some misunderstanding regarding payers and some relatively superficial surveys that were done Look, we're doing really great with payers right now. We're doing better with payers with 11 to we did with the PMOs. And I would note we've done really, really well with the PMOs over the time, I think, as anyone would agree, that the policies really set themselves into three buckets. Policies there's a lot of policies that are just dose to label. Give access to label more than there were with the PMO. So we're really excited about that. Some of our bigger payers are in that camp. There are some payers that have restrictions and there are some payers that have a lot of restrictions. The interesting thing is that those different policies will not [indiscernible] today the ultimate kid getting on a therapy what they do, do is internally they define the amount of time to get a kid on therapy and the amount of work that needs to be done to get a kid on therapy, but they get on therapy.

So I just want to get everyone's head around that idea.

And our PMOs with eight years of of battle hardened experience Our win rate if we a payer is going to be very resistant and take to an internal or external appeal, over ninety percent. With 100%. So no kid has been permanently denied therapy. Thus far. So in any event, all of these things describe this broad cadence that is about four month process. But, if you want to rank order then for Well, Brian, I think you can summarize everything that Doug is saying with one word, which is time, right? Everything here takes time. And so you really therefore cannot point to one thing. As I said in my prepared remarks, we have robust patient demand. We have more demand than can be treated today. We have ample site capacity. We have enough site capacity to treat our peak forecast. We've got positive trends in access and reimbursement that we're allowing to convert patients within that consistent three to five months timeframe.

So those together then when you layer in what Doug said, it's just a game of time to get these patients [indiscernible] line of sight into all of this, this is what informs our quarter. To quarter for growth and our guidance for the year.

And I will say, it's probably too since it's time and an insane attention to detail. Which Sarepta is really good at. I am sitting here and will tell you, at our national training meeting today with all of our folks focused on this and they the amount and attention obsessed into detail and the passion to make sure a kid never slips through the cracks but can get on this therapy and benefit from Levittis is insane. And that explains why we've been so successful.

And it explains why we are so comfortable with our guidance for 2025, which I would say is very robust guidance. Dollars 3,000,000,000 is a percent growth overall for the year and as it relates to Elevitas over 160% growth year over year, which speaks to the execution ability of this team out here at Scottsdale.

Thank you. And our next question will be coming from the line of David Hoenn of Deutsche Bank. Your line is open.

Hi there. Thanks for taking my question. So I just had one on if you have any thoughts on a recent data set that was generated by a next generation DMD gene therapy competitor? And do you have any in from your field force on how families' patients might think about receiving treatment with commercial ELEVADIS versus enrolling in a clinical trial for one of these other products? Thank you.

Well, first, there are no next generation gene therapy programs. So I'm going to going to correct the record on that. That's a mistake. But look, here are a couple of thoughts. On it. We do understand that the Zalman put out some very, very early first in human data. Couple of thoughts. First, fantastic. We are thrilled that a number of organizations are looking at researching new therapies for kids with Duchenne muscular dystrophy. And to be honest, we take a lot of pride in it because I think but for the success that we've had with our PMOs and with Alevidis, they wouldn't have this robust focus on finding new therapies for kids. So we're very excited about that. I do want to know that we have to remember that the families with Duchenne muscular dystrophy have to make difficult decisions today and they need accurate information to make them. That's for the families to make.

Clearly, there is one absolute overarching fact, which is there is one approved therapy that is transformative in nature that is a disease modifying gene therapy and that is a lever.

And that can treat eighty percent of children with Duchenne muscular dystrophy in young men. Occasionally women with Duchenne muscular dystrophy And our goal is to ensure that families have the right information, so they can make the right decisions, which is often a very difficult decision. Do you go get the current therapy? Do you look at a clinical trial? And take a therapy that's been tested less and the like. But just want to make sure the only thing I I'm very thrilled with others focusing on this. I think it's a really positive for the Duchenne community and everybody should applaud it. But I do want to make sure people are providing the right balance reasonable information, so people can make intelligent decisions and not make the wrong decisions. And the actual decision that people make between kind of entering into a clinical trial for a new experimental therapy versus getting on an approved therapy that's been shown to be safe and efficacious is a difficult decision that's going to be made between the families. And their healthcare provider hopefully properly informed with all the current data.

Thank you. Maybe just one thing to add to that and I'll turn it to Luis to to go into more depth. But I do think it's important for people to recognize and certainly Louise has done a lot of work empirical work for over many years looking at functionality And certainly as we've seen with other development programs different constructs have different efficacy and safety profiles and therefore when Louise tested all of these programs, she really moved forward with optimized construct from a functional perspective and that's why we were able to see data based on our expression lead to functional outcomes. And so so that's really important When patients are thinking about therapies that it's not just only expression but that actually the functionality of the construct.

And to Doug's point, we've been able to show that in clinical studies. But Louis, since you did the work, you probably have that that the best point of view on that.

Yes. Thanks for that. Yes, I think it's important in the fact about the dystrophin space is unique for gene therapy and that in the small dystrophin space, you are looking at different functional contributions from these constructs. So the quality of the dystrophin that you're producing is extremely important. Just one of the things that we noted in studies when we compare it to other constructs was the inclusion of SPECTREN REPEAT III for stability of the construct. And we found that over time that this was critical to the functionality of our construct and the corresponding functional improvements that we saw that corresponded from preclinical work to clinical work. So it was as you all know, you've been on this journey with us hundreds of patients over many years and multiple clinical studies showing the same thing in terms of the expression leading to functional benefit. And obviously with a traditional approval now. And over six hundred patients treated both clinically and commercially. So Certainly, the the quality of the constructs and the functional data that's demonstrated in the clinic is critical to making a decision about the the therapy that a patient chooses with their families.

Thank you. And the next question will be coming from the line of Rife Faucette of Guggenheim Securities. Your line is open.

This is Rai from Debjit's team. We have two questions. Number one, how is Sarepta modeling the impact of competitive gene therapies in DMD especially on the annual incidence population under the assumption that the prevalence pool is saturated And number two, for the 2E program, should we expect higher vector genomes per nucleus relative to historical SREpta data and protein expression above 50% And is there a threshold for regulatory submission?

I think I've answered the threshold question. Thank you for that. I think if we get expression consistent with what we've seen before with 09/2003 and before that with nine and one, I would remind you, we got really extraordinary vector genome copies for Nucleus. And we do it with a very rigorous approach, fairly unassailable approach looking at things like vector genome copies and expression ones that we worked on for years and years with input from the FDA. Might have to be very careful about that because it's very easy to do these things in ways that give false information. But if we get that those levels of vector genome copies per nucleus and we get the kind of expression that we've seen both in 09/2003 and 09/2001, we're very confident that we'll get an approval assuming the safety is there and we're very As far as modeling, it's way too early to be modeling competition from people that have one, two and three patients in these early experimental therapies probably haven't even figured out manufacturing at that point. Certainly, we wouldn't be modeling anything this decade in any event. It's something we can look people will actually start progressing.

Although I would say thank you for that question because The size of that incident population is really underappreciated. It's really double the size of the Zolgensma market currently.

We'll be ready for any competition when it comes. As Doug said, it's going to be a long time coming. And we really are [indiscernible] earlier in that patient journey. So it's a great question from the perspective of very underappreciated part of the Duchenne market opportunity.

Thank you. And the next question will be coming from the line of Anupam of JPMorgan.

Your line is open.

Hi, guys.

This is Priyanka on for Anupam. Thank you for taking our quick question. As the R and D days in the second half of the year, can we assume potential new data could be presented there from Arrowhead or other non Arrowhead pipeline programs? Thank you.

I'll turn that to Luis to comment.

I don't think we've said exactly the timing of when we will present the Arrowhead data It's It all depends on the timing of the data release and how that lines up with R and D Day or We're excited to talk about the platform. Generally, I would say that at as part of R and D Day. And our deep pipeline that we haven't really been able to share in detail. So we look forward to that and as we have more timing, we'll share with you.

Thank you. And the next question will be coming from the line of Byron Amin of Piper Sandler. Your line is open.

Yes. Hi, guys. Thanks for taking my questions. For the IMergeen trial, I think you're enrolling both ambulatory and non ambulatory patients, while the Phase one enrolled ambulatory So should we expect expression would be similar ambulatory data? And then when you report these data, will you be comparing these [indiscernible] the NCH National History cohort [indiscernible] Yes, a couple of things in there. So we've treated both ambulatory and non ambulatory patients since we see similar levels of expression. So the [indiscernible] analysis will analyze those two populations separate from a functional perspective that will be the follow on study, the confirmatory study, but from an expression level yes, we will evaluate.

Both. In terms of what we're comparing it to, we have our own journey, natural history study and that will be the comparator for the confirmatory study.

Yes.

And just our history has shown that we get great expression across the continuum of disease from very young to very advanced. On terminal value. So if I look at the outer year of consensus estimates, take 02/1933, I see about $2,200,000,000 in U. S. 11 of sales, that implies about eight fifty to nine hundred treated patients annually. Maybe, Dalen, you could just remind us like specifically what you're seeing on U. S. Incidents more broadly, believe this consensus estimate is plausible, Maybe explain what has to happen for Levittus to reach and stay into that range into the next decade? This is the incident population is sort of looking at what somewhere in the low four hundred, four twenty, four thirty. So you can do the math on that. And then of course, we'll have the PMOs on top of it because the PMOs are enduring. As well. And then by that point, although this might be speculative until we solved it, we will likely have solved the redosing issue by the 2030s as well. So you'll have to add to that that concepts as well. And of course, if you're talking about the terminal value on Levittis, it's not the terminal value on the company.

As you know, FOGO as well, we'll be launching three limb girdle programs in the next literally every year for the next few years. We have new ones coming, we have new INDs and if all goes well, we'll be launching FSHD in 2028. We'll be launching DM-one in 2029, both of those are multibillion dollar peak year sales opportunities. So obviously the terminal value will be significant on the organization as a whole.

Thank you.

One moment for the next question. And the next question is coming from the line of Sami Korwin of William Blair. Your line is open. Great. Thank you. Congrats on the progress and thanks for taking my questions.

Was curious how you're thinking about the evolution of your gross margins in 2025 and 2026 as Levittus begins to compromise a larger percentage of your revenue. And then a quick question on your FSHD program. Is this DUX4 assay new or was it developed in house and could you just elaborate on a little more.

Sure. I'll turn the evolution question to Ian and then Luis can touch on the DUC4 assay issue.

Yes. So from a margin perspective, what we've said is that obviously is the obviously we did already expense the inventory already. And so that's to come off And then over time as we continue to treat heavier patients, you're going to see the margin go down. We as we continue to penetrate into the non ambulant patient population. But as Doug said, as we continue to work on our suspension manufacturing process, we expect that to start getting much significantly higher trending towards 90%. So as we're treating the heavier population, we We expect the margins to improve in the 27 timeframe.

Thank you. [indiscernible] And just on the DEX-four assay, this is a quantitative assay developed by Arrowhead As we've mentioned, DUX4 is expressed at low levels somewhere around the instance of one in a thousand nuclei. So it's difficult to measure, but Arrowhead has successfully done that. And so this is an assay that will be on boarding as well, but we're excited to see it because it's not something that's been able to be accomplished in the field.

Thank you. And the next question will be coming from the line of Mitchell Kapoor of H. C. Your line is open. Good afternoon. This is Dan on for Mitch.

Congratulation on the positive cash flow for the year. So, Paris, we've spoken with and said that they have had patients experience two rounds of appeals and were ultimately denied.

Would an IRO denial not count as permanent denial? And if not, what qualifies as a permanent denial?

I'm not sure. I know that I'm not sure who the you spoke to. I know you did a survey. One was actually not a payer, it was PBM. And I think you might have talked to one payer. We have no kids that have been permanently denied. Therapy. I'm not suggesting it will always be 100%. Our PMOs trend above 90% over the last eight years, but we're seeing even a better response than the PMOs of the lebithis. We're doing quite well. We don't have We don't have any kid that's been permanently denied therapy. Some are still in process but no kid has been permanently denied therapy.

Yes.

So Yes, Dan, we've dosed patients in the plan that you're talking about. We're not to provide you any more details other than that.

Thank you. And the next question will be coming from the line of Yair of Mizuho. Your line is open. Hi, guys. This is Leo on for Roy.

For taking our question.

Could you provide some detail on the learnings from the pre BLA meeting with the FDA on 09/2003 and how these learnings might be [indiscernible] changes within the agency, how do you think FDA interactions might change going forward.

Thanks.

So Luis, do you want to touch on the sort of pre BLA discussions broadly?

Yes, broadly it was extremely positive meeting, I think, across all of the different things that you would speak to in terms of the nonclinical data The clinical plan for the clinical trial was endorsed CMC in terms of our plan. So that was endorse the using beta circular glycan as a surrogate biomarker for accelerated approval.

Was endorsed. So it was a very positive meeting that the agency certainly understands and ultra rare diseases the challenges that are faced with that in terms of trial design. In terms of manufacturing, So we've already set the stage for the other follow on Circle Glicin. So I think it bodes well for the entire platform. And we've we're certainly encouraged by it and certainly seeing a change in the agency over the last two years and really promising and that's something we look forward to as we complete the other two stargagliagans as well. And I do want to say, we are very proud of I am very proud of the work that Luis and her team have done, work with the agency to evolve and modernize the approach to ultra rare disease and it's paid dividends for the limb girdle programs not only 9,003 b and beyond. But I also want to give credit to the division itself. I have to say, the Center Director of Doctor. Marques has had a vision for being thoughtful and modernizing the division and comporting with modern science and not creating barriers that make it unviable to treat ulcerative air disease patients.

And I think that Doctor. Verdun, the Head of OTP has done really an exceptional job of taking that vision and operationalizing it in ways that we're seeing and I think others are seeing as well. Which as we think about rare disease day, coming up on Friday and I think we said some really brilliant thoughts on that. Mean, just plain and then I think we're moving in the right direction as a people to be able to a better life to patients with ulcerative care disease. And I give enormous kudos to OTP for playing their part in that.

Thank you. And our next question will be coming from the line of Salveen Richter of Goldman Sachs. Your line is open.

Thanks for taking our questions. This is Tommy on for Salveen.

Just overall, what do you see as Arrowhead's differentiation in terms of kind of their chemistry or structure versus some other RNA approaches in DM1 and FSH And on ellevitib, is there flexibility to expand upon existing infusion center capacity? Including, for instance, staffing needs? Thank you.

I'm going to turn the first part of the question to Luis. Let me briefly talk about Alevitas. So what we really need to understand is that this is a very detailed cadence from beginning to get a kid dose. So site capacity isn't alone. The issue People often say, well, why what if you found a way to have more and So then you need more single case contracts, then you need to think about back in the finance function, what are the credit limits associated with all of that. So it really is just a certain cadence. The thing that I'm excited about is team and really become experts in that cadence and that's why we're able to provide guidance at three billion dollars for the year because the team's figured out. But that is the cadence is the cadence. And I don't think the opportunity for dramatically changing that exists. And with that, I'll turn the first part of the question over to Luis.

Yes. On Arrowhead, the think the comprehensive answer is that Arrowhead is focused on every aspect of the construct. And so we like the diligence of their approach. I would like to call out their targeting ligases as being a differentiator because getting to the right tissue in the case of muscle for FSHD and DM1 using the [indiscernible] targeted ligand that we use the same one with MYO AAV, for example. We know that it works well in muscle. So that's a differentiator. But they focus on the design from the siRNA, from the the targeting ligands, from every aspect of the construct. And so we just comprehensive diligent approach, it's something that we model with gene therapy, for example. And so I think it's all of the above, but we certainly appreciate their targeting ligands for the various tissues.

Thank you. And that concludes today's Q and A session. I would like to turn the call back over Doug Yrum for closing remarks. Please go ahead.

Well, thank you everyone for your questions this evening. We've had a really tremendous 2024 and a great Q4 of twenty twenty four. And as we track into 2025, things are going very well. There's a couple of things. We're obviously going to continue to drive this launch of Alevidis and the team has done a really great job on that. And I they will continue to do that We're going to continue to focus on our PMOs and ensuring that patients are benefiting from our PMOs over this year. And then we have more milestones to read out in 2025 than any other time in our history. And so I look forward to updating folks across this year as we move forward with the girdles as an example, we get the FSA data and we get the DM1 data and then we keep driving as an organization. So thank you all very much and have a wonderful evening.

This concludes today's program and thank you for joining this conference call.

You may all disconnect.