Good afternoon, ladies and gentlemen. Welcome to the Sarepta Therapeutics First Quarter 2022 Earnings Call. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Mary Jenkins, Senior Manager, Investor Relations. Please go ahead..

Thank you, Chloe and thank you all for joining today's call. Earlier today, we released our financial results for the first quarter of 2022. The press release is available on our website at sarepta.com and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon.

Joining us today on the call are Doug Ingram, Ian Estepan, Dallan Murray and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements.

Please take a moment to review our slide on the webcast which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control.

Actual results could materially differ from these forward-looking statements and any such risks can materially and adversely affect the business, the results of operations and trading prices for Sarepta's common stock.

For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q filed with the SEC as well as the company's other SEC filings.

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

Doug?.

Thank you, Mary. Good afternoon, everyone and thank you all for joining Sarepta Therapeutics first quarter 2022 investor conference call.

As you will have seen from our press release issued earlier today, Sarepta enjoyed yet another straight quarter of strong revenue growth for our three approved therapies, EXONDYS 51, VYONDYS 53 and AMONDYS 45, achieving total revenues of $210.8 million in net product revenues of nearly $190 million.

Our net product revenue performance represents an impressive 50% growth over the same quarter last year led by AMONDYS, each of our three therapies contributed to our outsized growth over the same quarter prior year. While I have said it many times, it does indeed bear repeating.

We have achieved over five years of sustained growth with a compounded annual growth rate of nearly 40% and we've done that without a single price increase and by pricing all of our therapies at Parab or said another way, our consistently strong performance, come serving the patient community and it reflects the value that these therapies bring to individuals living with Duchenne.

Based on our performance to date, we can confirm our prior guidance of net product revenue of over $800 million for full year 2022, translating into product revenue growth of over 30% over 2021.

Our Chief Customer Officer, Dallan Murray, will provide additional color on our performance in a moment; and our CFO, Ian Estepan, will provide an update on our financials. In the first quarter, we continued to advance our large pipeline of potentially life financing therapies focused on rare genetic diseases across our three platforms.

As you know, that's RNA, gene therapy and gene editing as well. As you know, we are now in pivotal trials for our lead programs in both our gene therapy and our RNA platform. With respect to our gene therapy platform, we continue to initiate sites globally and to dose Embark, our 120-patient pivotal trial for SRP-9001.

SRP-9001 is Sarepta's gene therapy largely agnostic mutation to treat Duchenne by delivering a truncated but functional version of dystrophin. EMBARK is well powered and informed by the wealth of positive expression, safety and functional evidence that has come from previously dosing over 80 patients across three studies.

As I've said often, you should assume that the success in EMBARK, a well-powered Phase III pivotal study, will be our path to a successful launch of SRP-9001 in the United States and around the world.

As I've also confirmed in the past, we are exploring with the FDA the possibility of a more expedited BLA filing for SRP-9001, anticipating your question. We will provide an update once those discussions are completed and will not provide additional color until that time.

But again, for now at least, one should assume that EMBARK which will read out next year, is our pathway to approval. As we continue enrollment of EMBARK, we are also leveraging our world-leading gene therapy platform to advance our stick LGMD candidates, all of which share the same Rh74 vector and many of the same promoter as SRP-9001.

On the RNA side, we are enrolling and dosing in momentum Part B, our pivotal trial for SRP-5051, our next-generation RNA-based PPMO for the treatment of Duchenne patients amenable to skipping exon 51. We are particularly excited to move momentum forward given the results of Part A.

In Momentum Part A, we were encouraged to see 18x greater exon skipping and 8x greater district than over a Teperson and we saw it in half the time and at 1/5 the drug exposure. It confirmed Momentum Part B, SRP-5051 could be a profound and proved over the current standard of care.

At the same time, we are progressing the preclinical work for additional PPMOs to treat a much greater percentage of the Duchenne population than we currently treat. Our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Klapac, will provide additional color on the performance of our R&D pipeline and readouts in the first quarter in a moment.

Now I recognize that for many biotechs and for those that invest in them, the last 15 months or so have been challenging and some biotechs have particularly struggled in response to external environment. We feel no shame and sorry for that but Sarepta remains, on the other hand, in a very strong position despite the external environment.

We continue to enjoy strong revenue growth well on our way to eventually achieving that vaunted $1 billion in yearly revenue milestone. We entered 2022 with over $2.1 billion on our balance sheet. And even as we have aggressively invested in our pipeline, we exited the first quarter with over $2 billion in cash.

Our pipeline continues to perform and we are in pivotal trials with potentially transformative therapies in both our RNA and our gene therapy platforms and we have one of the strongest and most operationally excellent teams in all of genetic medicines. And with our success, we're not standing still but we are growing.

In addition to the expansion of our genetic therapy center of excellence in Eastern Ohio, we are building out a new 288,000 square foot facility in Bedford, Massachusetts where we will centralize our efforts, including RNA research and process development function, translational biology, gene therapy process development and quality control and we're building early phase GMP gene therapy manufacturing capacity that will help accelerate our future programs.

And we continue to grow and add best-in-class talent as well. In 2022, we will add another 40% to our employee base, the bulk of whom will be in research development, regulatory affairs, clinical development and technical operations. And with that, let me turn the call over to our Head of R&D and our Chief Scientific Officer, Dr.

Louise Rodino-Klapac for an update on our research and development activities.

Louise?.

Study 101, Study 102 and Study 103, having dosed 85 patients across these studies. Based on these results, we would expect the treatment benefit to continue to increase over time due to the progressive nature of Duchenne.

Across these studies, we have seen sustained functional improvements as compared to natural history, with the longest now in year four of follow-up. And notably, the safety profile has remained consistent across different patient ages and weights.

We continue to generate data from Studies 101, 102 and 103, including two year data from Part 1 of Study 102 and one year data from Study 103. As we have mentioned on our fourth quarter call, we plan to perform an integrated analysis of the one year data for Studies 101, 102 and 103 for all patients who received the target dose.

Our plan is to share the totality of these data with regulators and present all of these results at a medical meeting later this year.

In parallel, enrollment in EMBARK for our Study 301, our 120-patient global, multicenter, double-blind, placebo-controlled Phase III trial evaluating commercially representatives SRP-9001 material in patients with Duchenne between the ages of four to seven remains on track. We expect to have this trial fully enrolled in the middle of the year.

Now, continuing with our gene therapy franchise. For SRP-9003 and our other LGMD programs, we continue to make good progress with respect to building our manufacturing process, including assay development and validation. When we're ready to test commercially represented material in a clinical trial, we will discuss the study design with OTAT.

Moving now to our RNA-based platform. For our next-generation PPMO program, SRP-5051 in development to treat individuals with Duchenne amenable to exon 51 skipping, enrollment continues on pace for Part B of the MOMENTUM study.

To remind you, MOMENTUM Part B is a multi-arm global ascending dose study of SRP-5051 used monthly, assessing dystrophin protein level and skeletal muscles following SRP-5051 treatment. As we've guided previously, we anticipate Part B to be fully enrolled in the second half of 2022.

If the trial is successful, we anticipate Part B will serve as a pivotal study for SRP-5051 and we plan to seek accelerated approval. Now turning to some updates from the 2022 Muscular Dystrophy Association Annual Clinical implied to the conference that took place in March.

We shared data from across our private finance conference, included three podium and 10 poster presentations. Notably, for the SRP-9003 program for lead gene therapy in development for the treatment of limb-girdle muscular dystrophy Type 2E, or LGMD2E, we reported new data from the two dose cohorts in Study SRP-9003 and 101.

We also shared the full results from EXPLORE DMD, a study to assess the rate of preexisting antibodies to the AAV and Rh74 vector and individuals with Duchenne.

For Study SRP-9003-101, we presented three year functional and three year biopsy data from Cohort 1, the low-dose cohort and two year functional and biopsy data from Cohort 2, the high-dose cohort.

From a safety standpoint, since gene therapy is only dosed one time, the adverse events that were typically observed during the first few months after dosing. Therefore, as expected, we did not observe any new safety -- significant drug safety events at year three.

These results continue to reinforce the favorable safety profile therapies that use the AAV-Rh74 vector which also as read to other gene therapies administered with this vector.

In terms of the durability of therapy, the results show that the persistence of the SRP-9003 vector in transfused muscle continues to drive meaningful levels of beta-sarcoglycan protein expression over time, leading to sustained improvements in functional outcomes.

We are very pleased with these results because of the potential reach to our portfolio of five other LGMD programs which all share the same AAV rh74 vector.

These data are also important for the research for ongoing SRP-9001 program for Duchenne because the SRP-9003 program uses the same AAV rh74 vector and HDK7 promoter and design and approach of SRP-9001.

As we add to the growing body of clinical evidence for these programs, supportive, consistent, safety and durability data for one program has read through to the platform. Also presented at MDA were data from EXPLORE DMD, a study assessing the rate of preexisting antibodies to the AAV rh74 vector in individuals with Duchenne.

The final results demonstrate that the majority of patients screened, 86.1% were seronegative, meaning they have a titer of less than 100 to 400 for anti-AAV rh74 total binding antibodies. This low [indiscernible] problems to antibodies against AAV rh74 reports the broad applicability of AAV rh74-based gene therapy for patients with Duchenne.

The findings of this study are important for several reasons. Because pre-existing antibodies against AAV vectors can hamper this therapeutic efficacy and potentially pose a safety concern, the comparatives that we have a reliable way to prescreen individuals before they receive gene therapy.

Additionally, our goal is to treat all individuals with Duchenne. The ability to better understand the population with preexisting antibodies allows us to target our research and development efforts by novel ways to knock down three existing antibodies, so that these individuals could be eligible to receive therapy in the future.

Further, our comprehensive approach of measuring total binding antibodies may help improve the safety and efficacy of AAV-based gene transfer therapy. The results of seroprevalence study have also been observed in [indiscernible], including for the EMBARK study for SRP-9001.

We believe our observed low screen uprate will allow more patients to be eligible to receive SRP-9001 compared to other gene therapies. As I conclude today, I'd like to thank my Sarepta colleagues who remain grounded in our mission to translate the very best sites into the very best treatments for patients in the shortest time possible.

Thanks as well to our partners in science, clinical trial investigators and the patient community for their dedication. I will now turn the call over to Dallan for an update on our commercial activities.

Dallan?.

Thank you, Louise and good afternoon, everyone. Driven by continued demand for our three RNA-based PMO therapies, I'm pleased to report that the team delivered approximately $190 million in net product revenue for the first quarter of 2022.

This performance represents more than 50% growth, or greater than $60 million in net revenue growth over the approximately $125 million in net revenue for the first quarter of 2021.

For the first quarter of 2022 compared to the first quarter of last year, we delivered nearly 10% growth for EXONDYS 51 and more than 60% growth for VYONDYS 53, while maintaining our market leadership position in the exon 53 amenable population. The performance of a modest 45 continued unabated in the first quarter of 2022.

With 22 quarters of consecutive quarter-over-quarter growth, it is tempting to gloss over the day-to-day challenges the team has overcome to deliver on our objectives. I'll take a moment to elaborate.

Firstly, as we come to expect through our deep experience in serving the Duchenne community and consistent with our historical experience, insurance changes at the beginning of each year impacted our revenue across all three therapies.

Second, we saw competition for newly diagnosed patients in the four to seven year-old range from our own EMBARK trial for SRP-9001. We plan for this issue and factored it into our 2022 guidance.

This competition disproportionately impacts EXONDYS 51 and VYONDYS 53 due to our penetration in these populations and subsequent reliance on these patients for new starts.

Lastly, in addition to facing competition from the EMBARK trial, we are also actively enrolling exon 51 amenable patients in our MISSION study and Part B of the MOMENTUM study to support the approval of our PPMO candidate, SRP-5051.

Our performance for the first quarter is even more impressive in light of the fact that all of this competition is from our own R&D group. We expect the pressures from clinical trial enrollment will persist for the remainder of the year but we remain comfortable with our 2022 net product revenue guidance of over $800 million.

I'll now outline individual net product revenues for the first quarter for each of our three approved RNA-based PMO therapies.

Beginning with EXONDYS 51 which totaled roughly $117 million, representing approximately 9% growth over the first quarter of 2021, you'll notice the revenue dipped slightly compared to the fourth quarter of 2021 but this is expected and primarily driven by the insurance changes at the beginning of this year.

By the end of the first quarter of 2022, the team had worked through this challenge and we are now exactly where we forecasted we would be at this point in the year. The expectation for the remainder of the year is a return to the modest growth trajectory for EXONDYS 51.

For VYONDYS 53, revenue totaled approximately $28 million, representing roughly 60% growth versus the first quarter of 2021. As we have noted previously, the smaller revenue for VYONDYS 53 when compared to AMONDYS 45 is primarily driven by a larger-than-expected exon 45 amenable population compared to the exon 53 population.

This is also consistent with what we've seen in clinical trials. In general, we're pleased with the performance of VYONDYS 53 and particularly our continued leadership position within the exon 53 amenable population. For AMONDYS 45, revenue totaled nearly $44 million, representing greater than 25% sequential growth over the fourth quarter of 2021.

The team continued to execute in the launch phase of AMONDYS 45, driving both patient identification and also working hard to gain access for the patients who have already submitted start forms. We expect the growth of AMONDYS 45 to continue in the coming quarters.

I'm proud of this successful start to 2022 and of our dedicated and highly motivated team who work every day to execute on our mission and support the nearly 30% of patients who are amenable to one of our three approved RNA-based PMO therapies.

With a fully integrated biotechnology company focused on Duchenne and other unmet needs in precision medicine, we look forward to working closely with our R&D colleagues as they discover and develop therapies such as SRP-9001 for an even larger proportion of the Duchenne population as well as advancing our deep portfolio of therapies in gene therapy, RNA and gene editing.

And now, I'll turn the call over to Ian Estepan for an update on our financials.

Ian?.

Thanks, Dallan. Good afternoon, everyone. This afternoon's financial results press release provided details for the first quarter of 2022 on a non-GAAP basis as well as a GAAP basis. Please refer to the press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results.

For the three months ended March 31, 2022, the company recorded revenue of $210.8 million which consists of net product revenue and collaboration revenue compared to revenue of $146.9 million for the same period of 2021, an increase of $63.9 million.

Net product revenue for the first quarter of 2022 from our PMO exon skipping franchise was $188.8 million compared to $124.9 million for the same period of 2021. For the first quarter of 2022, individual net product sales were $117.1 million for EXONDYS 51, $43.6 million for AMONDYS 45 and $28.1 million for VYONDYS 53.

The increase in net product revenue primarily reflects higher demand for our products and a full quarter of AMONDYS 45 sales during the three months ended March 31, 2020, given its commercial launch in February of 2021.

And as noted earlier in the call, we are reiterating our 2022 total revenue guidance of greater than $880 million for our net product revenue guidance for our RNA franchise of greater than $800 million.

In each of the quarters ended March 31, 2022 and 2021, we recognized $22 million of collaboration revenue which relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $17.7 million for the first quarter compared to $13.4 million for the same period of 2021.

On a GAAP basis, we reported a net loss of $105.1 million and $167.3 million or $1.20 and $2.10 per basic and diluted share for the first quarter of 2022 and 2021, respectively.

We reported a non-GAAP net loss of $48.6 million or $0.56 per basic and diluted share in the first quarter of 2022 compared to a non-GAAP net loss of $114.5 million or $1.44 per basic and diluted share in the first quarter of 2021.

In the first quarter of 2022, we recorded approximately $31.4 million in cost of sales compared to $22.3 million in the same period of 2021.

The increase in cost of sales is primarily due to increasing demand for our products, partially offset by write-offs of certain batches of our products not meeting the quality specifications for the three months ended March 31, 2021, with no similar activity for the three months ended March 31, 2022.

On a GAAP basis, we recorded $194.3 million and $195.1 million in R&D expenses for the first quarter of 2022 and 2021, respectively, a year-over-year decrease of $800,000.

This decrease is primarily due to decreases in market research with academic institutions and decreases in upfront and milestone expenses during the first quarter of 2022 compared to the first quarter of 2021.

On a non-GAAP basis, R&D expenses were $173.2 million for the first quarter of 2022 compared to $177.5 million for the same period of 2021, a decrease of $4.3 million. Now, turning to SG&A.

On a GAAP basis, we recorded approximately $71.8 million and $71.1 million of expenses for the first quarter of 2022 and 2021, respectively, an increase of $700,000. The increase was primarily driven by an increase in professional service expenses.

On a non-GAAP basis, the SG&A expenses were $53.2 million for the first quarter of 2022 compared to $51.5 million for the same period of 2021, an increase of $1.7 million. On a GAAP basis, we recorded $17.3 million in other expenses, net for the first quarter of 2022 compared to $15.5 million in other expenses and that for the same period of 2021.

The increase primarily reflects an increase in our mark-to-market adjustment on our strategic investments during the three months ended March 31, 2022, compared to the same period of 2021. We had approximately $2 billion in cash, cash equivalents and restricted cash and investments as of March 31, 2022.

Based on our current assumptions, we believe our balance sheet provides us runway beyond the readout of Study 301 and into 2020. And with that, I'll turn the call back to Doug to start the Q&A.

Doug?.

Thank you very much, Ian. Chloe, let's open the line for questions..

[Operator Instructions] And we'll take our first question from Colin with UBS..

And congrats on all the progress. Doug, maybe you could just give us a quick update on when you expect to meet with FDA regarding the path forward of volume strategy for 9001. It seems that hasn't happened yet. And then, just quickly on your competitor, Pfizer, they're about to initiate trials in the U.S.

And so I just wanted your update thinking on how you view them as a competitor from a timing and, I guess, clinical profile perspective..

Yes. Colin, thank you very much for both of your questions. And actually, particularly appreciate the first one because it gives me the opportunity to answer this for everyone. The short answer is that, as I've said before, I said in the prepared remarks and I'm going to be consistent about this, we have said that we are going to talk to the FDA.

I -- and we will provide an update once we have concluded those discussions. And I would prefer not to provide additional color until we have all of those discussions completed and we are in a position to provide an update. And then I promise you all, we will provide an update.

In the interim, as I've said many times, the EMBARK is a very well-powered placebo-controlled study. We're very excited about it. It's recruiting and dosing and we're getting additional sites up and running literally on a weekly basis. And that will enroll around the middle of this year and then we will have a readout next year.

And that ought to be the assumption of our pathway to approval, both in the United States and around the world, unless and until we hear something different. As it relates to Pfizer, yes, we did see that Pfizer announced that it would recommence it’s study that had been placed on clinical hold for safety reasons.

Previously, it doesn't affect us is the short answer. We're focused on our program. We're focused on enrolling EMBARK. We're very, very excited about EMBARK. EMBARK's protocol is -- enjoys a very straightforward entry criteria and the like.

It is almost everywhere in the world, an outpatient protocol which will benefit not only the enrollment of EMBARK but will certainly benefit the label for EMBARK as well. And also, I'm very happy to say, it enjoys a relatively very low screen-out rate.

As you know, the screen-out rate for SRP-9001 and rh74 is less than 15% and that does not appear to be the case with other constructs. So we're very focused on our program, very focused on continuing EMBARK. And I think that we see as our primary competitor, Duchenne muscular dystrophy and we take that very seriously.

We're going to get EMBARK fully enrolled and then we're going to get that read out. We have a high conviction on the success of that therapy and then we're going to get that therapeutic kids in the United States and around the world with the success of EMBARK..

[Operator Instructions] We'll move now to Brian with RBC Capital Markets..

I think there's maybe a little bit of confusion around Phase III time lines. I was hoping you could clarify. It sounds like 9001 enrollment is on track for mid this year.

So when one considers screening and data analysis, should we be expecting top line data release around mid-2023 or closer to year-end? And then maybe on a similar note, on the registrational path for 9001, I recognize you aren't in a position to comment on the specifics of ongoing FDA dialogue.

But just taking a step back, should we be thinking about this as accelerated approval or full approval? Or are there any middle ground expedited scenarios we should contemplate such as maybe rolling BLA with existing data and integrated one year analysis that you could update at the end of the submission with the EMBARK data when that becomes available?.

Yes. So this -- so EMBARK is a 52-week study. So if we're fully enrolled around the middle of this year, that means we'll have data by around the middle of next year. And of course, then, we'll have to ensure that we get it collated and quality controls and all of the data, including the secondary endpoints, the biomarkers done.

So I'm sure it will be in the second half of next year. And then our goal is to file soon thereafter as possible and our goal is to file in 2023. With respect to -- so again, I'm going to be careful. I'm not going to provide update, so we have something to update on.

EMBARK is -- the goal of EMBARK is a full approval, just so we're very clear about that, not looking to EMBARK for instance, with an accelerated approval. We intend to have dialogue with the division at the FDA about the potential for a faster approach.

The most obvious faster approach would be the use of the accelerated approval pathway to bring this therapy to patients. We certainly think the data justifies that dialogue. We have three studies of data. We have exceptional expression. We have a very good and very superior safety profile.

We have very consistent functional benefits across all of the studies. So I think that dialogue makes a ton of sense for us but we'll provide an update on the outcome of those discussions when they are completed..

And we'll move next to Judah with Credit Suisse..

Just one on kind of time lines for Study 103 data readout. I think you've said that FDA would get that one year data before kind of it is shared publicly.

So should we expect that we'll get one year 103 data with the FDA conversation update? Or could that be reported before that potentially?.

We will -- we're at a medical meeting this year, Louise and team are sort of mapping it out right now. We will provide an update on SRP-9001. It will include some data from 103.

It will include two year data for 102 Part 2, some additional very interesting information, including an integrated analysis across our studies and that will be -- that will occur this year. We don't have the time to share yet with it but the team is working on that..

And we'll move next to Gena with Barclays..

This is Sheldon [ph] on for Gena. Maybe just two quick ones.

On the approval pathway for 901 outside of U.S., particularly in Europe, do you have any feedback from EMA on the approval requirements? Is it only pathway for a full approval? Or is there any other possibility for expedited process? And another question is on the related regulatory and sales milestone that you can receive from Roche.

I remember the total amount is $1.7 billion.

Could you give us some color on the breakdown of regulatory versus commercial milestones there?.

Sure. I'm going to leave the second question to Ian, who will answer consistent with what we said historically in the past. With respect to Europe, I just want to be respectful of our very good partner Roche and not step in front of them.

I will note, just simply noting the theoretical level that there, of course, is the opportunity for getting into sort of traditional approval in Europe and there is a more expedited pathway.

It's different than the United States but there is a conditional approval pathway that exists in Europe and I'm sure we'll be thinking creatively together about which of those pathways makes the most sense for the patients that we serve. And Ian, with that, you might want to touch briefly on milestones..

Yes. As it relates to the milestones, we haven't broken out the exact details between the split between commercial or regulatory. But the question we often get is in terms of timing and that is going to be very late in the either regulatory framework or obviously a post launch that will be the back end loaded milestone payments. .

And we'll take our next question from Brian with Baird..

So just going on to the Pfizer recent announcement, I know that they're moving back into the clinic in the U.S. But moving into the chronic sounds like there's some restrictions or believe someday hospitalization period post dose.

I was just wondering, can you remind us of any sort of protocol requirements 9001 has proposed dosing? Is there an overnight observation period or any sort of mandatory post-dosing observation period?.

Yes. Other than in Japan, everything is outpatient. Physicians obviously have the discretion if they want to keep a child overnight if they want but it's outpatient dosing and everywhere budget. So it's very different than the Pfizer protocol.

And I'm sure it's informed by the experience that we both had with these therapies and the safety profile of relative therapies..

Our next question comes from Gil with Needham & Company..

And congrats on the progress in this quarter. Just a quick one from us.

So assuming Pfizer is going to be opening starts in the U.S., doesn't that exacerbates the competition for patients that usually go on EXONDYS, if you have any commentary around that?.

I think that the greatest competition for EXONDYS is Sarepta. I think as Dallan noted for you earlier, EXONDYS in the United States competes with EMBARK. It competes with Mission. And I'm trying to remember, there's a third one. Dallan, you'll have to help me with it….

Momentum?.

And Momentum, of course, Momentum for PPMO 5051. But notwithstanding all of that and that existed, of course, tracking into this year, EXONDYS grew fairly substantially versus the first quarter of last year versus the first quarter of this year. And our guidance for the year has that in it. So we're not particularly concerned about it.

And then on the competition for patients for our relative gene therapies, without being excessively snarky, we are not at all concerned about the demand that we have for SRP-9001 and EMBARK..

And we'll move next to Ritu with Cowen..

This is [indiscernible] for Ritu. Two quick questions from us.

What updates are you presenting at the ASGCT this month and maybe PPMO also in June? And then when should we expect top line data from the MOMENTUM study?.

Louise, do you want to take that?.

Yes. At the ASGCT, we are presenting preclinical data on cardio outcomes for 9001. And then we'll be doing follow-up presentations for clinical programs consistent with we've done previously. But we don't have -- our outlines for PMT. .

We'll move next to Hartaj with Oppenheimer & Company..

Great. Just focusing in on PPMO, your part of your study actually had bores, most of the world with the age of 8, averaging 11, 13, 10 years. I think you just mentioned that you're seeing about 80%, 85% of patients without -- that are still negative for AAV rh74.

Can you talk about your PPMO opportunities in the context of older boys, also XES and then maybe boys that might not get gene therapy?.

Yes, Hartaj. Thanks for that question. I mean one of the answers to that question right now is that we don't know with certainty what the impact will be on the PMO and PPMO from the launch of gene therapy.

And I think one of the things I've said in a prior earnings call was making what I think is a relatively conservative assumption that there's going to be a pretty significant amount of cannibalization of the RNA technology, PMO and, maybe to a lesser extent, PPMO from gene therapy.

But to your very good point, I think there's reason to believe that's successively conservative. First, let's start with the fact that there will be about 15%, hopefully a little bit less than that, really slightly under 14% of our sterile prevalence study tells us that will screen out.

And so we have solved the issue of backing down treatment in neutralizing antibody. We'll screen out for gene therapy. There may be older children that have an opportunity to get on an RNA technology before they're able to get on a gene therapy. And so that opportunity will exist as well.

And I think there will be geographic areas that having -- I have worked in countries outside of the United States. I've launched products outside of the United States.

The vagaries of the various systems outside of the United States are different region to region and sometimes not perfectly aligned with what you might think is perfect in economic stance but you have to do with budgetary issues and yearly budgets versus longer budgets.

And I think there is a real opportunity geographically as well to offer some patients the PPMO or PMO as well. So I think there is a real potential, even if there's not co-dosing for a significant amount of the use of the PMO and when the PPMO is approved the PPMO and that's why we're going so strenuously forward with the PPMO, just to let you know.

We will just about double the number of patients that have a PMO available to them with the PPMOs that we're working on preclinically right now.

And all of that is before another theme which is the concept that we might be able to provide even greater longer-term benefit to patients through the use of a onetime therapy SRP-9001 and then a chronic therapy thereafter. There are issues associated with that. First, we need the science to support that conclusion.

And then we've got to do the pharmacoeconomic work to justify that concept. But I think there's a lot of potential promise with our PPMOs and that's why we're so excited about it. And with that said, I'm going to turn it over to LRK with a piece of this answer as well, if I'm not mistaken..

Actually, I missed the second half of the previous question. It was about the readout for Momentum. The Momentum study Part B is expected to complete enrollment at the end of the year. It's a 20-week -- 28-week endpoint, so we expect to present the top line data in 2023. Sorry for missing that question..

And we'll move next to Joseph with SVB Securities..

I was wondering if you can speak to the steroid treatment regimens being used in EMBARK and how balanced they are between the treatment and placebo arms? Are there any key differences? And are you doing anything to enhance the interpretability of the data and the contribution from 9001 in these patients when you report the data?.

Thanks, Joe. I'll give the board spoke answer and then let if they're a new one that I missed we tell you but the answer is there identical across both ops placebo-controlled trial, all kids are on stable steroids before they enter the trial. And then they both get the same regimen of termers, including the same regimen of pre-dosing steroids as well.

At least if there's any nuance that I've missed out..

That's accurate. It's actually the same. .

And we'll move next to Tim with William Blair..

And I promise I won’t ask an FDA question but maybe one on the base business. You mentioned that the exon 45 amenable population is larger than maybe originally expected. Can you dig into that a bit? Maybe how many patients do you expect a few years ago? What's your current thinking? And is this something that's also kind of an ex U.S.

phenomenon or just U.S.?.

Well, it's definitely -- whatever this phenomenon that we're seeing and then Dallan, you can take it from where I end [indiscernible], whatever we're seeing is definitely not a U.S.-specific issue because we've seen it in the U.S., we've seen it in Europe as well.

And how is that the case? It's because why would we have seen it in Europe because we have assets in Europe.

And one of the things we noticed fairly early on and it caught us off -- surprised us, was that enrollment for exon 45 went very fast relative to what we would have expected from our experience with VYONDYS which began to give us the view that there is perhaps a difference in the]indiscernible] versus what we thought.

And then, of course, we've launched the commercial therapy and the uptake has been tremendous. I do want to say -- I do really want to say significantly to our field-based force, our commercial colleagues, our medical affairs colleagues that a lot of that has to do with execution. We have gotten better and better and better.

Just me linger on that for a second to make the point. We have now had cumulative $2 billion in sales. We've already achieved that as an organization. We achieved the second $2 billion in -- significantly less than half the time of the first $1 billion.

And I think a lot of that has to do -- some of that, of course, has the approvals, some of it has significantly to do with execution. The team really knows how to serve these patient communities. None of it, by the way, has to do with pricing because it's because we don't take price increases. We certainly have not yet since the inception.

So as we look across it, we don't know with certainty yet what the prevalence rate is, the years between these two. But I think there are some studies. There is a study, if I'm not mistaken, down in Canada that would have put -- it was then consistent with what the sort of the common belief is but put exon 45 maybe up even above 10%.

But we're not standing behind that yet; we don't know. But Dallan, perhaps you have more insight into this provided..

Yes. No, as just exactly what Doug has said and thank you for the question, by the way, I think, historically, all of the epidemiology that we were looking to show that the two populations, the exon 53 amenable population and the 45 amenable population, were the exact same size.

And as Doug explained, the first hint that we got that this wasn't the case were -- was in our clinical development program. And what we saw in the clinical development program is exactly what we see playing out right now in the commercial market. And so, that was -- our assumptions were based on the older initial epidemiology.

And as Doug said, there are some new publications that are more in line with what we saw in the clinical development space and what we're seeing in the commercial market. So we're continuing to look at this as we go. There's no -- nothing obvious in terms of differences originally.

As Doug said, in the clinical development program, that enrollment was a global trial where we saw the same phenomenon. That's what we're seeing in this U.S. market. Again, thanks for the question..

[Operator Instructions] We'll move next to Kristen with Cantor Fitzgerald..

Want to ask one around longer-term plans of the company.

So if you see this cannibalization around gene therapy and are able to solve the problem for the 15% or so of patients with preexisting neutralizing antibodies, given the success you've seen, would you consider utilizing the PPMO platform for other potential indications or areas beyond DMD?.

Absolutely, we're exploring that preclinically right now. But perhaps, Louise is going to provide a bit more color on that..

Thanks for the question. We're extremely excited about the opportunity for PPMO, both in additional excellence in Duchenne but then also other indications which include muscle but also include other targets based on the PPMO's ability to penetrate other this issue.

So more to come on that but we're certainly very excited about the opportunity for multiple indications for PPMO..

And we'll take our next question from Yun with BTIG. .

So my question is on the LGMD program.

And sorry if I missed -- if you had provided an update but what about the next step and also the time line? Are you still working on the CMC issues? And so do you have a plan to move the 2E program forward? Or do you think given the prevalence that a basket study will make more sense than you're trying to align with the FDA on that plan, please?.

Yes. So first of all, we are definitely exploring the concept of a basket study which could be very interesting for us, or at least a basket approach for all of the sarcoglycan. But that isn't delaying our activity with respect to LGMD2E and SRP-9003. With respect to SRP-9003, the rate limiting step is CMC.

I want to be very clear about what kind of CMC. It's not really the process of element at all. In fact, we've manufactured therapy. So it's not about that and we've really benefited from all of the work we've done with SRP-9001. It's the analytical work and getting all of the assays together.

One would assume that you could have sort of generic assays across multiple programs. Such is not the case. There are a number of different assays that require them to be bespoke for each particular therapy. The good news is we know exactly how to do it. We've done it with 9001 to great effect. We don't have to guess about that.

The process takes some time. It's a combination of design but it's also testing and [indiscernible] and then testing. So it's moving along nicely, not ever as fast as I would want but I don't think there's anybody at Sarepta that thinks that I'm patient about anything. But it's just going to take a little bit of time but we're on track.

We just have to get the assays complete.

Louise, have I missed anything?.

No. That's accurate. I just will add that we are actively enrolling our natural history study called Journey for LGMD. And so that will certainly support us in moving ahead for our next stage of the trial in terms of patient identification and also understanding the national history which will inform our design and that's enrolling well ..

And we'll take our next question from Zhiqiang with Berenberg Capital..

This is [indiscernible] for Zhi. I just wanted to ask a quick question.

Can you just provide a bit more color about your statement that you made about the cost of sales where you said write-off of certain batches of the company's products are not meeting its quality specification?.

Sure. I'll turn that to Ian.

Ian?.

Yes, that was just related to -- and this was, to be clear, related to our PMO franchise, that there were a few batches last year that didn't meet our standards. And therefore, we wrote them off. But nothing to -- it wasn't significant at all and it didn't have any major impact. And we saw none of that.

It just happens that some runs don't meet our qualifications. So from time to time, it happens. Obviously, we didn't see any this quarter..

[Operator Instructions] We'll move next to Gavin with Evercore ISI..

Just wondering what the status of the ESSENCE confirmatory trial enrollment was? If I look at the clinical trusted enrollment should be done soon..

We should be fully enrolled by the end of this year..

[Operator Instructions] We'll move next to Matthew, Morgan Stanley..

This is [indiscernible] for Matthew.

So we are wondering whether you already have adding regulatory discussions with the FDA about the LGMD program?.

The LGMD program. I'm sorry, go ahead. Apologies..

Yes.

If so, then, what the minimum requirement you are expecting from the regulation?.

So apologies for having interrupted you. Yes, so we haven't had actual meetings with them. We've had written responses from the -- from OTAT. It was, if I'm not mistaken, last year. We haven't updated it.

We're going to have one comprehensive discussion with them once the CMC issues are in a position where we can have a discussion with them, both about the clinical design as well as -- and show them the CMC and get their blessing on the manufacturing.

We had a general discussion with them in writing last year in which they -- and then independently, interestingly enough, Europe as well confirms the potential for the use of beta-sarcoglycan as a surrogate endpoint. We obviously have additional discussions that we need to have and more concrete discussion about the actual development program.

But certainly, conceptually, there was an acknowledgment of that possibility. And of course, it makes brilliant sense. To remind everyone, with respect to SRP-9003, that is a gene therapy that treats a very rare disease.

And it's a disease that's characterized -- well characterized by the fact that it is patients that are degenerating and dying as a result of the lack of a structural protein, beta-sarcoglycan. Given the size of that gene, SRP-9003 is able to deliver a construct that codes for the full length wild-type beta sarcoglycan properly localized.

And we're seeing very, very good expression. We're seeing the kinds of expression that we see with 9001. We're seeing the kinds of safety that we see with 9001. Clearly, rh74 is performing very well. And so the idea of using a more expedited pathway and using surrogate endpoints makes a ton of sense.

Now, we just have to get our CMC done and then we have to have some dialogue with the division and get their concurrence on the design of that next trial. Then we'll get going on it and hopefully get going on that and the other sarcoglycan as well..

And it does appear there are no further questions at this time. I would now like to turn it back to Doug for any closing remarks. .

Well, thank you all very much for joining us this evening and for your questions. We appreciate all of them. We're very excited about the progress that we've made.

We're very excited about our ability to serve the community that we serve and to continue to advance our research pipeline as we advance our development programs, including completing our pivotal trial enrollment for EMBARK and including completing our pivotal trial for Momentum as well.

And I look forward, on behalf of all of the team at Sarepta, to provide additional updates as we give additional progress over the course of 2022. Thank you all and have a lovely evening..

This does conclude today's program. Thank you for your participation. You may disconnect at any time and have a wonderful evening..