Sarepta Therapeutics (SRPT) Q4 2020 Earnings Call Transcript

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Sarepta Therapeutics (NASDAQ: SRPT)
Q4 2020 Earnings Call
Mar 01, 2021, 4:30 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics fourth-quarter and full-year 2020 earnings conference call. [Operator instructions] 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.

Mary JenkinsSenior Manager, Investor Relations

Thank you, operator, and thank you all for joining today’s call. Earlier today, we released our financial results for the fourth quarter and full-year 2020. The press release is available on our website at sarepta.com, and our 10-K was filed with the Securities and Exchange Commission earlier this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, Dr.

Gilmore O’Neill, 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.

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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 differ — 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 annual report on Form 10-K 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 CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

Doug IngramChief Executive Officer and President

Thank you, Mary. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics fourth-quarter and full-year 2020 investor conference call. I am pleased to share with you this afternoon that the progress that we have made across our multi-platform portfolio, including our performance serving the Duchenne community with our approved products; the work we are doing in gene therapy, including SRP-9001 for DMD; and of course, the advancement of our RNA platform. Now, we have an enormous number of important milestones in 2021, and I am very pleased that we have what I believe to be the strongest, most committed, and focused team in Sarepta’s history to advance toward our goals.

To remind you, in December of 2020, I announced that Dr. Louise Rodino-Klapac was named our chief scientific officer, taking charge of our research efforts across gene therapy, gene editing, and RNA therapeutics. Dr. Rodino-Klapac is a renowned leader in genetic medicine research and organizing all of our efforts under her stewardship will ensure we maximize the opportunities in front of us.

At the same time, I elevated to chief commercial officer Dallan Murray, a commercial leader with expertise second to none in rare disease, DMD, and our RNA franchise. And I also elevated Ian Estepan to CFO. Now, I’m sure you all know Ian well and will appreciate that his nuanced knowledge of our company and our programs is only matched by his passion and commitment to our mission and the DMD community. Finally, I am pleased to announce that I have elected Ryan Brown, formerly our chief compliance officer and then interim head of our legal and compliance function, to be our permanent general counsel.

I have known and worked with Ryan for many years. And his intellect, judgment, and commitment to ethics and compliance will serve us well as we advance over 2021 and beyond. Moving to performance. 2020 was a challenging year for all of us and for the patient community.

And launching a new therapy, VYONDYS 53, just as the pandemic struck was not without its obstacles. Nevertheless, our commercial team, in concert with medical affairs and our supply chain, rose to the challenges, worked to keep our patients safe and to ensure their access to therapy. So for the fourth quarter of 2020, we achieved $122.6 million in product revenue. That’s a 22.5% increase from the same quarter of the prior year.

For the full year, we achieved product revenue of $455.9 million, and that’s a nearly 20% increase over the prior year. You will also recall that our guidance for 2021 is in a range between $537 million to $547 million, so we continue the strong growth. And to remind you, we have priced all of our RNA therapies at parity, and we have not taken a price increase on any of our therapies since the approval of EXONDYS 51 back in 2016. So our growth comes directly from our ability to serve our patient community.

Now, moving to our RNA platform. As you will have seen, on February 25, the U.S. Food and Drug Administration approved AMONDYS 45. The generic name for that is casimersen, and that’s for the treatment of those Duchenne muscular dystrophy patients who have a mutation amenable to skipping exon 45.

AMONDYS 45, our third approved RNA therapy, will bring a treatment option to another 8% of the DMD community. Our three therapies together can treat nearly a third of all patients with DMD. And with our RNA-PMO technology, we should be able to build constructs that can ultimately treat more than 80% of all of DMD. In the fourth quarter of 2020, we announced preliminary but encouraging results for the 10 mg per kg and the 20 mg per kg cohorts in our multi-ascending dose study investigating SRP-5051, our therapy based on our next-generation RNA technology.

That’s the peptide-conjugated PMO or PPMO for short. The goal of the PPMO is to use a proprietary peptide to increase cell penetration, improving exposure, exon skipping, and dystrophin production and all with the goal of profoundly improving outcomes. We are on track to announce results from our next cohort at 30 mgs per kg in the second quarter of this year. Moving to our gene therapy platform.

As you know, we announced the results of Part 1 of SRP-9001 Study 102 in early January of this year. While we did not achieve statistical significance on our primary functional endpoint, we did gain invaluable insight and strong proof of concept on our secondary endpoints. So we are clear. The miss on statistical significance on the primary functional endpoint has required a change in adoption in our regulatory filing strategy, but it does not impact our confidence or commitment in the program.

Indeed, quite the contrary. Consider the following: while we achieved statistical significance on important biomarkers, western blot, protein-positive fibers, intensity, and creatine kinase reduction, we did not achieve statistical significance on our primary functional endpoint. However, when one looks to the prespecified subgroup analyses, the reason for this becomes immediately apparent. In the six- to seven-year-old age groups, the baseline characteristics were so enormously different.

The treated group was far more severe than the placebo group with a p-value of literally 0.017 at baseline, that we compared profoundly different populations, making statistical significance practically impossible and rendering those results uninterpretable. However, in the four- to five-year-olds, the baseline characteristics were properly matched. In fact, the baselines on every functional measure were nearly identical. And when they were appropriately matched, so we were actually comparing similar populations in our prespecified analysis, we strongly achieved statistical significance and clinically meaningful benefit of the therapy over placebo.

This is to be sure that the first time in the history of DMD development that in a double-blinded, placebo-controlled trial of DMD patients, a therapy has shown this sort of statistically significant and clinically meaningful benefit on NSAA in DMD. You better believe we continue to be confident in our therapy and in this program. Second, we now have more in-depth, patient-level insight into these age ranges and how they traject with micro-dystrophin than any other organization. And we will use this insight to refine our strategy and the protocol for our next trial, which we intend to commence this year.

We are not only confident in our construct. We are confident that the unique insight that we can apply to our next trial will give us a much greater probability of success and a competitive edge. Now, there’s a lot to do this year to advance SRP-9001. First, as you will recall, last year, we commenced what we call Study 103, and that’s our trial to evaluate our commercially representative material.

We announced at the J.P. Morgan conference that all of our initial 11 patients in that study have been enrolled and dosed. To better balance the number of four to five and six to seven ages in that study, we’ve updated our IND so we can add additional four- to five-year-old patients, and we’ll commence that enrollment and dosing soon. However, just so you’re clear, that will not delay the evaluation of and report out of the results of our first 11 patients in the second quarter of this year as planned.

Next, we will complete the valuation of Study 102. We will update our protocol for our next SRP-9001 trial. We will meet with the division to discuss and gain alignment on that protocol, and we aim to commence that trial this year. Our goal is to commence that trial around the middle of this year with enrollment complete by the end of 2021.

Our baseline assumption is that, if successful, this will be the study to support our approval in the United States and around the world. And finally, it is important to recall that Study 102 remains blinded, and the last patient/last visit for the full results from Part 2 of that study will occur before the end of this year. This will be an extremely important and insightful moment, and it’s going to provide us all with an enormous amount of information on the performance of SRP-9001. We will see the impact of therapy at 96 weeks in 20 patients who were dosed at enrollment.

And equally important, we will have 48-week results from those patients dosed at crossover. Those patients will have had a 48-week run-in period to judge trajectory before they were provided therapy and to compare those patients against natural history predictions. Already, we have substantially more insight and proof of concept on our program than any other constructs, and that insight will greatly expand with the readout of Part 2 of Study 102. Let me now comment briefly on SRP-9003.

That is our gene therapy intended to restore the protein beta-sarcoglycan in those patients who have limb-girdle muscular dystrophy Type 2E. Last year, we announced very positive results in our proof-of-concept study for SRP-9003 in both our low-dose and in our high-dose cohorts. We will be updating those results at the 2021 MDA Clinical and Scientific Conference in March. Our goal this year is to align with the FDA on the development path for SRP-9003 and to commence a pivotal trial this year.

We will schedule that meeting with the agency once we have GMP material released for use in our next trial. Those discussions will inform our development strategy for our other limb-girdle programs. And this year, we will complete toxicology studies for SRP-9004 and SRP-9005. Those are for limb-girdle type 2D and limb-girdle type 2C, respectively.

And we will commence a proof-of-concept study using material from Nationwide Children’s Hospital for SRP-6004. Our dual-vector therapy for the treatment of limb-girdle type 2B in patients that are missing dysferlin. Beyond these programs, we continue the focused advancement of our gene therapy, RNA, and gene editing research under Dr. Rodino-Klapac.

In summary, I am reminded of the importance of our mission by Rare Disease Day, which was recognized yesterday, February 28. With a ruthless certainty, every hour of every day, the rare disease patients that we serve are harmed and they worsen. And if we are serious about our responsibility, we have little choice but to be ambitious and to move with a sense of urgency to intervene. And when one is ambitious, there will be obstacles, as there was at the beginning of this year.

But as we have shown before, we know what it takes to address and overcome obstacles, and we are doing just that. I have a passionate, expert team that is moving our programs forward. With $1.9 billion of cash as of the beginning of this year, augmented by strong revenue to reinvest in our programs and a razor focus on our top priorities, we have the strategy, the talent, and the resources to execute. And we have a mission that motivates us to get up each day, to work hard, to solve problems, and to stay focused on the patients who will be the beneficiaries of all of that effort.

And with that, let me turn the call over to Ian Estepan, who will provide an update on the financials. Ian?

Ian EstepanExecutive Vice President and Chief Financial Officer

Thanks, Doug. Good afternoon, everyone. This afternoon’s press release provided details for the fourth quarter of 2020 on a non-GAAP basis, as well as a GAAP basis. The press release is available on our website.

Please refer to our press release for a full reconciliation of GAAP to non-GAAP financial results. We are pleased to announce that in conjunction with our recent AMONDYS 45 approval, we have sold the rare pediatric disease Priority Review Voucher or PRV for $102 million. We expect the transaction to close in the next quarter after all regulatory conditions have been satisfied. Now, moving to net product revenue for the fourth quarter of 2020 from our products EXONDYS 51 and VYONDYS 53 was $122.6 million, compared to $100.1 million for the same period of 2019.

The increase primarily reflects higher demand for our products. Going forward in 2021, we will be breaking out revenues for our RNA franchise, including EXONDYS 51, VYONDYS 53, and AMONDYS 45. And I’d like to remind you, as Doug mentioned earlier, our 2021 guidance for our RNA franchise, inclusive of AMONDYS 45, is $537 million to $547 million. In the quarter ended December 31, 2020, we recognized $22.5 million of collaboration revenue, which relates to our collaboration arrangement with Roche.

The reimbursable co-development cost under the Roche agreement totaled $34.2 million for the fourth quarter. On a GAAP basis, we reported a net loss of $189.3 million and $235.7 million or $2.40 and $3.16 per basic and diluted share for the fourth quarter of 2020 and 2019, respectively. We reported a non-GAAP net loss of $145.1 million or $1.84 per basic and diluted share in the fourth quarter of 2020 compared to a non-GAAP net loss of $116.9 million or $1.57 per share and diluted share in the fourth quarter of 2019. In the fourth quarter of 2020, we recorded approximately $22.4 million in cost of sales, compared to $15.6 million in the same period of 2019.

The increase in cost of sales is primarily due to an increase in royalty payments to BioMarin Pharmaceuticals and the University of Western Australia, which reflects increasing demand for our products. On a GAAP basis, we recorded $207.2 million and $22.1 million in R&D expenses for the fourth quarter of 2020 and 2019, respectively, a year-over-year decrease of $15.9 million. This decrease is partially related to a $64.2 million decrease in upfront milestones and other expenses in the fourth quarter of 2020 as compared to the same quarter in 2019, which is primarily offset by a $58.1 million increase in manufacturing expenses due to the continuing ramp-up of our gene therapy programs. On a non-GAAP basis, R&D expenses were $180.8 million for the fourth quarter of 2020, compared to $135.4 million for the same period of 2019, an increase of $45.4 million.

The year-over-year growth in non-GAAP R&D expenses was driven primarily by a continuing ramp-up of our gene therapy programs. Now, turning to SG&A. On a GAAP basis, we recorded approximately $86 million and $81.4 million of expenses for the fourth quarter of 2020 and 2019, respectively, an increase of $4.6 million. The year-over-year increase was driven by an increase in stock-based compensation partially due to increases in headcount and stock price.

On a non-GAAP basis, the SG&A expenses were $65.2 million for the fourth quarter of 2020, compared to $65.8 million for the same period of 2019, a decrease of $0.6 million. On a GAAP basis, we recorded $17.8 million in other expenses net for the fourth quarter of 2020, compared to $4.8 million in other expenses net for the same period of 2019. The increase primarily reflects the interest expense on the company’s debt facilities, as well as a decrease in interest income and the amortization of investment discounts due to the investment mix of the company’s investment portfolio. We had approximately $1.9 billion in cash, cash equivalents, and investments as of December 31, 2020.

And with that, I’ll turn the call over to Dallan for an update on our commercial activities. Dallan?

Dallan MurrayChief Commercial Officer

Thank you, Ian, and good afternoon, everyone. Despite the challenges posed by the COVID-19 pandemic, Sarepta maintained its leadership position in Duchenne muscular dystrophy by continuing to serve patients and execute on our stated 2020 goals. Firstly, we were thrilled with the FDA approval of AMONDYS 45, casimersen, Sarepta’s third RNA exon skipping medicine, which occurred last week on February 25, 2021. The approval was based on a statistically significant increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45.

Based on our unrivaled expertise in DMD and our commitment to serving this community with excellence and urgency, AMONDYS 45 was launched immediately after approval. All facets of our commercial, manufacturing, and medical organizations, including case managers, supply chain, and field force, jumped into action on day 1 to support the roughly 8% of patients who are amenable to skipping exon 45. Our goal is to facilitate rapid patient access of AMONDYS 45 by leveraging our industry-leading knowledge and proven experience in having successfully launched two other RNA medicines to treat DMD: EXONDYS 51 and VYONDYS 53. In total, Sarepta now serves roughly 30% of the DMD community.

Moving on now to EXONDYS 51 and VYONDYS 53. We continue to provide uninterrupted supply of both products to patients. And there have been a few delays or stoppages as a result of the pandemic due to the fact that a large majority of the EXONDYS 51 or VYONDYS 53 patients, roughly 90%, are receiving weekly infusions in their homes. We are encouraged that the majority of payers have demonstrated a willingness to work with the DMD community and have shown flexibility to allow for continued access to these important therapies during this difficult time.

Any impact to date has largely been due to missed doses, one to two doses on average, as a result of pandemic impact on either immediate family or direct care team. Our patients are determined to adhere to their weekly infusions, and Sarepta is determined to continue to monitor and support these patients. The launch of VYONDYS 53 continues on pace with minimal impact to date from any competition, and our team continues to execute on its goals and provide consistent and ongoing support to the exon 53-amenable patients. In addition, we have thoughtfully deployed measures to minimize the risk of transmitting COVID-19.

These measures include sending personal protective equipment to all of our patients who have requested supplies to help ensure that they are protected when nurses administer their weekly infusions at their homes. We continue to monitor the pandemic and are ready to react quickly with additional modifications to our strategy, especially in those places experiencing surges in infections. Patient safety remains our top priority, and we will continue assessing any and all efforts that will ensure patients feel safe and supported during this unusual time. Now, I’ll turn the call over to Gilmore for an update on our research and development activities.

Gilmore?

Gilmore O’NeillExecutive Vice President, R&D and Chief Medical Offcer

Thank you, Dallan, and good afternoon, everyone. Doug has already shared the highlights from our most advanced gene therapy programs. I will focus my remarks today on Sarepta’s upcoming presentations at this year’s MDA meeting in March and the progress we’ve made in advancing our RNA portfolio. Let me start with this year’s MDA meeting.

You will not be surprised to know that COVID-19 continues to disrupt the format of scientific meetings. Thus, MDA will host its annual Clinical and Scientific Conference as a virtual meeting from March 15 to March 18, 2021, at which Sarepta plans to host two symposia and present 10 abstracts, which would include three podium presentations. The podium presentations will show previously reported data from SRP-9001-102 Part 1, our micro-dystrophin program, and new long-term two-year functional data from Study SRP-9003-101 for our limb-girdle muscular dystrophy type 2E program. Now, Doug covered the Part 1 results from our ongoing two-part SRP-9001-102 study.

But I do want to emphasize that, first, because of the study’s stratified randomization design, and second, because of its statistical analysis plan, we can state with confidence that the prespecified subgroup analysis of four- to five-year-old Duchenne boys demonstrated that SRP-9001-treated boys achieved NSAA gains that were clinically meaningful and superior to placebo-treated boys with statistical significance. This means that the SRP-9001 micro-dystrophin construct is functional in humans and confers a physiological and clinical benefit, thus substantially increasing the probability of success for this program. Moreover, the large amount of biological and clinical data that we have collected from the SRP-9001-102 study will further inform and optimize the design of our future study. Now, let me talk about our RNA portfolio.

We were delighted to announce last week’s approval of AMONDYS 45 for the treatment of Duchenne boys who carry an exon 45 skip-amenable mutation in their dystrophin gene. Now, you will be pleased to know that the ESSENCE study, a placebo-controlled confirmatory trial, which is designed to support the VYONDYS 53 and AMONDYS 45 approvals, remains on track. We expect data from this PMO trial in 2024. Notwithstanding our excitement about AMONDYS 45’s approval, which is our third FDA approval to emanate from our proprietary PMO technology, our goal is to continue to advance the science for patients with Duchenne.

We have successfully leveraged our PMO technology to selectively skip exons and restore the dystrophin-reading frame, thus creating a truncated but functional dystrophin protein. Based on this elegant approach and our deep understanding of Duchenne, we set out to engineer the next generation of this technology, which we called PPMO, with the sole purpose of safely delivering more of the PMO into cells. To do this, PPMO adds a positively charged cell-penetrating peptide or CPP to the PMO backbone. The addition of the peptide should increase cellular uptake.

And if we can safely drive more drug into the cells, we will see greater exon skipping and greater dystrophin production. This is no small feat, however, as we and many others have tried approaches to increase cellular penetration that have been hampered by dose-limiting toxicities. On December 7, 2020, we presented a clinical update of our ongoing MOMENTUM multi-ascending dose study of SRP-5051 for Duchenne muscular dystrophy. By way of reminder, MOMENTUM or SRP-5051-201 has two parts.

Part A is to evaluate the safety and tolerability of SRP-5051 in patients with Duchenne and determine the maximum tolerated dose or MTD. The dose levels for Part A are 4, 10, 20, 30, and 40 milligrams per kilogram administered once monthly by IV, with each dose cohort enrolling three to six patients. Part B will evaluate SRP-5051 administered at the MTD and will include patients who complete Part A and an additional cohort of approximately 15 patients. In that update last year, we reported that we had achieved human proof of concept that conjugation of our cell-penetrated peptide to our PMO chemistry does indeed increase cellular uptake of PMO in the muscle target tissue in association with an increase in downstream exon skipping and dystrophin expression.

These higher tissue exposures, higher exon skipping, and higher dystrophin expression were observed in the 20 mg per kg cohort of our 5051-201 MOMENTUM study at 12 weeks as compared to the PROMOVI 30 mg per kg eteplirsen cohort at 24 weeks. Please remember that at 12 weeks, the SRP-5051 20 mg per kg cohort saw increases in exon skipping of 1.6x and an approximately fivefold increase in percent normal dystrophin as compared to the eteplirsen group at 24 weeks. And, and this is important, those increased levels were observed with fewer doses of SRP-5051, four versus 25, compared to eteplirsen and has an approximately 10x lower cumulative drug exposure. Our next step will be announcing our 30 mg per kg expression data in Q2 of this year, 2021.

Once we have determined an MTD, we will commence Part B of the MOMENTUM study, which will include patients who complete Part A and an additional cohort of approximately 15 patients. Finally, and most importantly, I want to thank all the patients, their families, study sites and coordinators, my R&D colleagues, and our partners who have done so much work under incredibly difficult circumstances caused by the pandemic to maintain our urgent mission to deliver new, highly effective therapies to people with rare diseases. Now, I will hand the call back to Doug for Q&A. Doug?

Doug IngramChief Executive Officer and President

Thank you very much, Gilmore. Let’s turn it over to Q&A now, operator.

Questions & Answers:

Operator

[Operator instructions] Our first question comes from the line of Alethia Young from Cantor. Your line is now open.

Alethia YoungCantor Fitzgerald — Analyst

Hey, guys, thanks for taking my question. I know a lot’s been made of how to interpret what the 9001 data means for the next studies in DMD. But I just wanted you to talk a little bit about what you think it means for limb-girdle, your general confidence level there based on what you’ve seen with this technology, and then also how to perhaps fine-tune, think about what are the core key regulatory endpoints as you have those conversations with the FDA to make sure that study is successful. Thank you.

Doug IngramChief Executive Officer and President

Thank you very much for those questions, Alethia. I mean, first, our confidence in our constructs and the way we build them only increases over time. I would remind everyone that the limb-girdle program that we have, limb-girdle Type 2E and SRP-9003, uses not only the same capsid, which is rh74, but it also uses the same promoter as 9001. We have now treated patients that are well over 50 patients at the target dose.

And so we have a very stable safety profile. We’re seeing very good expression. And so this only increases our confidence level around SRP-9003. And so we’re excited about that.

With respect to the clinical and regulatory strategy as it relates to 9001, in particular, we have an enormous amount of insight that’s come out of Study 102, some of which we’ve shared, some of which we’re still working on and we’ll share when the protocol is complete. And so our goal here is to continue the work to really understand the data, and we’re coming to the end of that now, to build a protocol that’s fully informed by Study 102 and the positive proof of concept in 102 and some of the nuance that we’re seeing out of Study 102, to meet with the agency once that protocol is fully defined. Then we’ll update everybody on that. Then, of course, our goal is to commence our next trial this year, somewhere around the middle of the year, with the goal of having all of those kids dosed, if all goes well, before the end of this year.

And then, of course, the readout, we probably have last patient/last visit, if all goes well, by the end of next year. And they’ll read out shortly thereafter. And it is our current base assumption that that would be the study upon which we would obtain an approval first in the U.S. and then around the world.

Operator

Thank you. Our next question comes from the line of Brian Abrahams from RBC Capital Markets. Your line is now open.

Brian AbrahamsRBC Capital Markets — Analyst

Hey there. Thank you so much for taking my question. Now that you’ve had more of an opportunity to digest the 102 data set, and I think you mentioned maybe in January, you’re going to be looking at additional statistical analyses, including those normalized for baseline characteristics, I was wondering if you had any further learnings or insights that you’d be willing to share? And any maybe planned adjustments to the general approach you might take to the 301 design on things like inclusion criteria or analyses? Thanks.

Doug IngramChief Executive Officer and President

Yes. Brian, thank you. So the short answer is yes. We have an enormous amount of insight that’s come out of 102, and it will help us tune the next study.

We’re not yet in a place where we want to discuss that and provide additional details. We’ll do that once that protocol is fully designed, and then the agency has bought into the protocol. But we are convinced not only that there’s a lot of insight here, but that we can greatly increase the probability of success in the next trial in a very nuanced way. We have already out of Study 102 significantly more insight and data than anyone else would have regarding a construct for micro-dystrophin for the use of Duchenne muscular dystrophy.

That will help us design our next study. We candidly call that Study 301. And then we’ll have even more insight, by the way, at the end of this year. I really do want to point out how important that is.

Remember, Study 102 is a blinded study. What we saw in January was Part 1 of that study. And what we saw — while I’m not going to deny, I’m disappointed that we didn’t hit statistical significance in the primary endpoint, what we saw in the secondary endpoints confirms our belief in the value and the benefit and the transformative potential of this therapy. When you look at the four- to five-year-olds, that’s only 16 kids.

And in that 16-kid cohort, where the baselines were actually properly compared, we saw not just a strong statistical significance but also a very clinically meaningful benefit over placebo in only 48 weeks. And then at the end of this year, just to remind everybody, that study remains blinded. We’re going to have Part 2 that’s going to be last patient/last visit in the back half of this year. And so by the end of this year, probably very early next year, we will have the results of Part 2.

And that’s going to be enormously insightful on top of this. When you think about what you’ll have there, we’ll have, for about 20 of the kids, two years’ worth of data that we can look at in the way they’re trajecting on therapy. And then for the other 21 kids that we have something very interesting there, in some ways, really interesting, which is we’ll have a cohort of children who we’ve been able to follow and do a run-in for 48 weeks, our trajectory, without a therapeutic intervention. Then we have a therapeutic intervention, and then we get to judge when we unblind it what the impact of that therapeutic intervention was.

So we’ll have even more insight. So short answer on your — well, long answer, apologies, Brian, but long answer trying to get short on your question is we have developed an enormous amount of insight out of 102 that gives us not only a lot of confidence in the therapy but really keen understanding of how we ought to design the next protocol and fine-tune it. And we will do that, and we’ll get that blessed by the agency. And then we’ll all talk about it once that’s done.

Operator

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open.

Salveen RichterGoldman Sachs — Analyst

Good afternoon. Thanks for taking my question. Just maybe an update on your gene editing portfolio. You recently entered into a research collaboration with Genevant for LNP-based editing therapeutics, and you’ve had some other partnerships to date.

Could you just walk us through when we should expect kind of an update on programs moving forward here?

Doug IngramChief Executive Officer and President

Sure. I will turn this over to Dr. Louise Rodino-Klapac. Before I do, I will point out that you will notice that our goal is to look at all of the modalities.

We look at gene editing as something that’s very exciting for the future. In addition to partnerships and relationships that we have entered into over the course of the last 12 to 24 months, I should also note that we have built out a gene-editing center, what we call the Gene Editing Innovation Center in Durham, North Carolina, all of which is under the leadership of Dr. Charlie Gersbach from Duke University, who is one of the significant world leaders in the use of gene editing from a neuromuscular perspective. But perhaps in addition to that, Louise, you’d like to comment on our gene-editing efforts.

Louise Rodino-KlapacExecutive Vice President and Chief Scientific Officer

Sure. Thank you, Doug. I’d like to just second what Doug said about Charlie Gersbach being really the true leader in the field and having worked in the Duchenne space for quite some time. And really, we have the opportunity to develop a best-in-class technology.

And part of that is really scanning the landscape for delivery technologies in that there are other ways that you can deliver gene-editing machinery. And so our Genevant partnership was one way to look at that using lipid nanoparticles. And we’re certainly open to making sure that we have the best delivery vehicle for gene editing. And so we’ll continue to look at these research partnerships in a broad manner to make sure that we develop the best technology moving forward.

So thank you for the question.

Doug IngramChief Executive Officer and President

And I should also note, Salveen, with the nanoparticles, we have relationships to advance updated and more increasingly sophisticated AAV technology. And of course, we have a relationship to explore the use of exosomes as delivery devices as well, potentially both for gene editing and gene therapy and maybe even RNA as well.

Operator

Thank you. Our next question comes from the line of Ritu Baral from Cowen. Your line is now open.

Ritu BaralCowen and Company — Analyst

Hey, guys, thanks for taking the question. Doug, have you ruled out breaking the blind on 102 to generate more data before you start 301? Or do you have optionality to keep 301 adaptive, depending on what final 102 data will show? And given enrollment is going to be competitive, how confident are you that you can enroll 301 in six months?

Doug IngramChief Executive Officer and President

Yes. Thank you for both those questions, Ritu. So you raise a really interesting question, which is, could you do an interim analysis on Part 2 to gain even additional insight? The short answer is having thought about that, we’re not currently of a view that we should do that for a host of reasons. The first is that we already are going to have significant insight from Part 1 of Study 102 that will help us design what we’re calling Study 301 right now.

I mean, we’ve just got — I’m going to be very direct. Nobody has the kind of insight that we currently have, and the design that we’ll have for our next study will increase the probability of success. It will clearly put us in a competitively positive advantage, and that’s already with the Part 1. So we really do want to maintain that blind and get a readout on Study 102 at the end of this last patient/last visit by the end of this year and probably very early the following year to have that readout, because that’s going to be an enormously important set of data, a vast amount of information in this rare disease.

And we just really want to maintain the blind. As it relates to enrollment, there is an enormous need in Duchenne muscular dystrophy. And so I remain quite confident that we can enroll with rapidity. Physicians and investigators are very excited about the opportunity to work with us.

And so I think that won’t be our significant issue, I don’t believe, right now. Our big issue right now is getting that protocol really fine-tuned, meeting with the agency, getting the agency blessing on that protocol and the approach, and then really getting that kicked off and started in time to really start enrolling patients. And I suspect that patient enrollment will be robust once we get that going.

Operator

Thank you. Our next question comes from the line of Anupam Rama from J.P. Morgan. Your line is now open.

Tess RomeroJ.P. Morgan — Analyst

Hey, guys. Good afternoon. This is Tess on the call for Anupam. So one question here.

In your remarks, Doug, I think you said you’re expanding Study 103 to better balance four- and five-year-olds in the trial. I guess what is the rationale here given you’re planning to run 301? And what is the target end for 103 now? Thanks so much.

Doug IngramChief Executive Officer and President

Yeah. Thank you, and I really appreciate that question because I want to make sure that the reason I mentioned it at all is to make sure that it’s not a significant change or delay in anything. So just to remind everybody, Study 103 uses the commercially representative material, our new process that we would intend to launch this therapy with. And it’s our goal to test expression and safety and the similarity of that process.

And the great news on that was that we had all the kids dosed, as you know, by the end of last year, as we reported out at J.P. Morgan. That was about 11 children. What we’ve noticed is that there are more six and 7s than 4s and 5s.

And since this was intended to be a look at four- to seven-year-olds, we updated the IND that would allow us to add some additional four to 5s. But it is no more than that. We haven’t seen any data on this. We will not delay us in the evaluation and the report out of those 11 patients.

It’s just an attempt to get a better balance over time. So don’t consider that a delay in anything. It’s not a delay in the report out in the second quarter. There shouldn’t be any kind of delay in the start of 301.

It’s really just our effort to ensure that we have a nice balance of four to 5s and six and 7s in that study.

Operator

Thank you. Our next question comes from the line of Difei Yang from Mizuho Mutual. Your line is now open.

Difei YangMizuho — Analyst

Hi. Good afternoon and thanks for taking my question. Just a quick one. On the very high level, how do you think about gene editing relative to AAV-based gene therapy? Is there a possibility that in editing just leapfrog the virus-based gene therapy and come to commercialization first?

Doug IngramChief Executive Officer and President

Well, I think the answer is no. I don’t think that we’re going to see something that’s going to leapfrog gene therapy right now for a host of reasons. First, you raised a really good point because what you’ve said is that is it possible that gene editing would leapfrog this virus-based gene therapy that we have in front of us today as a biopharmaceutical industry. And the short answer is that, of course, gene editing today is virus-based as well.

And I think that to empower gene editing, we may want to look, as we are currently, as you’ve seen, both through LNPs and exosomes, about a delivery device that would move itself away from AAV as a potential. So that already is going to require a lot of effort and focus and research to think about it. AAV has been a very successful approach for delivery of gene therapy. And if we’re going to move away from that over time, that’s going to take time.

So gene editing is really exciting. But I think just temporarily, there’s a difference. Gene therapy is right in front of us right today. We just, as you saw, had the results of a placebo-controlled trial, at least Part 1.

And again, I would remind us that when we got the baselines right in the four to 5s, we see a really profound, never-before-seen benefit out of a placebo trial. So this is right in front of us. Gene editing is very exciting. But believe me, there’s a reason why we’re putting a lot of effort into gene editing, why we built this Gene Editing Innovation Center, why we wrapped our arms around the technology of someone like Dr.

Charlie Gersbach, why we’ve entered into partnerships to look at other delivery mechanisms to empower gene editing. But I think there’s just a difference in time between the opportunity to bring therapies to children today with gene therapy and to look down the road at gene editing as well. And then, of course, there are differences in — there are technological challenges in both areas. Gene editing edits, and that’s very interesting.

On the other hand, let’s be clear, you are going to have to edit and create truncated forms of the ultimate protein as well. And you’re either going to have to do that on an exon-by-exon basis with respect to gene editing, or you’re going to have to do what we are attempting to do with Dr. Charlie Gersbach, which is take a significant hotspot of gene editing where you can put something back in frame and create a therapy that could treat about 50% of the children. And that’s different than gene therapy where gene therapy really is agnostic to the mutations.

So there are differences. Short answer, I think there’s a difference in time. I think gene editing today is a really exciting research program. CRISPR/Cas9 is an unbelievably exciting technology.

There’s a reason why those individuals won a Nobel Prize for it. But it’s a little ways out. Gene therapy is right in front of us today and offers the hope of transforming lives of patients both in Duchenne muscular dystrophy and in a lot of other areas as well.

Operator

Thank you. Our next question comes from the line of Debjit Chattopadhyay from Guggenheim Securities. Your line is now open.

Debjit ChattopadhyayGuggenheim Securities — Analyst

Hey, good afternoon. Thank you for taking my question. I’m trying to find an explanation for the high 2.62 VCN per cell in the crossover patients but micro-dystrophin expression about the same as Study 101, whether VCN was 1.63 per — VCN was 1.63. And could you also sort of talk to any difference in dose between the first cohort of patients in Study 102 versus the crossover patients? Thank you so much.

Doug IngramChief Executive Officer and President

I’m going to turn the question over to Dr. Louise Rodino-Klapac, who can provide some insight into both. I would think — Louise will explain, I think, on the genome copies per nucleus. I wouldn’t over-interpret the delta between those genome copies.

Probably, there’s quite smaller numbers in the genome copies than in the Western blot expression. But, Louise, your thoughts on both those questions? I’m turning it over to Louise. I think she’s on mute. Apologies.

Louise Rodino-KlapacExecutive Vice President and Chief Scientific Officer

Apologies. I would agree with you about not over-interpreting the vector genome copy numbers in Part 2. I would add that in Part 2, as we mentioned, the first 11 patients, all receive the intended dosing level as opposed to the Part 1 patients, which we’ve discussed. So in that respect, we feel that Study 101 and what we’ve seen so far in Part 2 at the intended dose level are quite on target in terms of expression and vector genome copies within range as well.

Was there an additional question?

Doug IngramChief Executive Officer and President

No, I think those are the two questions. So just to remind everybody about Debjit’s question. So in the first part of the study, the titering method that was used, the standard was a, what’s called, supercoiled qPCR. It turns out with the benefit of having developed a linear standard for qPCR, we can look back and see that there were three lots.

One of the lots hit the target, the target tittering. Two of the lots were below the titering. In the first group of patients, that’s about 60% of the patients were in the lower lots. On the crossover, we used the linear titering for the purpose of the crossover patients.

And so we are right on the target titering and target dose on the crossover patients unless I’ve got that completely wrong factually, Louise.

Louise Rodino-KlapacExecutive Vice President and Chief Scientific Officer

No, that’s correct.

Operator

Thank you. [Operator instructions] Our next question comes from the line of Gena Wang from Barclays. Your line is now open.

Gena WangBarclays — Analyst

Thank you for taking my questions. So I have one question regarding Study 102. Regarding the crossover, did you align with FDA regarding prespecified natural history patient population for statistical analysis purpose? And for the steroid treatment, we know that Dr. Jerry Mendell tend to use weekend regimen.

Was that consistent across all the patients?

Doug IngramChief Executive Officer and President

Yes. Taking the second question first, we allowed patients — patients had to be on a long-term study dose of steroids. We allowed the patients to use their standard of care. And there is a — some people have daily dose.

Some people use weekend dose. That didn’t play a role as best as we can see. And as it relates to the crossover, that was all prespecified. I mean, we can update it again before we unblind.

Dr. Louise Rodino-Klapac or Dr. O’Neill, you can correct me if I’m wrong, but I think all of that was — all of that analysis was in the protocol at the commencement of the trial.

Gilmore O’NeillExecutive Vice President, R&D and Chief Medical Offcer

That’s correct. The protocol on the SAP were created prior to the unblinding of Part 1 interim analysis.

Operator

Thank you. Our next question comes from the line of Gil Blum from Needham & Company. Your line is now open.

Gil BlumNeedham & Company — Analyst

Hello, everyone, and thank you for taking our question. So as you mentioned before, Doug, the LGMD programs have certain similarities across them. From a regulatory perspective, if there’s positive data or continuing positive data for LGMD2E, does that translate across programs? Thank you.

Doug IngramChief Executive Officer and President

Well, the positive data on the LGMD programs from a strictly regulatory perspective, it may not. But from a confidence in the construct and the result, it definitely does. I mean, we’re seeing — and it does in both across all of the LGMDs, but also back on to 9001 because if you look at the safety profile, understand, of course, that a significant part of the safety profile comes from the capsid itself, in this case, rh74. And of course, rh74 is the capsid that we’re using for all of our limb-girdles, as well as 9001 for DMD.

And so there’s a value there. And then seeing the positive expression results gives us a lot of confidence both in the tropism of rh74 across all of the programs and also the promoter itself. It’s the same promoter in 2E that’s in 9001, and it’s the same promoter in, I think, three of the five– if I’m not mistaken, three of the five limb-girdle programs. So there is an enormous amount of built-in confidence that we have.

Now, I think with respect to limb-girdle and its pathway, I think that we are going to be meeting with the division this year once we have GMP material released from our commercial representative material, and then we’ll figure out what the pathway is for that limb-girdle. And I suspect that that pathway will inform the pathway of the other limb-girdles as well. And so that conversation will be an important one for us to have this year.

Operator

Thank you. Our next question comes from the line of Tazeen Ahmad from Bank of America. Your line is now open.

Tazeen AhmadBank of America Merrill Lynch — Analyst

Hi, guys. Maybe just to change gears to your current franchise. Just wanted to get a little bit of color, Doug, on what kind of penetration you have right now with EXONDYS in the targeted market. And can you give us an idea of how golodirsen’s launch is going and if you expect casimersen will also have a similar type of ramp to what EXONDYS had at the beginning? And maybe to tie it all up, how big of a market opportunity would the three drugs together represent? Thanks.

Doug IngramChief Executive Officer and President

Yeah. So thank you for that. Let me take them in the broadest of strokes together. So first of all, with respect to EXONDYS, we launched EXONDYS in late 2016.

We are going to start getting to the flatter side of the curve with EXONDYS over the course — probably by the end of this year. The reason for that is that there — and then we’ll be continuing to grow based on incident population and still we find new patients. And if we could ever unlock new patient screening, we would definitely see a significant increase. There’s still a ton of opportunity in EXONDYS even over the long term, but the issue there is it’s ex U.S., and we have to find an opportunity ex U.S.

to get approvals ex U.S. to really unlock that opportunity. We have ex U.S. sales, but they come from what we call the MAP program, the access program that’s responsive in nature.

The problem ex U.S. is that there isn’t in most countries the concept of an accelerated approval pathway. So that hampers us until we get a readout in some of our confirmatory trials with EXONDYS, and I think you have another opportunity for growth. Golo has done very well.

Now, golo’s launch has been somewhat attenuated as a result of the pandemic itself. Obviously, you would rather not launch a new therapy, particularly a therapy that has to start with, not only going into physicians’ offices but going into a hospital for your first infusions very typically. You would love to not have to do that launch in the midst of a pandemic. And yet the team did a brilliant job, and we had very good growth in VYONDYS.

But from my perspective, we should see VYONDYS as a continuing launch, which is actually a positive. There’s a lot of growth there. And then finally, if you look at casimersen, now this maybe just the honeymoon period of having just gotten approval. We just got approval last week.

And just so we’re clear, we’re ready to go. I mean, kudos to our team, supply chain, commercial, med affairs, and the like, because we’re able to immediately launch that. We’re able to get start forms. We got start forms in already.

We’ll have AMONDYS in warehouse by this week. By literally tomorrow, we’ll have it in sight. So AMONDYS is going to — I think looking at AMONDYS, obviously, scaled down to the size of the patient population, which is smaller than EXONDYS, I currently think that even with this pandemic, and Dallan’s probably scared I’m going to say this, but I think its launch trajectory is going to look a lot like EXONDYS. And there’s a lot of excitement and a lot of pent-up demand for therapy for exon 45-amenable kids that have been waiting a long time for this therapy.

On the size of the market, if you just look at this RNA alone, I mean, we are already in the mid-500s. And we’re really in a launch Phase 2 of the three therapies, and those two together are bigger than the other therapy. So there’s a ton of headroom. If we just didn’t leave the United States, we’re going to be getting up into the $1 billion range over time potentially.

And if we can get open up ex U.S., we’ll be significantly larger. And then the bigger opportunity than that that I think is — and I really want to hammer on this because I think people have underappreciated our RNA franchise, is the opportunity to bring therapies to patients. As exciting as these first three therapies are, this is 29% of the patient population. There are well over 80% of children with Duchenne muscular dystrophy whose mutations are amenable to this kind of exon-skipping technology.

We have a very reliable, consistent, precise way to build constructs safely that can bring therapies to these kids. So we have the potential over time, in addition to EXONDYS and VYONDYS and AMONDYS, to build therapies out for these kids in the U.S. and, hopefully, around the world that could get us over 80% up to maybe, I think, around 55% or so. We can do it in a very straightforward way from 55% to over 80%.

We have to find a platform approach because those mutations are fairly rare. We’ve already had some early dialogue with the agency about how we could do that. But we have a big opportunity there, and that big opportunity will either be the PMOs, which we, obviously, have developed now, and we’re just launching AMONDYS, which is a PMO, or it could be a peptide-conjugated PMO, the PPMO. And we’re going to see the 30 mg per kg readout on the PPMO in the second quarter.

So that will be really interesting to look at. As you know, we had the 10 mg and the 20 mg readout last year, and at least from a proof-of-concept perspective, we were pretty excited. We saw with the PPMO, at one-tenth the drug exposure and 5x the dystrophin production in a very short period of time. So either PPMO or PMO, there’s a lot of opportunity to do a lot of good in the Duchenne community.

And of course, there are significant revenues with that as well.

Operator

Thank you. Our next question comes from the line of Vincent Chen from Bernstein. Your line is now open.

Vincent ChenSanford C. Bernstein — Analyst

Thinking of the crossover data at the end of this year from Study 102, I was wondering if you could provide a bit more color on how you’ll evaluate the data and what you’re hoping to see. I guess what comparisons are specified in the protocol? And what would an — from your view, what would an encouraging result look like?

Doug IngramChief Executive Officer and President

Well, we’re looking at two things, really. We’re looking at — first, there’s a bunch of staples that we’re going to look at. And, of course, we can update on more insight, more thought into it. In the broadest of strokes, we’re going to be able to see — first of all, we’re going to be able to compare against natural history children, including children that have been on the therapy for nearly two years.

That’s going to be exciting. We’re going to have this trajectory analysis that we can look at as well, which is we have a unique opportunity to look at children who are blinded the whole time. So let’s be very clear. This is not an open-label study.

This will be blinded till the end. Look at them trajecting over the course of 48 weeks without any therapeutic intervention and then the therapeutic intervention and then we see what that looks like over time, both using themselves as their own control and also using a well-matched natural history set that would be prespecified to look at what you would have predicted out of a natural history set based on their trajectory over that 48-week period, including the — and then looking at their age. But beyond that, Dr. O’Neill, is there anything I’m missing here in broad strokes?

Gilmore O’NeillExecutive Vice President, R&D and Chief Medical Offcer

I think in broad strokes, you’ve hit it. And obviously, we’ll have second year of follow-up for the patients who were randomized to active treatment in Part 1. So you’ve got it.

Operator

Thank you. Our next question comes from the line Tara Bancroft from Piper Sandler. Your line is now open.

Tara BancroftPiper Sandler — Analyst

Hi, guys. Thanks for taking the question. And so staying on the topic from Tazeen’s question, what do you think is the next PMO in terms of which candidate you think could get approved next? Or do you think it’s actually more likely to be a PPMO? I know you said it could be one or the other. And on the PPMO topic, have you started dosing in the 40 mg per kg cohort yet? And will they be included in the data in Q2?

Doug IngramChief Executive Officer and President

Yes. So going to the last question first, the data that we’ll have in the second quarter will be the 30 mg per kg data. That’s what will happen in the second quarter. It’s a really interesting question.

We have construct built for — the great thing about RNA technology is that it’s the conjugation of a peptide to a construct that — PMO construct. So we can build the PMO construct. And if we want to go PPMO, we simply conjugate the peptide to the preexisting construct. We have a number of them built for all the fairly significant populations.

So the real question for us, the fork in the road is going to be what the data looks like in the PPMO. And then we can make a choice. And if the data looks great in the PPMO, then we’re obviously going to start building the constructs with peptide conjugation to them. And we’re going to start getting those kids on therapy and then hopefully seek accelerated approval via that mechanism and when it all ends up, we think that PMO is the better answer, we’ll start creating those constructs and bringing them forward.

And you’ve seen now that we have a fairly distinct approach. We can build the constructs. They’re highly precise. They have very good safety profiles in the PMOs.

Of course, the PPMO, that’s exactly one of the things we’re looking at, which is the safety profile in the PPMO. And then we can bring those forward with the accelerated approval pathway, which is very efficient. But we need to first decide if it’s going to be PPMO and PMO. As everyone knows, we saw very encouraging results in the PPMO last year.

And then in the second quarter of this year, we’ll see how it looks at 30 mg per kg.

Operator

Thank you. Our next question comes from the line of Brian Skorney from Baird. Your line is now open.

Brian SkorneyRobert W. Baird — Analyst

Guys, thanks for taking the question. A question on the ESSENCE study. You said it will read out in 2024. I guess is that study now blinded out until week 144? And I’m just wondering in terms of with three years to go before the readout, how do you intend on maintaining trial integrity in terms of keeping patients randomized given that both golodirsen and casimersen are now available?

Doug IngramChief Executive Officer and President

Yeah. That’s a great question. Yes, it’s blinded, and it’s very difficult. So a very good point.

We’ve done a great job. The team has done a brilliant job. And more than that, the patients have done a wonderful job in being committed to this trial. But it is blinded.

And having a long-term blinded trial, it takes a lot of commitment. So there’s no doubt on that. The trial integrity is not at risk as a result of the approvals of both AMONDYS and VYONDYS. It was one of the various things we talked about early with the agency as we were thinking about the accelerated approval approach both for VYONDYS and then AMONDYS.

And the way we achieved that was to ensure even as AMONDYS — I mean, as VYONDYS was coming close to approval is that we moved our recruitment ex U.S. So we moved to regions around the world that don’t have access to a commercially available therapy so that the access to the therapy in those areas can be via this trial. And then we don’t have to worry about what would be a very credible risk, which would be you get a commercially available therapy onboard, and then children are moving over to commercially available therapy as opposed to being in a placebo-controlled trial. But that risk is not significant at all as a result of the actions that we took a couple of years ago to start recruiting actually with us.

Brian SkorneyRobert W. Baird — Analyst

Got it. And I just want to clarify. So that blind — so what we’ll get from the blinded data in 2024, is that actually going to be week 144, six-minute walk? Is that the primary now?

Doug IngramChief Executive Officer and President

I think that’s right. Is that right, Dr. O’Neill?

Gilmore O’NeillExecutive Vice President, R&D and Chief Medical Offcer

Yes.

Operator

Thank you. Our next question comes from the line of Colin Bristow from UBS. Your line is now open.

Ting LiuUBS — Analyst

Hi. This is Ting on for Colin. Thanks for taking our question. So we have a follow-up question on the PPMO and how the data updates in second quarter.

So based on your modeling, what exon skipping or dystrophin expression levels are you expecting or should we expect from the 30 mg per kg or even higher dosing cohort? Thank you.

Doug IngramChief Executive Officer and President

Yeah. Well, the short answer is we don’t know yet. We haven’t seen any of the data. So I want to be very clear.

We don’t know yet what we’re going to see until we look at it. All we can do is model of the animal data. And of course, there’s a lot of risk in trying to correlate between animal data and human data and trying to figure out what the exact right model is. Is it weight-based? Is it allometric? Is it some mix in between? What we do know is — we know two things.

We know that at 20 mg per kg, which in animal models wouldn’t have yet been at that steep part of the dose-response curve from a dystrophin and exon skipping perspective, we nevertheless saw at one-tenth the dose exposure 5 times the dystrophin production. So we’ve already seen something that’s really interesting. And frankly, it’s interesting in a whole host of ways. We’re seeing 5 times the dystrophin.

The dosing schedule is much better for the PPMO than PMO. It’s monthly doses as opposed to weekly dosing. So already a very interesting concept. The second thing that we know — and we don’t know if 30 mg per kg will be the place we see it.

But at least in animal models, you do start seeing a steep increase at the right dose. So there is a potential that we see — either 30 mg per kg or at something higher than 30 mg per kg, we see a steep increase in the amount of dystrophin. But we won’t know that, frankly, until we have evaluated biopsies and we begin to see that in patients because all of the data that we had up until the 10 and 20 mg per kg, of course, were in animals.

Operator

Thank you. Our next question comes from the line of Marty Auster from Credit Suisse. Your line is now open.

Marty AusterCredit Suisse — Analyst

Hey, everyone. Congratulations on the AMONDYS approval last week. I had a follow-up from the prior question. I think looking back at my notes from the December call on 5051, Doug, you talked about possibly being able to commence dosing of the 40 milligram per kilogram arm by the end of Q1.

Is that still potentially on track? And if not, are you waiting to kind of get that 30 milligram per program data before advancing? And is that something you’re looking for on the biopsy side or something on the safety side to kind of make that determination to move forward? Thanks.

Doug IngramChief Executive Officer and President

We’re looking to — yes. So we are, in fact — updated view is we want to see the 30 mg per kg before we move to decide two things. We decide what the pathway is for a pivotal and also what the dose ranges should be and how much higher should we start thinking about going up in dose. So we’re going to see the 30 mg per kg and then make the decision on the 40 mg per kg right after we do that.

And we’ll see the 30 mg per kg in the second quarter.

Marty AusterCredit Suisse — Analyst

OK. Thanks.

Operator

Thank you. Our next question comes from the line of Joel Bady from Citi. Your line is now open.

Shawn EganCiti — Analyst

Good afternoon. This is Shawn Egan calling in for Joel. Thanks for taking my questions. It was great to hear about the pivotal trial for the beta-sarcoglycan trial this year.

When could you expect pivotal data for that study? Should we expect a similar cadence to Study 301?

Doug IngramChief Executive Officer and President

Well, we don’t know because we have to decide with the agency’s involvement in guidance what the right development pathway will be for the beta-sarcoglycan. It is significantly different from SRP-9001 in one important regard, which is the issue with SRP-9001. And one of the reasons that we’ve taken the approach that we’re taking, which is a placebo-controlled blinded study — well, there’s two reasons. One is that DMD is a large enough patient population that it is feasible to do that.

It has its own ethical challenges and, believe me, it required a lot of discussion with patient groups and patient advocates around that, but it can be done. So it’s executable. The second thing, of course, is that with respect to micro-dystrophin, you do have a truncated version of the dystrophin. So expression alone, it wouldn’t be sufficient.

You have to also show a function in that there is a sense to that, the agency has been clear about that, and it makes sense. With respect to beta-sarcoglycan, we’re in a different place. And that’s why I wouldn’t assume in advance that it’s the same cadence as SRP-9001 for two regards. One, this is a much rarer population.

The very concept of doing blinded placebo-controlled trial, I think, would be probably — it would be an understatement to say that that would be challenging from both an execution perspective and an ethical perspective. But the second thing that’s important is with respect to beta-sarcoglycan and 2E, the gene that we are delivering creates the native protein. This is the native protein. So with respect to those two issues together, the discussion that we’re going to have with the agency is around the ability to come up with a lean, efficient, executable approach to get this therapy to patients that are waiting.

We’ve already seen, both in our low-dose and our high-dose cohorts using the clinical supply from Nationwide Children’s Hospital that we’re seeing very high expression in both. We’re seeing correlates of a really strong functional endpoint. We’ll have an update on that, by the way, at MDA, and that will be a very important update. And so of course, our view is that given its native protein, the development pathway should be leaner, and it should be informed by the patient population and the fact that it’s a native protein.

But we’ll know that when we have the discussions with the agency, and we’ll have those discussions once we have GMP material to talk CMC with the division. And that will happen this year.

Operator

Thank you. Our next question comes from the line of Danielle Brill from Raymond James. Your line is now open.

Daniil GataulinRaymond James — Analyst

Hi, guys. This is Daniil Gataulin on for Danielle. Thank you for taking our question. On PPMO, in your last update, you mentioned that there were COVID-related biopsy delays that might have contributed to lower SRP-5051 muscle concentration in the 20 milligram per kilogram cohort compared to the lower dose.

I wanted to ask, with the improving COVID environment, can you comment on whether you’re still experiencing similar delays that may make data interpretation potentially more difficult? Thank you.

Doug IngramChief Executive Officer and President

Yeah. I don’t — yes. So to remind people, they were out of — the problem was the biopsy timing versus the dosing was out of window because of a delay that resulted from the pandemic itself. Dr.

O’Neill, you can confirm, but I don’t believe that will be an issue for the 30 mg per kg cohort that we’ll be reviewing in the second quarter.

Gilmore O’NeillExecutive Vice President, R&D and Chief Medical Offcer

Yes. That is correct. COVID has not forced important out-of-window biopsies.

Doug IngramChief Executive Officer and President

One thing I should comment on. I made an error earlier, and I apologize, and I would correct myself. The kids’ roll-off of the ESSENCE study, and I believe it’s two years. So they won’t — it won’t be — the study will read out, but kids will be rolling off the study.

So it’s, I believe, two years of blinded data, if I’m not mistaken, and not 144 weeks. Apologies for that error on my part.

Operator

Thank you. Our next question comes from the line of Joseph Schwartz from SVB Leerink. Your line is now open.

Kelly GirskisSVB Leerink — Analyst

Hi. This is Kelly Girskis on for Joe Schwartz. Maybe just one more on the PPMOs. You touched on this.

We’re hoping you could expand on the regulatory path you envisioned for 5051 and the other PMOs waiting in the wings. Might there be a creative way to do a single trial with multiple PPMOs in the future?

Doug IngramChief Executive Officer and President

Yeah. So a couple of thoughts on that. The big issue with the PPMO is finding the right dose. And then beyond that, our current working assumption is that the regulatory pathway will be the same or similar, whether the construct we’re going to use is a PMO or PPMO.

So one of the things that’s exciting about this RNA platform that we have is that we can precisely build constructs that are very predictable in their ability to induce exon skipping and, therefore, dystrophin production. And the other thing from a regulatory perspective is that we have the ability to avail ourselves of the use of dystrophin as a surrogate endpoint reasonably likely to lead to clinical benefit. And therefore, we have the ability to use the accelerated approval pathway. That is the pathway we’ve been able to officially use for EXONDYS, VYONDYS, and now AMONDYS.

So it’s our belief that regardless of whether it’s a PMO or PPMO, so long as we can induce substantial amounts of dystrophin that are reasonably likely to lead to clinical benefit, we’ll be able to use this efficient accelerated pathway to reliably bring constructs forward. Now, we can do that up to about 50%, 55% or so of DMD patients, so a significant number of additional patient populations. Then we have about 30% or so of patients with very rare exons where we would still use the accelerated approval pathway, but our goal is to build up a sufficient amount — I think we’re getting there, a sufficient amount of experience on both the dystrophin production and the safety side of things that we can do essentially a basket study with a collection of potential mutations that can get us to that next 30% of patients that would benefit from our therapy. And I think that would work similarly whether we had a PPMO or a PMO.

So a lot of potential opportunity, whether it’s PMO or PPMO, to do a lot of good in DMD. And that is, of course, our goal.

Operator

Thank you. Our next question comes from the line of Hartaj Singh from Oppenheimer. Your line is now open.

Jackie YanOppenheimer & Company — Analyst

Hi. This is Jackie Yan for Hartaj. Thanks for the questions. Just on the, I believe, $1.7 billion of potential milestones from your agreements with Roche.

Could you just remind us what proportion of that amount are going to be clinical milestones and what proportion are going to be for commercial milestone? Thank you.

Doug IngramChief Executive Officer and President

Yes. I’m not sure if we’ve disclosed that. Again, you can confirm or if we have, we can disclose again. But I don’t believe we’ve disclosed the nuances of our milestones.

Am I incorrect in that assumption?

Ian EstepanExecutive Vice President and Chief Financial Officer

That’s correct. And the milestones are mostly related to regulatory and commercial achievements. So they’re on the back end in the development program.

Operator

Thank you. At this time, I’m showing no further questions. I would like to turn the call back over to Doug Ingram for closing remarks.

Doug IngramChief Executive Officer and President

Well, thank you all very much for joining us this afternoon and this evening, and thank you for your probing and insightful questions. We, obviously, have a lot to do over the course of 2021, a number of very important milestones across this year. From a commercial and serving the patient community perspective, we’ll continue to serve the community with EXONDYS. We’ll continue to launch VYONDYS.

And we’re very, very excited about the opportunity to launch AMONDYS, which is already occurring. As I’ve said earlier, our therapy will be in warehouses this week, and we will be serving the community literally this week with that therapy. So I’m very excited about that over the course of this year. Staying with RNA, we’re very excited about the opportunity to update on the PPMO with a 30 mg per kg next quarter.

That could be a very exciting evolution of our RNA technology. In either regard, either PPMO or PMO, we have an enormous opportunity to do a lot of good in DMD, as I said a number of times tonight. We can serve over time up to 80% of the DMD community both in the United States and, hopefully, over time ex U.S., which is an enormous opportunity. On the gene therapy side, you know we have an enormous number of milestones, a lot of work to do this year with respect to SRP-9001.

We are very focused on that as that could be a significant transformative event for patients with Duchenne. And the results of Study 102, when you really look at it carefully, gives us increasing confidence about the potential of 9001 to bring a better, longer life to kids with DMD. And beyond that, of course, we have our limb-girdles that we’ll continue to focus this year. And I look forward to the opportunity to update everyone on milestones over the course of 2021.

And with that, thank you. Have a good evening. And of course, everyone, stay safe.

Operator

[Operator signoff]

Duration: 85 minutes

Call participants:

Mary JenkinsSenior Manager, Investor Relations

Doug IngramChief Executive Officer and President

Ian EstepanExecutive Vice President and Chief Financial Officer

Dallan MurrayChief Commercial Officer

Gilmore O’NeillExecutive Vice President, R&D and Chief Medical Offcer

Alethia YoungCantor Fitzgerald — Analyst

Brian AbrahamsRBC Capital Markets — Analyst

Salveen RichterGoldman Sachs — Analyst

Louise Rodino-KlapacExecutive Vice President and Chief Scientific Officer

Ritu BaralCowen and Company — Analyst

Tess RomeroJ.P. Morgan — Analyst

Difei YangMizuho — Analyst

Debjit ChattopadhyayGuggenheim Securities — Analyst

Gena WangBarclays — Analyst

Gilmore ONeillExecutive Vice President, R&D and Chief Medical Offcer

Gil BlumNeedham & Company — Analyst

Tazeen AhmadBank of America Merrill Lynch — Analyst

Vincent ChenSanford C. Bernstein — Analyst

Tara BancroftPiper Sandler — Analyst

Brian SkorneyRobert W. Baird — Analyst

Ting LiuUBS — Analyst

Marty AusterCredit Suisse — Analyst

Shawn EganCiti — Analyst

Daniil GataulinRaymond James — Analyst

Kelly GirskisSVB Leerink — Analyst

Jackie YanOppenheimer & Company — Analyst

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