Sarepta Therapeutics Inc

NASDAQ:SRPT

Earnings Call Transcript 2020-Q2

[Operator]

Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Second Quarter 2020 Earnings Call. [Operator Instructions] As a reminder, today’s program is being recorded.

At this time, I’ll turn the call over to Mary Jenkins, Manager, Investor Relations. Please go ahead.

[Mary Jenkins, Manager-Investor Relations]

Thank you, operator and thank you all for joining today’s call. Earlier today, we released our financial results for the second quarter 2020. The press release is available on our website at sarepta.com, and our 10-Q was filed with the SEC earlier this afternoon.

Joining us on the call today are Doug Ingram, Bo Cumbo, Ian Estepan, Dr. Gilmore O’Neill and Dr. Louise Rodino-Klapac. After our formal remarks, we’ll open up 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 slides 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 risk 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 and most recent quarterly report on Q-10 filed with the Securities and Exchange Commission 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.

With that, let me turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

[Doug Ingram, President and Chief Executive Officer]

Thank you, Mary. Good afternoon and thank you all for joining us for Sarepta Therapeutics second quarter 2020 investor conference call. As I have mentioned in the past, on March 13 of this year, all but the small contingent of our workforce transitioned it to a virtual work environment. Notwithstanding this unusual approach, we are not merely remaining productive, but have arguably become even more efficient and effective as we advanced our multi program, multi-platform genetic medicine ambitions. As you will hear this afternoon, we have continued to serve the patient community with our approved therapies, have already achieved or remain on track or many planned 2020 milestones expanded our three-pronged approach to building our enduring gene therapy engine. And as we have generated additional evidence in 2020, continued to build confidence in our unique approach to gene therapy is proving successful and highly differentiated.

With that, let us review our performance. As we continue to serve our patient community, while endeavoring to keep them safe in this pandemic, I am pleased to report that our second quarter net sales stand at $111.3 million, an 18% increase over the same quarter last year. As I mentioned in our last quarterly conference call, we withdrew our 2020 guidance in light of the potential impact of COVID-19 on clinic visits. As you can see, that impact has thus far been modest. Given the uncertainties of the external environment, we are not ready yet to set full year guidance. However, consistent with what we have seen thus far in 2020, we anticipate that any continuing impact from COVID-19 will remain modest.

Moving to our development programs, let me begin by commenting on our RNA franchise. In the second quarter, we completed our NDA submission for casimersen. Our RNA therapy built on our PMO platform and designed to treat the 8% of the Duchenne community who are exon 45 amenable. The PDUFA date for casimersen should be in the first quarter of 2021. If we are successful in obtaining this approval, casimersen will be our third FDA approved therapy, bringing the percentage of Duchenne community with available PMO therapies to nearly 30%. With a successful casimersen approval, we will have more than doubled the size of the treatable patient population since eteplirsen was first approved.

As successful as our PMO platform has been, we are not satisfied with the status quo. We have been working on our next generation of the PMO, which if successful, they profoundly improve the efficacy and convenience of our RNA technology. We are in our multi-ascending dose study called the MOMENTUM study for a peptide-conjugated PMO or PPMO and that is candidate 5051. Here we are using a proprietary positively charged peptide to increase penetration. In animal models, we have shown that if we can safely achieve appropriate dose levels, the PPMO greatly increases tissue exposure in turn greatly increasing exon-skipping and thus dystrophin production.

Treating Duchenne is all about increasing the production of the structural shock absorber dystrophin. So if the PPMO candidates are able to increase exon-skipping and dystrophin production, we could see a profoundly more efficacious RNA platform. And at monthly dosing versus the PMO weekly dosing, we would have a far more convenient therapy as well. In the second half of this year, we will have completed and we’ll release our safety tissue exposure, PK/PD and comparative exon-skipping for our PPMO 5051 candidate at 20 mg per kg. This will be an important proof of concept for that therapy, not only within DMD, but more broadly as a potential RNA platform to treat diseases where our steric blocking RNA technology could provide therapeutic benefit.

Let’s move now to our gene therapy engine. There are three pillars upon which we are building our gene therapy engine. First, our pipeline, second manufacturing capacity and manufacturing expertise, and third advancing and improving the science and effectiveness of gene therapy itself. Over the course of 2020, we have not only stayed on track, but having successfully dosed a significant number of DMD and LGMD patients. And with the additional data we have generated already this year, we continue to build confidence that our unique approach to gene therapy research and development is first-in-class and replicable. Consider the additional confirmatory data on our gene therapy platform that has been generated already this year. One of the most significant challenges with full body neuromuscular gene therapy is safely delivering the proper number of genome copies to cell nuclei.

In this regard, Sarepta’s programs have shown good tolerability and exceptional expression at reasonable doses. Now you will recall that in 2018, we announced the results of study 101, our first four DMD patients on SRP-9001, reporting a mean of 3.3 genome copies per nucleus, protein expression approaching normal as measured by western blot, IF positive fibers and IF intensity and that all patients improved significantly on each and every functional endpoint measured. On that basis, we commenced a placebo-controlled trial for SRP-9001 in the fourth quarter of 2018 using clinical material. Then in 2019, we announced the results from our three patient low dose cohort for SRP-903 to treat LGMD2E.

This is important for our platform because SRP-9001 and SRP-9003 share much in common within the design approach under the guidance of Dr. Louise Rodino-Klapac, the same viral vector, AAVrh74 and the same promoter the heavy chain MHCK7. We were pleased to report that even at a quarter of our SRP-900 dose, we had exceptional expression. As an example, over 50% of beta-sarcoglycan positive fibers were achieved. Every child improved significantly on every functional measure at nine months.

In 2020, we have generated additional consistent data and gained more experience with our constructs. In the second quarter, the one year results for Study 101 in Duchenne were published in JAMA Neurology, showing that every boy in the study improved significantly on each and every function line point at one year. In the same month, we announced the results of our second three patient cohort treated with SRP-9003 for LGMD2E, using the same dose that we have used for SRP-9001 for Duchenne.

We were very pleased to announce that with the increased dose, we yet, again confirm the ability of our construct to safely deliver gene therapy robustly. The children in the study had 4.2 genome copies per nucleus on average. There was a significant dose dependent increase in expression with children achieving 62% of normal on western blot, 72% of protein positive fibers, and 73% on intensity. Additionally, in our 41 patient placebo-controlled Study 102 using SRP-9001 for DMD, we dosed all children for the main analysis and are dosing children on crossover as well. By now between our two studies for SRP-9001 and our study for SRP-9003, we have dosed over 35 patients with active therapy, far more than any similar clinical programs in the studies are proceeding at pace.

The second pillar of our gene therapy engine is our manufacturing expertise. And there we have built impressively over the last two years. We have among the greatest capacity available for gene therapy in biotech in just two years between our dedicated suites at Catalent and our dedicated site in Lexington with Thermo Fisher. At the same time, we have built out our centralized gene therapy, manufacturing expertise within Sarepta. It is this group that drives the analytical and process development approaches across our programs and with our partners. Across Burlington and over Cambridge and our gene therapy center of excellence in Columbus, we now have some 270 professionals dedicated to technical operations, manufacturing and quality. For SRP-9001, we have completed process development and analytical development and have completed GMP runs for the material with land views, both for our next clinical trial and commercially. For SRP-9003, we’re in GMP runs now.

The third pillar of our gene therapy engine is bringing together the technology and tools necessary to improve and advance the science and effectiveness of gene therapy. We are a science driven company, and I am pleased to note that COVID-19 has done nothing to slow our progress in this endeavor. Having built out one of the deepest and most valuable gene therapy pipelines commencing in 2017, and then spending an enormous effort in the last two plus years on building out our manufacturing process, commencing in 2019, we began to aggressively look for opportunities to advance the science of gene therapy to compliment our internal program development.

In this quarter alone, we have added four new approaches to our armamentarium. In May, we announced our partnership with Dyno Therapeutics for the use of their AI and machine learning approach to develop improved capsids. From there, we entered into a partnership with Selecta Biosciences to use their ImmTOR technology in an effort to empower re-dosing. And then we entered into a partnership with Hansa Biopharma to access imlifidase with the goal of using it to ablate pre-existing neutralizing antibodies and to open gene therapy to patients that would otherwise be left behind. And then from there, we entered into a relationship with Codiak BioSciences to explore the use of exosomes across gene therapy, gene editing and RNA.

Now looking forward, we have important gene therapy engine milestones across the remainder of 2020. First with respect to SRP-9001, we have two major efforts ongoing. We must complete Study 101, our blinded placebo-controlled trial using clinical material. That trial is on track to have last patient last visit by the end of this year and to read out in the first quarter of 2021. Secondly, with GMP in the commercial material now in hand, our goal is to start our next trial in the second half of this year, our remaining gating items there are the following; first, engaging sites and obtaining IRB approvals. The pandemic has certainly created some challenges here, but the team is working through them and things are going quite well, and second, gaining alignment with the FDA on the initiation using the GMP material, which will occur this quarter.

With respect to SRP-9003, our goal is to start our pivotal trial in 2021. Our two gating items here are these; first, completing assay development and obtaining the release of our GMP runs, and second, completing a dialogue with the agency on the appropriate regulatory and development pathway for SRP-9003. Now this is an important dialogue, it will not only inform the development for SRP-9003, but we believe, it will provide insight into the development pathway for our other five LGMD candidates. We will provide an update on the LGMD discussions and our GMP material for SRP-9003 in early 2021.

If you will indulge me on a personal note, the second quarter marked my three year anniversary at Sarepta. In three years, we have made an enormous amount of progress toward our goal of bringing a better, longer life to those living with and too often dying from their disease. And we have done so by building and articulating an ambitious vision to become the leader in rare disease genetic medicine, with a robust and productive RNA platform and an enduring gene therapy engine. By gathering the resources and talent to make that a reality, and by then ruthlessly executing with a rapidity that to the extent possible matches the urgency of the very patients that we serve, patients who have their movement and their lives stolen from them bit by bit daily and hourly.

In the last three years, we have built a pipeline with over 40 programs, are now in 10 clinical trials advancing multiple therapies. Have made enormous progress in building from ideation to reality, our three pillar gene therapy engine and are seeing consistent and confirming results thus far. As I reflect on our progress, the credit should go to three groups, the sophisticated, dedicated and hardworking professionals that make up our over 1000 strong workforce at Sarepta. Our external partners, in my opinion, the best and brightest in genetic medicine around the world. And of course, our patient community, a community that not only relies upon us, but also informs us and guides us and often pushes us. So we are clear now is not yet the time for a victory lap or premature celebration. We are encouraged by our success so far, but we have much to do over the course of the next 15 months and still much more to prove. But you can count on this team, stay on mission, to address and remove obstacles that appear here in front of us and to execute for patients waiting for our therapies.

And with that, I’ll now turn the call over to Bo for a commercial update. Bo?

[Bo Cumbo]

Thank you, Doug. Good afternoon, everyone. Our experienced teams at Sarepta are continuing to work through the headwinds of the COVID-19 pandemic. I’m pleased to report that our product revenue for the second quarter of 2020 totaled $111.3 million. We’ve overcome some unique obstacles created by the pandemic and are extremely proud of the teams and their accomplishments and the face of these challenges. While we’re still navigating and responding to the strain the pandemic has placed on the healthcare systems. The modifications we’ve made to our commercial execution strategy have allowed eligible patients to start and stay on therapy in this unprecedented time.

Our strong relationships with partners have played a key role in the ability to start new patients, keep others on therapy. This is a testament to our team’s expertise and commitment to our mission to serve the Duchenne community. We continue to provide an uninterrupted supply of therapies to our patients and mitigate major treatment disruptions through a unified effort with our manufacturers, distributors, especially pharmacies, healthcare providers and payers.

Many of our patients are choosing not to delay or stop therapy. And we believe this is partly due to the fact that the majority of patients on EXONDYS 51 and VYONDYS 53 are receiving weekly infusions in their homes. We are currently working closely with healthcare providers and specialty pharmacies to transition additional patients to weekly home infusions. Since many clinics and hospitals still have restrictions in place.

We have thoughtfully deployed measures to minimize the risk of transmitting COVID-19, which includes making personal protective equipment available to all our patients who have requested supplies. This will help ensure that patients have access to protective equipment, when nurses’ administer their weekly infusions at their homes. Patient safety remains our top priority, and we will continue assessing any and all efforts that will help patients feel safe during this unusual time. We continue to monitor the pandemic and are ready to react quickly with additional modifications to our commercial strategy, especially in places seeing surges and infections.

As noted last quarter, the dynamics of initiating treatment with EXONDYS 51 and VYONDYS 53 remain effective. Since many clinics are not seeing patients for normal in-person appointments. This has resulted in fewer patients initiating treatment. Physicians typically want to monitor patients in the clinic for the first couple of infusions, and we’ve worked with key opinion leaders to find options for patients to safely initiate treatment with VYONDYS 53 or EXONDYS 51 in their home or an alternative site rather than the clinic. This has provided physicians and patients, a path to initiate care. Hospitals in each state are operating under different rules and regulations. We anticipate the intake of Star performance will slowly increase, the states ease restrictions and clinics resume normal operations.

From the reimbursement standpoint, our healthcare providers have become experts regarding the authorization and reauthorization process for our products and due to the ongoing education to manage care organizations, reimbursement efforts have been productive. We are confident that over time eligible patients will ultimately receive access to reimbursements for VYONDYS 53 and EXONDYS 51 and start therapy in the timely manner.

We have successfully adapted our weekly engagements with key opinion leaders and payers through virtual interactions. Our discussions with key opinion leaders and other healthcare providers are focused on identifying patients amenable to exon 51 and 53 skipping and driving prescriptions. We also continue to educate payers about the importance of patients starting staying on therapy, regardless of ambulation status, age, or gender. We’re encouraged by these efforts, which has resulted in new start forms and new patients initiating treatment starts during the quarter.

Moving on exon 45. In June, we announced the completion of our NDA submission for casimersen or SRP-4045, as we await FDA’s response, our commercial and medical affairs teams preparing for another successful launch. The foundation of our plan will be tailored to reaching patients who are amenable to exon 45 skipping, who represent another 8% of the Duchenne community. We will leverage our knowledge and experience from the EXONDYS 51 and VYONDYS 53 launches to facilitate patient access to casimersen as quickly as possible.

While we’re very proud of the accomplishments that the team has made to date, we still have an immense amount of work ahead of us. With each new therapy that is developed and advanced in our pipeline, we have the responsibility to pave the way for patients to access these treatments. This is an incredible responsibility and one that we do not take lightly. The depth of our experience on our teams has helped us navigate through complex launches in these unprecedented times. With each new launch and lessons learned, we’ve become a stronger company. One that’s better able to serve our patients and deliver on our mission as the global leader in precision genetic medicine.

And with that, I will now turn the call over to Ian for an update on our financials. Ian?

[Ian Estepan]

Thanks Bo. Good afternoon, everyone. This afternoon’s press release provided details for the second quarter of 2020 on a non-GAAP basis, as well as a GAAP basis. The press release is available on Sarepta’s website. Please refer to our press release for a full reconciliation of GAAP to non-GAAP financial results.

Net product revenue for the second quarter of 2020 from our products, EXONDYS 51 and VYONDYS 53 was $111.3 million compared to $94.7 million for EXONDYS 51 alone for the same period of 2019. The increase primarily reflects higher demand for our products. In the quarter ended June 30, 2020, we recognize $26 million of collaboration revenue, which primarily relates to our collaboration arrangement with the Roche. The co-development costs under the Roche agreement totaled $8.9 million for the second quarter and are included as a reduction to our R&D expenses.

On a GAAP basis, we reported a net loss of $150.8 million and $276.4 million or $1.93 and $3.74 per basic and diluted share for the second quarter of 2020 and 2019 respectively. We reported a non-GAAP net loss of $117.9 million or $1.51 per basic and diluted share in the second quarter of 2020, compared to a non-GAAP net loss of $61.2 million, or $0.83 per basic and diluted share in the second quarter of 2019.

In the second quarter of 2020, we recorded approximately $13.3 million in cost of sales compared to $15.9 million in the same period of 2019. The decrease was primarily due to write-offs of certain batches of EXONDYS 51, not meeting our quality specifications for the three months ended June 30, 2019 with no similar activity for the three months ended June 30, 2020.

On a GAAP basis, we’ve recorded $188.5 million and $113.3 million in R&D expenses for the second quarter of 2020 and 2019, respectively, which is a year-over-year increase of $75.2 million. This increase is primarily related to $81.6 million increase in manufacturing expenses, primarily due to the continuing ramp up of our micro-dystrophin program. On a non-GAAP basis, R&D expenses were $160.4 million for the second quarter of 2020, compared to $87.5 million for the same period of 2019 and increase of $72.9 million. The year-over-year growth in non-GAAP R&D expenses was driven primarily due to a continuing ramp up of our micro-dystrophin program.

Now turning to SG&A, on a GAAP basis, we recorded $73.7 million and $67.4 million of expenses for the second quarter of 2020 and 2019 respectively, a year-over-year increase of $6.3 million. On a non-GAAP basis, the SG&A expenses were $55.1 million for the second quarter of 2020 compared to $52.3 million for the same period of 2019, an increase of $2.8 million. The year-over-year increase was driven by significant organizational growth and expansion that supported our commercial launch as well as our over 40 therapies in various stages of development across several therapeutic modalities.

On the GAAP basis, we’ve recorded $12.4 million in other expenses, net for the second quarter of 2020, compared to $0.9 million in other expenses, net for the same period of 2019. The unfavorable change primarily reflects interest expense on our debt facilities entered in December 2019. We had approximately $2.1 billion in cash, cash equivalents and investments as of June 30 2020.

And with that, I’ll turn the call over to Gilmore for an update on our research and development activities. Gilmore?

[Gilmore O’Neill]

Thank you, Ian, and good afternoon, everyone. Doug has already shared the highlights from our most advanced gene therapy programs. I will thus focus my remarks on the progress of our RNA portfolio, which comprises one of the three platforms Sarepta uses to drive its precision genetic medicine therapeutic strategy. I would begin with the PMO portfolio.

As Doug mentioned in June as planned, we completed the NDA rolling submission to the FDA for casimersen. If accepted and subsequently approved, we will have more than doubles the size of the treatment patient population since eteplirsen was first approved. Importantly, our post-marketing requirements or PMR studies are progressing despite the challenges arising from the COVID-19 pandemic.

In summary, the mission 402 PMR study for eteplirsen is dosing, and we have enrolled the first cohort of patients. The ESSENCE of study of golodirsen and casimersen is progressing. Thanks to the immense efforts of investigators, patients, and their families and our clinical operations teams. We have managed to minimize the disruptive impact of COVID-19 on the trial. Prior to the onset of the pandemic, we had already been moving many patient visits, including per dosing to their homes.

In recent months, we have significantly increased the number of patients using home visits. As we were accelerating plans for at-home visits, we did initially see some patients miss doses and visits. Nevertheless, now I am pleased to say that the new mitigation has significantly improved the situation and most patients are on track again. All of our mitigation strategies comply with guidances from regulatory agencies around the world, on the conduct of trials during the COVID-19 pandemic. Indeed the pandemic has served not only as a disruptor, but a catalyst to permanently change our approach to clinical trial execution. Thus, while not being complacent, we are confident that we can deal with and minimize the impact on all of our future trials in the face of surges in COVID-19 infections.

Before I turn to the PPMO platform and the PPMO 5051 program for DMD specifically, let me give you an update on the USAMRIID collaboration. In late April, we announced an early research collaboration with USAMRIID that would exploit our PPMO technology as a potential therapeutic for COVID-19. The work is ongoing with USAMRIID and we have expanded the collaboration to work with the leading research group in Sweden. Early results support performing additional confirmatory experiments.

Now turning to PPMO development. A key element of Sarepta’s R&D strategy is to enhance tissue or muscle penetration of our PMO chemistry and thus enhance efficacy by increasing dystrophin expression. We have a number of research programs that support this strategy. To remind you, our PPMO platform fuses a cell-penetrate peptide in PMO to enhance failure as nuclear penetration. Our most advanced PPMO program is SRP-5051. Our ongoing SRP-5051-201 multi-ascending dose trial named MOMENTUM is advancing, at all patients in the 20 mg per key cohort have been dosed.

COVID-19 relation shutdowns caused one patient to miss the dose. But since then with new mitigations in place, we are executing well. Just to remind you, we started the MOMENTUM study had 4 mg per kg and have it escalated already to 20 mg per kg. This represents dosing beyond that, which we originally anticipated. We plan to continue to dose escalate based on reviews of safety. And so far, we have not seen any safety signals.

This year, we will be reviewing 12-week data from our 20 mg per kg cohorts of Duchenne patients treated with PPMO 5051. We will be examining systemic PK, tissue penetration, safety, and exon’s skipping data. We will measure exon skipping by additional drop PCR or ddPCR allowing us to directly compare the efficacy of our PMO and PPMO candidates. Our preclinical in vitro and in vivo models have demonstrated a robust correlation between the amount of exon skipping and amount of dystrophin production. We would publish these data soon.

Thus exon skipping is a good marker for the kinds of dystrophin production we expect to see over time. It is important to note that while 12 weeks is an early time point to access exon skipping. We are confident that this is an appropriate time point to demonstrate proof-of-concept that the cell-penetrating peptide for CPP will enhance muscle tissue exposures and thus enhance downstream exon skipping. This allows us the potential to move this technology forward with the urgency necessary to meet the needs of patients with Duchenne.

It is also important to remember that dystrophin accumulates over time as we have observed in PMO study. And so we expect to see higher levels of dystrophin at leisure time points, if the therapy is successful. Muscle biopsies at later time points are planned in the latter part of the MOMENTUM study, once we have selected our final dose. To readout for MOMENTUM would be important for the 5051 program dose selection, but additionally would potentially extend to other PPMO Duchenne programs. We have already designed and selected five additional PPMO candidates. In fact, that could treat 50% of Duchenne patients who carry skip amenable in their dystrophin gene.

I do want to highlight that rare deletions susceptible to exon skipping impacts an additional 35% of patients with Duchenne. And we are creating a development strategy that would attempt to accelerate the approval of PPMO compounds, if successful for these patients using a novel platform or extrapolation strategy. Proof-of-concept for PPMO in DMD or Duchenne would also read through to the selection of that chemistry to target new non-muscle therapeutic areas. Non-DMD and non-muscle therapeutic area targeting is a key pillar of Sarepta’s R&D strategy.

In summary, I am very pleased with our response to the incredible challenges created by the COVID-19 pandemic and the progress we’ve made during this time. Finally, 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 to maintain to our urgent mission to deliver new highly effective therapies to people with desperate diseases.

Now, I will hand back to Doug for Q&A. Doug?

[Doug Ingram, President and Chief Executive Officer]

Thank you very much, Dr. O’Neill. And Crystal with that, let’s open the call for questions.

[Operator]

Thank you. [Operator Instructions] And our first question comes from Tazeen Ahmad from Bank of America. Your line is open.

[Tazeen Ahmad, Bank of America]

Okay, good afternoon. Thanks so much for taking my question. Doug, I just wanted to get a little bit more color as it relates to the FDA discussion this quarter. Can you talk about some of the more important items that you’ll need to get alignment on from the agency? And also do you plan on asking them about the plan to pass the non-ambulatory or older patients as well? Thanks.

[Doug Ingram, President and Chief Executive Officer]

Thanks a lot for that Tazeen. So let’s review, one of the things, we had said earlier this year that we would have GMP material on hand by July of this year. And the good news is that we did. So we’ve got two things to do. As you know, we’ve got a – get our next study using commercial process material up and running and getting patients dosed. And we’re going to do that in the second half of this year and the team outstanding COVID-19, and the distractions that occur, and some of the challenges occur with COVID-19 have done really a remarkable job keeping on pace and moving to get that study started. But before we can do that, we have to have our meeting with the agency.

And I said in my prepared remarks, we will be meeting with the agency this quarter and there really are just two things that there are significant things, but there are two things that we need to get alignment and concurrence on with the agency. The first, of course, is our CMC approach itself for the commercial material to use the commercial material in the next study. We’re very pleased at how these GMP runs have come out, very, very confident in the approach that we’re taking from our perspective. There are no significant quality attributes that are different from the clinical material in a manner that would be predicted to affect the therapy in anyway functionally or efficacy wise or safety wise. So that’s one significant concur as we need.

And of course, the second one is to gain concurrence on the next study. Certainly, in connection with that, we will have conversations with the agency about our non-ambulatory study as well. It is one of our goals to commence the non-ambulatory study as soon thereafter as it’s possible, perhaps even close to being concurrently with the next study, the main study that we’ll be using if we’re successful for the approval of the therapy in the United States.

[Operator]

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

[Salveen Richter, Goldman Sachs]

Good afternoon. Thanks for taking my question. It’s successful, how do you see the PPMO platform fitting into the treatment paradigm versus PMO in gene therapy in DMD and what are your plans for non-DMD approach on the forward?

[Doug Ingram, President and Chief Executive Officer]

Yes. That’s a great question. I’m going to – I’ll answer that briefly and then I’ll turn this over to Dr. O’Neill. Could he maybe talk about some of the areas we could take this RNA technology. So first and foremost, the excitement of the PPMO, if it is successful is for an even more profound impact from an RNA perspective, with respect to Duchenne muscular dystrophy. Now, of course, the question will immediately arise thereafter, what is the – how will gene therapy and RNA co-exist? In the short answer to that is, we don’t yet know. There will certainly be even with a transformative gene therapy. There will be a place for a profound RNA for Duchenne muscular dystrophy in children who for instance, are screened out for gene therapy in places where gene therapy is not available or not yet available.

So there will already be a significant place for it. And if one considers just that preexisting neutralizing antibodies alone, that is with respect to our capsid right now about 15% or so. And that population that would be screened out until we’ve been able to address that issue scientifically that is larger than the 10% population, but of course, with a significantly more impactful RNA platform. And they very well be the case that there is a role for a combination, both of gene therapy and of RNA. So first we need to see what the PPMO will look like. And then we are doing work even as we speak right now from a non-clinical perspective to test the hypothesis about whether a profound gene therapy followed either in the near term or in the longer term with a profound RNA would be synergistically beneficial to patients.

But beyond that, of course, if one of the things about our PMO is that the PMO is a neutrally charged. It is creating phenotypic change in these children and giving them longer time out of a wheelchair, et cetera, but move beyond the MD. We need a more penetrative RNA technology like the PPMO if it works. But if it does, the theory is that we can take this far beyond DMD and the research group is already working on the kinds of areas we would take that. But perhaps with that, I can turn this over to Dr. O’Neill, he can touch on that issue.

[Gilmore O’Neill]

Thanks very much, Doug. I think you actually articulated very nicely. The beauty of the RNA technology and the PMO chemistry is specifically is that we have proof-of-biology. We have demonstrated that we can deliver the PMO to a muscle as actually see downstream, skipping and dystrophin up-regulation or rather skipping dystrophin either from expression by returning into in-frame. With the PPMO experimentation with 5051 and the study readouts, we hope to test the hypothesis best increased exposure driven by the cell pattern peptide fusion. Two of the PMO will enhance tissue exposure in muscle. But we actually also know is that that will extrapolate beyond just that muscle tissue to other tissues. And as you are aware, many tissues are amenable and certainly the PPMO and PMO have demonstrated tropism for other tissues, including liver, kidney, heart, et cetera. And we are actually doing a comprehensive at genome-driven at review of those tissues and the associated diseases to identify those that are amenable to exon skipping. So that is worth it is ongoing and I’m very excited by it.

[Doug Ingram, President and Chief Executive Officer]

One final thing, I will say, moving back to DMD, just – and I think people know this, but I’ll remind you. We’re currently using 5051 exon 51 PPMO as our proof-of-concept. And of course, later this year, we’ll have some of the PK/PD tissue dosing safety and exon skipping. Importantly, exon skipping for 5051 as our proof-of-concept, we have already built beyond 5051 constructs with the peptide conjugated to them for exon that could treat already about 50% of the Duchenne community with a path as Dr. O’Neill mentioned in his opening remarks, with a path to get to a significant percentage beyond that perhaps another 35% beyond that with a slightly more exotic platform approach. And so – and we will start moving as rapidly as we can, assuming of course that the results are support that when we look at them later this year.

[Operator]

Thank you. Our question comes from Anupam Rama from JPMorgan. Your line is open.

[Anupam Rama, JPMorgan]

Hey, guys. Thanks so much for taking the question. I got a quick one here on we’ve gotten a lot of inbounds on 9001 safety recently, and I think some of it may revolve around some comment from Dr. Mendell, maybe at ASGCT that 9001 will be associated with some sort of mild compliment activation. Any context you can provide here and just maybe remind us of how frequently did the DSMB for Study 2. Thanks so much.

[Doug Ingram, President and Chief Executive Officer]

Sure. I’m going to turn this question over to Louise, who can answer this. But I will say upfront, just so we’re absolutely clear. That was a misunderstanding. There is absolutely no signal that we’ve seen as compliment associated with 9001 at all, but I think Dr. Rodino-Klapac can provide the context around that misunderstanding.

[Louise Rodino-Klapac, Senior Vice President-Gene Therapy]

Sure. Yes. Dr. Mendell was speaking about his broad experience in gene therapy and not includes other vectors like AV9. As Doug mentioned, we presented our data in both different medical meetings, as well as investor calls on LGMD2E, as well as our terminology paper. And just to reiterate, we’ve not seen any evidence of compliment activation in our study. And Study 1 continues on as planned no interruptions.

[Doug Ingram, President and Chief Executive Officer]

I think people were reading through comments. He was making about other programs. This has been seen in a number of other programs, primarily associated with AV9. He wasn’t speaking about AAVrh74, we’ve seen nothing relating to compliment there. And just to remind you, and of course, I know Dr. O’Neill is a proper scientist. We have to measure ourselves by the evidence on hand, but the good news for us is that with respect to rh74 across both Duchenne muscular dystrophy and Limb-Girdle, we have now dosed, as you heard in my opening remarks over 35 children, and the Study 1 and 2 continues to move a pace. So I think the evidence on our broad safety profile, I think is only getting bolstered over the course of the last 24 months and really significantly this year.

[Operator]

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

[Technical Difficulty]

Pardon me, sir. We’re not able to hear you. And then we’ll move on to our next caller Matthew Harrison with Morgan Stanley.

[Max Skor, Morgan Stanley]

Hi, this is Max Skor on for Matthew Harrison. Just a quick question, based on the recent agreements you signed, how are you thinking about integrating these new technologies into your pipeline? Thank you.

[Doug Ingram, President and Chief Executive Officer]

We are – thanks a lot for that question, Max. So to just remind everybody, I think you heard in my opening remarks, we’ve done a number of really interesting transactions over the last quarter to evolve the science and gene therapy, as there’s – we’ve got Dyno, which is artificial intelligence and machine learning for making better CapsidMap. We’ve got Codiak, which is an entirely different approach using exosomes for delivery device, that you can use an RNA gene therapy, gene editing.

And then I think it was sort of more near term perhaps, but really impactful is both Hansa with imlifidase, and Selecta with ImmTOR. Hansa’s technology would ablate preexisting neutralizing antibodies so that you could essentially empower – at a minimum empower the people that would otherwise have preexisting neutralizing antibodies that they would have got environmentally have them in frames for the ability to get gene therapy. Of course, Selecta, with this concept of co-administering their ImmTOR technology with a gene therapy so that you could essentially trick the body into believing that the gene therapy that it’s receiving and the candidates receiving itself and not for it, you don’t build up neutralizing antibodies, which could empower re-dosing even multiple doses every time.

The short answer on your question, however, is we’ve just entered into these agreements. These tools have gone into the armamentarium that Dr. Rodino-Klapac and her team have to advance this. And we’re looking carefully at the timelines and how we can move these as fast as possible forward. As you can imagine, as a mission-driven organization, it is our goal to move these technologies as fast as possible, and improve gene therapy as much as possible. More importantly, bring the largest number of patients into frame for gene therapy. So we don’t have timelines right now, but we’re moving as fast as we can on that. And I suspect we’ll have updates early next year on that.

[Operator]

Thank you. My next question comes from Martin Auster from Credit Suisse. Your line is open.

[Mark Connolly, Credit Suisse]

Hi everyone. This is Mark on for Marty. Thanks for taking my question. So my question relates to the upcoming readout for SRP-5051. I know that you frame the program relative to exon does in terms of dystrophin expression. I’m curious, what is the level of exon skipping that exon does achieves in humans? And could you speak to the magnitude of improvement in exon skipping, you’re hoping to see SRP-5051 as part of this initial clinical trial update? Thank you.

[Doug Ingram, President and Chief Executive Officer]

Sure. Dr. O’Neill, you might want to take this and talk a little bit about what we’ll be looking for in the second half and perhaps the way we would look at to compare it to what we might be seeing with eteplirsen, golodirsen and casimersen?

[Gilmore O’Neill]

Yes. So I think the key thing is that we will be looking, first of all, it’s very important to understand that we are using digital drug PCR and we will actually be looking of that for PMO and PPMO. It’s important to actually distinguish that from the older quantitative RTP service being used in the past. And we will actually be looking at data from both PMO historical samples, and then looking at our ddPCR in our 5051 program. I think the other point that wants to make is that, or restate is that we have actually with our non-clinical data both in vitro and cell line, as well as in animal model. As seeing a robust correlation between dd digital drop PCR and dystrophin levels. And what we’ve actually seen there is a ratio of between two to three. Obviously, we have to validate that in human, but what we’ve seen in our experimentation to date has been how should I say gives us confidence with regards to both the robustness of the correlation and the ratios and what we hope to see in our human studies.

[Operator]

Thank you. Next question comes from Alethia Young from Cantor Fitzgerald. Your line is open.

[Alethia Young, Cantor Fitzgerald]

Hey guys, thanks for taking my question and congrats on the quarter. I just wanted to talk a little bit about kind of hitting the GMP pre-material and the compatibility. It seems like that’s a big deal for you guys and want to talk about what that means going forward for this and other platforms of your? And then just on Selecta and that ImmTOR, I’m always just interested in Dr. Klapac perspective on like, how to think about re-dosing and how this technology in hypothetically might be important in that. Thank you.

[Doug Ingram, President and Chief Executive Officer]

Okay. Before I turn it over to Louise and talk about Selecta at all. So thank you, Alicia. I agree with you, it a big deal. I mean it, and it’s not a one quarter effort. The fact that we have GMP material on hand right now is the result of an enormous amount of work by a significant number of professionals over a long period of time. We started this really at ideation stage a couple of years ago that we were going to build out this gene therapy engine. And we knew at that time that we need to build out manufacturing, not simply for capacity, but also expertise, process development, analytical development, et cetera.

And you’ve sort of lived with us as we’ve worked through that process, optimized or the process of optimizing process development, getting all of our analytical development done this, 24 assays involved here, all are complete, even qualified or validated, and if the case is required for each of those. And then, of course, we’ve done numerous runs and having GMP material on hand right now is enormously important. And it will – now I will also say, of course, we also have to meet with the agency. We’re going to do that this quarter. We have to get them do concur in our view the material, et cetera, but we feel very good about where we are and the results that we’ve seen.

And to your very good question, it’s going to pay significant dividends on our platform more broadly, as I said, and I think in my prepared remarks, this concept of a gene therapy engine isn’t simply a narrative. It is a platform that is built on three significant pillars, all of which are required to build an enduring gene therapy platform. The first of course is the pipeline. And we have a significant pipeline between research and things in the development stage, and even in the later development stage, we have approaching 30 programs right now, at least depending on how you count them.

And then, of course that’s the latter part I’ve talked about is that Louise will talk to you about is the advancing the science, making gene therapy even more effective and bringing more patients in so they can get treated. And of course, that middle concept of manufacturing is crucial. And I’m very proud of this team for having decided early on at the very ideation of this concept of building a gene therapy platform to begin to invest significantly both in the talent and beyond the talent in building manufacturing. And so the fact that we have GMP material on hand right now speaks reams to 9001, but also 9003, also the rest of our limb-girdles. And I believe beyond that into the other gene therapy programs that are sitting behind us programs.

So we’re – I don’t want to – I said in the end of my opening remarks. It is so easy to become to get hubris when you have a little bit of success and we don’t want to do that. We have a lot yet to do. I think meeting with the agency is that is a significant next step for us. But we’re very excited about the progress to date. And we’re very excited, frankly, about the results that we’ve received to date. We’re still we have more results to come in. We have to see 102 at the beginning of next year, but certainly as you triangulate the results, we’re getting both 101 than the nine months on 101, then the start of 102 in the fact that we’ve been able to dose all of the kids for the main study and then the low dose on 9003 and the nine months there. And then the low dose of 9003 and the successful one year there, then the one year on 101 and now of course, the high dose on 9003 and exceptional expression, we’re getting there. And the good safety profile that we’re seeing across all of the programs gives us some confidence that we’re on the right track to be able to do what we’re trying to do.

And what we’re trying to do is more simply something that will be commercially successful, but far more profoundly than that. We want to bring a much better life to these patients when heard on Duchenne patients, and then beyond that we’re living with and degenerating from, as I said before, far too often. So coming to these rare genetic diseases. So thank you for that question. And with that, I apologize if I rambled for a second. So I should turn this over to Dr. Rodino-Klapac to talk to Selecta at all.

[Louise Rodino-Klapac, Senior Vice President-Gene Therapy]

Yes. Thank you for that question. So we’re excited about both Hansa and Selecta. Hansa gives us an opportunity to ablate antibodies in patients that are positive for AV antibodies. So that helps us potentially get to those 15% or so patients that have pre-existing antibodies and also gives us the opportunity to potentially for re-dosing down the road. Selecta, we’re particularly excited about because it has the potential to prevent those antibodies from forming in the first place. So and with the first dose of gene therapy patients could be co-administer this, is strives to potentially prevent those antibodies from forming with the potential to re-dose down the road. So we just entered into these agreements. And then there’s additional non-clinical studies to be able to prove that these will be effective and safe. But we’re definitely excited about the potential there. We want to make sure that we have every, every tool to reach all patients and that’s our goal. So we’re just we may never need it. But it’s better to be looking at it proactively. And that’s what we’re doing. So thank you.

[Operator]

Thank you. Our next question comes from Tyler Van Buren from Piper Sandler. Your line is open.

[Tyler Van Buren, Piper Sandler]

Hey, good afternoon. I had Just a quick follow-up question on the MOMENTUM trial. So you mentioned that you started at 4 mgs per kg and are up now to 20 mgs per kg, but if I’m not mistaken, you mentioned you could also potentially go higher than that. So based upon the animal model data, can you just define potentially a ceiling or a dose ceiling that you observed and what that was based on? I’m assuming it was some sort of safety or toxicity.

[Doug Ingram, President and Chief Executive Officer]

Yes. Thank you for that question. So the short answer is that we’re going to continue – so first understand the following. We are already above what we had – we would have considered success at least from our preclinical models. Now, please, don’t over read that we’ve got to get the data and we’ve got to see the biopsies and we’ve got to do the work. And so I don’t want to oversell this. But I will say, if you look from a preclinical prediction perspective, we’re already beyond that point where we would have said, we are very excited and this is great. We are going to continue to push that dose. We know what we’re looking for and what it is showing. And in preclinical models, that will be the dose limiting signal that will help us choose the dose.

Our goal of course, is to achieve – reasonably achieved the highest dose that is safe for these kids. And so we’re going to continue to dose up until we get to a place where we think we’ve seen a signal that tells us that we’re at the right margin between safety and efficacy. And certainly we’re going to go to 30 mgs per kg this year. So you won’t have a doubt on 30 mgs per kg. It won’t come in time, but we’ll have the 20 mgs per kg, which will be – they’ll be certainly insightful for us. Is there anything there that I missed, Dr. O’Neill?

[Gilmore O’Neill]

No, you nailed this. The target organ is the kidney and that’s what we’re monitoring closely. And it’s been good so far.

[Operator]

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

[Brian Abrahams, RBC Capital Markets]

Thanks for taking my question and congrats on all the progress. With the full one year data for 9001 now published. I’m curious how this longer-term data guides you with respect to conduct patient selection, endpoint selection for your next studies. Just when we look across some of the positive results, but maybe a little bit of variability measure to measure and CK and function across the NSA components as well as the learnings may be there from the cardiac MRI. Thanks.

[Doug Ingram, President and Chief Executive Officer]

I would say, broadly one of the values of Study 101 is that it allows us real time insight as we build out – as we build out Study 102 and then as we look forward to our commercial process trial as well. So we already had a significant amount of experience with 101 by the time we commenced Study 102. So it already informed our thinking and it informed the powering of that study, as well as the selection of the primary functional endpoint being NSAA. We’ve had an opportunity to continue to monitor these children as you saw, of course. And then we have the one year data that reported out in JAMA Neurology. And I will tell you that it is confirming of the approach that we took with respect to Study 102, the way we’ve chosen NSA, and frankly, the way we have powered that study. So we feel very good about where we are and I think 101 has been very helpful in helping us power that study and give us confidence that we’re on the right track.

[Operator]

Thank you. Our next question comes from Gena Wang from Barclays. Your line is open.

[Gena Wang, Barclays]

Thank you for taking my questions. I have one question regarding PPMO has three parts. So the first is just follow-up with the earlier question. Could you remind us the percentage of exon-skipping for X down the 51 in early animal data? And the second question is for the non-muscle non-DMD program. What peptide you have in mind for the PPMO program? And lastly, do you see antibody oligo-based therapy as threat to your PPMO franchise?

[Doug Ingram, President and Chief Executive Officer]

Yes, fine. Okay. So first of all, to the last question I’ll answer now, and we’re excited that other folks are looking at researching ways to bring better last to Duchenne muscular dystrophy. But we certainly feel that – our programs are the most advanced and the most hopeful. So we’re really focused on our own programs. Going back to your other two questions, and I will turn this over to Dr. O’Neill, who can give you some perspective. But broadly speaking – and I’ll let Dr. O’Neill touch on this with more expertise than me.

So, first of all, know that the percentage of exon-skipping you might look to in the historically with respect to eteplirsen, it won’t be meaningful here because the approach to looking at exon-skipping is different. We’re using digital drop PCR now, in the past we used a different form. I think it was rPCR. But Dr. O’Neill will remind us of that. And so it’s a bit apples to oranges. The good news, just so we know is that when we announced the results the 20 mgs on the PPMO, we will have data using the same exon-skipping technology for eteplirsen, so there will be an ability to see what we might’ve seen with eteplirsen versus what we will see with 5051. And then I believe I’ll let Dr. O’Neill confirm it, that we would be using the same proprietary peptide that we’re currently using, that we put a lot of work into. But Dr. O’Neill, you can correct me if I’ve said anything incorrect there.

[Gilmore O’Neill]

No, that’s correct. And I think Gena, you asked – just to restate, you have two questions about peptide and the PMO skipping. I think I could do one better with regards to the ddPCR in the animal, and that we did actually look at it at 24 weeks, actually over several week period, but at 24 weeks in the PROMOVI in humans – in patients we saw about 0.6% skipping that exosome, but it’s very important to emphasize that’s digital drop PCR, it’s not the quantitative PCR that was used in prior descriptions. And that I think it’s disclosed in our MDA poster. So the beauty of the ddPCR is very tight and actually allows you then to compare across patients and very importantly, and more importantly to protein expression downstream.

And then you asked other question about peptide. We’ve not disclosed the nature of the self entered peptide. But I think Doug and I have already highlighted in this earnings call and in others that we continue to – we’re never complacent. We’re never satisfied with the status quo and we continue to invest in exploring and optimizing possibly better peptides. And obviously our Codiak collaboration that we announced is also a part of an overall approach to both improve tissue penetration and frankly specific our target or tissue specific targeted.

[Operator]

Thank you. Our next question comes from Joel Beatty from Citi. Your line is open.

[Shawn Egan, Citi]

Hi. This is Shawn Egan calling in for Joel. Thanks for the updates today and for taking my questions. Maybe could you talk a little bit about the package you plan to go to the FDA with in regards to the path forward for limb-girdle muscular dystrophies in general? I guess, from the fact that these are mostly monogenic conditions, what other factors help make the case for an accelerated path to approval? And what else should we be kind of considering?

[Doug Ingram, President and Chief Executive Officer]

Yes. Thank you for that. Great question. So I think I said in my opening remarks, we have two significant things to do over the course of this year. One is to complete the GMP runs, which is a combination of two things. Just so we’re clear, it’s not simply the runs themselves, but it’s of course all the assay work. We can leverage a lot of what we’ve done. I mean, an enormous amount of what we’ve done with 9001. But there are the spoke assays for each particular program. So we’ve got to complete that work as well.

And the second thing to your good question is, we need to engage in a dialogue with the agency about the appropriate regulatory and development pathway forward. And one of the things we said is that we will – we’ve already started – we are commencing a dialogue there and we intend to have a meeting before the end of this year on that issue as well. And to your point, why would we – we are, I think we’re unabashed about our view at least and we’ll see where we end up that it would be in the best interest of patients and also appropriate from a development and regulatory perspective to have a rapid and accelerated approach to the development of not only limb-girdle 2E but also at a minimum, the other cervical eye cancer, perhaps beyond that. There really are a number of characteristics of this disease and this therapy that we at least believe justify that. To your point, these are well-characterized monogenic diseases. We know what is causing these diseases, and it’s the lack of a structural protein that is the sole and exclusive reason that these children are degenerating and are living shortened lives.

Second of all, these are ultra rare diseases. So these are as rare as Duchenne muscular dystrophies. These are in aggregate, limb-girdle is significant individually these are small disease states. So that creates a compelling reason to find accretive approach. The third reason of course, is that this is the therapy at hand because of the particular genes and proteins at issue here. We are able to comfortably package in our rh74 casted, a gene that codes for the native protein. So we can replace the precise native protein that these children are lacking and the assets of which is causing their demise. And so the only remaining question then is, can we produce a significant amount of it? And the short answer is that we’ve seen in those who have low dose and the high dose that indeed we can. And the low dose, we were already producing a significant percentage. It might be off by a 1% or 2%, but on western blot I believe we were in the 30% and on approaching positive fibers, we were over 50%. And then of course, as you’ve seen in the higher dose, it was well tolerated. And even as it’s well tolerated, we’re able to – we get 4.2 genome copies per nucleus. The expression is over 70% on both protein positive fibers and on intensity and nearly bad on western blot. And so, from our perspective, this is – if you look at the guidance and you look at the statements that the agencies made publicly about opportunities and gene therapy that seems on its face at least to be the kind of gene therapy that would justify an accelerated approach to bringing these therapies to these kids.

With that said, we have work to do over the course of this year, both in GMP and in dialogue with the agency to align on that. I won’t make promises in advance about where we’ll end up with those, but we certainly will come back at the beginning of next year and give you an update on those discussions with the agency. And at that time, hopefully we can plan out exactly what the path is, not just for 2E but for all of the other limb-girdle as well.

[Operator]

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

[Vincent Chen, Bernstein]

Thanks for taking the question and congrats on the progress. Over the last few months, in addition to, I guess, your updated one year data for your DMD gene therapy program, like I said, we’ve also seen some updates from your competitor or peer Pfizer’s micro dystrophin gene therapy program. And clearly they’re different programs, but I was wondering whether you have a sense, do you think that their findings could provide some insights into the likely effect size with micro dystrophin gene therapy? And if so, how has this affected how you think about what is the likely effect size with a micro dystrophin gene therapy and your thinking around the powering of Study 102?

[Doug Ingram, President and Chief Executive Officer]

Well, let me say this, I’m going to do my best to talk about our programs and not about others. I will say that to the extent that others see some functional signals, even with very modest expression, that of course only gives us additional confidence in what we have seen both pre-clinically and given the robust expression that we’re able to achieve with our current constructs the functional results that we ought to see. And that frankly, although they are small numbers, what we appear to be seeing already is, we’ve talked about – we Study 101 in the first four kids, every child, they’re not stabilized, they’re improving on every functional endpoint with respect to those kids. And then you go over to limb-girdle, very similar, there’s an enormous amount of read through. And of course you see the same thing and you get great expression.

And it appears to be tolerable and safe and we’re getting even at a low dose. In one year with low dose of LGMD, can we construct SRP-9003, you’ve seen a significant benefit on every functional endpoint there. And then we’ve got great expression with respect to the higher dose 2E using super coil PCR. So we’re excited there. What I would say, this is – what I’m going to try to do is avoid talking about other programs, because as I was, especially with someone earlier today. For those of you on the call that may play chess, there’s a famous strategy in chest, it says you’re supposed to play the board, don’t play the opponent and that’s what we’re going to do.

And frankly, we’re excited about the way the words wide out, laying out right now. Our gene therapy engine and the approach that we take with these constructs is unique to us and it is differentiated from others. It starts first, frankly, and I say this with the potential of embarrassing Dr. Louise Rodino-Klapac at our team, but it does start with that team under Louise’s guidance, the design empirical testing and optimization of these constructs is unique to our approach. And it’s – I think it’s yielding benefits. Our cap state is different than others. We alone use rh74, our promoter is unique to us. It’s MHCK7, we alone use MHCK7. And the transgene that we use is unique to us.

And I think that’s why, frankly, just focusing on our programs and not on others, the evidence continues to build that our approach hopefully is not only differentiated, but it’s paying off to the benefit of patients. And I’ve talked about this already, but I’ll remind you, Study 101, we’re very excited about the results that we’ve seen, both from expression, tolerability and safety, but also function. And we’ve seen that out to one year as we’ve seen in JAMA Neurology this last quarter. And then of course we had the start of 102, and we’ve now dosed all of the kids for the main study and we’re dosing kids on crossover. And that study continues pace. And that’s – I think that says a lot about the construct. But I think it also says a lot about the team that was able to overcome obstacles in the middle of this pandemic, both at nationwide and at Sarepta.

And then of course we have 9003 both low dose and high dose. And what we’re seeing both from an expression perspective, but also at least currently with respect to the low dose, from a functional perspective and what we’ve seen from a safety and tolerability perspective. So just we really want to focus on our programs, but we’re very excited about the results that we’ve received so far. And from our perspective, our goal is to move as fast as possible. And this only creates for us an obligation to get going for these kids.

[Operator]

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

[Joseph Schwartz, SVB Leerink]

Thanks very much. So given the NSAA is comprised of 17 domains and they’re scored from zero, 1 and 2. I was wondering if there are certain patterns in the patients that have been treated with 9001 that make you confident that the results will replicated in the Phase 3 or different time course observations. Any sorts of characterizations you can share that make you particularly optimistic.

[Doug Ingram, President and Chief Executive Officer]

Yes. I can turn this over to Louise. I’ll make an introductory statement about it. I mean, what – look, first of all, of course there is always risk in over analyzing small data sets. This is for children with respect to 9001 and so far three children with respect to 9003 that we’ve seen functional results regarding. But with that said, you asked a very good question, which is, so you’re seeing these significant improvements across this composite score of NSAA, which is built on lots of individual tasks.

It could be the case that what we’re seeing in aggregate is one function that is significantly improving versus all of the other functions. And then you can worry about what that might mean. The thing that gives us a lot of – it excites us and gives us confidence both in DMD with 101 as well as with currently with the low dose of limb-girdle, because that’s where we’ve seen the functional results so far is that every kid is benefiting on every functional endpoint. And if you look at the composite, they’re benefiting across all of the functions in that composite. It is really, they are generally improving functionally both on time tests on NSAA and on the individual components of NSAA, which is certainly confirmatory. But with that, Dr. Louise, you might have some more nuance news than I’ve just given.

[Louise Rodino-Klapac, Senior Vice President-Gene Therapy]

I think you captured it well. I think what’s important is that across the components of the NSAA, as well as the other supportive measures, like time to rise as well as all of the time tests, we see supportive data coming out of our 101 study that led to the power end our Study 101. And so we feel confident based on those results across those measures as well as our other studies, like our limb-girdle study that we will – it’ll be successful.

[Operator]

Thank you. Our next question comes from Difei Yang from Mizuho Securities. Your line is open.

[Difei Yang, Mizuho Securities]

Hi. Good afternoon and thanks for taking my question. I have a quick one with regard to the 9001 program registrational pathway. So to what extent do you expect the interim analysis of a Study 301 will be part of that package?

[Doug Ingram, President and Chief Executive Officer]

It is certainly our goal that if they’re successful with 102 and with interim analysis of Study 301, that the interim analysis of 301 would play significant role in the registration of the trial. One of the things I said, if all goes well and we start the study in the second half of this year, then we should have in the first quarter, a significant data set on the functional aspects as well as the safety and tolerability aspects were 9001 to treat Duchenne muscular dystrophy. Across both Study 102 and an interim analysis of 301, we would have functional results showing in a placebo-controlled manner that the therapy provides functional benefits to these children and then it’s method is working and it’s benefiting them, we would have a very significant data set on safety and tolerability across the two studies.

And then of course, with biopsies and that’s one of the things that we get here, but in some programs you don’t get, like for instance Zolgensma in that program, there are no biopsies. But here we have the opportunity to get biopsy. So that means in the first quarter of next year, we could have it be an interim analysis, not only all of the CMC work that we’ve already done showing that in all of the material ways that how operate in the same way as the clinical material. But also we would have actual empirical in vivo biopsy data, showing the expression levels as well as safety and tolerability. And on that basis, we would certainly intend to approach and discuss with the agents, the opportunity to submit for a BLA. But that will be a discussion that we’ll have with data in hand in the first quarter of 2029.

[Operator]

Thank you. And I am showing no further questions from the phone lines at this time. I’d now like to turn the conference back over to Doug Ingram for any closing remarks.

[Doug Ingram, President and Chief Executive Officer]

Thank you very much. Thank you all for participating this evening and thanks for the questions. We really appreciated the opportunity to answer them. I’ll repeat – apologies. I will repeat what I said in my opening remarks, which is simply we have a lot to do as an organization. We’ve had a lot of success. We’re very excited about the progress we’ve made to date on our gene therapy engine. We’re very excited about the opportunity to continue to serve our Duchenne muscular dystrophy community with our two approved therapies. And hopefully if approved three therapies by the first quarter of next year and we’re very excited about the potential for our next generation RNA technology PPMO to deliver even more profound impact both in Duchenne muscular dystrophy and beyond Duchenne muscular dystrophy, the other areas where steering blocking technology could bring therapeutic benefit for patients.

We have a lot to do. So as much as we are excited about the progress we’ve made to date, it would be a mistake for us to develop hubris or complacency. And hope you would agree with me that the team at Sarepta does not intend to do that. This is a team that’s very focused. I’m really proud of our team. I’m very proud of our partners. I’m very proud of our clinical investigators who have continued to serve these patients during what has been for everyone, a trying time over the course of 2020. We’ll stay on mission and I look forward to providing additional updates as we progress across 2020. With that have a wonderful evening and the rest of the week.

[Operator]

Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program. You may all disconnect. Everyone have a wonderful day.