Sarepta Therapeutics, Inc. Q2 FY2020 Earnings Call

Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Second Quarter 2020 Earnings Call. 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.

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 Form 10-Q 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.

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 a small contingent of our workforce transitioned 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 for 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, proving successful and highly differentiated. With that, let us review our performance. 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 is 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 the 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 PMO, which if successful, will 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. If the PPMO candidates are able to increase exon-skipping and dystrophin production, we could see a profoundly more efficacious RNA platform. At monthly dosing versus the PMO’s weekly dosing, we would have a far more convenient therapy as well. In the second half of this year, we will complete and 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 us now move 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 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 have successfully dosed a significant number of DMD and LGMD patients. 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. 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. 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. This year, 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 functional endpoint 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 report that with the increased dose, we yet again confirmed 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. 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, and the studies are proceeding at pace. The second pillar of our gene therapy engine is our manufacturing expertise. 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. For SRP-9001, we have completed process development and analytical development and have completed GMP runs for the material with end 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 starting 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 complement our internal program development. In this quarter alone, we 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. 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. We also 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: To complete Study 101, our blinded placebo-controlled trial using clinical material. That trial is on track to have the last patient’s last visit by the end of this year and read out in the first quarter of 2021. Secondly, we must complete preparations for our next trial in the second half of this year, challenging though it may be, we’ve been preparing for this trial in the second half of this year. With respect to SRP-9003, our goal is to start our pivotal trial in 2021. This is an important effort and one we plan to remain focused on. If you’ll indulge me for a personal note, the second quarter marked my three-year anniversary at Sarepta. In three years, we have made enormous progress toward our goal of providing a better, longer life to those living with diseases such as Duchenne muscular dystrophy. We have done this by establishing 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. We are grateful to the sophisticated, dedicated and hardworking professionals that comprise 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, which relies upon us, informs us and sometimes pushes us. So now is not yet the time for a victory lap or premature celebration. We are encouraged by our successes so far, but we still have much to accomplish over the course of the next 15 months, and much more to prove. But you can count on this team to stay on mission, addressing and removing obstacles that appear in front of us and executing for the patients waiting for our therapies. And with that, I’ll now turn the call over to Bo for a commercial update.

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 in 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 and 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, which we believe 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 to assess 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 in 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 with a path to initiate care. Hospitals in each state are operating under different rules and regulations. We anticipate the intake of star performance to slowly increase as 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 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 a 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 and 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 the FDA’s response, our commercial and medical affairs teams are preparing for another successful launch. The foundation of our plan will be tailored to reaching patients who are amenable to exon 45 skipping, representing another 8% of the Duchenne community. We’ll 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 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.

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 recognized $26 million of collaboration revenue, which primarily relates to our collaboration arrangement with 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 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 an $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, which is an increase of $72.9 million. The year-over-year growth in non-GAAP R&D expenses was driven primarily due to the 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 a GAAP basis, we 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.

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 doubled 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 study of golodirsen and casimersen is progressing thanks to the immense efforts of investigators, patients, 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, I am pleased to say that the new mitigation has significantly improved the situation and most patients are back on track. All of our mitigation strategies comply with guidance 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 also as 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 several research programs that support this strategy. To remind you, our PPMO platform fuses a cell-penetrating peptide to PMO to enhance nuclear penetration. Our most advanced PPMO program is SRP-5051. Our ongoing SRP-5051-201 multi-ascending dose trial named MOMENTUM is advancing; all patients in the 20 mg per kg cohort have been dosed. COVID-19 related shutdowns caused one patient to miss a dose, but since then, with new mitigation in place, we are executing well. Just to remind you, we started the MOMENTUM study at 4 mg per kg and have escalated already to 20 mg per kg. This represents dosing beyond what we originally anticipated. We plan to continue to dose escalate based on reviews of safety. 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 examine systemic PK, tissue penetration, safety, and exon 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 the amount of dystrophin production. We will publish this 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 assess 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 observed in the PMO study. We expect to see higher levels of dystrophin at later 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. The readout for MOMENTUM will be important for the 5051 program dose selection, but additionally could potentially extend to other PPMO Duchenne programs as well. 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. Now, I will hand back to Doug for Q&A.

Thank you very much, Dr. O’Neill. Let’s open the call for questions.

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

Okay, good afternoon. Thanks so much for taking my question. Doug, I just wanted to get a little bit more color regarding 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.

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. We have two significant things to do. As you know, we’ve got to get our next study using commercial process material up and running and getting patients dosed. We’re going to do that in the second half of this year, and the team has done 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. I said in my prepared remarks that we will be meeting with the agency this quarter, and there are two significant things for us to get alignment and concurrence on with the agency. The first, of course, is our CMC approach itself for the commercial material to use in the next study. We’re very pleased with how these GMP runs have come out, and we’re very confident in the approach we’re taking. There are no significant quality attributes that are different from the clinical material that would predict any impact on the therapy in any way functionally, efficacy-wise, or safety-wise. So that’s one significant concurrence we need. 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 as possible, perhaps even concurrently with the next study, which we’ll be using if we’re successful for the approval of the therapy in the United States.

Good afternoon. Thanks for taking my question. If successful with the PPMO platform, how do you see it fitting into the treatment paradigm versus PMO in gene therapy in DMD, and what are your plans for non-DMD approaches going forward?

That’s a great question. I’ll answer that briefly and then I’ll turn this over to Dr. O’Neill. The excitement around the PPMO, if it is successful, is for a potentially more profound impact from an RNA perspective with respect to Duchenne muscular dystrophy. The short answer is, we don’t yet know how gene therapy and RNA will coexist. There will certainly be a place for profound RNA, even with transformative gene therapy. For instance, there will be children screened out for gene therapy in places where gene therapy is not yet available. So there will already be a significant place for it. The same goes for pre-existing neutralizing antibodies. That population that would be screened out until we’ve addressed that issue scientifically is larger than the population treated with gene therapy. But of course, we need to see what the PPMO will look like and we are already doing work to test the hypothesis whether a profound gene therapy, followed either in the near term or long term with a profound RNA would be synergistically beneficial to patients. But beyond that, there are several areas we are looking at from a non-clinical perspective. So perhaps I can turn this over to Dr. O’Neill, who can provide more detail on that.

Thanks very much, Doug. The beauty of the RNA technology is that we have demonstrated we can deliver the PMO to muscle, then skip and upregulate dystrophin expression. As we are working with PPMO 5051, we hope to test the hypothesis that increased exposure driven by the cell-penetrating peptide fusion enhances muscle tissue penetration. We also know that the technology can extrapolate beyond just muscle tissue to other tissues. Many tissues are amenable, and the PPMO and PMO have demonstrated tropism for other tissues, including liver, kidney, and heart. We are doing a comprehensive review of those tissues and associated diseases to identify those that are amenable to exon skipping. This is ongoing and I am very excited about it.

One final thing, I’ll say, moving back to DMD. Currently, we’re using the 5051 PPMO as our proof-of-concept. We’ve built beyond 5051 constructs that could treat 50% of Duchenne patients and have a development strategy to potentially accelerate the approval of PPMO compounds, if successful, for these patients.

Hey, guys. Thanks so much for taking the question. I got a quick one here on the 9001 safety recently. Can you provide context around comments made by Dr. Mendell that 9001 could be associated with mild complement activation? How frequently does the DSMB for Study 102 meet?

Sure. I’ll turn this question over to Louise, who can provide the context around that misunderstanding. There is absolutely no signal that we’ve seen with respect to complement activation in 9001 at all.

Sure. Dr. Mendell was speaking about his broad experience in gene therapy, which includes other vectors like AV9. We’ve not seen any evidence of complement activation in our study. Study 1 continues as planned with no interruptions.

I think people were misinterpreting his comments about other programs associated with AV9. We’ve seen nothing related to rh74, and the evidence on our broad safety profile continues to strengthen as we’ve dosed over 35 children, and the study continues to move at pace.

Just a quick question, based on the recent agreements you signed, how are you thinking about integrating these new technologies into your pipeline?

Thanks a lot for that question. We’ve entered into a number of interesting transactions to evolve the science in gene therapy. For instance, the partnership with Dyno uses AI and machine learning for making better capsids, while Codiak uses exosomes for delivery mechanisms with RNA gene therapy. We’re also looking at Hansa’s technology to ablate preexisting neutralizing antibodies. These tools add to the resources Dr. Rodino-Klapac and her team have to advance this work, and we intend to move as fast as possible to improve gene therapy.

My question relates to the upcoming readout for SRP-5051. Could you provide the level of exon skipping that SRP-5051 achieves in humans and the improvement you’re hoping to see?

Sure. I’ll turn this question over to Dr. O’Neill, who can give you insights on the measures for exon skipping.

Yes. We will be looking at data from both PMO historical samples and our ddPCR in our 5051 program. In our preclinical in vitro and in vivo studies, we have seen a correlation between the amount of exon skipping and dystrophin production. In the past, we reported approximately 0.6% skipping in humans at 24 weeks. However, it is important to emphasize that we are now using digital drop PCR, which allows for more precise measures.

I wanted to discuss the GMP pre-material and its compatibility. How significant is this for your programs, and what are your thoughts on Selecta’s ImmTOR technology for re-dosing?

Having GMP material on hand is a big deal. It’s the result of significant effort from our team over a long period. We embarked on this journey with a goal to ensure both capacity and expertise in manufacturing, which is crucial for our gene therapy platform. We’re excited to have reached this milestone. Now, regarding Selecta, they have the potential to prevent antibodies from forming with the first dose of gene therapy, allowing for re-dosing opportunities down the line. We want to make sure we have every tool available to reach all patients.

Regarding the MOMENTUM trial, can you clarify the maximum dose level you’ve observed in animal models, and what ceiling or safety concerns have you noted?

We’re already above what we would consider success based on our preclinical models. We will continue to push the dose to find the optimal level while monitoring safety closely. Our goal is to safely achieve the highest dose that benefits these kids, and we anticipate testing up to 30 mg per kg this year.

With the one-year data for 9001 now published, how does this data guide your thoughts on patient selection and endpoint choice moving forward?

The results from Study 101 have given us significant insights as we build out Study 102. The results confirm our approach and boost confidence in our choice of functional endpoints. We feel we are on the right track.

Could you remind us of the percentage of exon-skipping for EXONDYS 51 in animal data? What peptide do you have in mind for the PPMO program? Lastly, do you see antibody oligo-based therapy as a threat to your PPMO franchise?

We’re focused on our programs, which are the most advanced and hopeful. Regarding exon skipping, the recent percentage will be compared with our ddPCR using better methods. As for the peptide and PPMO, we continue to optimize it and are excited about the potential outcome.

With respect to the limb-girdle muscular dystrophies, what package do you plan to present to the FDA, and what factors help justify an accelerated path to approval?

We’ll engage in a dialogue with the agency, which we’ve already started. There are clear characteristics of this therapy that we’ll present, as these are well-characterized monogenic diseases. We believe this warrants a rapid approach to treatment and patient access. By the end of the year, we anticipate making further progress in these discussions.

Considering recent updates from peers, do you think their findings could offer insights into the effect size expected from micro dystrophin gene therapy?

I’m going to focus on our programs and observe that showing positive functional signals can only give us confidence as we continue to receive positive results from our studies.

Could you share any patterns in the patients treated with 9001 that ensures these results will be replicated in the Phase 3 study?

The most encouraging aspect is that every child treated has seen improvements on each functional endpoint. This strengthens our confidence that the 9001 results will hold in the Phase 3 trial.

What role do you expect interim analyses from Study 301 will play in your regulatory submission pathway?

If all goes well, the interim analysis of 301 should significantly contribute to our registration package, along with data from Study 102. Our goal is to showcase functional benefits with data from both studies. Thank you for participating today and your insightful questions. We look forward to updating you on our progress down the line. Have a great evening.

Ladies and gentlemen, thank you for participating in today’s conference. This concludes the program. You may all disconnect.