Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Second Quarter 2018 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. If anyone should require operator assistance, please press star then zero on your touchtone telephone. As a reminder, this call is being recorded. I would now like to turn the conference over to Ian Estepan, Vice President, Chief of Staff and Corporate Affairs. You may begin.
Thank you, Sonia, and thank you all for joining today's call. Earlier today, we released our financial results for the second quarter of 2018. The press release is available on our website at www.sarepta.com. Joining us on the call today are CEO, Doug Ingram, our CFO, Sandy Mahatme, our Chief Commercial Officer, Bo Cumbo, Dr. Gilmore O'Neill, our new Chief Medical Officer, and Dr. Louise Rodino-Klapac, our new Vice President of Gene Therapy. After our formal remarks, we will 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 slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainty, any of which are beyond Sarepta's control.
Actual results could materially differ from these forward-looking statements, as any and such risks could materially and adversely affect the business, results of operations, and the trading price of Sarepta's common stock. For a detailed description of applicable risks and uncertainty, we encourage you to review the company's most recent quarterly report on Form 10-Q filed with the Securities and Exchange Commission, as well as the company's other SEC filings. We filed our 10-Q this afternoon, August 8th, 2018, for the second quarter of 2018 by the SEC required filing deadline. 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 Doug Ingram, who will provide an overview of our recent progress. Doug?
Thank you, Ian. Good afternoon, and thank you all for joining Sarepta Therapeutics' Second Quarter 2018 Results and Corporate Update Conference Call. In the second quarter, we took very significant steps, perhaps leaps, in the direction of achieving our strategic vision of becoming one of the most meaningful global genetic medicine companies, while continuing to remain focused on executing on our plans and fulfilling our commitments. We indeed have much to discuss this afternoon, including our newest gene therapy partnership, which will give us three new programs and move us into CNS-targeted therapies. Our recent and very productive meeting with the FDA to advance casimersen to a potential near-term accelerated approval in the United States, and our progress in responding to the FDA's clinical hold for our microdystrophin program.
As Sir Winston Churchill famously observed, "However beautiful the strategy, you should occasionally look at the results." Let's begin with our second quarter results. We were pleased to announce earlier today another very strong quarter. Sales of EXONDYS 51 revenue reached $73.5 million, an increase of 110% over the same quarter last year. With strong first-half sales of approximately $138 million, we do remain on track to achieve our 2018 guidance of $295 million-$305 million. If you will indulge me, I would like to give special credit to Bo Cumbo and his commercial organization, as well as our very strong medical affairs team for a fabulous first half of 2018. Sarepta is that rare breed of fully integrated biotech company that can take a therapy from conception, development, and approval, and then support it in the community with strong commercial execution.
We also announced in the second quarter that we received a negative opinion from the Committee for Medicinal Products for Human Use, the CHMP, regarding our Marketing Authorization Application, or MAA, for eteplirsen in Europe. We have commenced a re-examination of the CHMP opinion. The CHMP will hold a scientific advisory group, or SAG, meeting of neuromuscular experts in the fall of 2018 to discuss our application and re-examination. While we believe we have a strong case for access to eteplirsen for patients with Exon 51 amenable mutations in Europe, the re-examination process remains challenging. We expect a final decision by year-end. Moving on to our next PMO candidates. We are very pleased with the accelerating progress we are making with our next two PMO candidates, golodirsen and casimersen.
You will recall, following a positive meeting and guidance from the FDA in the first quarter of 2018, we are in the process of submitting our rolling NDA for golodirsen, our PMO designed to treat patients with Exon 53 amenable mutations, which will be complete by year-end with a target approval date in 2019. Last week, we held a Type C meeting with the FDA to discuss, among other things, our proposal to conduct an analysis of muscle biopsies at week 48 of Exon 45 amenable patients in our ESSENCE trial for the purpose of supporting a potential accelerated approval for casimersen, our PMO therapy designed to treat Duchenne patients with Exon 45 amenable mutations. Our preclinical models suggest that casimersen as a sequence is as efficient at exon skipping and dystrophin expression as golodirsen.
I am pleased to report that the FDA was supportive of our proposal to perform an analysis for dystrophin expression and agreed that it is possible to do so without compromising ESSENCE as the confirmatory trial for golodirsen and casimersen. We will be in a position to conduct that analysis before the end of this year, which means that if we have significant dystrophin expression with casimersen, we should be in a position to file for accelerated approval by mid-2019. Golodirsen and casimersen combined serve an even larger population than EXONDYS 51. The near-term opportunity to bring these therapies to the community is very significant. To put this into perspective, if successful, we will have three PMO candidates approved in the United States by 2020, serving nearly 30% of the Duchenne community.
Our next generation RNA technology, the PPMO, is progressing with a single ascending dose study underway for our 51 candidate, where we will get dosing insight by the first quarter of next year, and IND-enabling tox work is being performed for the next five skip-amenable mutations beyond 51. Turning now to our gene therapy progress. The second quarter of 2018 has been an extraordinarily important one for our fight to bring a longer, brighter life for those with rare disease, and in particular, those with Duchenne muscular dystrophy. As you know, at our R&D Day on June 19th, Dr. Jerry Mendell of Nationwide Children's Hospital presented the early results from the first three Duchenne patients who received our microdystrophin therapy. To remind you, our microdystrophin gene therapy construct has been very elegantly designed by Doctors Mendell and Louise Rodino-Klapac.
First, as a rhesus monkey-derived AAV vector, RH74 appears to show lower immunogenicity rates compared to other humanized AAV vectors, meaning it should be available to more patients. Second, the microdystrophin promoter was specifically chosen for its ability to robustly express in the heart, which is critically important for patients with Duchenne muscular dystrophy who typically die from pulmonary or cardiac complications. In preclinical models, microdystrophin expression in the heart was observed to be up to 120% of the microdystrophin levels observed in skeletal muscles. Third, the transgene was designed to maintain spectrin repeats two and three, which has been recently reconfirmed to be crucial in protecting the muscle from damage.
As you no doubt are aware, Dr. Mendell reported that the three-month biopsy results showed robust gene expression as measured by Western blot and immunohistochemistry, with all three patients showing an unprecedented drop in creatine kinase levels, the enzyme associated with ongoing muscle damage that is the hallmark of Duchenne muscular dystrophy. What is particularly fortuitous is that on July 11, the FDA issued its innovative draft guidance on gene therapy for rare disease that aligns with our goal of rapid drug development, creating an efficient pathway to the market for new therapies. Specifically, FDA has encouraged sponsors to design first in-patient studies as potential pivotal trials and to consider alternative trial designs.
Encouraged by the guidance, but also mindful of its recommendation that early discussions with the agency are crucial, before executing our next study, we are preparing to submit for a Type B FDA meeting to align on the clinical pathway for our registration trial. It is our goal to hold that meeting and to commence the next trial before the end of 2018. Separately, we announced on July 25 that the FDA placed our microdystrophin program on clinical hold based on a third-party plasmid supply issue. As we noted previously, that third-party material was research grade, as is the current standard for early clinical programs in the academic setting. We have committed to moving to GMP-source plasmid material going forward and have already completed our audit of the third-party supplier.
Pending the completion of Nationwide Children's Hospital's review, we will be in a position to fully respond to the FDA's clinical hold letter in the near future, and certainly before the end of August. Given the nature of the hold, we anticipate it should be lifted in advance of our meeting with the agency to align on our clinical pathway. Moving next to our limb-girdle program. As you will recall, we announced in the second quarter a transaction with Myonexus for five new gene therapy programs, all under the broad umbrella of limb-girdle muscular dystrophy, also known as LGMD. The current plan is to dose the first patient in the so-called 2E program, which is a beta-sarcoglycanopathy, in August. We are working with Myonexus to map out the dosing of the next four LGMD diseases, and we'll have an update later this year on that.
To remind you, the five LGMD programs represent about 70% of the opportunity of Duchenne and share much in common with our microdystrophin program. Consistent with our long-term vision, we continue to build upon the breadth of our gene therapy franchise. As you have seen in this afternoon's announcement, we have today entered into yet another gene therapy transaction, this time with Lacerta Therapeutics. Lacerta was founded as a spin-out from the University of Florida by a number of world-renowned gene therapy researchers. Like Nationwide Children's, University of Florida is one of the top centers of excellence in gene therapy research. Lacerta's founders have led numerous clinical stage gene therapy programs and made significant advances in and contributions to the gene therapy field. Under the terms of the partnership, Sarepta will make a $30 million equity investment in Lacerta.
We have also received an exclusive license to Lacerta's CNS-targeted Pompe gene therapy program, and rights to two additional CNS-targeted programs. Lacerta will manage the majority of the preclinical development, while Sarepta will lead clinical development and commercialization. Sarepta will pay Lacerta development and sales-based milestones, as well as single-digit royalties on net sales. Our partnership with Lacerta accelerates our gene therapy strategy in a number of very discreet ways. First, access to world-class talent. As we have said, we are meeting our gene therapy ambition by associating with the world's best and brightest genetic medicine scientists. Lacerta's founders, nine in all, who are widely published in leading peer-reviewed journals, over 500 papers among them, are highly regarded in gene therapy clinical research, and hail from leading centers across the U.S., including the University of Florida, Nationwide Children's Hospital, CHOP University of Pennsylvania, and Weill Medical College of Cornell.
Second, of course, is the expansion of our gene therapy pipeline. To our pipeline of eight gene therapy programs, Lacerta adds three new gene therapy programs focused on a very close adjacency, CNS. Indeed, the first program addresses a CNS approach to a neuromuscular disease, Pompe. We also have rights to two additional CNS-specific therapies. Third is access to gene therapy tools. Lacerta's novel capsid library could potentially support next-generation therapies that are optimized for targeted delivery of drugs to treat these CNS diseases. Lacerta is developing an alternative approach to dose patients with antibodies to AAV, potentially enabling a broader and more robust application of the technology for a wider patient population. Lacerta's One-Bac proprietary manufacturing platform allows for potentially a more reproducible, scalable, stable, and potent AAV manufacturing process.
While this will not be the approach we use for the commercial launch of our microdystrophin and LGMD programs, it provides an opportunity to explore new and potentially more efficient manufacturing avenues in the future as we build our gene therapy division. Next, I will discuss the infrastructure and talent-related achievements we have made this quarter. First on people. We started 2018 with 255 dedicated, passionate employees. As people see the value of our mission, the breadth of our goals and opportunities, and our operational commitment to achieve our goals, over the last year, Sarepta has become one of the top places to work if one is creative, ambition, and wants to make a positive impact on the world. We've been hiring at nearly 1.5 employees a business day at Sarepta. That's chemists, biologists, developers, manufacturing experts, and the like.
We will exit 2018 with nearly double the number of employees at the beginning of this year. Next on leadership. I entered 2018 with a strong, committed executive team that shares a common vision and great pedigrees. I was pleased in the second quarter to welcome to that already strong team, two first-class scientist and biotech leaders, Doctors Gilmore O'Neill and Dr. Louise Rodino-Klapac, both of whom are present on this call with me today. It speaks reams to the opportunities we have at Sarepta to improve lives that we were able to attract these talents to our senior team. Next on infrastructure and manufacturing. In this quarter, we commenced our hybrid manufacturing gene therapy strategy, starting with our partnership with Brammer Biosciences, which we anticipate will provide us with sufficient commercial supply for our microdystrophin gene therapy launch, even under the most aggressive development assumptions.
On infrastructure, even as we have taken additional space in Cambridge and built out our facility in Andover, we are also building an 85,000 sq ft gene therapy center of excellence in Columbus, Ohio, with the goal of strengthening and deepening our commitment to gene therapy, to Columbus, and to our relationship with Nationwide Children's Hospital. Finally, there's one thing that will drive our success above all of these others. When we achieve our vision of becoming among the most meaningful genetic medicine companies the world over in the coming few years, and I am asked what was the greatest predictor of our success, I will say one thing, purpose. For us, there is no ambiguity. We know why we get up every day and work as hard as we do. We know that those living with life-robbing rare disease and their families are relying upon us for their futures.
This is what fuels our culture, and this is what makes me so confident in our continuing success. With that, I will now turn the call over to Sandy for an update on our financial performance. Sandy?
Thanks, Doug. Good afternoon, everyone. Over the past year, we've built a strong foundation that uniquely positions us to execute on our strategic vision. Namely, EXONDYS 51 continues to perform well and is a fuel source that has driven and continues to drive the expansion of our pipeline in DMD and new therapeutic areas. Our healthy balance sheet supports the expansion of our geographic footprint and our investment in manufacturing capabilities, which are necessary to deliver innovative therapies to patients around the world. To support these initiatives, we will be growing to over 500 employees by the end of 2018. Despite this rapid expansion, we will continue to thoughtfully manage our expenses by only taking programs in-house when the probability of success justifies the full dedication and support of our internal resources. This model allows us to continue to economically move multiple programs forward in parallel.
Moving to the financials. This afternoon's press release provided details for the second quarter of 2018 on a non-GAAP basis as well as a GAAP basis. The press release is available on the SEC as well as Sarepta's websites. Please refer to our press release for full reconciliation of GAAP to non-GAAP. I'd like to add a quick reminder here that our 2018 non-GAAP financials exclude net interest expense, depreciation and amortization expenses, one-time extraordinary expenses, and stock-based compensation. Net product revenue for the second quarter of 2018 was $73.5 million, compared to $35 million for the same period of 2017. The increase primarily reflects high demand for EXONDYS 51 in the U.S.
We reported a non-GAAP net loss of $28 million, or $0.43 per share, compared to non-GAAP net loss of $26.5 million, or $0.48 per share in the second quarter of 2017. In the second quarter of 2018, we recorded approximately $6.7 million in cost of sales, compared to $half a million in the same period of 2017. The increase was driven by higher inventory costs related to increasing demand for EXONDYS 51 during 2018, accrued royalties and payments of $3.7 million to BioMarin, which were a result of the settlement and license agreement we entered into BioMarin in July of last year. We expect our cost of sales to modestly increase in Q4 of 2018 due to depletion of materials that were expensed prior to approval.
On a GAAP basis, we recorded $122.8 million or $58.9 million of R&D expenses for the second quarter of 2018 and 2017 respectively, a year-over-year increase of $63.9 million. This increase is primarily related to a $60 million payment we made to Myonexus. On a non-GAAP basis, the R&D expenses were $57 million for the second quarter of 2018, compared to $34.1 million for the same period of 2017, an increase of $22.9 million. The year-over-year growth in non-GAAP R&D expenses was driven by increased patient enrollment in our late-stage clinical trials, a ramp-up of manufacturing activities for our PPMO platform, and an expansion of our research and development pipeline, and collaboration costs with Summit Therapeutics. As of January 1, 2018, we started to share 45% of the costs related to Summit's research and development expenses for the utrophin program.
Due to the termination of Summit's utrophin program during the second quarter of 2018, we expect this expense to significantly decline over the upcoming quarters. Turning to SG&A. On a GAAP basis, we recorded $47.2 million and $36.1 million of expenses for the second quarter of 2018 and 2019, respectively, a year-over-year increase of $11.1 million. On a non-GAAP basis, the SG&A expenses were $37.3 million for the second quarter of 2018, compared to $24.2 million for the same period of 2017, which is an increase of $13.1 million. The year-over-year increase was primarily driven by continued build-out supporting our research and development and commercial expansion. On a GAAP basis, we recorded $4.7 million in net interest and other expenses for the second quarter of 2018, compared to $100,000 of net interest income for the same period of 2017.
The unfavorable change is driven by higher interest expense in Q2 of 2018, resulting from our debt instruments that we entered into the latter half of 2017. We had approximately $950 million in cash equivalents, and investments as of June 30, 2018. In addition, we have prepaid approximately $33.7 million towards future manufacturing expenses in connection with our gene therapy and RNA programs. With that, I'd like to turn the call over to Bo for a commercial update. Bo?
Thank you, Sandy. Good afternoon, everyone. As we head into the eighth quarter of an ultra-rare disease launch, we're very proud of the progress and the accomplishments the team has made. We had a strong quarter and remain on track to achieve our full-year guidance of $295 million-$305 million. The team has been able to successfully navigate challenges this year and maintain patients on therapy without significant disruptions. The measurable progress over the last few years is due to the motivation and commitment of the patient community and the team here at Sarepta.
Our U.S. commercial efforts are still focused on identifying patients amenable to exon 51 skipping and driving prescriptions. Continuing active dialogue with payers to support broad coverage and reimbursement decisions, and ensuring all patients with DMD have a current genetic test, know their mutation, and are appropriately identified, not only for EXONDYS 51, but for clinical trials and future therapies. Until newborn screening is a reality, we will need to continue to work with key offices to help educate around the importance of patient identification, early diagnosis, and potential treatment options. We continue to be pleased that we're seeing adoption across all age groups. The average age of patients on therapy is 13 years of age. We do not expect the average age of patients to dramatically change until newborn screening for Duchenne becomes standard medical practice, which would identify hundreds of new patients with DMD.
From an adherence and persistency perspective, we continue to see high compliance rates and minimal discontinuations. We also do not expect to see a change in the percentage of patients who are opting for ports at this time. Patient demographics have remained fairly consistent throughout the launch. The mix of patients on commercial and government payers has slightly changed in 2018, as mentioned on the last earnings call. The mix was approximately 55% commercial, 45% government in Q1 and Q2 in 2018, compared to 60/40 in 2017. Our national accounts team and medical affairs organization continue to have ongoing engagement with both commercial and government-level payers. As a result, payers have a better understanding of the disease and the number of patients who will benefit from EXONDYS 51 with their plan.
Tier 1 and tier 2 centers continue to receive referrals or identify new patients amenable to exon 51 skipping and submit start forms as appropriate. We continue to call on top-tier centers but have purposefully expanded our efforts. A portion of our educational endeavors has shifted to large pediatric offices within key states, where we are helping to educate on the importance of early identification for children who have not been diagnosed with Duchenne. These efforts are now focused on supporting early testing and diagnosis and ultimately shortening the timeframe from pediatrician offices to the neuromuscular specialist. As Doug highlighted, Sarepta's mission is to develop precision genetic medicine that improves the lives of all patients with DMD, as well as other life-altering neuromuscular and CNS diseases. We are able to do this by collaborating with the most notable experts worldwide and continuously striving to advance our multi-platform pipeline.
We currently have 23 programs in development at Sarepta. With each new program comes the responsibility of ensuring treatment access for patients. This brings me to the commercial success of EXONDYS 51, which has provided the framework to support future launches. Building a global company requires complex coordination and flexibility that will work across diverse markets, as well as highly skilled and motivated people. As we continue to build the infrastructure needed to be the worldwide leader in precision genetic medicine, we remain committed to executing upon one goal, which is to keep patients at the center of all conversations. We will also continue to review and refine our strategies to include a variety of innovative approaches to enhance patient access to these therapies.
During the re-examination period with the EMA, we have continued to strengthen our global presence in Europe by solidifying our relationships with key opinion leaders and advancing our distribution network. While we have already built the infrastructure needed for a potential European approval and a future launch of EXONDYS, we are also focusing our efforts to build out and support future launches in other countries. We have recently hired our country manager, medical director, head of government affairs, and patient advocacy in Brazil. These recent new hires will begin to support the patient and medical community within this country. We know what our aspirations are. We know how to get there. We are putting all the framework in place from distribution networks, market access, sales, medical affairs, and patient support, which will allow us to reach patients globally when new therapies are approved.
Our focus and commitment of providing new treatment options, which are so desperately needed to patients around the world, has not wavered. In summary, the U.S. commercial success of EXONDYS 51 has provided the framework and resources to support future rare disease launches. We are leveraging this knowledge to prepare ourselves for operational and executional success. Between our gene therapy programs for both DMD and limb-girdle, as well as the in-licensed assets from Lacerta, our team is preparing for the potential launch of multiple gene therapy products over the coming years. This is in addition to our multiple PMO and PPMO-based programs for Duchenne, which, if successful, could be launching during the same period of time. From a commercial aspect, we are very excited about the future at Sarepta.
We continue to have one of the deepest rare disease pipelines in biotech, and each day, we are taking steps to strengthen our position as the global leader in precision genetic medicine. We will continue to pave the way to bring access to future therapies within rare neuromuscular and CNS diseases. With that, I'll turn the call back over to Doug for closing remarks.
Thanks, Bo. As we move into the latter half of 2018, we are pleased with the progress that we have made to date, advancing our ambitious vision, married to a continuing focus on practical execution.
For the remainder of 2018, we will be focused on key areas of the business and catalysts, including the following: completing the rolling NDA submission for golodirsen, evaluating dystrophin data for casimersen, completing the re-examination for eteplirsen in Europe, advancing SRP-5051 and the rest of our PPMO platform, removing the clinical hold on our microdystrophin program, meeting with and gaining insight from the FDA on the registration pathway for our microdystrophin program and commencing the enrollment of patients in a pivotal study for microdystrophin, dosing patients in our first limb-girdle clinical trial, and continuing to build for the future, including hiring more colleagues, advancing our manufacturing capabilities, and building out our gene therapy center of excellence. With that, operator, can you please open the call for questions?
Thank you. Ladies and gentlemen, if you have a question at this time, please press star then 1 on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Our first question comes from Ritu Baral of Cowen. Your line is now open.
Good afternoon, everyone. Thanks for taking the question. Maybe I'll start with the Lacerta deal. Doug, can you talk about the difference between the Lacerta Pompe program and some of the others like Audentes and Spark? Just a quick follow-up question on golodirsen and casimersen. How are you thinking about the pricing of those programs in relation to EXONDYS 51?
Okay, great. The first on our Pompe program, obviously, to say it's early days would be an understatement. I think we just announced it less than 60 minutes ago. We'll have a lot more to say about that, and we'll build out the thesis on our Pompe program, our Pompe gene therapy program, over time with Lacerta. The one thing I will say is that we have a unique approach to our gene therapy program with our Pompe program, which is that it is a CNS-targeted approach to what is a disease that is in many regards CNS-driven but has neuromuscular manifestations. I think in that regard, we will be differentiated from others, at least as a beginning. The second thing I would say is-
Motor neuron-targeted, Doug?
Yes.
Okay.
Yes. The second thing I would say about it, just to credential our Pompe program, is it was invented and developed at the University of Florida by none other than Dr. Barry Byrne, who along with folks like Dr. Jerry Mendell and now our very own Luis Rodino-Klapac is among that rarefied group of world luminaries in the development of gene therapy constructs. Then answering your question about golodirsen and casimersen, while we haven't gotten that far to really pull out a sharp pencil on either one, the short answer is that it will be priced at parity with eteplirsen.
Got it. Thanks for taking the question.
Thank you. Our next question comes from Brian Abrahams of RBC Capital Markets. Your line is now open.
Hi there. Thanks very much for taking my questions. Congratulations on all the progress. Two from me. First on the microdystrophin clinical hold. Sounds like you've already made good progress there. Wondering if you could give us a little bit more in terms of specifics with respect to what needs to be done at NCH, maybe based on your initial audit of the third-party supplier and ongoing regulatory feedback, if you could characterize your level of confidence in the rapid resolution. Then I had a follow-up on casimersen.
Great. Okay. First I'll start with the clinical hold. The short answer is that, as you said, we've made great progress. We have, from our perspective, drafted what we believe would be a complete response. We've completed an on-site significant audit of our third-party supplier that went very well. With respect to our partner, Nationwide Children's Hospital, they did their own independent review as well, and they're also reviewing our work, and it really is just kind of getting that all collated and together and then putting together a complete response to the clinical hold letter that is polished. We really are in the final strokes of getting our response. As I said before, I'm very confident this will get done by the end of August, and frankly, I would be disappointed if it was the latter part of August.
On what we found, we've completed our audit of the third-party supplier, and it went very well. We had great cooperation. We also had great confirmation of the approach that our third-party supplier takes to the development and release of GMP-sourced plasmids. We feel very good. I would say at this point, I am frankly very confident in the rapid resolution of the issues associated with the clinical hold.
That's really helpful. Just on casimersen, I was wondering if you could give us any more detail on how you're able to work the 48-week biopsies into ESSENCE and I guess working around methodologically, I guess overcoming the challenges of maintaining study integrity but still getting that data. Thanks again.
Yeah. The short answer is very carefully. I will say, we definitely don't want to put ourselves in the position that through the process of looking at these biopsies, we compromise the integrity of ESSENCE, which will act as, not only it's an independent study, it also acts as the confirming study for golodirsen, and of course, if we get good results, it'll act as the confirmatory study for casimersen. The good news is that we came up in advance with a protocol that would essentially sort of hive off a group that would blind it to everyone else, would look at the biopsies themselves from the active arm for the casimersen arm, and that we could do it in a way that wouldn't compromise the results, wouldn't unblind the study to those who would be looking at it and the like.
We've presented that, shared that with the division, the division is in agreement with us that we have an approach that works. We feel very good about it.
Thanks. Thanks, guys.
Thank you. Our next question comes from Christopher Marai of Nomura Internet. Your line is now open.
Hi. Thanks for taking the question and congrats on the progress. Just thinking about dosing your next patients with your dystrophin gene therapy, assuming the hold is removed, do you see any opportunity to dose additional patients before the start of the registration trial, which I think you said you hope to start by year-end, would those patients dosed be part of that trial? Then secondarily, I was wondering how you look to interpret competitor data as it may come out with respect to these biopsies. We understand maybe World Muscle will be the site of a competitor data release of maybe three patients or so. Wondering how you internally will be evaluating, I suppose, biopsy and dystrophin data. Thank you.
Well, okay. Let's start on the dosing side. Our focus right now, really, frankly, independent even of the clinical hold, is to focus on a meeting with the agency to get alignment around the clinical path and the appropriateness of what we envision to be a pivotal trial for the therapy. That really is our big focus right now. Even if we came off of clinical hold immediately, which is not going to happen, it's going to take some time to get this response, and then the agency has 30 days to review it. We still really want to focus our effort and energy into getting a meeting with the agency, getting alignment around the clinical pathway, and then dosing patients.
If things work well and we execute brilliantly, we think we can get that all done, and we can start not only enrolling patients by the end of 2018, but actually dosing patients in what hopefully is a pivotal trial by the end of 2018. That's going to be our focus. It really is informed not only by our own ambition, but also by this draft guidance from the FDA regarding gene therapy and rare disease, which came out, I believe, as I said, on July 11, which really gives us a lot of confidence that the agency wants to look innovatively at gene therapy, particularly gene therapy and rare genetic diseases, but also provides very explicitly that it's important to have early and robust communications with the agency. That's our focus right now.
Then, on how we deal with competitors, I guess the issue about competitors is a simple one. It's great for us. It fuels us to work fast and work hard. We'll wait to see what we have. What I will say, rather than speak about others' programs, I can speak again to our own. We have a very elegantly designed construct. We have a construct quite apart from just the fact that we have extraordinarily good dystrophin production through immunohistochemistry and through Western blot, as revealed in the first three patients at our R&D Day. We have a construct that's very elegant a number of other ways. We have low screen out rates for preexisting antibodies, likely because we're using RH74, which is unique to us. We have a promoter, which again, is unique to us, that expresses very robustly in the heart.
In fact, in animal models, it expresses 120% of what we would see in skeletal muscles. If that held true, for instance, for these three patients, it means that they would have 100% or so of expression on immunohistochemistry in the heart, which is great. Then, of course, there was really an elegant design around the cassette itself. It maintains spectrin repeats two and three, which just very recently in a paper, I believe it was in March of this year, confirmed was extremely important to avoid muscle damage and to protect from muscle damage. We think we have a fantastic construct, and marrying that with the fact that we're going to move as fast as possible, we think we have a real opportunity to benefit a lot of patients if the trial works out.
Talking about trial design, one of the things we focus on is the discussions with the agency, which, of course, is extraordinarily important to make sure we're aligned with the FDA. It's even more complicated than that because we want to make sure that we're designing a study that's not only appropriate for the U.S. and for the FDA, which is important, and we certainly want to make sure we do that, but that is fit for purpose for the rest of the world. As we've said many, many times before, and as Beau just said a moment ago, our goal is not to treat a subset of patients with Duchenne muscular dystrophy.
We really want to treat as many patients living with muscular dystrophy as is possible around the world. There are 70,000 or so individuals around the world who are living with Duchenne muscular dystrophy. Our goal is to create a program that gives us a pathway to be in the communities all around the world treating patients.
Okay. Just to clarify, we don't expect additional dystrophin production data from your gene therapy program to be presented? That would be number 1.
Yeah.
Sorry, go on.
No, I apologize. Go ahead. Finish your question. Apologies.
Well, with respect to, I guess, just interpreting potential competitive data. I guess what I was wondering is how does the company look at it? Obviously, you're going to see it, you're going to be interested in it. How should we look at that? Should we look at vector genome copy, dystrophin levels, CK levels, all the above? I would love to understand how you guys want to compare and contrast the potential data that we may see here later this year from a competitor and what might be most meaningful, because obviously there are problems interpreting dystrophin data from biopsies, et cetera, and it's a cross-trial comparison. I'd love to understand just maybe from your lens as gene therapy experts in Duchenne, how you'd look at that. Thank you.
Yeah, those are great questions. One thing I want to make sure I clarify, it is very possible, in fact, it's probable that there'll be additional data out of our first treated cohort by the end of this year. Dr. Mendell will be making the choices about the forum, and it'll be at a medical forum likely before the end of this year. Remember, we'll have two things. We'll have biopsy data from a fourth patient. There was a fourth patient dosed, even before the June 19th date. We just didn't have a three-month biopsy yet, there was no ability to provide that information. He'll be able to present that. There'll also be biomarker data, including obviously CK level data for all of the patients.
At least in the first patient, there'll be nearly a year's worth of biomarker and CK level data that will be presented by the end of the year. I suspect that we will get more and increasingly robust data out of our program, even though we're going to spend a lot of our focus on designing our pivotal trial. As we think about other therapies and what they might present later this year or otherwise, I think you raised some very good points. I think obviously dystrophin expression is extraordinarily important. One of the issues with dystrophin production is measuring it. We tend to be expert at measurement. We tend to be very conservative at measurement as well. Frankly, I think most people that would look at us say that we're so thoughtful that we're conservative.
One of the things we'll be looking at very carefully, as others might be looking at things like immunohistochemistry and Western blot, is to ensure that they've done it in ways that are similar to ours, or looking at the ways they've done it and sort of comparing and contrasting associated with that. I think there's other things that you need to look at beyond that. Obviously, CK levels and CK drops is very valuable. We frankly are very excited about the CK level drops that we've seen. They're unprecedented. I think as you know, in the first three patients that we have, the drops were nearly 90%. That's never been seen before in a three-month period or otherwise. I think Dr. Mendell's already revealed, so I don't think I'm revealing anything secret, that the initial drop in the fourth boy was quite significant as well.
Certainly at least in the hunt of that, if not even maybe a little better than even that. I think those are important things to look at. Beyond that, there are other things to consider, and that's why we really talk a lot about the elegance of our construct. I think frankly the fact that we're seeing less than a 15% screen out rate is really important, and it's important even in addition to the great results that we're seeing so far, because it means that we're going to have the opportunity to treat an enormous number of patients, and that seems to be better than at least what the literature would suggest for other AAVs. I think probably extraordinarily important, and it would be, is the amount that a promoter expresses in the cardiac muscle.
These children are taken from us, these patients are taken from us, either from pulmonary or cardiac complications, being able to protect the heart is enormously important. Other promoters have shown some expression in the heart, but I'm not sure we've seen animal models from any other promoters associated with other programs that would show the kind of expression that we're seeing here, which is 120% of what we're seeing in the skeletal muscle. Now, to look at these patients and to start to correlate cardiac expression is really going to require us to look at preclinical models and the animal models. We've been willing to share that, presumably others will do the same, and we'll get to see what other people look like there.
I think quite apart, we've got to sort of start predicting what's going to happen over the long run with the protective quality of the construct that's been created. We know that microdystrophin works in animals. We know that there is a wonderful natural case study associated with this. A 61-year-old patient started all of this, was a Becker's patient who had essentially a naturally occurring form of microdystrophin and was 61 years old and remained ambulatory. There's a lot of hope that there's protection associated with microdystrophin, and certainly our CK levels would lead us to believe that that's what's occurring here. Really looking carefully at the construct itself and seeing if that construct matches that 61-year-old patient, and also seeing how elegantly it matches the natural dystrophin protein is important.
That's why we continue to emphasize what others have independently emphasized in published literature recently, that maintaining spectrin-like repeats two and three is extremely important to predict the protective quality of the dystrophin. There's a lot to consider when we consider comparing across programs.
Great. Thanks, Doug. I appreciate the color.
Thank you. Our next question comes from Brian Skorney of Baird. Your line is now open.
Hey, good afternoon, guys. Thanks for taking the two quick questions from me. First one, assuming you guys get the clinical hold lifted in the outlined timeframe, just wondering, are you at production scale that would allow you to dose every patient in the third cohort immediately, or is that a rate-limiting step to completion of enrollment? On ESSENCE, it looks like on ClinicalTrials.gov, the study's still enrolling. Just wondering where you're at in the enrollment process there. It seems like it's taken longer than originally expected. Do you guys have an updated timeframe on that?
Yeah. Thank you for that. First, on the clinical hold, if we are off clinical hold and we have alignment from the agency, clinical supply won't be a rate limiter for us. We'll be in good shape with clinical supply for our next cohort or trial. As relates to ESSENCE, we are continuing to enroll ESSENCE, and we're continuing to enroll ESSENCE in Europe, not in the U.S. That's an important thing to remember, because one of the things we want to ensure is that if we obtain accelerated approval, either for golodirsen or for casimersen, we want to make sure that it doesn't compromise our confirmatory trial, or we would have a fundamental issue associated with it.
We've also increased the N of ESSENCE, the number of patients in ESSENCE, frankly, in light of the fact that we're going to use it as a confirmatory trial. We just want to increase the probability of success by placing more patients in the trial. Frankly, it was one of the issues that we discussed with the agency, who was enthusiastic about the concept of increasing the N and gave us their approval for that.
Great. Thanks, guys.
Thank you.
Thank you. Our next question comes from Matthew Harrison of Morgan Stanley. Your line is now open.
Great. Good afternoon, and thanks for taking the questions. I think I'd like to focus a little bit just on manufacturing and just understand where you are in terms of process development and scaling now. What are the steps that you need to take over the course of the next year, let's say, to be in a position to be able to have commercial supply and, assuming that cohort C plays out as you previously described, be able to dose crossover patients with commercial supply? Thanks.
Yeah. We have provided only a certain amount of information regarding the entire process for competitive reasons. What I can tell you is the following. We are in the process development, tech transfer process with Brammer. We've informed our thinking from the experience that others have had. For instance, AveXis has been very informative on the sidelines as they really went through the exact process we had from Nationwide Children's Hospital, and that's helped inform our thinking. From a bridging perspective itself, we are making essentially only those changes necessary from a process development perspective that are necessary to scale up. Otherwise, we're trying to remain as close to the original process as possible so we don't create unnecessary risks associated with bridging.
The Brammer relationship will provide us, as we've said, with sufficient supply to robustly launch in the U.S. and elsewhere, even assuming very aggressive development assumptions and timelines. We will be comfortably in a position to use the potential commercial supply to dose patients at crossover after one year. Those are our plans.
Thank you. Great. Thanks very much.
Thank you very much.
Thank you. Our next question comes from Salveen Richter of Goldman Sachs. Your line is now open.
Hi, thank you for taking the question. This is Ross on for Salveen. You've initially indicated your strategy is really to broaden your reach as a neuromuscular-focused company. However, you're now expanding into more broadly CNS and lysosomal storage disease. How should we be thinking about your long-term strategy here? Is Sarepta more of a broad play gene medicine company?
Here's the way we marry two things at Sarepta. We marry big, ambitious, strategic vision with very strong execution-oriented abilities. That's an interesting concept. We have very significant ambitions, and I wouldn't envision if you looked out 5 years from now that we would necessarily be limited to neuromuscular and CNS. We will be, on the gene therapy side, a multi-therapeutic area, significant gene therapy company. As I said, our aspiration is to be one of the most meaningful, if not the most meaningful genetic medicine company in the world over the coming years. The approach that we're taking to get there isn't going to stray from what we know. We're going to continue to build on what we know as we move out in concentric circles of focus. Our most recent Partnership with Lacerta is a perfect example of that.
We start with Duchenne muscular dystrophy and RNA technology. Then we're moving to gene therapy. We're becoming the world's experts, hopefully, in gene therapy. I hope you agree with me on that. Then we've moved to Limb-girdle. Limb-girdle was right next door to Duchenne muscular dystrophy. As I said before, it was basically the Goldilocks type of transaction. Very similar in many ways. When we're going to move from there, moving to CNS is a very logical next step. It's very similar to neuromuscular in many ways, and the kinds of CNS programs that we're looking at right now are the kinds of CNS programs that are closely aligned to neuromuscular. Pompe is a perfect example of this. We are taking a CNS approach, but to a disease that has a significant neuromuscular manifestation.
With that said, we're going to continue to build our expertise, build our ambition, build our gene therapy center of excellence. We are not limiting ourselves in how far that takes us from a therapeutic area perspective. Just know we're not going to wake up one day, sort of crazy over our skis in areas that we don't understand. There's a number of things that we look at. We are a rare disease company. For the time being, we will remain a rare disease company. We are looking for monogenic diseases that were understood and well-characterized. We're going to do a combination of two things over time. We're going to continue to do thoughtful transactions like Lacerta and Myonexus, our Nationwide Children's Hospital transaction and the like, to in-license. We're also going to build the capability of building our own as well.
Great, Doug. Thank you for that. Then just two follow-up questions. On the Lacerta deal, can you specifically provide more details around the types of AAV vectors you're going to be bringing in? Really what highlights about these programs just sparked your interest in comparison to other players out there?
A couple of things. We're not prepared to provide a lot of detail on that now, but I promise you we will in the near term. It won't be a year from now when we start discussing some of that. We're going to discuss that over time, some of the capsid-related issues and vector-related issues. Even, we have two early-stage CNS programs beyond Pompe, and we'll discuss that over time when they get closer to being in patients. The thing that's really got us interested about Lacerta is a couple-fold. Certainly, we're excited about the programs that we have and the access to these two programs and the access to Pompe disease, which really fits with our mission and our passion brilliantly. The opportunity to work with these types of genetic medicine luminaries, like the nine founders of Lacerta, is extraordinarily important to us.
The ability to get closer to University of Florida is extraordinarily important to us. One of the things that we've built a lot of our gene therapy thinking around was this relationship with Nationwide Children's Hospital, and the ability to take that and extend it to University of Florida, which is unquestionably one of the world's centers in gene therapy, is valuable to us. The other tools. We are building a significant gene therapy division, and we need tools. The idea that we have access to a breadth of capsid library to play with is really valuable. The fact that they have really innovative ways of looking at manufacturing that might benefit us in the future is really valuable to us. All of that together aligns with our vision of becoming a very, very significant, meaningful genetic medicine company.
Got it. Finally, just on limb-girdle. How can we think about the severity of the LGMD2E program compared to DMD? Really, what's the read-through we can expect from this initial program onto the remaining four others?
I can allow Dr. Louise Rodino-Klapac to talk a little bit more about this, but let's start with 2E. 2E is the most straightforward. It is very similar to Duchenne muscular dystrophy in its manifestations and the like. 2E, in fact, there's many things about it that have symmetry with our Duchenne muscular dystrophy. First of all, the size of the program is about the same size as EXONDYS 51 amenable patients. It's sort of in that same hunt. The capsid that we're using, Rh74, is the same, which is the same across all five programs. This is a dystrophinopathy. It results in the lack of dystrophin. We're using a promoter that expresses in the heart. It's the same promoter that we're using with DMD. There's enormous symmetry there.
Beyond that, Louise, if you'd like to comment a little bit more on sort of extending to the other four as well.
Three of our five programs are focused on the sarcoglycans, which, if you remember from our R&D day, are components of the dystrophin-associated protein complex. They're very similar in the fact that when you have a deficiency in one, you have a deficiency in the others, and by restoring dystrophin, you restore those, and conversely, when you restore sarcoglycan, you restore the others. There's a lot of similarities, as Doug mentioned, in the severity of the disease. There's cardiomyopathy involvement in 2E. There's a lot of adjacencies between the programs, and we expect that we'll see similar results with the Rh74 and also the same promoter between the two programs.
Great. Thank you guys for taking the question.
Thank you. Ladies and gentlemen, as a reminder, due to time, we ask that you please limit yourself to one question. Our next question comes from Joseph Schwartz of Leerink Partners. Your line is now open
Hi guys. Good afternoon. Thanks for taking our question. This is Dagon dialing in for Joe. One quick one and one follow-up, if I may. With regards to your cohort C plan as you're contemplating it. You mentioned the draft guidance that was very supportive of a single trial for marketing authorization. Going back to that, the draft guidance also stipulates evaluating multiple doses as highly appropriate. Given that you have had some great success with your initial cohort, how are you thinking about implementing perhaps multiple doses in your cohort C? And then as a follow-up, the microdystrophin program, I was wondering if you could comment on the RH74's transduction efficiency in satellite cells. And as we look at the satellite cells specifically, what observations have you made in terms of asymmetric cell divisions there? Thank you.
Let me briefly mention on the dosing issue, then I'll pass it over to Dr. Rodino-Klapac on the satellite cell related issue. The short answer is that there was an enormous amount of preclinical work that supported the dosing that went into what we call cohort B, the dosing of the patients that you saw on June 19th. As a result of that, it provided Dr. Louise Rodino-Klapac and Dr. Mendell, and the FDA, and Sarepta with the comfort to go to what was very robust dosing. Just to remind you, for instance, regarding other ones. One of the other programs is about a quarter of the current dose of our program, then the other one, Pfizer's, is half the dose of our current program. We really went to very robust dosing.
Given the expression levels that we're seeing, just to remind everyone, we're in the 75%-80% dystrophin positive fiber range and just by any measure, extremely robust Western blot dystrophin expression. We have no intention of increasing the dose beyond where we are right now, which is very robust. On the satellite cell, I'll certainly pass it over to Dr. Rodino-Klapac for her views.
What we know from our preclinical models is that we are getting transduction of satellite cells with RH74. Moreover, as I alluded at R&D Day, also in the patient biopsies, we are very intrigued to see that we are also getting transduction in the patient biopsies of satellite cells that were also expressing microdystrophin. What we're doing now is doing careful quantification to be able to say what the percentage of these cells are, but I think it provides a strong rationale moving forward that if we're also transducing satellite cells, we'll get even a more sustained enduring effect. More to come on that.
Great. Thanks for taking our questions.
Thank you. Our next question comes from Debjit Chattopadhyay of H.C. Wainwright & Co. Your line is now open.
Hey, good afternoon. On the ESSENCE study, do we need to reconsent the patients because I believe not all patients were undergoing biopsies because the biopsies are staggered between week 48 and week 96. On the GALGT2 program, any updates on that on getting it to maybe a systemic dosing and restarting the program with more frequent dosing schedule as opposed to once every month?
On the ESSENCE trial, we're not reconsenting kids or we're not doing any new biopsies. These are biopsies that are either already completed, one-year biopsies already completed for children or biopsies that are coming up that were already planned in the trial. This is frankly, this is a pretty simple concept. We've created a protocol that allows us to look at what already would have existed before the end of this year, actually, I think by the end of the third quarter, then analyzing. Am I missing anything there, Dr. O'Neil ?
No, that's exactly it. The only changes are in expanding of the sample size, but from the procedures have not changed, we do not need to reconsent for procedures.
On GALGT2, we're still in discussions with Dr. Flanigan on GALGT2. As we know, he wants to move informed by the results that we've seen with RH74 and the great safety that we've seen associated with RH74, he wants to review the program and change to full infusion. He had some work to do to set that up, we're actually in the process of discussing that right now.
Thank you.
Thank you. Our next question comes from Liisa Bayko of JMP Securities. Your line is now open.
Hi, this is John on for Liisa. Thanks for taking the question. Just to follow up on casimersen. I'm wondering if you could provide any more color on your interactions with FDA in terms of how many samples they'd like to see as far as dystrophin for something that would be sufficient for accelerated approval. Is there a certain number they've given you or how robust does this data have to be to proceed forward?
Our proposal to them was to show them biopsies from 25 patients, which is identical to what we showed with respect to golodirsen, and that was the basis for our type C meeting, and they were comfortable with those numbers as they were comfortable with golodirsen. Do you agree with me, doctor?
Yeah. That's absolutely correct.
Was there any discussion about a lower number of patients?
We didn't propose it, I'm just quite confident they wouldn't have proposed it if we did. We think 25 patients was appropriate. That's what we had with Golodirsen, we get there very soon.
We're on track for that to generate those data by the end of the year.
Great. Thanks a lot.
Thank you.
Thank you. Our next question comes from Hartaj Singh of Oppenheimer. Your line is now open.
Hey there. Great. Thank you for the question. I just had a couple of housekeeping questions. One is that you've got some still ongoing preclinical expenses for wrap-up and tox studies for PPMO platform, golodirsen, casimersen. If I remember correctly, you had to do an ADME study last year for eteplirsen before you filed with CHMP, which actually was the reason for the delay of the filing last year with Europe. Are these just ongoing clinical, preclinical tox studies, or are there additional requests coming from the regulators? The second question was this. Your inventory levels have gone up almost 25%, to $104 million. I assume all the casimersen, golodirsen gene therapy manufacturing is running through the R&D line, because they're still in clinical development. So just any thoughts on that? Is that sort of the norm as you're just having more and more sales of EXONDYS 51?
Thanks.
Before I pass the inventory question over to Sandy, the short answer on the preclinical expenses are they're all part of the current strategy that we have. We're doing IND-enabling toxicology work for five additional PPMOs beyond our 51, what we call SRP-5051, our PPMO for the 51 amenable mutations, and we're doing all of that work, including ADME work. It's not coming as a result of additional requests from agencies at all. It's coming from our strategic plan.
That's correct.
Sandeep?
Yeah. Our inventory levels did go up, and that's primarily stocking up subunits as well as API for 45 and 53, as well as our PPMO study. Yes, the inventory levels did go up because of all our expanded manufacturing for the clinical programs.
Great. Thank you, Sandy. Thanks, (Doug).
Thank you. Our next question comes from Tim Lugo of William Blair. Your line is now open.
Hi, Miles. I'm for Tim. Thanks for taking the question. Congratulations on the quarter. Just at your R&D day, I believe you alluded to an oligonucleotide therapy that you might intend to develop for Pompe disease. Given today's announcement with Lacerta, is it safe to assume that you're just going solely gene therapy for the therapeutic rationale in that indication? Or are you taking the approach like you do with DMD, where you might have a patient on EXONDYS 51 and a microdystrophin gene therapy? I'm just trying to get our heads around that.
Yeah. I should really turn this over to Dr. O'Neill, who I know is very passionate about this particular issue, as it was the very first thing we discussed at our very first interview. Let me just say in the short end, our goal is to be a precision genetic medicine company, and the best way to provide the most benefit to patients from our perspective is wherever possible to provide multiple modalities that could treat and enhance lives. With that said, it's obviously our goal to proceed with our Pompe program and gene therapy, but to be looking at Pompe from an RNA perspective as well.
Yeah, I would agree with that. I am actually quite passionate about the idea that we should offer multiple modalities that can either be selected by patients based on preference or actually look at combinations to maximize the effect. From a strategic point of view and a strategic intent, our goal and objective would be to never exclude a number of approaches, and I think the best way to look at it is the way we're approaching Duchenne with a Morpholino platform and a gene therapy platform.
Beautiful. Thanks for the color. I'll give it to John. Thanks.
Thank you. Our next question comes from Yun Zhong of Janney. Your line is now open.
Hi. Thanks for taking the question. On the agreement with Lacerta, I see from the company website under pipeline, there are a couple of indications. Is it fair to assume that the two CNS indication will come out from those indications listed on the website? Are you able to share whether the delivery is going to be systemic or local or still to be determined?
Yeah. On your first question, the answer is yes. It'll come from among their previously disclosed CNS assets. On the second one, the Pompe program, and I believe the other programs as well, will be intranasal in its delivery.
Okay. On manufacturing, I believe you said that it's slightly different from what you're using for microdystrophin and limb-girdle. At some point, do you plan to maybe make it more consistent so that all programs can be integrated?
Well, we'll look at that over time. Here's the exciting thing and then the interesting thing about their program. Lacerta has a very innovative approach to manufacturing that we might want to explore, and we want to explore it for future programs. One of the things I want to make very clear is that we're not going to jump at that program and start moving over to this program, as innovative as it may be from a manufacturing perspective, because it would almost certainly ensure that we wouldn't be able to get to the community and treat patients as fast as we want. The program that they have is a baculovirus approach. We're a mammalian cell approach with respect to our microdystrophin limb-girdle programs. It's certainly the possibility that we could, in the future, look at other innovative ways to manufacture.
As we stand here right now, as I've said before, we want to constantly marry strategic vision with practical execution. We're going to take the programs that we currently have that we're very excited about, Duchenne muscular dystrophy with microdystrophin and our limb-girdles in particular, and we are going to move as fast as we can to get those therapies, assuming that they work and assuming that they get across the finish line to the community and to patients, and that's going to mean that we're going to make the least number of changes necessary to scale up from a commercial perspective. We have over here from a research perspective and a future therapy perspective, and maybe even a future perspective with respect to current programs down the line, a really interesting approach to manufacturing that we're going to look at very carefully.
Okay, great. Thank you.
Thank you.
Thank you. Our next question comes from Timothy Chiang of BTIG. Your line is now open.
Hi, thanks. Doug, do you guys have a re-examination date set yet for the CHMP review for eteplirsen before year-end?
We'll have two things. We have a SAG, a scientific advisory group, that we will be invited to, then subsequent to that, we'll have a re-examination and oral explanation, and it'll occur in the fall.
Okay, maybe just one follow-up. I know Dr. Mendell, there was certainly a lot of interest in the three patients with the data and all the biomarker data that he showed. I think you cited that it's likely he's going to show some additional follow-up data from those three or four patients. Is it possible that we might even see some functional data at year-end?
Obviously, the decision on functional data will be Dr. Mendell's. Almost certainly he's going to want to present the fourth biopsy data as well as the biomarker data, and he may also present some functional data as well. At least one of the patients will be almost nearly a year post-therapy, so there might be some insight that can be provided. One of the things we want to be very careful about, of course, is not to overanalyze functional data after a short period of time and on a limited number of patients. The good news by the end of the year is we'll have one patient that'll be 11 months on therapy, almost a full year. Ultimately, we'll leave that to Dr. Mendell to make the decision on the exact data that he wants to present.
Okay, great. Thanks.
Thank you. Our next question comes from Gena Wang at Barclays. Your line is now open.
Thank you for taking my questions. Just one quick question regarding the PPMO data update later this year. Just wondering if you can share with us some color regarding the type of data you'll be presenting. For example, number of patients, how many dose cohorts and type of data. Is that protein level, safety? If you can share with us any of these information.
Well, it's a little difficult to say numbers of patients because it kind of depends on how we proceed in dosing and how many cohorts we get up to, et cetera. What we'll have by the first quarter of next year will be very important, but will seem to many very soft data. Because what we're going to get by the first quarter of next year is dosing insight. We'll be able to know through a combination of the doses that we've escalated to and the modeling that gets done off of that dosing, because we're in a single ascending dose study right now, and then we'll move to a multi ascending dose, where the data tells us we can go from a therapeutic dosing perspective. It'll be a very interesting discussion because it will seem to people very soft.
To us, it's very hard data to be real direct because, we know from animal models that we get significant increases in the therapy at the right place as a result of the use of the peptide, and we know when we get that therapy there, we get very significant exon skipping and dystrophin production, literally as much as a fold higher, an order of magnitude higher, I should say, versus what we get with the PMO. The biggest issue for us is ensuring that we can get to those kinds of therapeutic doses that do induce very significant dystrophin. It'll be very soft, Gena, to be honest. It'll be dosing insight, essentially, how high we can get from a therapeutic perspective without concern from a safety perspective. It will also be very meaningful to us and to the rest of the program.
I will assume we will also see the protein level, right? The biopsy protein data from these patients in addition to safety data.
We won't have that kind of data because these are single ascending dose. These are literally single ascending dose studies, so they're just single doses. The issue, this is purely a safety issue right now. How high can we get the dose?
it'll be some time, it'll be about 12 months thereafter, before we actually see dystrophin production. One might therefore think that this is really less interesting than we think it is. This is really an interesting issue because the animal models tell us if we can get to good, robust therapeutic doses, we are going to see significant increases in dystrophin production because we're going to see very significant increases in exon skipping. We see exon skipping in animal models at high therapeutic doses, far better than 50% and 70%, even 80% of exon skipping range and dystrophin production, as measured by a Western blot that is an order of magnitude or even more in some muscles. The dosing insight we get is going to be very telling for us and for the future of the program.
Okay. Just one quick follow-up regarding the Lacerta partnership. For the AAV library strategy, just wondering, are you collaborating with them looking for some vector can cross brain barrier or would that be some local delivery directly to the CNS system?
We're going to look at sort of all of those interesting issues. We just have an entire capsid library to play with. I mean, we already know there are capsids obviously that cross the blood-brain barrier. We know that, for instance, AAV9 crosses the blood-brain barrier in a very promiscuous way. Which makes tons of sense for something like SMA, which benefits both in the periphery and in the central nervous system. Makes, one would argue, significantly less sense in something like Duchenne muscular dystrophy, where you don't actually want the therapy crossing the blood-brain barrier. Good news is we don't use AAV9. We use RH74 there. We're going to look at the capsid library across all of our programs over time, including programs that we don't yet have developed or in-licensed.
How's the IP regarding these vectors?
The good news is we've got good intellectual property around the constructs that we have.
Okay. Thank you.
Thank you. Ladies and gentlemen, this does conclude our question and answer session. I would now like to turn the call back over to Douglas Ingram, Sarepta's President and Chief Executive Officer for any closing remarks.
Thank you everyone for joining today's calls and for your questions. We look forward to updating all of you on the ongoing progress over the coming months as we track toward our goals and toward our catalysts, otherwise, have a good evening.
Ladies and gentlemen, thank you for participating in today's conference. This concludes today's program. You may all disconnect. Everyone, have a great day.