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. As a reminder, this call is being recorded. I would now like to turn the conference over to Ian Esteepan, 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 our CEO, Doug Ingram our CFO, Sandy Mahatme, our Chief Commercial Officer, Beau Kumbo, Doctor. Gilmore O'Neil, our new Chief Medical Officer and Doctor.
Luis Rodino Klapac, our new Vice President of Gene Therapy. After our formal remarks, we will open up the call for Q And A. I'd like to note that during this call, we will be making a number of forward looking state questions. Ernie, any of which are beyond Sarepta's control. Actual results could materially differ from these forward looking statements as any in such caterially and adversely affect the business, results of operations and the trading price of Sarpta's common stock.
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 this afternoon, August 8, 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. And 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 while continuing to remain focused on executing on our plans and fulfilling our commitments. Our newest gene therapy partnership, which will give us 3 new programs and move us into CNS targeted therapies.
A 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 micro dystrophin program. But as sir Winston Churchill famously observed However, beautiful, the strategy, you should occasionally look at the results. So let's begin with our 2nd quarter results. We were pleased to announce earlier today another very strong quarter.
Sales of EXONDYS 51 Our revenue reached $73,500,000, an increase of 110 percent over the same quarter last year. With strong first half sales of approximately $138,000,000, we do remain on track to achieve our 2018 guidance of $295,000,000 to $305,000,000. If you will indulge me, I would like to give special credit to Bukumbo and his commercial organization, as well as our very strong medical affairs team for a fabulous first half of twenty eighteen. Sarepta is that rare breed of fully integrated biotech company that can take a therapy from conception development and approval, and then supported in the community with strong commercial execution. 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 ateplirsen in Europe.
We have commenced a reexamination 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 reexamination. While we believe we have a strong case for access to Ateplirsen for patients with Exxon51 manable mutations in Europe, the reexamination 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 2 PMO candidates Golodirsen and CASMersen.
As 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 tight C meeting with the FDA to discuss among other things, our proposal to conduct an analysis of muscle biopsies at week 48 of EXOND 45 amenable patients in our SSENCE 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 model suggests 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 serve an even larger population than EXONDYS 51.
So the near term opportunity to bring these therapies to the community is very significant. To put this into perspective, if successful, we will have 3 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 5 skip amenable mutations beyond 51. Turning now to our gene therapy progress. For our fight to bring As you know, at our R and D day on June 19, Doctor.
Jerry Mendell of Nationwide Children's Hospital presented the early results from the first in the United States Mandel and Rodino Klapic. 1st, as a Reese's monkey derived AAV vector, to other humanized AAV vectors, meaning it should be available to more patients. 2nd, the micro dystrophin promoter, which specifically chosen for its ability to robustly express in the heart, which is critically important for patients with Duchenne muscular dystrophy, who typically expression in the heart was observed to be up to 120 percent of the micro dystrophin levels observed in skeletal muscles. And third, the TransUnion was designed to maintain spectrum repeats 23, which has been recently reconfirmed to be crucial in protecting the muscle from damage. As you no doubt are aware, Doctor.
Mendell reported that the 3 month biopsy results showed robust gene expression as measured by Western blot and immunohistochemistry with all three patients showing an add 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 1st 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 before the end in the United States.
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 3rd party supplier. Pending the completion of nationwide children hospitals 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. 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 5 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 1st patient in the so called 2E program, which is a beta sarcoglycanopathy in for lgMD diseases, and we'll have an update later this year on that. To remind you, the 5 lgMD programs represent about 70% Now 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 LacerDA Therapeutics.
LaSERDA was founded as a spin out from the University of Florida by a number of world renowned gene therapy research. Like Nationwide Children's University of Florida is one of the top centers of excellence in gene therapy research. We Sertus 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 $30,000,000 equity investment in Lucerne. We have also received an exclusive license to Laserta's CNS targeted Pompe gene therapy program and raised 2 additional CNS targeted programs.
Lucerta will manage the majority of the preclinical development, while Sarepta will lead clinical development and commercialization. Sarepta will pay LacerDA 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 discrete 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. Lucertis founders, 9 and 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 United States.
Including the University of Florida, Nationwide Children's Hospital, CHOP University of Pennsylvania, and Wheel Medical College of Cornell. Second, of course, is the expansion of our gene therapy pipeline. To our pipeline of 8 gene therapy program, programs, Lucera adds 3 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 2 additional CNS specific therapies.
3rd is access to gene therapy tools. Lucerne's novel CAP of library could potentially support next generation therapies that are optimized Lacerta is developing an alternative approach to dose patients with antibodies to AAV, potentially enabling and Lasserta's 1 back 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 we've made this quarter. So 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 chemist, biologists, developers, manufacturing experts and the like. And we will exit 2018 with nearly double the number of employees at the beginning of this year. And 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 to 1st class scientist and biotech leaders, doctors Gilmore O'Neil and Doctor. Luis 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 the quarter, 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 80 5000 Square Foot 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 coming among the most meaningful genetic medicine companies the world over in the coming few years. And I'm 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.
And with that, I will now turn the call over to Sandy for an update on our financial performance. Eddie.
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 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 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 internal resources. This model allows us to continue to economically move multiple programs forward in parallel. Although the company will continue to dramatically transform as it did last year, in the years to come our approach to managing our finances and building shareholder value, remain much 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 website. Please refer to our press release for a full reconciliation of GAAP to non GAAP.
I'd like to add a quick reminder here 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 $73,500,000 compared to $35,000,000 for the same period of 2017. The increase primarily reflects high demand for EXONDYS in the U. S. We reported a non GAAP net loss of $28,000,000 or $0.43 per share compared to non GAAP net loss of $26,500,000
or
to be $6,700,000 in cost of sales compared to $500,000 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 $3,700,000 to BioMarin, which were a result of the settlement and 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 $122,800,000 20182017, respectively, a year over year increase of $63,900,000. This increase is primarily related to payment we made to MyNexis. On a non GAAP basis, the R and D expenses were $57,000,000 for the second quarter of 2018, compared to $34,100,000 for the same period of 2017, an increase of $22,900,000.
The year over year growth in non GAAP R and 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 Eutrophin program. Due to the termination of Summit's Eutrophin program during the second quarter of 2018, we expect this expense to significantly decline over the upcoming quarters.
Turning to SG and
second quarter of 2018 2019, respectively, a year over year increase of 11,100,000 On a non GAAP basis, the SG and A expenses were $37,300,000 for the second quarter of 2018 compared to $24,200,000 for the same period of 2017, which is an increase of $13,100,000 The year over year increase was primarily driven by continued build outs supporting our research and development and commercial expansion. On GAAP basis, we recorded $4,700,000 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 $50,000,000 in cash, cash equivalents and investments as of June 30, 2018. In addition, we have prepaid approximately 33 $700,000 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 our commercial update.
Bo?
Thank you, Sandy. Good afternoon, everyone. As we head into the 8th quarter of an ultra rare disease launch, we're very proud of the progress and accomplishments the team has made. We had a strong quarter and remain on track to achieve our full year guidance of $295,000,000 to 305,000,000 The team has also 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 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 test, know the 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. Groups.
The average age of patients on therapy is patients to dramatically change until newborn screening for Duchenne becomes standard medical practice, which would identify 100 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 out 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-fifty one skipping and submit start forms as appropriate. We continue to call on top tier centers but have purposely expanded our efforts. A portion of our educational endeavors has shifted to large pediatric office 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 mezz that improves the lives of all patients with We're able to do this by collaborating with the most notable export experts worldwide and continuously striving to advance our multi platform pipeline. We currently have 23 programs in development at Sarepta. And with each new program comes the responsibility of ensuring treatment access for patients. This brings me to requires complex coordination and flexibility as we continue to build the infrastructure needed to be the worldwide leader in precision genetic medicine, we remain committed to executing to include a variety of innovative approaches to enhance patient access to these therapies. During the reexamination 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're also focusing our effort to build out and support future launches in other countries. We have recently hired our Country Manager, Medical Director, Head of Government Affairs 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 and we know how to get there. We're 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 US commercial success of EXONDYS 51 has provided the framework and resources to support future rare disease launches. We were leveraging this knowledge to prepare ourselves for operational and executional success. Between our gene 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 PMO 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 one of the deepest rare disease and precision genetic medicine. We will continue to pave the way diseases. And with that, I'll turn the call back over to Doug for closing remarks.
Thanks, Beau. As we move into the latter half of twenty eighteen, we are pleased with the progress that we have made to date advancing our ambitious vision married to a continuing focus on practical execution. 18, 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 reexamination for ateplirsen in Europe, advancing SRP-five thousand and fifty one and the rest of our PPMO platform, removing the clinical hold on our micro dystrophin program, meeting with and gaining insight from the FDA on the registration pathway for our micro dystrophin program and commencing the enrollment of patients in a pivotal study for micro dystrophin. 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. And with that, operator, can you please open the call for questions?
Thank
you. Question has been stated. Our first question comes from Ritu Baral of Cowen. Your line is now open.
Thanks for taking the question. Maybe I'll start with the LacerDA deal. Doug, can you talk about the difference between those Serta Pompe program and some of the others like Audentes and Spark. And, just a quick follow-up question on Golodirsen and Kazimersen, how are you thinking about the pricing of those programs in relation to EXONDYS?
Okay, great. So the first on our Pompe program, obviously, to say it's early days, it would be an understatement. I think we just announced less than 60 minutes ago. So 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 Lucerne. The one thing I will say is that we have a unique approach to our gene therapy program with our compet 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.
And I think in that regard, we will be differentiated from others, at least at a beginning. So
motor neuron targeted, Doug?
Yes.
Yes.
And the second thing I would say about it, just the credential art Pompe program is it, it was, invented and developed at the University of Florida by none other than Doctor. Barry Byrne, who, along with folks like Doctor. Jerry Mendell, now our very own Luis Rodino Klapac is among that rare, verified group of world luminaries in the development of gene therapy constructs. And then answering your question about Golodirsen and casimersen, while we haven't gotten that far to really pull out a a sharp pencil on either one. The short answer is that it will be priced at parity with, to versus.
Our next question from Brian Abrahams of RBC Capital Markets. Your line is now open.
Hi there. Thanks very much for taking my questions and congratulations on all the progress. 2 from me First on the micro dystrophin clinical hold. Sounds like you've already made good progress there. I'm wondering if you could give us a little bit more in terms of specifics with respect to what needs to be done at NCH.
And maybe based on your initial audit of the 3rd party supplier and ongoing regulatory feedback, if you could characterize your level of confidence in the rapid resolution? And then I had a follow-up on casimersen.
Great. Okay. So first, I'll start with the clinical hold. The short answer is that as you've said, we've made great progress. We had from our perspective, drafted what we believe would it be a complete response.
We've completed an on-site significant audit of of our 3rd party supplier that went very well. With respect to our partner, Nationwide Children's Hospital, there, 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 in together and then putting together a complete bonds to the, to the clinical hold letter that, that is polished. So it's we really are in the final strokes of, of getting our response. So I've 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 of August. So, and then on what we found so we've completed our audit of the 3rd party supplier 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.
So we feel very good. I am would say at this point, I am frankly very confident in the rapid resolution and the issues associated with the clinical hold
That's really helpful. And 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 getting that data. Thanks again.
Yes. The short answer is very carefully, because we certainly, I will say we don't 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, of essence, which will act as a not only is it independent study that also is 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've We came up with an advance with a protocol that would essentially, sort of hive off a group that would blinded to everyone else would look at the biopsies themselves from the active arm for the casimersen arm. 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.
And we've presented that shared that with the division and the division is in agreement with us that we have an approach that works. So we feel very
good.
Thanks, guys.
Thank you. Our next question comes from Christopher Mara of Nomura Instinet. Your line is now open.
Hi, thanks for taking the question and congrats on the progress. So just thinking about dosing your ex patients with your dystrophin gene therapy and 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, but what those patients dosed to be part of that trial? And 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 a site of for competitor, data release, maybe 3 patients or so.
And wondering how you internally will be evaluating, I suppose biopsy and dystrophin data? Thank you.
Well, okay. So let's start on the dosing side. So our focus right now really is 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 envisioned to be a pivotal trial for the therapy. So that really is our big focus right now. So even if we came off of going to 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 path way and then dosing patients. And we if things work well and we execute brilliantly, we think we can get that all done. 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. So that's going to be our focus.
And it really is informed not only by our own ambition, but also by this, this draft guidance from the FDA regarding gene therapy and rare disease, which came out, I believe, as I said on June, July 11, we which really gives us 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. So that's our focus, right now. And 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.
And, 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. So We have a construct quite apart from just the fact that we have extraordinarily good, dystrophin production immunious chemistry and, and, through Western blot as revealed in the first three patients at our R and D day, we have concert that's very elegant in a number of other ways. We have low screen out rates for pre existing antibodies, likely because we're using R874, 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 read it expresses 120 percent 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. And then, of course, the there was really an elegant design around the cassette itself. It maintains spectrum repeats 23, which just very recently in a paper, I believe it was in March of this year confirmed was extremely important to to avoid muscle damage and to protect for muscle damage. So 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 if the trial works out. One final thing I do want to point out, apologies for being a little winded, a little long winded on this. But 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. But 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 United States 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 because as we've said many, many times before and as Beau just said a moment ago, our goal is not to treat registry 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. And then just to clarify, so we don't expect additional dystrophin production data from your, gene therapy program to be presented about 1 and the number 2 just to indicate with respect to just thinking about how you coming, sorry, go on.
I apologize. Go ahead and 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. Should we how should we look at that?
So we look at vector genome copies, dystrophin levels, CK levels, I mean, all of the above? Or I mean, I would love to understand how you guys want to compare and contrast essential data that we see here later this year from a competitor? And what might be most meaningful? Because obviously there are problems interpreting dystrophin biopsies, etcetera, and it's a cross trial comparison. So I'd love to understand just maybe from your lens as gene therapy experts and Duchenne, how you'd look at that?
Thank you.
Yes, 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. Doctor. Mendell will be making the choices about the forum but it'll be and it'll be at a medical forum likely before the end of this year.
But remember, we'll have 2 things. We'll have biopsy data from a 4th patient. We had a There was a 4th patient dosed, even before the June 19th date, we just didn't have a 3 month biopsy yet. So there was no ability to provide that information. So he'll be able to present that.
They'll also be biomarker data, including obviously CK level data for all of the patients, and at least in the first patient, it'll be nearly a year's worth of biomarker and CK level data will be presented by the end of the year. So 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 other therapies and what they might present, later this year or otherwise. I think there's you raised some very good points. 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 very we're so thoughtful that we're conservative. And so 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 are unprecedented, as you know, in the first three patients that we have, the drops were nearly 90% that's never been seen before in a 3 month period or otherwise. And I think Doctor.
Mendell's already revealed, so I don't think I'm revealing anything secret that the initial drop in the 4th Boy was quite significant as well. Certainly, at least in the hunt of if not even maybe a little better than even that. And so I think those are important things to look at. But then beyond that, there are other things to consider. And that's why we really talk a lot about the elegance of our constructs.
So 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 that 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. And so 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 percent of what we're seeing in the skeletal muscle. Now to look at these patients into 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 get to see what other people look like there.
And then I think quite a part, 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 micro dystrophin works in animals. We know that there is a wonderful natural case study associated with this, a sixty one year old patient, started all of this was a Becker's patient who had essentially a naturally occurring form of micro dystrophin and was sixty one years old and remained ambulatory. So there's a lot of hope that there's protection associated with micro dystrophin and certainly our CK levels would lead us to believe that that's what's occurring here. But really looking carefully at the construct itself and seeing if that construct matches that sixty one 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 public literature recently that maintaining spectrum like repeats 23 is extremely important to predict the protective quality of the dystrophin So there's a lot to consider when we consider comparing across programs.
Thank you.
Our next question comes from Brian Skorney of Baird. Your line is now open.
Hey, good afternoon guys. Thanks for taking two quick questions from me. First one, assume you guys get the clinical hold listed in the outline timeframe just wondering, are you at production scale that would allow you to dose every patient in the 3rd cohort immediately or is that a rate limiting step to of enrollment. And on essence, it looks like on clinical trials, the study is still enrolling. Just wondering, where you are at in the enrollment process there seems like taken longer than originally expected.
Do you guys have a updated timeframe on that?
Yes. Thank you for that. So first on the clinical hold, if if we are off clinical hold and we have alignment from the agency, we won't have a clinical supply won't be a rate limiter for us. Okay. So we're, we'll be in good shape with, with clinical supply for our next, our next, cohort trial.
As it relates to Essence, so we are continuing to enroll lessons and we're continuing to roll lessons Europe, not in the United States. 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 end of essence, the number of patients in essence, And 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. And we frankly 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 to that.
Great. Thanks guys.
Thank you. Thank
you. Our next question comes from Matthew Harrison Morgan Stanley. Your line is now open.
I think I'd like to focus a little bit just on 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, covert C plays out as you've previously described, be able to dose crossover patients with commercial supply?
Thanks. 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 have we've informed our thinking from the experience that others have had.
So for instance, Vexis 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 said, with sufficient supply to robustly launch in the United States and elsewhere even assuming very aggressive development assumptions and timelines.
And we will be comfortably in a position to use the potential commercial supply to dose patients at crossover after 1 year. Those are our plans.
Our next question comes from Salveen Richter of Goldman Sachs. Your line is now open.
Hi. Thank you for taking the questions. This is Ross on for Salveen. So you initially indicated your strategy is really to broaden your reach as a neuromuscular focused company. However, you're now expanding into more broadly CMS and life of some of storage fees.
So how should we be thinking about your long term strategy here, is Sarepta more of a broad play gene medicine company?
So the here's the way we're we married 2 things at Sarepta. So we married big ambitious strategic vision with very strong execution oriented, ability. So, and that's an interesting concept. So we have very significant ambitions. And I wouldn't envision if you look 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, we will 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. But 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 we kind of move out in concentric circles of focus. And our most recent, partnership with Lacerta is a perfect example of We start with Duchenne muscular dystrophy and RNA technology. And then we're moving to gene therapy.
We're becoming the world's experts, hopefully, in gene therapy. And You agree with me on that. And then we've moved to limb girdle. Limb girdle was right next door to Duchenne muscular dystrophy. I think as I said before, it was basically the Goldilocks type of transaction, very similar in many ways.
So 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 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.
And we are not limiting ourselves in how far that takes us from a therapeutic area perspective, just know you're we're not going to wake up one day, sort of crazy over our skis in areas that we don't understand. So there's yes, so there's a number of things that we look at. We're, 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.
And we're going to do a combination of 2 things over time. We're going to continue to do thought full, transactions like Lacerta and Myonexus, our nationwide Children's Hospital transaction and the like, license, we're also going to build the capability of building our own as well.
Great Doug. Thank you for that. And then just two follow-up questions. So on the Serta deal, can you specifically provide more details around like the types of AAV vectors they're going to be bringing in? And really what highlights about these programs to spark your interest in comparison to other players out there?
Well, 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. We won't be a year from now when we start discussing some of that. But we're going to discuss that over time, some of the capsid related issues and vector related issues. And even we have 2 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 Lisserta is couple fold. Certainly, we're excited about the programs that we have and the access to these 2 programs and the access to Pompe disease, which is, which really fits with our mission and our passion brilliantly. The opportunity to work with these types of genetic medicine luminaries like the 9 founders of LaSerta 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 built that we 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 and gene therapies valuable to us.
And then the other tools, we're building a significant gene therapy division and we need tools. So 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 manufacturing that might benefit us in the future, is really valuable to us. So all of that together, aligns with our vision of becoming
Got it. And then finally, just on limb girdle, so how can we think about the severity of the V2E program compared the DMD? And really what's the read through we can expect from this initial program onto the remaining 4 others?
I can allow Doctor. Rudina Klapic to talk a little bit more about this. But let's start with TUI. TUI is the most straightforward. It is very similar to Duchenne Mus her dystrophy in its manifestations and the like.
2e's, in fact, there's many things about 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 CASK that we're using our A74 is the same, which is the same across all five programs. This is a dystrophinopathy. It results in the lack of And so we're using a promoter that expresses in the heart, it's the same promoter that we're using with DMD.
So there's enormous symmetry there. And then beyond that, Luis, if you'd like to comment a little bit more on sort of extending to the other 4 as well.
So 3 of our five programs are focused on the sarcoglycans, which if you remember from our R and D day are components of drophin associated protein complex. They're very similar in the fact that when you have a deficiency in 1, you have a deficiency 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 disease. There's cardiomyopathy involvement in 2E.
And so there's a lot of adjacencies between the programs and we expect that to similar, results with the, R874 and also the same promoter between the two programs.
Thank you.
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, Dae Gon dialing in for Joe. So one quick one and one follow-up, if I may.
1, with regards 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. So going back to that, the draft guidance also stipulates evaluating multiple doses as highly appropriate. So 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 micro dystrophin program, I was wondering if you could comment on the rh74s 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?
Well, let me briefly mention on the dosing issue, and then I'll pass it over to Doctor. Rodino Klompic on the satellite cell related issue. So The short answer is that we 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 2019. And as a result of that, it provided the Doctor. Louise Rodino Klapic and Doctor.
Mendel, and the FDA and Sarepta with the comfort to go to what was very robust dosing. Just to give you, to remind you, for instance, regarding other ones. So, like, one of the other programs is about a quarter of the current RAM. And then the other one, Pfizer's is half the dose of our current program. So we are we really went to very robust dosing.
Given the expression levels that we're seeing, just to remind everyone, we're in the 75% to 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 send the pass it over to Doctor. Renocrapin for her for use.
What we know from our preclinical models is that we are getting transduction of satellite those as ARS74. And moreover, as I alluded at R&D Day, also on the patient biopsies, we are very intrigued in to see that we are also getting transduction in the patient biopsies of satellite cells, that we're 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 and enduring effect. So more to come on
Great. Thanks for taking our
question comes from debjit Chattopadhyay of H. C. Wainwright. Your line is now open.
Hey, good afternoon. On the Essence study, Do we need to re consent the patients? Because I believe not all patients were undergoing biopsies at because the biopsies are staggered between week 4 week 48 week 96. And then on the GOL G2 GT2 program, any updates on that on getting it to maybe systemic dosing and restarting the program with more frequent dosing schedule that's supposed to once every month?
On the essence trial, we don't have to re we're not re consenting kids or we're not doing any new biopsies. These are biopsies. They're that are either already completed. 1 year biopsies already completed for children or biopsies that are coming up that were already planned in the So this is simply 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.
And then, and analyze them. So do am I missing anything there?
No, that's exactly it.
The only changes are in expanding at the sample size, but for the gut of the procedures, the procedures have not changed. And so we do not need to re consent for procedures.
And then on Gauzy T2, we're still in discussions with, Doctor. Flanagan on Gauzy T2. He's, he, as we know he wants to move is informed by the results that we've seen with, 24 and the great safety that we've seen associated with our 74, he wants to review the program and change to full infusion. He had some work to do to set that up and we're actually in the process of discussing that right now.
You. Our next question comes from Lisa Bayko of JMP Securities. Your line is now open.
Hi, this is John on for Thanks for taking the question. Just a 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 that's 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 that they were, they were comfortable with those numbers. As they were comfortable with Golodirsen. Do you agree with me, Doctor. Ernie?
Yes. That's absolutely correct.
Was there any discussion about a lower number of patients?
We didn't propose it. So, and I'm just quite confident they wouldn't have proposed it if we didn't. So, we think 25 patients was appropriate. That's what we with Golodirsen and we get there very soon.
And 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 know, Dave, you've got some still ongoing expenses, preclinical expenses for, you know, ramp up and talk studies for PPO worm, Golodirsen, CASMERS.
And if I remember correctly, you had to do a AdvairD study last year or e cutlers in before you filed with CHMP, which actually was the reason for the delay of the filing last year was Europe. Is there any kind of are these just ongoing clinical kind of preclinical tox studies or is there additional requests coming from the regulators? And then the second question was this, just, your inventory level have gone up almost 25 percent to $104,000,000. I assume all the casimersen, Golodirsen, gene therapy, manufacturing is running through the PR and 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 effects on this with you? Thanks.
Before I pass the inventory question over to, the Sandy The short answer on the preclinical expenses are they're all part of the current strategy that we at. We're doing IND enabling toxicology work for 5 additional PPMOs beyond our 51, what we call 5151, our PPMO for the 51 Metabolic mutations. And we're doing all of that work, including add new work. So it's not it's not coming as a result of additional requests from agencies at all. It's coming from our strategic plan.
That's correct.
And then Sandy?
Yes. So our inventory levels did go up and that's primarily stocking up subunits as well as API for 45.53. As well as our PPMO study. So 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, Myles on for Tim. Thanks for taking the question. Congratulations on the quarter. Just at your R and D day, I believe you alluded to an Oligo nucleotide therapy that you might intend to develop for Pompe disease. And given today's announcement with FlacerDA, is it safe to assume that you're just going solely gene therapy for 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 micro dystrophin gene therapy?
I'm just trying to get our heads around that.
Yes, our I should really turn this over to Doctor. O'Neal. I know it's very passionate about this particular issue. It was the very first thing we discussed in our very first interview. But let me just say in the short end, we are we our goal is to be a precision genetic medicine company and the best way to provide the most benefit to pay from our perspective is wherever possible to provide multiple modalities that could treat and enhance lives.
So with that said, it's obviously our goal to proceed, with our Pompe program in gene therapies, but to be looking at Pompe from an RNA perspective as well. 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. And so from a strategic point of view and a strategic intent, our goal and objective would be 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.
Question comes from Yong Jong of Janney. Your line is now open.
Hi, thanks for taking the question. So on the agreement with Lacerta, I see from the company website under pipeline, there are a couple of indications. So is it fair to assume that the, the 2 CNS indication will come out from those indications listed on the website. And also, are you able to share whether the delivery is going to be systemic or local or still to be determined?
Yes. So on the first your first question, the answer is yes. It'll be it'll come from among their previously disclosed CNS assets. And on the second one, the Pompe program, and I believe the other programs as well will be fecal and it's delivery.
Okay. And manufacturing, I believe you said that it's a slightly different from what you're using for micro dystrophin and lean Girdle. At some point, do you point to maybe, to 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 really like want to explore and we want to 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 back of a virus approach we're mammalian virus with a mammalian cell approach with a respect to our micro dystrophin and limb girdle programs.
So it's certainly the possibility that we could in the future look at other innovative ways to manufacture. But as we stand here right now, as I said before, we are going to constantly marry strategic vision with practical execution. And so we're going to take the programs that we currently have that we're very excited about to shed muscular dystrophy with micro dystrophin 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. And then 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 careful
Okay, great. Thank you.
Thank you.
Our next question comes from Tim Chang of TIG. Your line is now open.
Hi, thanks. Doug, do you guys have a reexamination date set yet for the CHMP review for Enerfloors before year end?
We have a we have we will have 2 things. We have a STAG, a scientific advisory group that we will be invited to. And then subsequent to that, we'll have a reexamination and oral explanation, and it'll occur in the fall.
Okay. And maybe just one follow-up. I know Doctor. Mendell, there was certainly a lot of interest in the 3 patients with the data and all of the biomarker data that you showed. I think you cited that it's likely he's going show some additional follow-up data from those 3 or 4 patients.
Is it possible that we might even see some functional data? At year end?
Obviously, the decision on functional data will be Doctor. Mendell's. We will almost certainly he's going to want to present the 4th biopsy data as well as the biomarker data And you may also present some functional data as well. At least one of the patients will be almost nearly a year of 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 over, and to analyze, functional data after a short period of time and limited number of patients. The good news the end of the year is we'll have one patient that'll be 11 months on therapy, almost the full year. But I'm ultimately we'll leave that to Doctor. Mendel to make the decision on the exact data that he wants to present.
You. Our next question comes from Gena Wang of Barclays. Your line is now open.
Thank you for taking my questions. Just one question regarding the PTMO 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?
Yes. Well, it'll be 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, etcetera. What we have by the first quarter of year will be very important, but we'll see into many very soft data. Because what we're going to get by the first quarter 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 dosing because we're in a single ascending dose study right now that will move to a multi ascending dose where we imagined where the data tells us we can go a therapeutic dosing perspective.
So, 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 the therapy there, we get very significant excellent 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. So the biggest issue for us is ensuring that we can get to those kinds of therapeutic doses that it do induce very significant dystrophin. So it'll be very soft. Gina, to be honest, it'll be, it'll be dosing insight essentially how high we can get from a therapeutic without concern from a safety perspective, but it will also be very meaningful to us and to the rest of the program.
So I will assume we will also see the protein level, right, about the protein data from these patients in addition to safety data.
Yes, we won't have that kind of data because these are single ascending doses. These are literally single ascending dose studies. So they're just single doses. So issue, this is purely a safety issue right now. How high can we get the dose?
And then it'll be some time. It'll be about 12 months thereafter, where we actually see, dystrophin production. Now one might therefore think that this, that this is really, less interesting than we think it is. But 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 ex skipping. We see exon skipping in animal models at high therapeutic doses in the far better than 50% in the 70 percent, even 80% of Exxon skipping range and dystrophin production, as measured by a Western blot that is order of magnitude or even more in some muscles.
So the dosing insight we get is going to be very, very telling for us and for the future the program.
Okay. And just one quick follow-up regarding the LaSeta Partnership for the AV library strategy. Just wondering, are you looking for like are you collaborating with them looking for some vector can cross bring Blobberi 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 across 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. These are 874 there.
But 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 IT regarding these factors? It's
we have the good news is we've got good intellectual property around the constructs that we have.
Okay. Thank you.
Thank you. And ladies and gentlemen, this does conclude our question and answer session. I would now like to turn the call back over to Doug Ingram, Sarepta's President and Chief Executive Officer, for any closing remarks.
Thank you, everyone, for joining our 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 and 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.