Sarepta Therapeutics (SRPT) Q1 2019 Earnings Call Transcript

Sarepta Therapeutics (SRPT 0.17%)
Q1 2019 Earnings Call
May. 08, 2019, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics first-quarter 2019 earnings conference call. [Operator instructions] As a reminder, today's program is being recorded. I'd now like to introduce your host for today's program, Ian Estepan, senior vice president, chief of staff, and corporate affairs. Please go ahead.

Ian Estepan -- Senior Vice President, Chief of Staff, and Corporate Affairs

Thank you, Valerie, and thank you all for joining today's call. Earlier today, we released our financial results for the first quarter of 2019. The press release is available on our website at www.sarepta.com, and our 10-Q was filed with the SEC earlier this afternoon. Joining us on the call today are Doug Ingram, Sandy Mahatme, Bo Cumbo, Gilmore O'Neill, and Louise Rodino-Klapac.

After our formal remarks, we'll open the call up for Q&A. I'd like to note that during this call, we'll 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 uncertainties, any of which are beyond Sarepta's control.

Actual results could materially differ from these forward-looking statements and any such risk can materially and adversely affect the business, results of operations and trading prices for Sarepta's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q filed with the Securities and Exchange Commission, as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. With that, let me turn the call over to Doug Ingram, our CEO, who will provide an overview of our recent progress.

Doug?

Doug Ingram -- Chief Executive Officer

Thank you, Ian. Good afternoon, and thank you all for joining Sarepta Therapeutics on its 2019 first-quarter results and corporate update conference call. In 2017 and 2018, we defined our ambition and then gathered the tools necessary to achieve that ambition. Our vision was audacious but also very specific.

As a fully integrated commercial stage biotechnology company with a multi-platform approach, we attempt on being among the world's leaders in precision genetic medicine. For our RNA platform, that means advancing our PMO technology to treat greater segments of the patient population with our exon skipping therapies; advancing our next generation PPMO technology which, if successful, could be a significantly more efficient version of our PMO technology; and bringing our RNA platform and expertise to new therapeutic diseases that could benefit from our steroid-blocking technology. And for our gene therapy platform, it means building out our durable gene therapy model by focusing on two interrelated exercises: one, advancing our multi-therapeutic gene therapy engine, already producing the broadest late-stage gene therapy pipeline in biotech; and two, advancing our hybrid manufacturing model with the goal of having the most robust capacity available in gene therapy, coupled with the ability to quickly transition constructs from proof of concept to commercial process supply. The other ones we built in 2017 and 2018 to fuel that vision are these: First, pipeline.

Through internal development and external collaborations, we built what is currently a 26-program pipeline second to none. That includes 11 gene therapy programs, 14 RNA programs and a gene editing collaboration. It also includes multiple therapeutic areas from Duchenne to 6 limb-girdle diseases to Charcot-Marie-Tooth to MPS 3A, multiple additional CMS applications, and the list goes on. Second, resource.

We entered 2019 with $1.2 billion in cash, and we raised another $375 million in the first quarter to ensure that we fuel our aspirations and we meet our very specific near-term goals. And third, talent. When I joined Sarepta, we had about 200 employees. We have increased the number of employees, such as chemists, biologists, genetic experts, regulatory professionals and factory experts and the like by some 300 -- in fact, 300% since then, and we are, in fact, tracking to about 850 employees by the end of this year.

Moreover, the sophistication of our talent is second to none, including our gene therapy center of excellence in Columbus, Ohio, headed by Dr. Louise Rodino-Klapac and our very talented head of R&D, Dr. Gilmore O'Neill. When one assesses our ability to achieve our goals, it should be done in reference to the tools that we have gathered, and that's assets, our gene therapy manufacturing platform, our balance sheet and our talent.

Now having gathered the tools to fuel our ambition, I know that at the inception of this year that 2019 would be the year of execution as it is our goal to build our reputation, not only on the breadth of our ambition and the quality of our science, but also on our operational excellence to drive performance and to execute. And I am very pleased to say that in the first quarter, our team executed brilliantly. Let's start with our RNA franchise. In our third year from launch, EXONDYS 51 continues to perform, with sales standing at $87 million and quarter over same quarter last year growth an impressive 35%.

In early 2018, I represented that we would build a positive relationship with the FDA and we would define an Accelerated Approval pathway for the bulk of our RNA platform. I am pleased to say that in the first quarter of 2019, the FDA accepted our next PMO therapy golodirsen for filing, gave us priority review, set a PDUFA date of August 19, 2019, and informed us that they do not intend to panel an advisory committee at this time. In the first quarter of 2019, we announced positive results from our third PMO candidate, and that's casimersen. If successful, with golodirsen and casimersen, we will have three therapies serving the community by the first quarter of 2020, representing nearly 3% of the Duchenne population and more than doubling the coverage that we have today.

This is particularly impressive when one considers that in the entire history of biotech, there are less than 15 companies that have commercially launched three or more internally developed therapies. And we're now progressing our next generation PPMO technology as well. To remind you, our PPMO is a proprietary peptide conjugated version of our PMO RNA technology which, in animal models, has robustly increased cellular penetration, greatly enhancing exon skipping and dystrophin production. In the first quarter, we transitioned from our single-ascending dose study to our multi-ascending dose study for our first of 6 candidates, SRP-5051.

We have screened our first patient in the study, and we should have insight on dosing levels by the end of 2019 to the first quarter of 2020. Moving next to our gene therapy franchise. We have made very significant progress in the first quarter. Having fulfilled our commitment to commence our placebo-controlled microdystrophin gene therapy trial by the fourth quarter of 2018, we have now made great progress on enrollment, having now dosed 18 patients thus far and we are comfortably on track to complete all dosing in the trial in this quarter, the second quarter of 2019.

And we are on track to commence a multi-center trial with commercial supply by year end. In the first quarter, we also announced very positive results from our first cohort of limb-girdle 2E, that's our first program. Mean protein positive fibers was 51%, some 250% of the predefined milestone of success of 20% in the study. Mean intensity was an impressive 47%, and western blot modification was at 36%.

Creatine kinase enzyme, a marker of muscle damage, dropped by an unprecedented 90%. These results are particularly telling since they come at a quarter of the dose of our microdystrophin program. Given the lack of expression at another recent neuromuscular program in the stage at [Inaudible], these results suggest the elegant design of our construct, with potential positive readthrough to all of the other limb-girdle programs in our pipeline and also back to our microdystrophin gene therapy construct, which not only shares the same vector and promoter but the same designer Dr. Louise Rodino-Klapac.

Commercial process supply of the limb-girdle 2E pivotal trial will be available in the first half of 2020. We have decided to use the available time to dose escalate the clinical supply from the Nationwide children's facility. We plan to dose three patients in cohort 2 at 2E to the 14th. This strategy will inform the dosing regimen not only for the 2E pivotal study but it should also inform dose selection for all six of the limb-girdle programs.

We have planned to initiate dosing in this cohort in the middle of this year. As we announced earlier today, we continue to build out our gene therapy engine. This time with an additional partnership with Nationwide Children's Hospital and Dr. Zarife Sahenk for our sixth limb-girdle therapy, limb-girdle 2A, otherwise known as calpainopathy.

We are excited to deepen our relationship with Dr. Sahenk, the inventor of and the principal investigator for, our Charcot-Marie-Tooth program. And we are pleased to add a gene therapy treatment for calpainopathy to our pipeline. Calpainopathy is an autosomal recessive limb-girdle disease that results in very serious muscle degeneration and wasting.

It is also the most prevalent form of limb-girdle, accounting for about 30% of all limb-girdle muscular dystrophy. Dr. Sahenk's approach relies on r874 and the LEM replaces the missing data protein from the calpain 3 gene, the root cause of the disease. Going on.

With our partner, Lysogene, in the first quarter, we commenced dosing in our Phase 2/3 gene therapy program to treat MPS 3A, also known as Sanfilippo disease, a devastating neurological disease that often robs the life of children before the age of 15. In the first quarter, we also made great strides toward the build-out of our gene therapy manufacturing plants. We are near completion of our process development and yield optimization efforts and have advanced our analytical development for our microdystrophin commercial process. Our goal is to complete all process analytical development and to be in a position to commence our commercial process to apply trial by year end.

As many of you know, two of our CMOs were recently acquired in multibillion-dollar transactions. Both of their investments further validate Sarepta's programs and our approach to manufacturing in so far as we are the most significant long-term customer of both Brammer and Paragon. Our hybrid manufacturing approach is a purposeful strategy designed to allow us control of the most differentiated aspects of the manufacturing process, while affording us the speed the scale and the risk mitigation to match our goal of rapidly completing the safety and efficacy of our first program and bringing it to the community. Our strategy includes building internal talent and ability around high-value differentiated process development, analytical development and early stage manufacturing and entering into long-term partnerships for large-scale supply.

The goal then is to control the highly differentiated parts of manufacturing, those have allowed us to move rapidly from conception to commercialization, and to partner and outsource those choices that will become the commoditized aspects of manufacturing. For that end, we are near completion of a 75,000 square-foot dedicated Sarepta gene therapy manufacturing facility with Brammer Biosciences and its parent Thermo Fisher in Lexington, Massachusetts, targeted for commercial manufacturing beginning in late 2019 this very year. We also have dedicated supply with Paragon. And as recently announced by Paragon and its parent, Catalent, we are in discussions for a deeper commercial supply relationship, including a second dedicated site for Sarepta supply.

We set very ambitious targets for ourselves for 2019, and I am proud to say that the Sarepta team has, so far in 2019, executed well against those targets. And yet again, we must remind ourselves that there is much left to be done in 2019, and an enormous number of important milestones and inflection points left to achieve. We will complete dosing of our placebo trial for microdystrophin in 2019. We will dose additional limb-girdle patients in 2019.

We will report out our progress of our first 2E cohort of patients later this year, a medical meeting or a scientific conference. We will continue the dosing of our trial for MPS 3A or Sanfilippo disease. We will commence dosing of our first Charcot-Marie-Tooth gene therapy cohort. We intend to obtain our second PMO approval this time for golodirsen and to launch golodirsen in 2019.

We expect to submit an NDA for casimersen in 2019. We will execute our multi-ascending trial for our next generation PPMO in 2019. We intend to complete our process development, build commercial supply for microdystrophin and commence our commercial supply trial before the end of this year, 2019. And we will very likely find additional attractive assets to fuel our gene therapy engine this year.

The remainder of 2019 will be busy, but it will certainly be consequential. If we achieve our goals, we will profoundly improve the lives of countless patients living with and otherwise dying very young from rare disease. We will build an enduring genetic medicine powerhouse designed to outlive all of us, and we will certainly create enormous shareholder value. And with that, I will turn the call over to Sandy Mahatme to provide an update on the financials.

Sandy?

Sandy Mahatme -- Executive Vice President, Chief Financial Officer and Chief Business Officer

Thanks, Doug. Good afternoon, everyone. We are pleased with our financial performance for the first quarter of 2019. Some of the highlights include $87 million of net product revenues, flat operating expenses compared to the prior quarter and approximately $1.4 billion in cash, cash equivalents and investments on hand as of March 31, 2019.

We continue to see attractive opportunities to expand our portfolio of products, leveraging our business development expertise to accelerate this expansion and augment our progress in internal research. This is further evidenced by this morning's announcement around our agreement with Nationwide Children's Hospital that added a candidate for limb-girdle muscular dystrophy type 2A to our pipeline. We feel that with the capabilities and expertise we have internally and the directed nature of genetically targeted therapies, we can identify programs that have a high probability of success, that we have the expertise to efficiently move to clinical development and that fit into our commercial portfolio. Our recent limb-girdle muscular dystrophy 2E clinical results provide additional support for the strategic path that we are on and solidify our position as the leading gene therapy company.

This agreement brings our pipeline to 26 products in development, 11 of which are in gene therapy. We expect to continue our current pace of expansion, maintaining our selective approach around both the science and financial metrics. Investments in developing our pipeline will grow in 2019 as we continue to add programs and invest programs from smaller early stage trials into late-stage development. We will also continue to invest in our gene therapy center of excellence in order to internally identify new targets for development.

The expansion of our pipeline must be fully supported by investments in manufacturing capacity. Shortly after Q1, we secured the remaining suites at Brammer Bio and, as a result, their site in Lexington, Massachusetts is not fully dedicated to Sarepta DMD therapy programs. We also purchased more iCELLis units at Paragon to build additional capacity for commercial supply in anticipation of commercial launches of both our microdystrophin and LGMD programs. From a cash perspective, we remain well positioned to execute our plan and invest in our business.

We maintain a very strong balance sheet, which allows us not only to invest appropriately in our current pipeline, but also to secure opportunities, such as the limb-girdle muscular dystrophy 2E agreement that have a higher probability of success than traditional business development deals. Now moving to the financials. This afternoon's press release provided details of the first quarter of 2019 on a non-GAAP basis, as well as the GAAP basis. The press release is available on Sarepta's website.

Please refer to our press release for a full reconciliation of GAAP to non-GAAP. I'd like to add a quick reminder here that our 2019 non-GAAP financials exclude net interest expense, depreciation and amortization expense, as well as one-time expenses and stock-based compensation. Net product revenue for the first quarter of 2019 was 87 million compared to 64.6 million for the same period of 2018. The increase primarily reflects increasing demand for EXONDYS 51 in the United States.

We reported a non-GAAP net loss of 53.8 million or $0.75 per share in the first quarter of 2019 compared to a non-GAAP net loss of 17.5 million or $0.28 per share in the first quarter of 2018. In the first quarter of 2019, we recorded approximately 12.1 million in cost of sales compared to 5.6 million in the same period of 2018. The increase was driven by higher inventory costs and royalty payments to BioMarin, primarily related to increasing demand for EXONDYS 51 in 2018 and into 2019. On a GAAP basis, we recorded 90 million or -- and $46.2 million of R&D expense for the first quarter of 2019 and 2018, respectively, which is a year-over-year increase of 44.4 million.

The year-over-year growth in GAAP R&D expenses was driven largely by increased manufacturing activities related to gene therapy, increased patient enrollment in our early and late stage clinical trials, as well as higher employee-related costs due to significant hiring in 2018 and into 2019. On a non-GAAP basis, the R&D expenses were 81.4 million for the first quarter of 2019 compared to 43.3 million for the same period of 2017, an increase of 38.1 million. Turning to SG&A. On a GAAP basis, we recorded 60.6 million and 43.3 million of expense for the first quarter of 2019 and 2018, respectively, a year-over-year increase of 17.3 million.

On a non-GAAP basis, the SG&A expenses were 47.8 million for the first quarter of 2019 compared to 33.7 million for the same period of 2018, an increase of 14.1 million. The year-over-year increase was primarily driven by continued expansion to support our commercial launch globally and 20 therapies in various stages of development across therapeutic modalities. On a GAAP basis, we recorded $200,000 in net interest expense for the first quarter of 2019 and with 4 and a half million of net interest expense for the same period of 2018. The decrease in interest expense is primarily driven by payoff of certain debt instruments during the fourth quarter of 2018, as well as high return on investments over the first quarter of 2019.

We ended Q1 with approximately $1.4 billion in cash, cash equivalents and other investments. This was an increase of 175 million in net cash positions from the prior quarter and was driven primarily by the equity raise of $365 million net cash, offset by 54 million related to manufacturing initiatives and other net cash from operations. With that, I'd like to turn the call over to Bo for our commercial update. Bo?

Bo Cumbo -- Executive Vice President and Chief Commercial Officer

Thank you, Sandy. Good afternoon, everyone. As you can see from our revenue of 87 million in Q1 of 2019, physicians continue to be committed to helping patients start and stay on EXONDYS 51. Duchenne patients and the Duchenne community continue to be core of who we are and what we do.

Our work will not be complete, and we will not rest until we've helped the broadest number of Duchenne patients in the quickest amount of time, providing a clear path to access for these potential life-changing treatments. We continue to focus on genetic testing and enhance our efforts on identifying new patients. As you know, we have a very successful program with Decode Duchenne, established in conjunction with PPMD many years ago, which focuses on the U.S. patient populations.

Since then, Decode Duchenne has genotypes more than 1,000 DMD patients. And as a result, patients got into care or on a treatment or into clinical trials. We have now started supporting genetic testing in other areas around the world, and we'll continue to bolster opportunities to help the community by supporting genetic testing in certain regions. Rounding out our RNA franchise, our two other chemo-based therapies for Duchenne currently in development, golodirsen and casimersen.

As Doug mentioned, the FDA granted golodirsen priority review status with a PDUFA date of August 19, 2019. In response, we will be ready to launch golodirsen later this year. The foundation of our plan will be tailored to reaching those individuals, the Duchenne community who are exon 53 skip amenable. We will leverage our knowledge and expertise in EXONDYS 51 to assist patients accessing this medication as fast as possible.

Sarepta's commercial and medical teams are prepared for the potential approval of golodirsen. We remain on track to submit our NDA for casimersen in 2019 with a target approval in the first quarter of 2020. If approved, casimersen will serve approximately another 8% of the Duchenne community. With that said, our goal by early 2020 is to have three approved drugs borne out of our RNA platform for individuals living with Duchenne.

While the majority of the commercial and medical teams are focused on EXONDYS 51 and ready for the potential launch of golodirsen, we have already begun planning for a successful launch with microdystrophin. As part of that plan, we've already begun to build out our four microdystrophin launch team and are preparing for commercial site readiness to ensure multiple clinics, not only in the U.S., but globally in identifying and treating patients safely with our microdystrophin gene therapy, if approved. While the core of the company is focused on Duchenne, the science continues to lead us into other therapeutic areas of need. As Doug mentioned, we are excited about the addition of our limb-girdle 2A program.

Based on our market research, limb-girdle muscular dystrophy 2A has the highest frequency in the United States, Europe and Brazil. We're excited to have this opportunity to partner with a new community where there's such a high unmet need. In support of the immense opportunity for us, we started meeting with the leading KOLs around the world to have a deeper understanding of the limb-girdle muscular dystrophy disease state. We will continue our educational initiatives at global conferences to build a foundation of knowledge on how vectors, promoters and R&D chemistries fit into various disease states.

In the coming quarters, we will report on the progress we've made on these initiatives. In addition, we recently hired genetic testing professionals who have a background in rare disease and will focus on our 6 limb-girdle muscular dystrophy programs, as well as our many other gene therapy programs, such as MPS 3A and a few other programs yet to be named. We're also thoughtfully building out our global infrastructure to enable us to launch RNA therapies if we have approvals in other regions or prepare for potential launch, global launch, in the coming years with our microdystrophin and limb-girdle muscular dystrophy programs. With the help of gene therapies before us, we must ensure access and reimbursement is top of mind.

There are structural hurdles to access on reimbursement of a single-dose transformative gene therapy. And as a leader in genetic medicine, Sarepta is working to play a leading role in resolving those hurdles. So that if our therapy is approved, patients can rapidly benefit from it. As we consider access, reimbursement and affordability, we do not believe that the primary impediment will be price.

For life-changing single dose therapies that can improve and extend the life of those with devastating rare genetic disease, even the most conservative cost-effectiveness models will support a multimillion-dollar proposition. Pfizer itself has noted, health technology assessment models can often justify prices for gene therapy in the 20 million to 25 million range, far above the actual price that an innovator would actually charge for therapy, which means the vast share of value will benefit society and patients. A good example of this are the recent statements by Novartis that is SMA gene therapy, Zolgensma, is cost-effective at the price of 4 million to $5 million. Now far from the issue of price, the fundamental issue is the structural impediments that come from the unintended consequences of a healthcare reimbursement system that has for many decades been built around chronic symptomatic therapies.

Sarepta has been in detailed engagement with private and governmental payers to find solutions that would provide early access to waiting patients, provide to the innovators the value that justify investment in gene therapy and that ensures that payers, both public and private, can absorb the cost of a transformative therapy without overwhelming the system. For Sarepta, no solution is off the table. We are exploring payments over time, risk-based contracting so that Sarepta shares in the outcome and durability risk with payers, subscription models that can provide payers with more certainty and flat or a firm patient pricing over weight-based pricing. We're also working with those who are focused on legislative changes that would allow states and private payers to negotiate these sort of access, empowering relationships, and are beginning the process of working with CMS and state Medicaid to ensure that our therapies are equally available to private and Medicaid patients.

We have created a dynamic internal team made up of market access, government affairs, national accounts, distribution professionals and other key functions to collaborate with healthcare leaders and stakeholder groups to work together and truly address new models for reimbursement. Sarepta has already initiated multiple exec to exec meetings with major commercial Medicaid healthcare leaders in addition to influential stakeholders within the federal government or leading reimbursement working groups around the country. To date, we've already held numerous meetings with key decision makers to help inform a path forward so that the promise of gene therapies and new models around pricing and reimbursement can be realized. Sarepta fully appreciates this goal in this conversation and that if we are to remain true to our mission of placing human health central to all that we do, then we must, as innovators and drug developers, come to the table with not only solutions and ideas but actual plans to execute on.

We appreciate all the payers and thought leaders who are already engaging and partnering with us on these efforts. We look forward to finding a solution together. Our mission is to be the global leader in precision genetic medicine. It all started with EXONDYS 51.

We have broadly depended our pipeline to potentially treat tens of thousands of patients in need and including our patients being dosed with gene therapies in Duchenne, limb-girdle muscular dystrophy, MPS 3A and Charcot-Marie-Tooth, as well as had two approved RNA therapies for Duchenne in the coming quarters. This is truly an exciting time for all patients living with rare and debilitating diseases. All of us at Sarepta look forward to the future of precision genetic medicine. I will now turn the call back over to Doug.

Doug Ingram -- Chief Executive Officer

Thank you, Bo. And with that, let's open up the line for questions.

Questions & Answers:

Operator

[Operator instructions] Our first question comes from Althea Young of Cantor Fitzgerald. Your line is open.

Althea Young -- Cantor Fitzgerald -- Analyst

Thanks for taking the question, guys. I was just curious, in light of the Pfizer data readout and, obviously, you guys have a lot of experience with gene therapy. Can you talk about maybe potentially what you might expect to see where this data's at, at the current dose they're at? And just any other kind of observations from being an NDA, just -- and around the competitive landscape would be helpful as well?

Doug Ingram -- Chief Executive Officer

OK. Thank you for that question, Alethia. So a couple of things. Just to bring everyone up to speed, it's our understanding now that Pfizer has confirmed that it is going to do a data release at a patient advocacy conference in late June of this year at the PPMD conference, I believe it's down in Orlando.

So a couple of things. First, of course, we're very interesting in seeing the data. We can't, obviously, speculate on what that data will look like in advance of the meeting, but we look forward to seeing it, we'll obviously be there. There are a couple of things, however, to consider as we wait for and review that data.

So first of all, I think based on where we are in development and Pfizer's most recent public statements, we are in the lead on development. Our best guess is we're, as it stands right now, about one year ahead of Pfizer in our development program. I will remind you that we will be done dosing our placebo control trial this quarter. Obviously, that could change.

But as it stands now, I mean, we're about one year ahead of Pfizer. And there are some other things to consider as we consider what we'll see at PPMD. First, to evaluate the results, I think it's important to consider their dose. So just so everyone understands, we use different titers, so comparing dose requires some mathematical adjustment between us.

Sarepta uses supercoiled GPCR, and we understand that they use something that's called linearized GPCR and go through a conversion. And that conversion between those two titers, based on our analysis, is about two to one. That means that on an apples-to-apples basis, Pfizer's current dose is about 300% of our current dose, about 300%. Theirs is a truly staggering dose and an enormous viral factor of burden for the patient.

So when one eventually sees their expression data, you will need to judge that expression data against the viral burden to which the patients are being subjected, and that burden does implicate safety not merely in those first three patients, but also in patients across the entire spectrum of the disease, ages, weights and the like. Obviously, we take no position on their dose selection as we are not privy to their preclinical data or otherwise. But one would assume that in light of their dose selection, they will need to show a very impressive concomitant expression benefit to remain competitive. In fact, at 300% or so of our dose, if they are unable to show expression levels that are greater than our expression, it raises at least a question whether they have a viable program from a risk-benefit perspective.

But we'll see what they have when we see them in June. And there is one other thing. It'll be interesting to see how they quantify dystrophin. As you will recall, Sarepta was very transparent when we announced our data last year.

First, of course, we provided quantification of dystrophin using Western blot. Western blot has been the gold standard and the only measure that the FDA has yet accepted as the basis of approval for a dystrophin-producing therapy. And second, we use immunohistochemistry. We did both dystrophin-positive fibers and we did intensity, and we went so far as actually to show images, and we not only showed images for the immunohistochemistry, we actually showed images as well for Western blot, so you could see we were essentially doing our math for you.

This is extremely important, immunohistochemistry because all of the literature, for now decades on Duchenne, has been done on immunohistochemistry and dystrophin-positive fibers and intensity. So judging expression without IHC would be impossible. It would be impossible to make meaning of data. And third, you will know we provided genome copies for nucleus, a very important metric for gene therapy coverage and transduction.

Now, so we're clear, Pfizer is an incredible company, and so they should and we will assume they will transparently provide Western blot dystrophin-positive fiber intensity and genome copy data for their data release. I think clearly, you should have this data. We've noted, they also looked at -- they are looking now, I believe, at an experimental new measure using math that hadn't ever been used before, but this cannot possibly take the place of the measures that allow for a meaningful analysis and a comparison of expression with reference to the great body of literature and prior trials and the like, all of which rely on Western blot and immunohistochemistry. Transparency demands Western blot dystrophin-positive fiber data, intensity data genome copies.

And the level of this transparency will become extremely important for a number of reasons. Obviously, it'll be impossible for an investor, an analyst or a physician to make any meaning of their data in the absence of these measures. But there's something far more important than this, and that is the issue of patients. Gene therapy is unique.

It has a particularly unforgiving treatment, in a sense, because it has unique bioethical considerations. If a patient is given a gene therapy, they will likely be unable to get any other gene therapy literally for the rest of their lives unless the science on that changes. Patients choosing to participate in clinical trials and their physicians deserve accurate information that can inform that decision making. Now we're going to assume that Pfizer knows and understands that they will do the right thing, we have no reason to believe they won't.

But given that Pfizer's chosen to make the data disclosure at a Duchenne patients' conference, it would be particularly unconscionable for them to hide Western blot and IHC data, and we will assume that that will not occur. So I think we don't know the data. It'll be very interesting to see it in June. When we review the data, as everyone does, we'll need to review it in the context of their dosing and we'll certainly like to take a careful look at their Western blot data, their immunohistochemistry data, dystrophin-positive fibers and intensities so that we can make meaning of the data that we see in Orlando.

Operator

Thank you. Our next question comes with Ritu Baral of Cowen. Your line is open.

Ritu Baral -- Cowen and Company -- Analyst

Hey, guys. Thank you for taking the question. A question for Bo. You mentioned that you're putting together your strategy for the microdystrophin gene therapy even now.

What are your high-level thoughts on treating the prevalent population? How are you looking at the low-hanging fruit age-wise, mutation-wise, baseline function-wise? What percentage of that prevalent population is an ideal candidate out of the gate, especially with how you're thinking about pricing?

Bo Cumbo -- Executive Vice President and Chief Commercial Officer

Well, I mean, currently, we think that the entire population based on the clinical trial design is more -- and the team is looking through, will be eligible. So if there's not a "low-hanging fruit," I think we'll combine that there's going to be a mad rush coming in. Now that when you start talking to physicians and Gunnar sort of mentioned this on clinical trial improvement, about how his patients are literally trying to bang down the doors to get in, if you start thinking about clinical -- I mean commercial readiness, the physicians are telling me that patients are already lining up, they're already trying to identify whether they're going to be eligible or not. So really, it's about site readying in this space to show that we have enough sites that can dose the drug completely after approval, making sure that they're up to speed and safely administer the therapy in a very quick time.

I think the biggest thing that I want to do beforehand is work on access and reimbursement, making sure -- and sort of this is as we speak, making sure that the system is ready for these once-in-a-lifetime transformative therapies, and that we can get to the patients as fast as possible. So I'm putting a lot of emphasis on access reimbursement and site readiness over the next couple of years. And this will be globally, especially not only in the U.S. but some of our large markets such as Brazil, Germany, etc.

Operator

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

Brian Abrahams -- RBC Capital Markets -- Analyst

Hey, guys. Congrats on all the progress. And thank you for taking my quiestion. A question on limb-girdle 2E program.

Can you talk about how you chose -- how you selected the dose that you're going to be moving to? Will you be doing any additional monitoring or supportive treatment to monitor for LFTs and manage LFT elevations? And then can you talk about the type of patients that you're going to include in this next cohort? Should we assume these are going to be patients with the more severe phenotypes, mutations and exons three and four, just to enable the most apt comparison to the low dose?

Doug Ingram -- Chief Executive Officer

I will turn the question to Dr. Louise Rodino-Klapac.

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

Sure. The dose selected was based on our non-clinical data and it was predesigned in the protocol already for dose escalation. We will be enrolling a population as in the same first cohort of four to 15 years of age for continuity between them. And I think there was one more, sorry?

Doug Ingram -- Chief Executive Officer

So I think exons -- included in exons to make sure that there's an apples-to-apples comparison.

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

Right. Yes. So that represents a majority of the population anyway as it's between these exons, the exon three to six.

Doug Ingram -- Chief Executive Officer

And the one thing I would just remind is that we're in a luxury position in one sense. We've seen great results thus far with our first cohort, but to get to commercial supply, which we will need to do to our pathway to get into the community, we have some time, we're over a paradigm working on that as we speak. And so we should dose escalate during this period of time and test a higher dose and see if that higher dose provides a better benefit to safety perspective that our current. But the good news is we're already sitting in a really good position.

To remind us, on protein positive fibers, we were at 51%, which is two and a half times higher than what the predefined level of success was for the trial. So we're already in a good position and now we have the luxury of dose escalating without having to worry about any kind of delay.

Gilmore O'Neill -- Executive Vice President, R&D and Chief Medical Officer

I think there was another part to the question as well. Let me handle it. This is Gilmore here speaking. You had asked also about monitoring; liver functions and we are obviously, keeping a close eye on that.

It is our working hypothesis now and I think supported by the data we've seen to date, that these liver enzyme changes are amenable to prednisone management, and we are continuously updating and amending and adjusting or optimizing our steroid regime. So we will be keeping a close eye on that, but our hypothesis is that we will be able to control that well with steroid use during that initial dosing period.

Operator

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

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Hi. Good afternoon. Thanks for taking my question. Wondering if you could give us a little bit more color on LGMD2A.

How does that compare pathologically to the other subtypes that you've studied? And seeing that you're adding, presumably, you've mentioned another 30% of LGMD patients, how does that change any manufacturing constraints for Paragon?

Doug Ingram -- Chief Executive Officer

Well we're in the -- a couple of thoughts and then I really should turn this over to Dr. Louise Rodino-Klapac. I've gotten a good primer on it, so you're at serious risk of me just answering the question, all right? So I'll go to the manufacturing issue first. We really are in the process of dance charting out the pathway on manufacturing and clinical program perspective across all of these limb-girdle programs.

As you rightly know, we now have six limb-girdle programs and little to no competition here. Notwithstanding the fact that we have little to no competition, we need to move with enormous sense of urgency to bring these therapies forward. We're really excited about 2A. I think we mentioned earlier the -- this is about 25% or 30% of the limb-girdle community.

That means that we are just about -- there's some arrow bars around this, but probably 70%, maybe higher than 70%, maybe even 80% of the limb-girdle patient population that could be served by our six programs. And then, as Louise will tell you about this, obviously, given that this largest one, it presents itself a little later because it relates to essentially an issue associated with the inability to properly repair a muscle as it gets damaged as opposed to what things like [Inaudible] does and microdystrophin program does. But with that said, I'll turn this over to Louise to answer properly.

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

Sure. I think Doug set it up well. If you think about our limb-girdle programs, they roughly fall into two buckets which is the sarcoglycan and, as well as calpain fits in quite nicely with our dysferlin and anoctamin five program. Just thinking about the mechanism of action of these important proteins.

Calpain, as well as dysferlin in anoctamin five are involved in the repair of the generation process and muscle. And that's generally why you see a slightly later onset in the mid-teens for these. So as far as the mechanism, over time, you'd just lose that regenerative capacity and that leads to this really devastating disease. As far as readthrough, we're using the same rh74 vector as we are for the other 5 programs.

We're using the same promoter, the tMCK promoter that we're using in two of our other programs, such as LGMD2D and LGMD2L or anoctamin 5. So there's been a lot of shared learnings. We've obviously had to collaborate with Dr. Sahenk over the years and there was a shared development of these programs.

So we're really excited to be continuing to work with her and move these programs forward.

Operator

Thank you. Our next question comes from Matthew Harrison of Morgan Stanley. Your line is open.

Maxwell Skor -- Morgan Stanley -- Analyst

Hi. This is Maxwell Skor on for Matthew Harrison. Just a quick question on the progress you're making on manufacturing. I believe you've executed tech transfer from Nationwide, but have you started to produce vector at any of Brammer's facilities? And can you comment on how many lots you'll need to produce of GMP vector?

Doug Ingram -- Chief Executive Officer

Well, this is Doug. I can give you the broad strokes, but thank you for asking about manufacturing. It gives me an opportunity to mention something that I had intended to mention in the opening and I didn't. I would like to brag a little bit about what we're -- the people at Sarepta.

I mentioned that we have Dr. Louise Rodino-Klapac and Dr. Gilmore O'Neill and there's a lot of great folks, but as you think about our hybrid model, just figure you're talking about that, one of the things we're doing is gathering -- to gather at Sarepta expertise around process development and analytical development in an early GMP manufacturing is that is going to allow us to hold all of the differentiating aspects of manufacturing and also, as we keep bringing in assets to move them rapidly through the preclinical to the clinical stage to the commercial stage. And I'm really proud in relation to that to talk about Dr.

Reed Clark. Dr. Reed Clark, who is now a Sarepta employee, is a pioneer in the field of process development and AAV biology. He actually is the person that developed Nationwide Children Hospital's manufacturing process, and he actually collaborated with Dr.

Louise Rodino-Klapac on early development of the microdystrophin and limb-girdle programs. Every time I mention his name, Louise smiles, so I know it's positive. We are building under Dr. Clark a formidable team focused on process and analytical development.

And just so we understand what that all means, by the end of 2019, we will have 200 employees dedicated to manufacturing at Sarepta, and that's manufacturing, process development, analytical development, technical operations, quality control, quality issuance, regulatory CMC operations. We have folks in Cambridge, in Burlington. We have a 30-acre facility in Andover that we own. And of course, we have our Gene Therapy Center of Excellence and some manufacturing down in Columbus, Ohio.

And we'll be spending 600 to $650 million on manufacturing in just the next 15 months or so to make sure that we're ready to fully serve this community. Now, where are we with microdystrophin? Yes, we certainly have some time to do tech transfer over to the Brammer facility from the -- from Nationwide Children's Hospital. As we stand right now, in the broadest of strokes, we are in the latter stages of process development. We are just about done on yield optimization and we are deeply in analytical development.

There's going to be a lot of assay work that has to get done in the next couple of months, but we are deep in that as well, and we are very fortunate to have Dr. Reed Clark on top of that as well. So we're in good shape right now. We have done run.

I'm not going to give you the number of that, but we have done runs. We have iCELLis units up and running. We've done some early runs, and we've got good data from that. We're tracking.

And our goal now, there's a lot of work to be done, but we are on track as it stands today to meet our goal. Our goal is to have our next commercial supply trial fully embedded with the agency, and then our commercial process fully embedded with the agency and to commence our commercial supply trial before the end of 2019.

Operator

Thank you. Our next question comes from Debjit Chattopadhyay of H.C. Wainwright. Your line is open.

Debjit Chattopadhyay -- H.C. Wainwright and Company -- Analyst

Hey, good afternoon. So given the price point that you mentioned and the reappears you're alluding to, how are you thinking about non-ambulant patients, especially in the commercial supply study in the microdystrophin program? Also, have you had any additional dialogue with the agency regarding the design for that study?

Doug Ingram -- Chief Executive Officer

We have not had direct discussions -- further discussions with the agency on the design. Obviously, we're tracking to do that in the near term. We will be the burdening the agency with a lot of discussions across our programs over the course of 2019 and that will be one of them. The short answer on non-ambulatory patients is that there is no way that Sarepta is leaving them behind.

This -- just to remind us of where we are, the vector that we have not only robustly expresses in skeletal muscle and cardiac muscle, it actually over expresses by about 120% in cardiac muscle, which means that there should be no child or young adult who is beyond the ability -- beyond the place where our microdystrophin program, if it is successful, could help them and benefit them and extend and improve their lives. So we don't want to leave them behind, and we will ensure that the design of our next trial includes sufficient focus on older and non-ambulatory patients that we will not only get a label for that, which of course, is our day goal, but also puts us in a place where we can get, to the fullest extent possible, rapid access post-approval from payers.

Debjit Chattopadhyay -- H.C. Wainwright and Company -- Analyst

So just as a follow-up on the PPMO program. Again, given the investment that you're seeing from peers, how important is this PPMO program to the overall franchise, especially focused on rescuing the non-ambulant patients?

Doug Ingram -- Chief Executive Officer

Yes, thank you. Well, we're very excited about the PPMO program. We don't -- we try not to talk a lot about it because we don't want to pump it right now. We're in the middle of a multi-setting dose.

We've had a very successful single-setting dose trial. We're starting our multi-setting dose at 4 mgs per k. We need to get a lot higher. We'd like to get a lot higher than that.

But one of the things we know in the PPO is just to remind people -- I'll remind people [Inaudible] people are otherwise unaware, the PPMO program, which is our RNA therapy, it is the same back-up as PMO. We conjugated a peptide that allows, No. 1, the [Inaudible] becomes positively charged. It allows much greater penetration into the cell.

And in preclinical models, if we could get up to high enough doses, we can see as much as an order of magnitude, more expression and therefore, more benefit than our PMO technology. So we're really focused on that. And so it is a very big part of our thesis. It's a big part of our thesis for patients with Duchenne muscular dystrophy both, frankly, ambulatory and non-ambulatory patients, and it will be an important part of our platform going forward, beyond Duchenne muscular dystrophy.

One of the things that Dr. O'Neill and his team in research are working on is target selection, both from our PMO, our PMO plus and our PPMO programs, that the target selection beyond Duchenne in the areas where our RNA technology would make brilliant stands, sometimes even -- sometimes in ways that perhaps gene therapy couldn't actually address, places where, for instance, the gene is so large, it's not easily packaged in AAV and the like. So the PPMO program is important. We're tracking to get inside by the end of this year and in the first quarter of next year.

We have 6 constructs in the PPMO program. They cover about 43% of the Duchenne community, and we'll certainly provide an additional update on that at the end of this year, early into 2020.

Operator

Thank you. our next question is from the line of Christopher Marai of Nomura. Your line is open.

Christopher Marai -- Nomura Instinet -- Analyst

Hey, good afternoon. Just regarding your limb-girdle 2A program, wondering if you could further elaborate on how you might be testing that in the clinic? It looks like patients with this disease express normal levels of the protein, if I'm not mistaken. And I guess, there's another option perhaps, to measure something like proteolytic activity. How do you look to -- I guess, to study this gene therapy relative to the others as it seems a little bit different?

Doug Ingram -- Chief Executive Officer

I'm dying to answer the question. I -- personally we're much better than [Inaudible], so I'll let Dr. Rodino to answer this question.

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

One thing I just want to clarify, there's a variety of mutations so you can have a complete loss of function, there's like a lot of the mutations, that to your point, do lead to normal levels of calpain, but is nonfunctional. This is an enzyme kind of lack of activities, to your point, measurements of the gene that we're transferring, the wild type version of the protein will be important. So that will be part of our development plan is to make sure that we are accurately measuring not only the quantity of the protein, but the wild type version that we are delivering.

Gilmore O'Neill -- Executive Vice President, R&D and Chief Medical Officer

And we will be -- this is Gilmore. I mean, we are mapping that out, and we will be actually be working on the design of these clinical programs, and we're finding them in parallel with the nonclinical work that we're undertaking right now.

Mike Triplett -- President and CEO, Myonexus Therapeutics, Inc.

But in some ways, this is Mike, although on the face of it, one might look at this and try to compare it for instance to dystrophin expression, wonder if you -- if that's the way to look at it, maybe this will be challenging to be successful. This actually might be easier in some ways because an enzymatic activity might very well show a very strong direct correlation between proteolytic, enzymatic activity and genotype. So actually, in many ways, it may be more –

Gilmore O'Neill -- Executive Vice President, R&D and Chief Medical Officer

Yes, it may be. But I think the key point that Louise has made also to support that is the fact that it is not universally expressed. Only some mutation association with a high level of protein expression or others which are associated with. So just let me clear that that nuance is correctly understood.

Operator

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

Mark Connolly -- Credit Suisse -- Analyst

This is Mark on for Marty. Thanks for taking my question and congratulations on the progress. So with -- Novartis' gene therapy is expected to be approved this month, at which time we would expect the company to announce its pricing scheme. With payers you talk to, do they see your DMD gene therapy in a similar light as SMA gene therapy in terms of potential value to patients? And how should we think about potential readthrough from Zolgensma pricing?

Doug Ingram -- Chief Executive Officer

Well, we'll wait and see it before we can really comment on it, obviously. We're doing a lot of work. We haven't given precise information externally on the way we're looking at the pricing issue. We're dealing significantly with structural issues.

I think one of the things you hear -- if you went and did a survey of payers right now, you'll hear a lot of payers talking very positively about Sarepta and this program in a couple of ways. One, they'll just -- I think you'll hear from people because you can do a whole Google search, and I think you'll find people saying positive things about our proactive outreach. We, I think, more aggressively than most companies in gene therapy have been reaching out to payers and to begin a dialogue about the structural issues. And I think they're also -- they're also well aware of these early results that we've seen with our program and many of them have made the point that we have to find solutions together to ensure that patients get access and they see the value here.

So I do think that -- and I think if we -- we don't really go into depth and compare and contrast with other programs, but I suspect that they're probably excited about SMA as well. For a host of reasons, I think there may be reasons why our pricing model might be different than SMA kids which are smaller kids, these are younger age than our program, but we're going to wait and see what -- where this stands and then we'll look at it, come back at a later date and talk more about some of the structural issues and the work we're doing and this team are doing there. And then we'll also, at some point, start talking about the pricing issues that we're a little premature on that right now.

Operator

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

Gena Wang -- Barclays -- Analyst

Thank you for taking my questions. I will follow Alethia's question regarding the Pfizer data. I know, Doug, you commented a lot on the bowel market data. Just wondering what would be your thoughts on the North Star data.

I know, we all know their patient is slightly older than your patient. How would that data read through to your program? And a quick follow-up question regarding the microdystrophin gene therapy 102 study. For the three months biopsy data, of which if you complete enrollment in second quarter, then they should be ready by 4Q, so I know it is a placebo-controlled study, double-blind, but wondering, will you be able to see the data? What would be the earliest time you would be able to see the data?

Bo Cumbo -- Executive Vice President and Chief Commercial Officer

We're at work now. This is -- so you've answered the question for me, I appreciate it. On the latter part, this a placebo-controlled trial, we're not going to risk the lives. So you'll see the data when all the patients have made it to one year so that's when we'll obviously see the data.

Doug Ingram -- Chief Executive Officer

So we are really excited about the program, it's going really well from a dosing perspective. Dr. Jerry Mendell has been a real hero and we're -- he's our principal investigator and for this trial, sole investigator. Going back to the Pfizer data, the thing -- look, I have always been -- or at least I hope I've been careful in talking about the functional data for a few days it's an open label.

We are very excited about what we're seeing, the signals that we're seeing from a functional perspective with respect to our microdystrophin program. As I think everyone knows, we've seen very good results. All of the kids are improving on all the time points across all of the measures with very significant reductions MCK, which gives us a lot of hope. The danger in all that, of course, is that it's a small cohort and it's a delta line of study.

What we really need to see there from a functional perspective is the results of a low controlled placebo controlled trial, and we're doing that right now and we feel confident about where we are, and where we're going to end up there. So what I would say as we look across to the Pfizer data in June, I think you -- it would be nice if they had some data and function that just said that there was some benefit that they might be seeing in kids but we all understand together, that is open-label, that there's motivational issues associated with it as well, and who knows what they're looking at from a functional perspective. And that the real thing that we all need to look for and the real thing we need to consider is expressional. What kind of expression are you getting? The biggest issue with these gene therapy constructs before we showed our data was that we could actually do this.

Could you actually do full body confusions and get significant -- first get significant transduction across the entire skeletal muscle and cardiac muscle? And then, could you create a gene construct that was clever enough to be able to show rate expression was there? That's the big question in these early studies. Obviously, we're very excited about the fact that the answer was a resounding yes to both of those questions for us last year, and that's going to be the question that one needs to look to in June. And it may very well be the case that the answer is yes to those, as well as with Pfizer. But given the fact that it's 300% of our dose, I hope that will be resounding yes with a good quantification.

And then on function, I think the answer is you're really just getting some comfort as you track into a better control study on function.

Operator

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

Brian Skorney -- Baird -- Analyst

Hey good afternoon guys. Thanks for taking the questions. I guess, to start, just jumping off of your answers to Alethia's questions on the upcoming Pfizer data, do you happen to know tighter comparisons between their 3E to the 14 dose on ARDS disease, 3E to the 14 dose that they had just reported the other week? And is there anything you would read into the safety events from the program that you're seeing particular around the thrombocytopenia and cholestasis? and then just as a follow-up, I heard you said that you're pretty much done with the yield optimization for the commercial manufacturer. Can you tell us what the downstream yield that you're getting on a single iCELLis 500 run is?

Doug Ingram -- Chief Executive Officer

We're -- I'll answer the last question because it's a nod answer, but I'm willing to give you information, so we're a little early on that. Going back on Aventis. A couple of things, I don't know -- we don't know enough about the tied room between the two to make brand comparisons between those two. I will point one thing when you evaluate the safety issues associated with the Pfizer construct and the Aventis construct.

Just remember that those Aventis patients were almost all, not all of them, but almost all of them newborns. So while it is still a big dose, it's a big -- it's not actual big aggregate dose. These were, I think the great majority of these were newborn, and then newborns and 12 year olds were almost all of them, and that's going to be very different, obviously than with muscular dystrophy. And then of course, there are a lot of different things, different vector, different promoter and all that.

Operator

Our next question comes from Salveen Richter of Goldman Sachs.

Ross Weinreb -- Goldman Sachs -- Analyst

It's Ross on for Salveen. I just have two. The first one on the limb-girdle muscular dystrophy 2E program. You're going to start the cohort 2 in the middle of this year.

When could we expect an initial read on that data?

Doug Ingram -- Chief Executive Officer

Do we have the answer that yet?

Bo Cumbo -- Executive Vice President and Chief Commercial Officer

No.

Doug Ingram -- Chief Executive Officer

We'll give you an update as we start getting in closer to dosing and we know the exact timing of the dosing. I'm not attempting to be elusive here, but we don't have the full answer.

Operator

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

Vincent Chen -- Sanford C.Bernstein -- Analyst

Hey, thanks for taking the questions. A couple of quick ones for me. The first one is, given your commentary on Pfizer's dosing. I was wondering if you could comment on whether you have flexibility to go up on dose for your micro gene therapy and whether you've made plans to do so? Or if there are no plans, whether you might potentially choose to this depending on what you see from the Pfizer readout?

Doug Ingram -- Chief Executive Officer

OK. So I'll answer that first. From the preclinical perspective -- so first, from the preclinical perspective, there is headroom on dose escalation for our construct. And certainly, in the first four patients that we've seen, there's nothing about that that would contra -- would be inconsistent with that viewpoint, actually.

And just to remind everyone, in the first four patients, it was very well-tolerated. There was some mild nausea for a couple of days and three of the four patients had elevated liver enzymes, but then all of them rapidly responded to a bump-up in steroids and resolved back to baseline very quickly. So we could dose up. We don't currently have plans to dose-up for the simple reason that we're seeing significant expression.

One of the things that -- one reason we chose the dose that we chose is id we did -- we do have a belief that it is inappropriate to underdose patients in gene therapy for all those bioethical reasons that we talked about earlier. We can't use children as guinea pigs. We've got to try to find a dose that provides advocacy benefit from the very beginning and two times E to the 14 is frankly a fairly significant dose. Even using supercoiled qPCR as a measure.

And then in the pre-clinical model as well, there is -- there was significant headroom, some significant headroom on the ability to dose-up. When you see the kind of level we're getting here, 90% expression level on a Western blot, it isn't quite clear whether we would get a concurrent benefit from dosing up. So as it stands today, we are not considering dosing up. We're very interested to see what Pfizer has.

It's an interesting experiment to learn, we'll look at it when we see it. As it stands right now, we know where we're going.

Operator

Our next question comes from Danielle Brill of Piper Jaffray. Your line is open.

Danielle Brill -- Piper Jaffray -- Analyst

Hi guys. Thanks for the question. Just another quick follow-up on Pfizer's data. We also heard that they may present expression data measured by mass-spec.

I'm curious if you guys can generate a data using this assay just to allow a personal level of comparison in the event that they don't provide Western blot NIH measurements?

Doug Ingram -- Chief Executive Officer

So we don't have any data on mass-spec. Mass-spec has never been used, never been accepted by the agency as a measure for dystrophin quantification. It's an interesting experimental measure, and we certainly laud them for thinking around the corner about other interesting measures. I know they are scalable MRI, cardiac MRI and a lot of other things that people are thinking about.

But if one wants to try to find a way to make meaning of expression either against all of the literature that exists on dystrophin-positive fibers and correlating that with functional issues or looking at a prior -- therapies or prior trials or other programs, one has to use a combination of Western blot quantification and immunohistochemistry quantification and localization, including dystrophin-positive fibers and intensity. And they have that data, they like to have that data. They certainly have done Western blots and they certainly what would have done immunohistochemistry. So while it might be interesting to see there, mass-spec experiment, one would assume that they really want to be -- if you want to have a meaningful discussion about their program, they're going to have to show Western blot and IHC data.

And genome copies per nucleus, which is also equally interesting.

Operator

Our next question comes from Joel Beatty of Citi.

Shawn Egan -- Citi -- Analyst

This is Shawn Egan on for Joel. Two for me today. The first one is kind of a high-level strategy question. Kind of, as you consider building your gene therapy pipeline, now as an established vector promoter combo already in-house, can you help us understand kind of the factors that go into the decision process to either pursue an external partnership like the one that was announced today versus developing these in-house at the transgene is 100% homologous? And my second question is also on the kind of Pfizer competitor data.

Could you help us frame how important biopsy location is? I think you guys have kind of pulled from the gastro while Pfizer is pulling from the upper limb. Is there a lot of difference between those muscles and how they could express the transgene?

Doug Ingram -- Chief Executive Officer

I'll let Louise answer the second question. But as it related to the first question here, we are -- we will be -- we are moving to the place where we're going to be agonistic about pulling from external or developing internal. So we are -- Louise, when she came over to Sarepta, brought with her, I'm proud to say, I tried to get her entire map with her, and we're building from there. I think I mentioned before, we have about an 80,000 square-foot facility in Columbus, Ohio, which is our Gene Therapy Center of Excellence, and we are listening to -- we are in the middle of target identification, beginning to build constructs there.

We've got some pretty significant ambitions to -- don't hold us to this because, obviously, the discovery process is as it is. But our goal is to -- to look to identify and elevate as many as two targets a year internally over time, and we're building that. But at the same time that we do that, we're going to do what is externally as well. The 2A program is a perfect example of that.

We have enormous regard for saying that's one of the reasons headed into our agreement with her on study 202 and she's advanced in this 2A. And so the idea that we can work with her with 2A, take the construct that she's already built and advance it and accelerate the program is very meaningful. So we're going to do, looking at both internal and external and frankly, we're -- it's going to be, sort of best athlete from a construct perspective is going to win out over time. And then as it relates to the other question.

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

So to your question based on upper limb versus lower limb. Speaking for our nonclinical data, we looked at every single muscle and we saw no significant difference in microdystrophin levels across those muscles. So whether it was triceps, biceps or lower limb like [Inaudible] that there was no difference. So theoretically, there should be no difference in where you take the virus, is that you should be consistent results.

Operator

Our next question comes from Anupam Rama of JP Morgan. Your line is open.

Tessa Romero -- J.P. Morgan -- Analyst

This is Tessa, filling in for Anupam this evening, and congratulations from us on all the progress. One is on what your latest thinking is on the commercial supply trial? And what the gating factors are to finalizing design here? What are the key components we should be considering? And how will that impact time lines to market?

Doug Ingram -- Chief Executive Officer

I didn't get the last question. Did you?

Bo Cumbo -- Executive Vice President and Chief Commercial Officer

[Inaudible]

Doug Ingram -- Chief Executive Officer

I'll answer the broad strokes, and actually, Sadesh will let you know -- the broad question is what are the gating factors and where are we with the commercial supply trial. So we are finalizing the trial, in the arms on that trial. Even as we speak, we're pretty close to getting it done. In broad strokes, it remains a very similar to what we've talked about before, which is it will be a trial that will ensure that we have good data from a commercial perspective, both on the ambulatory and on the nonambulatory patients.

It will have the largest breadth of inclusion of exons that is possible as well. And we will have a multicenter -- multisite trial, both in the United States and there will be some sites ex-U.S. as well, and it will be larger trial and the current placebo trial that we're doing. And it is in the hutch of the numbers I've given before, kind of the $50 million, $60 million, $70 million, but we haven't nailed that all down yet.

We're doing some work on that. And now the gating items to that, obviously one of the things that we're going to want to do is share our views with the agency, I'm sure the agency is in agreement with the path we're taking and the target profile that we would envision that path would get us, including a broad label across all age groups, for instance. The other big gating items are manufacturers. So getting this, the manufacturing process up and done and getting all the analytical work done, the process development finally finished, the outpatient finally complete, getting the agency bought-in on all of that and then getting some runs done is a big gating item.

But we're on track for all of that. And our goal is to in a place, as I said, that by the end of 2019 we'll commence the trial. And then while the future of that trial, at least as we currently envision its interim analysis of that trial on three-month biopsy data. So we have the opportunity to look at biopsy data on the interim basis and compare that when we are -- when we actually open our placebo trial, compare that to the expression levels we're seeing in the placebo trials so that we can confirm the comparability of our commercial supply to our clinicals.

Sandy Mahatme -- Executive Vice President, Chief Financial Officer and Chief Business Officer

No, I think you've captured everything and obviously, the site engagement is something that we already -- so the site engagement is something that we're actually already doing around the world and obviously, talking not just to FDA but other agencies around the world.

Operator

Our next question comes from Liisa Bayko of JMP Securities. Your line is open.

Liisa Bayko -- JMP Securities -- Analyst

Hi there. Thanks for taking my question. Perhaps, a simple question, perhaps one that's more complicated, but could you -- based on just your assumptions at this point, and I know there's a lot of details to be worked out, give us a sense of how many patients you think you'll be able to treat from a facility such as Brammer?

Doug Ingram -- Chief Executive Officer

We are -- I can give you broadest stroke answer, which is our goal is to be in a position that when we launch -- so I want you to envision a world in which we could -- is that everything works brilliantly, be in position by the end of 2020, the logic there -- and I would say, there's a lot of good reasons why I could slip. So I don't want to envision that that is some hard Gantt Chart view, but you could imagine a world that would set the cadence. We are building commercial supply. We have the most aggressive assumption on launch cases, so that we're in a position if everything goes well to launch then.

And if we did that, we want to be in a position that -- so starting with our first commercial launch in the United States, and then moving rapidly ex-U.S., we can completely serve the community with therapy. So that's the short answer. And that's, we want to be in a position where we're able to robustly support the community. And what that means is we're going to mention all of this gating items to get the commercial supply ready for a commercial supply trial by the end of this year.

And then what we're going to be doing once we get there is building supply and inventory over the course of 2020 in advance of the commercial launch of the therapy. That's why we're spending, in addition to everything else, over $600 million in the next 15 months. And if I said, I hope I didn't pass, I noted in my opening remarks, we have a 75,000 square-foot facility dedicated to Sarepta, that we're building with Brammer Bioscience as an experiment company, for sure, even as we speak, that's just about done in the next couple of months, it should be ready for commercial supply before -- obviously before the end of this year, because we will be using that supply to commence our trial.

Operator

Our next question comes from Yun Zhong of Janney. Your line is open.

Yun Zhong -- Janney Montgomery LLC -- Analyst

Hi. Thank you for taking the question. So the question is on the comparison between your microdystrophin program versus the other 2. And specifically, on patient own criteria, I believe the initial Phase 1/2 study had the specific requirements for patient to have prem shift or premature stop codon between exon 18 and 58.

Is the -- does the 24-patient study still have that criteria? And if not, why was that removed? And what about the commercial scale of study?

Doug Ingram -- Chief Executive Officer

The short answer is that the current Study II has that exclusion in it out of an abundance of caution. There is good reason to believe that that is an overly abundance of caution and we are doing some work so that, in the next trial, we are expending the inclusion criteria significantly, and we are removing the exclusions that are unnecessary. And there are almost, certainly many of the exclusions from an exon perspective are unnecessary. So our goal is to get you as close as is possible without creating undue risk to be close as possible to all of the exon mutations in the next trial.

That's our goal.

Yun Zhong -- Janney Montgomery LLC -- Analyst

And then -- OK. And then on the age of the patient, the 24-patient study still have patients between the ages above four and seven?

Doug Ingram -- Chief Executive Officer

Right. Correct.

Yun Zhong -- Janney Montgomery LLC -- Analyst

And that will be expanded in the commercial scale study as well?

Doug Ingram -- Chief Executive Officer

Yes. But they'll be more -- they'll be other ages as well. Now understand that there's been a bit of a -- I think people -- let me be very clear about this and I think it will come as a surprise to people. It is not our goal to have a therapy that works brilliantly for seven-year-olds so well.

That is not the reason we have what is a fairly tight range. The reason we have it is that across the journey of Duchenne muscular dystrophy, there is -- your phenotype is going to change as you grow. And in fact, the measures won't even work. The analytical data we're using at four- to seven-year-olds would be inappropriate for younger children.

They have to use something like [Inaudible]. And then when you get past about seven, [Inaudible] begins to become more difficult and we have start using some other functions like [Inaudible]

Sandy Mahatme -- Executive Vice President, Chief Financial Officer and Chief Business Officer

But in fact, you can actually use, as the reason that we have four to seven-year-olds, because that's the point when they are gaining, or the majority. They're coming up to a plateau, sort of around that age 6 to 7. But then after seven-years-old, what you begin to see is those young boys are now in a stage to tried. So combining them within the same study actually creates problems.

Doug Ingram -- Chief Executive Officer

It wouldn't work. So the goal here is to show -- the goal is to confirm effect in a small group of people. The next study, it's going to have different arms. So we will explore dosing in older patients, as well as we will be exploring destinations even younger patients, very likely.

So again, all through -- for two goals. The goal No. 1 is, of course, the label. You need a label as we launch this therapy that allows to fully serve the community across all age groups.

And of course, the second one is to ensure that we have a robust package that acts as a reimbursement, so that when this therapy is available to the community, patients can get it without having to wait inordinate amounts of time.

Operator

Our next question comes from Timothy Lugo of William Blair. Your line is open.

Timothy Lugo -- William Blair -- Analyst

Thanks for taking the questions. Just back on the microdystrophin gene therapy, I'm wondering whether you do actually have internal data or this data out that suggests an expansion of the coverage of the exon mutations would actually be safe. You said it was overly cautious to exclude earlier, but I'm wondering what's changed now? And secondly, what's your advice to patients that you've currently screened that has an exon mutation outside of your current Gene Therapy Program? Did you tell them to go seek therapy? Do you go to another additional gene therapy program or standard of care? I want to know what your advice is for those patients.

Sandy Mahatme -- Executive Vice President, Chief Financial Officer and Chief Business Officer

I'll answer the second one and I'll let Louise answer the first. So the point here is, like, we're not giving specific advice to patients, and along this with the specificities you're saying. What we are saying and recommending to all patients is that they should actually pursue the standard of care, optimal standard of care, and should not be concerned about that and its pursuit while our trials are ongoing and being designed. So we're actually quite frank about that advice to patients where comparable standard of care is what they should pursue, whether or not they're eligible for say -- or are waiting to see if they are eligible for studies.

And then I'll pass it to Louise about what's changed in our philosophy?

Doug Ingram -- Chief Executive Officer

One final thing to say on that, particularly as it relates to symptomatic therapies, steroids and our PMO and those kinds of therapies. There's a different issue with effective gene therapy because, as I've said before, that we should talk about -- often as a group. There is an unforgiving nature to gene therapies, you can get multiple gene therapies, so you've got a problem with it. But symptomatic therapies, you don't have an issue yet.

But one of the things you definitely do want to do is protect yourself. There are gene therapies coming. If you assume they will be successful, there is a potential to have a transformative moment. The likelihood that one can rescue and bring back function that's long been gone, I think you can probably rig a bridge too far.

It's probably asking too much of a therapy. Protection as the biggest issue, which means you need to protect yourself while you're waiting for a therapy. If you have an opportunity to protect yourself with an existing therapy and your physician agrees you should be on it, you should be fighting to stay on it, protect yourself while companies like Sarepta and Pfizer and others, work like mad to advance therapies that might be truly transformative and rescue you from future damage. And with that, I would turn it over to Louise to answer the question about the exons.

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

Sure. Just to get back to the exons, Doug mentioned this. It was really instituted as an overly abundant -- with an overabundance of caution. It was really based on what I would call a case study in an earlier trial with a patient with a very large deletion of N-terminus.

And really, what it shows is there's a potential, theoretical potential to recognize that area deletion. But really, the implications of that were unknown whether there was even any consequence of that. So based on that, 18 to 58 mutations are not found within the microstructural transgene net worth, that's where the number came in. So it's very conservative, and so we feel very good about expanding beyond that just based on mutations that already have a normal amount of the -- trace amounts of the protein.

So we are definitely expanding in a rational way, we think that we have a very good reason to do so.

Operator

Our next question comes from Tim Chiang with BTIG. Your line is open.

Tim Chiang -- BTIG -- Analyst

Thanks. Doug, when I was at the MDA conference. The -- Pfizer, they've gone up to 3E to the 14 on the dose, and then they had come back down to 2E on 14 of the dose. Is that something that you guys have heard as well? Then also on limb-girdle 2A phenotype.

Louise, could you compare and contrast to 2A phenotype to 2B phenotype? I mean, are there very clear distinct differences? Obviously, a different gene you're delivering. But I guess, what the 2B phenotype, it's a dual vector. Is it -- could you just confirm, is the 2A a single vector that you do, delivering on the gene?

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

Yes. To answer your question. So with the LGMD2C it's for limb-method dual vector. And the calcium program within the calcium gene, that's a single vector.

In both cases, we're delivering the full length gene. There are tier point similarities between the phenotypes. We know there's interactions between the two proteins, so it's not surprising. But there are similarities in the disease.

Doug Ingram -- Chief Executive Officer

OK. And so let me answer on this. So the answer on -- I really am reticent to sort of pass along rumors, because there has been a lot of talk about this drop-downs. Just for those -- to make sure we're all on the same page, recently was this -- it was revealed by Pfizer that they have a protocol, it's an interesting protocol, an unusual one, what I think, where a dose of -- their one-time is E to the 14.

So I will remind you, it's probably about the same as our – two times E to the 14, kicking the tires .And then they chose to go to three times E to the 14, which again is probably something like six times E to the 14, using our measures. And then they have what we recently discovered was -- that we've discovered, is that they have this chart of the drop-down, where they could drop back out to some middle those between the two, at two times -- that they are two times E to the 14, which again would be our four times -- it would be -- well, you get my general [Inaudible]. Most recently, we've heard that they are saying that they have not yet dropped down in-between those 2. So what we're envisioning right now is we're going to see in June, what we understandably -- at least, from the investors, is that we're going to see two cohorts.

One cohort with three patients at one times E to the 14, and then one cohort with three patients at three times E to the 14. And then I don't know if they have made a final decision about whether they put in a drop-down. I will note that we're -- this is -- we don't have anything like that. So, for instance, with respect to our 2E program, as we've mentioned, our protocol provides that we dose at five times E to the 13, and we are now going to dose at a higher dose to explore a few times E to the 14.

And then as when we're done, we're going to make a decision about the risk-benefit and the efficacy and safety of those two doses and make a decision between the two, and the good news is that we've already got good expression at five times E to the 13. So we don't see a significant benefit for going higher, and obviously, we're not going to put these kids under an unnecessary amount of viral -- of –

Gilmore O'Neill -- Executive Vice President, R&D and Chief Medical Officer

So this is Gilmore here. I just wanted to follow-up on something, when you asked the question, you talked about the two programs, the microdystrophin program from our end and the microdystrophin program out of Pfizer. I just want to follow-up on the mass-spec question, because I know you're all sophisticated thinkers and would be very careful about comparing apples and oranges Western versus mass-spec. I think there are certain things that you should likely look into methodology, be clear about the methodology being used, not least of which is that in the developing our Western blot, we and Louise, Nationwide, optimized that methodology to ensure that the Western blot was measuring monomer.

The -- is an issue potentially, and you have to look at how the mass-spec actually pulls down the peptide because that mass-spec doesn't actually use the full protein. It actually digests the protein and then actually measures peptide fragment, and then essentially computes them together. So one has to be very careful in understanding how much our authenticity is of the spec -- mass-spec methodology for identifying and quantifying monomer. So I think it would be very -- it is very important for everyone that's looking at mass-spec to actually consider the methodology and the details of that and take -- be very cautious about comparing across method.

Operator

Our next question comes from Joseph Schwartz from SVB Leerink.

Dae Gon -- SVB Leerink -- Analyst

This is Dae Gon dialing in for Joe, and congrats on all the progress. So I have two broad questions, one on manufacturing and one on the competitive landscape. And no, that's not Pfizer. I don't want to go into Pfizer data.

But briefly, on manufacturing. At the recent ASCCT, there was a lot of presentations and talks on manufacturing and the various methods. So looking at the press release, you have the 75,000 square feet at Brammer. And so I just wanted to get your take on question 1, what kind of conversations or interactions and feedbacks have you received from the FDA with regards to systematizing multiple iCELLis units to make your material? And the second question is as it pertains to manufacturing, we've heard a lot about how the downstream and the analytical methods are a huge opportunity for optimization.

So can you briefly comment on where you stand with those analytical and downstream recuperation yield?

Doug Ingram -- Chief Executive Officer

So in the broadest of strokes, just to remind everyone, we've chosen -- we were at -- we're using clinicals of life from Nationwide, and that's an ramellian inherent process in the hyperstacks, but is not a very scalable process because it's a two-dimensional process. iCELLis is very similar to the inherent process just, as well as well ramellian as well, but it's the three dimensional process, which allows more scale. We're on ongoing dialogue with the agency and on issues and questions relating to the iCELLis units and analytics and the like. The good news is, just so we're all clear, one comforting aspect of all this is that there is -- and even though gene therapy is in many ways, nascent, there is good precedent for this one thing, which is moving from hyperstack to iCELLis units and systematized iCELLis units.

And the reason for that is because this is exactly what Novartis is doing it, hands down. Novartis' program was sister a program, in a sense, to our program over at Nationwide Children's Hospital. Their program started at hyperstacks and ramellian and transitioned over to commercial supply at -- iCELLis units with the same ramellian and the puron process with iCELLis. So while there's a lot of work to be done, we are confident that the pathway has been trodden with Novartis, which we understand should be native roots here.

So I think we're in a good shape there. We've got a lot of ways to go on the downstream side and a lot of work to do on the analytics side. And certainly, there is optimization to be done on the downstream side and the group is looking at that, even as we speak. And Louise is playing part of that as well.

Operator

I'm showing no questions at this time. I'd like to turn the conference back over to CEO, Doug Ingram, for any closing remarks.

Doug Ingram -- Chief Executive Officer

Thank you very much. First, I want to thank everyone for joining us this evening for our conference call. Hopefully, you'll come away with the understanding first that, at least -- so for this year, the team that I have gathered around me at Sarpeta, has been doing very good job at executing, I'm very proud of all them. And then beyond that, one would understand that we have a lot more to execute on 2019, and that this will behave very consequentially here first, for patients, and then for Sarepta and our long-term goals.

And certainly, if we're successful in all that, for our shareholders and the shareholder value. And we look forward over the course of 2019, not only in executing but in bringing more updates to the investment community. So thank you, and have a good evening.

Operator

[Operator signoff]

Duration: 94 minutes

Call participants:

Ian Estepan -- Senior Vice President, Chief of Staff, and Corporate Affairs

Doug Ingram -- Chief Executive Officer

Sandy Mahatme -- Executive Vice President, Chief Financial Officer and Chief Business Officer

Bo Cumbo -- Executive Vice President and Chief Commercial Officer

Althea Young -- Cantor Fitzgerald -- Analyst

Ritu Baral -- Cowen and Company -- Analyst

Brian Abrahams -- RBC Capital Markets -- Analyst

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

Gilmore O'Neill -- Executive Vice President, R&D and Chief Medical Officer

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Maxwell Skor -- Morgan Stanley -- Analyst

Debjit Chattopadhyay -- H.C. Wainwright and Company -- Analyst

Christopher Marai -- Nomura Instinet -- Analyst

Gilmore ONeill -- Executive Vice President, R&D and Chief Medical Officer

Mike Triplett -- President and CEO, Myonexus Therapeutics, Inc.

Mark Connolly -- Credit Suisse -- Analyst

Gena Wang -- Barclays -- Analyst

Brian Skorney -- Baird -- Analyst

Ross Weinreb -- Goldman Sachs -- Analyst

Vincent Chen -- Sanford C.Bernstein -- Analyst

Danielle Brill -- Piper Jaffray -- Analyst

Shawn Egan -- Citi -- Analyst

Tessa Romero -- J.P. Morgan -- Analyst

Liisa Bayko -- JMP Securities -- Analyst

Yun Zhong -- Janney Montgomery LLC -- Analyst

Timothy Lugo -- William Blair -- Analyst

Tim Chiang -- BTIG -- Analyst

Dae Gon -- SVB Leerink -- Analyst

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