Audentes Therapeutics, Inc. (BOLD) Q2 2019 Earnings Call Transcript

BOLD earnings call for the period ending June 30, 2019.

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Audentes Therapeutics, Inc. (NASDAQ:BOLD)
Q2 2019 Earnings Call
Aug 6, 2019, 4:30 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good afternoon, ladies and gentlemen, and welcome to the Audentes Therapeutics Second Quarter 2019 Earnings Conference Call. [Operator Instructions]. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions] As a reminder, this conference call is being recorded.

I would now like to turn the call over to Andrew Chang, Head of Investor Relations at Audentes. Please go ahead.

Andrew Chang -- Head of Investor Relations

Thank you, operator, and good afternoon everyone. Just after market close today, we issued a press release with earnings and operating results for the second quarter 2019. The press release and live webcast access are available on the Investors and Media section of the Audentes' website at www.audentestx.com. The webcast link will be available for approximately 30 days.

Joining me on the call today are Matt Patterson, Chairman and Chief Executive Officer; Natalie Holles, President and Chief Operating Officer; and Tom Soloway, Executive Vice President and Chief Financial Officer.

Before we begin with prepared comments, I'd like to remind callers that the information discussed on the call today is covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act. I caution listeners that the Company's management will be making forward-looking statements, actual results could differ materially from those stated or implied by our forward-looking statements, due to risks and uncertainties associated with the Company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the Company's SEC filings.

The content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 6, 2019. Audentes undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of today's call, except as required by law.

I would now like to turn the call over to Matt Patterson, Chairman and Chief Executive Officer, Matt?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Thank you, Andrew, and good afternoon everyone. The first half of 2019 has been an exciting and busy time and we are pleased to share the progress we have made across our product portfolio, as well as several important key milestones we expect for the remainder of the year and into 2020. We have a lot to cover, so let's get started.

Beginning with AT132 our lead product candidate for the treatment of X-Linked Myotubular Myopathy or XLMTM. We are pleased to announce that we recently initiated enrollment and what we are calling a pivotal expansion cohort in our ASPIRO study to confirm the safety and efficacy profile of AT132 at a dose of three times 10 to the 14th vector genomes per kilogram.

We have selected this as the optimal dose, based on the safety and efficacy data collected to-date and the input of our scientific and medical advisors. We expect enrollment in the pivotal expansion to complete this fall. And we believe the results will support the submission of a biologics license application for AT132 in mid-2020 and an MAA in Europe in the second half of 2020.

The decision to add a pivotal expansion cohort to ASPIRO and its design was based on a series of productive interactions with the FDA and EMA over the past several months under our RMAT and PRIME designations respectively.

The intent of these discussions was to collaborate with both agencies regarding how to rapidly advance AT132 to license applications, based on the medical need and existing clinical data. The specifics of the conversations, largely focused on how best to further establish the benefit-risk profile of AT132 at three times 10 to the 14th dose with rigor and minimal subjectivity. As always it's a dialog and it's incumbent upon us as the sponsor to take the feedback and design a study that both meets the regulators' objectives and allows us to move as efficiently as possible toward filing.

This need feels particularly urgent in XLMTM, perhaps half of these boys don't live to see their second birthday and there are currently no treatment options available. We are confident that we have developed a plan that balances these needs and will support the filing of license applications in the US and the EU.

Before sharing the details of our regulatory discussions. Let's first review the overall enrollment of ASPIRO to-date.

We started the Cohort one at a dose of one times 10 to the 14th vector genomes per kilogram, in which we enrolled 6-treated patients and 1-delayed treatment control. We then escalated to Cohort 2 at a dose of 3 times 10 to the 14th vector genomes per kilogram, in which we have now also enrolled a total of 6-treated patients and 1-delayed treatment control.

However, it's important to remember that to-date we have only reported data from three patients treated at the proposed commercial dose of three times 10 to the 14th. So it was not surprising that a first recommendation of the regulators was to see more data from additional patients treated at that dose prior to filing.

Beyond this request to increase the number of patients treated at the proposed commercial dose, the regulators feedback was focused in three main areas. Endpoint selection, study design and duration of follow up post-treatment. I'll talk about how we've addressed each of these areas in turn.

Let's start with endpoints selection. Consistent with our expectations, both agencies recommended focusing on endpoints that are clinically meaningful. Based on our own work and other publications in the field, we know that reduction of ventilator dependence is considered to be closely correlated with morbidity and mortality outcomes in children living with neuromuscular disease including XLMTM. In addition, as you can imagine, the decision to initiate and maintain young children on ventilator support is an important determinant of quality-of-life for both patients and their caregivers.

As such, we've defined the primary efficacy endpoint for the pivotal expansion, as the change from baseline in hours of ventilatory support over time through week-24 post-treatment. Both the FDA and EMA have agreed that this is a clinically meaningful efficacy assessment and importantly the data we have generated to-date, give us confidence that we can meet this endpoint. Recall, as of the April 29, ASPIRO data analysis, we saw sustained and meaningful reductions in ventilator support in all 9 patients treated, with 4 patients successfully completely weaned off of mechanical ventilation. So we believe we are on solid footing for the primary efficacy analysis.

Now let's turn to the second main area of focus, study design. We have designed the ASPIRO pivotal expansion cohort to enroll 8 patients, consisting of 4 age-matched pairs, defined as being within plus or minus 6 months of age of each other. One patient from each pair will be randomized to receive a single dose of AT132 at three times 10 to the 14 vector genomes per kilogram and the other will serve as a delayed treatment control. Delayed treatment control patients will be administered AT132 once 24-week data are collected from the full pivotal cohort.

In discussing the ventilator support endpoint, the regulators were focused on ways to reduce subjectivity and minimize potential bias in the decision-making around ventilator weaning. As is usually the case, the recommendation for us was to run a double-blind placebo-controlled study. This was met with resistance from our investigators and data monitoring committee, who strongly questions performing sham infusions and serial muscle biopsies on controlled patients.

So balancing the two perspectives, we have introduced multiple elements of control to the design of the pivotal expansion, to increase the overall rigor and objectivity of the efficacy assessment. First, we've gone from a 3 to 1 randomization in the dose-escalation cohorts to a one-to-one randomization, which amplifies the overall power to assess the treatment effect. Secondly, we've age-matched the one-to-one randomized pairs, to control for any motor or respiratory functional changes that could be attributed to subject's age.

And thirdly, the ventilator weaning protocol now includes a blinded review of all respiratory functional data by an independent panel of pulmonologists to approve all ventilator support reductions. This third point, in particular, we view as critical as it enables blinding of the primary endpoint without requiring the placebo control. We are confident that our approach to study design will enable the regulatory authorities to interpret the data from the primary efficacy evaluation as reliable and accurate.

Finally, turning to study duration, the regulators were appropriately focused on assessing durability of benefit of AT132 and as is always the case, the more data and the longer the follow-up, the better. The key question is one is the optimal time point to perform the data cut to support a filling. here, not surprisingly, the FDA guided toward 48 weeks follow up. As we have previously shared, all patients in ASPIRO will be followed-up for safety and efficacy for 5 years.

Our plan is to submit our license application once we collect 24-week data from the pivotal expansion cohort, by which time the filing will also include over 24-months of follow-up data from patients in Cohort 1 and approximately 12- to 24-months of data from patients in Cohort 2. In total, we plan to submit with data from 22 patients. 18 treated, 10 of whom will have been followed-up for 48 weeks or longer, which we believe will strongly support the durability of benefit with AT132.

So in summary, we believe we have put together a robust plan that addresses the feedback of the regulatory authorities, moves this important program forward rapidly and in the end will demonstrate a positive benefit-risk ratio and support of potential licensing approval for AT132. As I mentioned earlier, we have already initiated enrollment of the pivotal expansion cohort and plan to complete dosing by the fall and importantly, all other aspects of our preparation for license applications are proceeding well, including on the CMC side as Natalie will touch on in a moment.

Before we turn to the remainder of our pipeline. I'd like to thank all of our partners and collaborators, the BOLD team members, our scientific and medical advisors and of course the XLMTM community, whose courage and strength are a constant reminder of our mission to bring AT132 to patients as quickly as possible.

With that, I'll turn the call over Natalie, walk you through the rest of our pipeline and make a few wrap up remarks. Natalie?

Natalie Holles -- President and Chief Operating Officer

Thank you, Matt, and hello everyone. We've made tremendous progress in our pipeline programs in the past quarter and I'm pleased to walk you through the highlights of our recent work. Starting with our Pompe program, we continue to advance our product candidate, AT845 toward an IND filing later this quarter.

We've now completed our dose-ranging and GLP toxicology studies in both the Pompe mouse and NHPs respectively and are in the process of finalizing study reports and preparing the IND submission with an eye toward initiating clinical studies early next year.

Our expertise in systemic administration of AAV-8 to drive broad muscle tissue transduction and transgene expression provides us with a highly differentiated approach in Pompe disease.

We believe AT845 is the only gene-therapy in development today, which is delivering an expressing GAA directly in the tissues affected by the disease. This potentially best-in-class approach stands in contrast to both enzyme replacement therapies and liver-directed gene-therapy candidates that rely on an inherently inefficient cellular uptake mechanism of GAA from plasma to deliver the enzyme to its intracellular site of action. As such, we avoid the need to engineer the GAA trans-gene to optimize for serum stability or cell surface receptor binding affinity with this approach. We're excited to bring this program through to IND submission, as we believe it has transformative potential for the treatment of Pompe disease.

Turning now to our Duchenne Muscular Dystrophy programs. We're excited about the rapid progress we've made since we announced our platform and pipeline expansion in early April. As a reminder, in DMD, we are initially advancing three vectorized exon skipping product candidates, which we believe together have the potential to address more than 20% of the Duchenne patient population. AT702, which is the most advanced of these programs, is designed to treat DMD caused by duplications of exon-2 or mutations in exons 1 to 5 of the dystrophin gene.

Nationwide Children's Hospital, our collaborator for this program, plans to initiate patient dosing next quarter, using their clinical material, which is manufactured at their facility. We expect Nationwide to dose 1 to 2 patients prior to the clinical program transitioning to our construct and clinical material early next year. In parallel with the NCH work, we have successfully completed work to transition to and manufacture our AT702 construct in-house. Dose-ranging and toxicology studies are under way to support an IND filing for the Audentes product in Q1 of next year. We expect to initiate a full Phase 1, 2 study of AT702 quickly, once the IND clears.

We took the time over the past few months to refine the NCH construct, because we intend to use the backbone as a platform for rapid expansion of our vectorized exon skipping approach into additional DMD genotypes and to good effect. We have achieved meaningful improvements in the manufacturing productivity and product quality, in making the transition to our construct. So importantly, as we did with XLMTM, we expect to initiate our Duchenne clinical work with the commercial product and manufacturing process in place.

From here, we're well-positioned to rapidly advance our pre-clinical work on AT751 and AT753. Our additional product candidates designed to treat DMD's patients with genotypes amenable to skipping of exon 51 and 53. We expect to provide more refined timelines for moving these programs into the clinic and are coming updates. In myotonic dystrophy vector screening studies for AT466 are under way and we plan to submit an IND in 2020. While relatively early in its development, we're excited about the potential of this program.

As a reminder, we are evaluating both vectorized RNA knockdown and exon skipping approaches, each of which have been mechanistically validated to block the accumulation of toxic RNA in affected cells. The key pathologic mechanism in DM1. We believe that by combining antisense with the delivery and tissue transduction power of AAV, we overcome the recognized limitations of making antisense and create the potential to provide transformational impact on this devastating disease, which affects more than 100,000 people in the US, Europe and Japan. So more to come here and we're certainly pleased with the early progress.

Turning to manufacturing. We continue to view our investment in our own internal large scale cGMP manufacturing operation as a key strategic value driver for the Company. It has enabled our rapid progress through clinical development toward BLA and MAA filings for AT132 as not shared earlier. And more recently, has allowed for accelerated pre-clinical development of our Pompe, Duchenne and myotonic dystrophy programs.

Our current operation utilizing a mammalian serum-free suspension culture production process at a 1,000-liter scale, is expected to meet the anticipated global commercial demands for AT132 and the near-term development needs for our other product candidates. Also in April, we were pleased to announce our new state-of-the-art cGMP plasmid manufacturing facility. We brought plasmid manufacturing in for reasons similar to our early decision to bring in vector production.

To improve control over our supply chain, reduce cost and accelerate production timelines for this key starting material. We expected internal capability to take months off of our development timelines across the pipeline over time. Leveraging all aspects of our AAV manufacturing leadership, for rare neuromuscular diseases, will continue to be a cornerstone of our strategy for long-term value creation for our shareholders.

Finally, we continue to maintain a strong balance sheet with $378.6 million of cash, cash equivalents and marketable securities as of June 30. Our balance sheet strength positions us to make meaningful progress across our pipelines and we are excited by the multiple upcoming milestones and look forward to sharing further updates over the coming months.

That concludes our prepared comments for today's call. Operator, you may now open the line for questions.


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Questions and Answers:

Operator

[Operator Instructions] Our first question comes from Anupam Rama with J.P. Morgan. Your line is now open.

Anupam Rama -- J.P. Morgan -- Analyst

Hey guys, thanks for taking the question and congratulations on all the progress. Just two quick ones from me, for the 8 patients in the pivotal ASPIRO cohort, have these patients all been identified. I think you said enrollment would complete this fall. And then a second question for the World Muscle update later in the year, what additional analyses could be presented beyond the endpoints we already know. And can you remind us the duration of follow-up we'll get at the conference. Thanks so much.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Hey, Anupam, it's Matt, thanks for your question. Those are pretty quick ones. 8 patients indeed our identified. I can remind people that we've been continuing our INCEPTUS natural history run-in study in the background alongside ASPIRO all along. And so, we've maintained a pool of patients that might be candidates for ASPIRO should we need additional enrollment, and so patients were identified and it's just a matter of working through the logistics of enrollment over the coming couple of months here in the fall, as we said. So yes, we expect to complete enrollment this fall, and obviously that's what helps get us to the BLA mid next year.

WMS, you know it's a little fluid, Anupam, is the honest answer. We certainly will have a data update, but I'm not in a position today to articulate exactly how much additional data and then exactly how many patients. The team is working on that and finalizing that plan right now.

At the same time, they're working on enrollment in the study and BLA preparation activities, et cetera. So, we'll have a little more color on that as best as we can here in the coming weeks. But I would say that I don't expect it's going to be quite as much of a data update as we had at ASGCT. It will be a meaningful update but it probably won't be quite as much data as we had at ASGCT, that's my initial read on it.

Anupam Rama -- J.P. Morgan -- Analyst

Awesome. Thanks for taking my questions and congrats, again, all on the progress.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Thanks Anupam.

Operator

Our next question comes from Chris Raymond with Piper Jaffray. Your line is now open.

Nicole Gabreski -- Piper Jaffray -- Analyst

Hi. This is Nicole Gabreski on for Chris. Thanks for taking the question, I guess, I just had a quick one on AT132, so you guys have highlighted that you've used the same process and the same facility, is at the same scale from pre-clinical IND enabling work all the way now, almost to commercialization. But I was just curious, are you currently manufacturing or moving to manufacturing plasmid for AT132 in-house for the program prior to BLA filing. And then also just wondering, what the regulatory hurdles might be or if there is certain data, you need to show FDA to confirm that you have an equivalent product, when you switch to plasmid made at a new production site? And then just lastly, does this have any impact on BLA filing times at all for the MDM program?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Hi, Nicole. Thanks for the question. A bit of a work-in-progress, I would say, but plasmid manufacturing up and running and going well. I would say that our current vision is to include it in the license application. But we certainly want to make sure that, that plan is comfortable to the agency and if there is any work to be done, which in terms of comparability that we handle that, our guess would be that animal data would be satisfactory for that frankly. But that's a bit fluid and -- but I can assure you that we're in a position where, it won't become rate limiting for the BLA filing. And if for some reason, we needed to do a little bit more work, we would file it as opposed to approval change, we're in a position to be able to be flexible in that regard. So certainly, we'll do our best to get it in and leverage it as much as we plan to, but we won't let it delay any BLA filing.

Nicole Gabreski -- Piper Jaffray -- Analyst

Thank you.

Operator

Our next question comes from Joseph Schwartz with SVB Leerink. Your line is now open.

Dae Gon Ha -- SVB Leerink -- Analyst

Great. Good afternoon and thanks for taking the question. This is Dae Gon dialing in for Joe and congrats in all the progress. So, Matt. Just two questions from me, one on AT132 and the second question on DMD. Apologies if there kind of multi-part questions, but I guess, starting with the 132. I just wanted to get your take on sort of that 8 patient number. I think you previously talked about enrollment -- expansion cohort enrolling 3 to 5 patients and we now have 8. I understand that it's now randomized one-to-one. So maybe it is just a semantics kind of a thing where four patients does fit in with a 3 to 5 guidance you provided previously. So, any color there would be good.

Second question is on DMD. So you mentioned that 702 will enter the clinical trial in 1 to 2 patients using the NCH-based material. I'm assuming that's adherent based system and you're working through the conversion to suspension base. So, how many patients are you thinking in terms of Phase 1, 2. And as we think about your subsequent programs in 51 and 53. Any chance you could run a basket trial, especially since those 53 patients are somewhat of a small under-represented genotype among the DMD population? Thanks.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

All right. Thanks, Dae Gon, I took some notes, hopefully, I get these right. But check me, if I don't. So regarding the AT132. Yes, so I tried to say in the script, but let me just restate the patient numbers because I understand that potential for a little confusion. Cohort 1, we all agree and understand 6 patients were treated and there was one untreated control. Cohort 2, we first we treated 3 patients and we had an untreated control and then we announced that we were going to expand that to enroll another 3 to 5. Today we're announcing that we did enroll additionally, those 3 patients into that cohort. So that's done, that is in fact distinct and separate from the pivotal expansion cohort, which is 8 patients 4 treated and 4 delayed treated.

So, hopefully that's clear and that gets me to those numbers. I mentioned in the script, which is that in the end, the BLA would be filed on a number of -- 22 total number of patients, 18 who've been treated, 12 of whom have been treated at the proposed commercial dose of three times 10 to the 14th. So hopefully, that makes sense.

And then on the DMD side. So, yeah, -- so look the program -- early research as everyone knows started in Nationwide. They're our partners on this, they have done additional work to answer FDA's questions and get a trial started. But indeed you're right, it looks like they'll get started with treating 1 or 2 patients with the material they have made at Nationwide, with their version of the construct. And that's on track to start here later -- later this year as I previously guided to. But we've also chosen to optimize the construct we're switching a to an AAV8 construct, which of course is what we use in our other programs. And as Natalie mentioned, we're pleased with how that has gone, and that's going to result in our own distinct IND that we're going to file in Q1, which is for that optimized construct manufactured by our same in-house large scale serum-free suspension culture system, so that's the plan.

So, the vast majority of the clinical work will be from the Audentes products and starting first half of next year. NCH we'll get started with a couple of patients, and we'll see what we learn from that as part of the program. And then finally -- but as far as the specifics of the clinical protocol for that Audentes IND in Q1, and the number of patients and specific endpoints. I don't have the details to go into on that today, but I expect we'll have that information and more color to provide there later in the year. It won't come as any surprise that we expect to evaluate a lot of the same assessments both in tissue and clinical assessments that have been seen to-date in the Duchenne community, which will probably also translate over to what we end up doing in the clinic for 51 and 53.

And finally, your question about a basket IND, a little early to say there we're engaging with FDA. But you can bet that we are taking a creative approach to how to do this. We have highlighted previously, that we're optimistic about our ability to move this program quickly, given the fact that it's the same backbone, same basic constructs in each case, but for the specific antisense sequence for each exon. And so, one can envision a scenario that is very logical and credible, where you can rapidly move through preclinical development for future exons and even clinical, if you can find ways to be creative and leverage experience with various endpoints and designs to move the whole thing quickly. So -- but we expect to engage with the FDA in that sort of creative dialog in the coming months, as well, and as we have progress we'll keep you posted.

Operator

Our next question comes from Ritu Baral with Cowen. Your line is now open.

Ritu Baral -- Cowen -- Analyst

Hey, guys. Thanks for taking the question. On the pivotal cohort, what are your powering assumptions around the one-to-one, the 8 patients randomized one-to-one, you mentioned the primary endpoint is reduction hours of ventilator support through 24 weeks. What's your powering and what are your sort of placebo assumptions -- not placebo sorry, delayed treatment control assumptions for what's going to happen to their ventilator support?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Well, no surprise, the team has done a thoughtful analysis of this and reviewed all of the -- thanks Ritu -- sorry -- for the question. No surprise team has done a thoughtful review of all the data we have to-date and has gotten quite comfortable that 8 will power the study adequately to determine a statistically significant difference. And as far as the controls, I mean, we have the benefit of having monitored their controls during the early part of the study, and of course you know the data as well as anyone and we know that there were no changes in ventilatory status in 2 control patients and so, of course, it's logical that one would expect the same in the control patients in this study.

So, there's a lot of high degree of confidence about 8 as a number to achieve that goal. And obviously, that's why we settled on the plan and are optimistic about next steps.

Ritu Baral -- Cowen -- Analyst

Was that placebo -- sorry, delayed treatment assumption, was that powered at all by some of the INCEPTUS patients or just the 2 patients in ASPIRO?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

I don't actually know the answer to that, off the top my head, but I'm not -- I could, I'm certainly happy to follow up and double-check. But -- so, rather than speculate I guess I can follow-up on it, but there is no data in any of our work, whether it's INCEPTUS or even RECENSUS our natural history or medical record review, we did a while back or, of course, the ASPIRO in those 2 control patients, they suggest that any patient would have -- that's untreated would have any other outcome except just remaining on ventilatory support the whole time from baseline onward.

Ritu Baral -- Cowen -- Analyst

Got it. And then just moving to your potential Pompe study. Can you just give us broad strokes outline us to what you think that first clinical study will look like. Will you be able to enter pediatric patients immediately, will there be a biopsy endpoint, will there be functional endpoints and when?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Sure. It's a little early to go into total detail but I'll share some introductory thoughts and our expectation would be to be able to articulate more details once the IND is in and cleared and we have any agency feedback. So -- but that being said, it's reasonable we believe to assume that this will be a study that more likely than not starts in adults, but certainly, we appreciate the importance of rapidly evolving the program to also treat patients, who are suffering from infantile Pompe disease given the medical need. So -- but we have a lot of experience in Pompe around the table, so we have some thoughts and how best to do that. But I think starting in adults and no surprise, the endpoints are likely to include both biopsy-based assessments where one is looking at protein expression GAA in this question and glycogen levels, as well as relevant clinical endpoints, which are reasonably well established in the Pompe community from various clinical studies that have been done over time. A little bit distinct obviously between what one measures in the adult population versus the infantile, of course, and that's why those may very well be appropriately studied in separate protocols, as has also been done in the past. So that's probably all I can do for today, but I'm happy to provide more details later in the year as we have any agency feedback on our plans.

Ritu Baral -- Cowen -- Analyst

Sounds good. Thanks for taking my questions.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Sure.

Operator

Our next question comes from Whitney Ijem with Guggenheim. Your line is now open.

Whitney Ijem -- Guggenheim Securities -- Analyst

Hey, guys. First question is just on DMD given the vector switch, I guess, just wondering what -- if any read through or kind of how you guys are thinking about the read through from the first 2 NCH patients that will be treated, and kind of what the read through from the data, you'll get there as we think about the data from your program. And the second question was just -- going back to the plasmid manufacturing, can you just could remind us the benefit there other than obviously having control of your own supply. Are there any financial kind of benefit as we think about COGS?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Sure. Hi, Whitney. I would say, how we think about the NCH versus our product is that the NCH data will be interesting and certainly we'll take a look at it and learn what we can. But in the end, it will be a very low and it's going to be 1 or 2 patients. And as Natalie articulated, we've made what we feel are our powerful improvements to the construct for product quality and productivity in the manufacturing system. And it sets us up for this template approach for future programs. So I would encourage people to things like we do, which is that the key data to begin interpreting will be the data from patients treated with Audentes product over the course of next year.

If there's something interesting to be gleaned from the first couple of patients at Nationwide, so be it. We'll talk about it, but it feels a bit unlikely to me, given the low end and some of the product differences.

Sorry, second half of the question on the plasmid side. Yes, no question that it's multifaceted positive. And remember, this is particularly critical when you work in neuromuscular diseases and we're working with larger doses of AAV. And of course, as we expand into Pompe, Duchenne and myotonic we're beginning to work with larger patient populations and patients who are heavier with per kilo dosing. So the plasmid manufacturing is absolutely about control and we've seen some examples of setbacks for programs because there has been a quality question related to the raw material. But it's absolutely also about cost and we believe this operation is going to pay for itself rapidly, given what we see as the cost of working with outside vendors in that arena so far these days.

And finally, I would say timelines. I mean it's a long lead time. It's just like trying to book a space at a CMO for manufacturing your product and reserving a suite and spending money upfront and then hoping everything tracks, OK, and then it works out. In this case, it gives us much more certainty over our timelines and ability to hit our program development milestones. So it's really three things, quality, fast and confidence in our timelines that are behind that investment.

Operator

Our next question comes from Steve Seedhouse with Raymond James. Your line is now open.

Steven Seedhouse -- Raymond James -- Analyst

Good afternoon and thank you. So given -- it sounds like the FDA requested a certain design for the AT132 pivotal expansion cohort and you said, a lot of bit different, design details and duration of follow-up. I apologize, if I missed this, but I think here, what then was the FDA's response or receptivity to your ultimate study design, subsequent to the initial exchange. Do you have a written agreement on the final protocol or what's your level of confidence that the FDA is amenable to the trial design details that you laid out?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Sure. Thanks Steve for the question. We had a whole series of back and forth interactions with both FDA and the European -- European is largely in the context of scientific advice procedure, but both written and verbal exchanges that's sort of guided us to where we landed.

I would say that not surprising to us, FDA has sort of final agreement, so that one can file a BLA is something that they differ to the time when they have the full dataset. And there is nothing surprising about that to us. That's standard course of business for rare disease drug development, in particular where you have a relatively small number of trials and patients treated.

And so -- but in the end, based on our digestion of their feedback through those multiple rounds. We feel very confident about our plan and that was part of what I was hopefully able to articulate in the script's conversation there as our written remarks that when you really dig in, you try to evaluate what the agency is looking for with their requests and if really it does end up coming down to getting some additional data at that dose studying a meaningful clinical endpoint. Collecting data in just a reliable and meaningful way, so they can believe that it's real and accurate.

And of course, they always say, they like as much as possible. So we really worked very hard to accommodate all those, and so through all that we feel a high degree of confidence that in the end, we're going to strike a good -- we're going to put together a big good presentation of data that produces a very positive benefit-risk ratio, which is another important perspective to keep in mind. This is X-linked Myotubular Myopathy a fatal disease with no treatment. And so, I think in the end, it's going to be a very compelling story and likely to move forward in a positive manner.

Steven Seedhouse -- Raymond James -- Analyst

Okay, thank you. And I wanted to ask if I could. Considering the focus of the Company now on neuromuscular disease and move into vectorized exon skipping pretty novel approach and given the success of SPINRAZA in SMA, so gene replacement was showing that you can target with AAV in SMA pretty effectively and pre-clinical data that shows vectorized exon inclusion in SMA is possible. You're already collaborating with NCH has a history here is SMA an appealing indication clinically to you. And would there even be freedom to operate with vectorized exon inclusion approach there you are interested in?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

We're certainly excited to go into vectorized exon skipping and in addition to standard gene replacement as we've done historically and we find that there is a wealth of opportunities out there that are interesting. But for now, I would say that our focus in the near-term remains on the pipeline that we've recently announced and executing on Pompe, and Duchenne and myotonic. There is a tremendous amount of opportunity right in front of us with the pipeline, we've established. That being said, the vision of the Company will be to continue to add interesting programs over time. And if we think it's something with good medical need, and a strong scientific rationale and a good strategic fit for us. You can bet, we'll take it seriously.

So -- but for now we feel really good about the progress we can make and the value we can generate with MTM, Pompe, and Duchenne and myotonic. We're obviously in a position where we're really setting up for a very exciting 2020 in particular with BLA filing in MTM and the potential for proof of concept data in Pompe and Duchenne in the IND and myotonic, so plenty of work to do.

Steven Seedhouse -- Raymond James -- Analyst

Thanks for the questions.

Thank you.

Operator

[Operator Instructions] Our next question comes from Debjit Chattopadhyay with H.C. Wainwright. Your line is now open.

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

Hey, good afternoon and thank you for taking my questions. I've got a couple. So, just could you walk us through your updated thoughts on the XLMTM addressable commercial opportunity and how do you think the label could play out, given that you're enrolling patients primarily under the age of 5 and what fraction of patients alive over the age of 5?Thanks so much.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Sure. Thanks for the question. No meaningful changes from our previously stated commercial guidance. We think that the recent publications about MTM incidents and prevalence, as well as our own data still guide us to a place where we believe that there is an incident population of several hundred patients in the markets we would expect to pursue and a prevalent population of 2 or 3 times of that. And indeed, you're right, that we're focused on enrolling patients who are less than 5 years of age. And -- but that doesn't -- that does cover the majority of MTM patients.

That being said, we're taking a very thoughtful eye to our commercial preparations and wanting to ensure we have a very robust package of information for future payers, to ensure patient access for -- treatment access for all patients with MTM. And so, we're evaluating additional opportunities to collect any data in slightly older patients, if that would be helpful to payer. So while we don't have a set plan on that today. That's something, certainly we're interested in. But you can bet that, as we're looking into next year, we're turning into a very commercial-oriented Company across the board and collecting data that supports that story is key to us. As you know we've already historically done a lot of work in this regard, largely focused on characterizing the burden of MTM, which we think will be critical to those future payer conversations, and then you combine that with the incredible value that we believe we're demonstrating with our clinical data both the patients and their caregivers and we feel very good about the commercial opportunity as it continues to mature.

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

And then on the AT702 program. I understand, it's not in the clinic yet but based on the pre-clinical data, where do you think dystrophin expression should line-up for you guys. And given the relatively smaller opportunity in the first program, the regulatory path forward. Does that mimic the exon skipping approaches in terms of a dystrophin expression based filing or the micro dystrophin gene therapy based approaches where it's more functional data? Thanks.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Well, with 702 program, as we previously shared, when we announced the program. We're extremely pleased with what was observed in terms of dystrophin expression of 42 near-normal levels of dystrophin expression across a range of muscle tissues that were sampled in animal studies. And importantly that's 40% to 100% of normal full-length dystrophin. Not 40% to 100% of a 30% sized truncated form of dystrophin, which is what one mix with the micro dystrophin programs and that of course is the crux of why we believe we have the potential to be superior safety and efficacy profile over time. That our approach produces a full-length or near full-length version of the missing protein.

So we believe the pre-clinical data track very positively. And that we look forward to studying that in biopsies in the clinical program as well and sharing that information as soon as we can. As far as the regulatory approach and template for future programs, I mentioned earlier, we believe we can move very efficiently through the other exons. As far as what endpoints are appropriate to study for approval. I think this is a very fluid subject frankly in Duchenne, we read everything that everyone else reads. But, I think it remains to be seen whether the agency will support approval of these sorts of products on dystrophin expression alone or whether clinical data will be required. It could actually vary I think program-to-program depending on medical need, even within given exon. So, we'll see about that, so it's difficult to know, but right now we're just intent on finalizing our clinical plan and coming up with a thoughtful approach to generating positive safety and efficacy data and differentiating our program over time as we go.

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

Thank you so much.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Thank you.

Operator

Our next question comes from Raju Prasad with William Blair. Your line is now open.

Sami -- William Blair -- Analyst

Hi there guys. This is Sami [Phonetic] on for Raj. Congrats on all the progress. I had a question jumping off the commercialization strategy for AT132. Are you guys looking to partner with any kind of specialists centers, in order to recruit patients?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Sorry to recruit patients for clinical work or to support commercialization?

Sami -- William Blair -- Analyst

To support commercialization.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

I don't have a good answer for that today. Honestly, I think the commercial team is actively working on all the sort of key planning activities. So it's an interesting question. I don't have a good answer for you today. But happy to talk more about it in the future, in particular, as the commercial team begins to refine our strategy for ensuring rapid penetration of the market. No surprise, things are moving quickly, but we're particularly focused in efforts to sign patients, which is really I think what you're getting at. As well as to continue to build our story of value and preparation for our conversations with payers. So -- but we'll certainly have more to share on this in the coming months. So obviously, as we approach the BLA filing and future commercialization.

Sami -- William Blair -- Analyst

Great, thanks. And then just one more. Did the FDA and EMA seem overall pleased with the current efficacy and durability data to-date? And do you think they were just looking for a maintenance of what has been seen previously with a greater number of patients?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

I think that's a fair conclusion. I mean, certainly, you wouldn't have gotten RMAT in PRIME designations as we did, if they weren't very encouraged by the early data. So that was the first step in recognizing that they believe the product has great potential. And our take away from the interactions was also that, that they see the potential, they're very engaged, responsive. And -- but in the end, absolutely, as we've said in this call and as you just said, I think it's a matter of getting a bit more data in patients treated at the proposed commercial dose. And ensuring that we're focused on an endpoint, we all agree is clinically meaningful and gathering those data in as robust a manner as possible. And none of that is a surprise, and so we've put together a good plan that accommodates all that. And we are confident that it's going to result in a BLA filing next year as we said. So I hope that helps.

Sami -- William Blair -- Analyst

Yeah. Thank you.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

All right.

Operator

Our next question comes from Matthew Luchini with BMO Capital Markets. Your line is now open.

Matthew Luchini -- BMO Capital Markets -- Analyst

Hi, guys. Great. Thanks for taking the questions. A couple from me, if I may. So first, on MTM, we've obviously heard a lot about the primary analysis for the pivotal expansion cohort and I was just wondering if there had been any addition or changes to any of the secondary endpoints that might be worth noting at this point?

And then second question would be on Pompe, given that you're going to be filing the IND this quarter, can you talk just a little bit about where you guys are in terms of trial set up, whether its site selection or KOL involvement. Just a little bit of color there would be helpful.

And then last question would be just as a point of clarification, Matt. Since it sounded a little bit like you are hedging with regards to the DMD patients that are treated with the NCH, construct is the plan to share those data. Not sure those data or only share if there is something I guess unexpected or untoward that should come out of them?

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Thank you. Hi, Matthew. Thanks for the questions. Yeah, glad you asked about the secondary endpoint question on MTM. So through our conversations, I would say that the both authorities zeroed on both the ventilator time -- time on vent as a key clinical endpoint. Obviously, we land on that as our primary endpoint, but they're also really enthusiastic about achievement of key motor milestones, which is something that we've heard and seen -- observed as important also in the SMA clinical -- gene-therapy clinical trial work. So it wasn't a surprise to us, and so out of that we chose to include as a secondary endpoint, the ability to sit un-assisted for 30 seconds, which is obviously a basic and really important motor milestones for kids this age, so that is in fact a secondary endpoint. It's something that we had a lot of success, achieving in the patients early in the study. So again, it's something we feel very confident that we can meet and we believe it will be strongly supportive. We also certainly believe in the biopsy data as strongly supportive. Everyone is familiar with the fact that we have high evidence of VCN protein expression near or above normal levels and significantly normalized histopathology. And so, that's all very supportive data too that's key to the pivotal expansion cohort study plan.

So, as far as Pompe, yeah very active on trial preparations. Again, multiple members of the team here have worked on Pompe in different forms and we know the community and so we've been engaged with the KOLs for quite some time, actually. They've been in the background guidance work in the program. And so we feel good about that and look forward to sharing more details about our now just a protocol, but also operational details, but I believe we'll be able to get up and running efficiently. And then finally on Duchenne, yeah, I certainly didn't mean to sound hedging, I just trying to be realistic that I think data from one patient with a -- 1 or 2 patients with a product that's going to be outdated quickly, just wasn't sure how much we'd be able to rely on that and talk about that, but we certainly, if we see something interesting that we feel is important to share with the community, you can bet, that we will share it. But I just want to be straightforward about, I think how to think about the program more holistically and it's likely that the data from our products are manufactured by our process will be really what we should be evaluating for the future of the program and the safety and efficacy of that product.

Matthew Luchini -- BMO Capital Markets -- Analyst

Perfect. Thanks so much for taking the questions.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Sure. Thanks.

Operator

And our next question comes from Difei Yang with Mizuho Securities. Your line is now open.

Difei Yang -- Mizuho Securities -- Analyst

Hey, good afternoon and thanks for taking my quick question. So with regards to AT132, Matt would you remind us, if we were going to see reduced ventilator utilization, what typically -- what timeframe are we going to observe that post-treatment? And then secondarily, with regards to onset of action with the higher dose, do you expect an acceleration on onset of -- onset of seeing this reduction of ventilator use?

Unidentified Speaker

Sure. Hi, thanks for the questions. When one reviews the data from the study to-date, we see evidence of improvement in respiratory function very rapidly. First and foremost through -- in a matter of weeks, through first patients ability to control their airway on their own, to then improvements in the maximum inspiratory pressure tests that we've been doing for some time. And then that in turn leads investigators to get comfortable reducing time on event. So there is plenty of evidence from a number of patients that you see improvements and reductions in time on a ventilator over the course of the first 12 to 24 weeks of the study.

And so that's why, when you look at the data, we're very comfortable that at 24 weeks we're likely to hit this endpoint and to truly distinguish a statistically significant difference from the controls, who are as we said earlier, extremely unlikely to change at all from baseline and the requirement that all patients have a baseline, which is to be mechanically support ventilated for 20, 24 hours a day. So there's reason to be very optimistic that at 24 weeks we'll hit that endpoint.

As far as the higher dose and a faster onset. What we observed and it was a part of the decision making process for choosing 3T14. We did not see a meaningful difference in the safety profile of the two doses nor the efficacy profile one measured by the key clinical measures like CHOP INTEND or even ventilator reduction. Where you started to see differences was in the tissue and the biopsies and you certainly saw bit higher levels of protein activity, but really in the histopathology what we felt we observed was that you got a little closer even to normal over the lower dose and that it seem to happen a bit faster.

And so, that's the only area where I thought we were able to distinguish a difference between the two doses and that certainly contributed to our decision to go with the higher dose. I'm not sure that one could ever see a difference -- a meaningful difference when it comes to ventilator reduction between the two doses. I don't know that's practical with that endpoint. But -- anyway we feel really good about the high dose for all the reasons that I think we've talked about before. And of course, it also has a little bit of an eye toward long-term durability of effect and that's a goal we all have as well so, and I hope that helps.

Difei Yang -- Mizuho Securities -- Analyst

Okay, thank you.

Operator

At this time, I'm showing no further questions, I'd like to turn the call back over to Mr. Matt Patterson for any closing remarks.

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Great. Thank you again everyone for your participation and for the opportunity to share our updates. Looking forward to a busy remainder of 2019 and to updating you on our progress again soon. Operator, that concludes our call today.

Operator

[Operator Closing Remarks]

Duration: 55 minutes

Call participants:

Andrew Chang -- Head of Investor Relations

Matthew R. Patterson -- Co-Founder, Chairman and Chief Executive Officer

Natalie Holles -- President and Chief Operating Officer

Unidentified Speaker

Anupam Rama -- J.P. Morgan -- Analyst

Nicole Gabreski -- Piper Jaffray -- Analyst

Dae Gon Ha -- SVB Leerink -- Analyst

Ritu Baral -- Cowen -- Analyst

Whitney Ijem -- Guggenheim Securities -- Analyst

Steven Seedhouse -- Raymond James -- Analyst

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

Sami -- William Blair -- Analyst

Matthew Luchini -- BMO Capital Markets -- Analyst

Difei Yang -- Mizuho Securities -- Analyst

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