Boundless Bio Inc

NASDAQ:BOLD

Earnings Call Transcript 2019-Q2

[Operator]

Good afternoon, ladies and gentlemen, and welcome to the Audentes Therapeutics’ Second Quarter 2019 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [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, IR]

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 would 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?

[Matt Patterson, 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 in 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 3x1014 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 second half of 2020.

The decision to add a pivotal expansion cohort to ASPIRO and its design were based on the 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 further establish the benefit risk profile of AT132 at the 3x1014 dose with rigor and minimal subjectivity. As always, it’s a dialog and its incumbent upon us as the sponsor to take the feedback and design a study that will meet the regulators objectives and allows us to move efficiently as possible towards filings.

This need feels particular urgent in XLMTM perhaps half of these boys don't live to see their second birthday and there are apparently 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 U.S. and the EU.

Before sharing the details of our regulatory discussions, let’s first review the overall enrollment of ASPIRO to-date. We started with Cohort 1 at a dose of 1x1014 vector genomes per kilogram in which we enrolled six treated patients and one delayed treatment control. We then escalated to Cohort 2 at a dose of 3x1014 vector genomes per kilogram in which we have now also enrolled the total of six treated patients and one delayed treatment control.

However, it’s important to remember that to-date we have only reported data from three patients treated as the proposed commercial dose 3x1014. So, it was not surprising that our first recommendation of regulators was to see more data from additional patients treated at that dose prior to filing. Beyond this request increased 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 fall of those treatment.

I’ll talk about how we’ve addressed each of these areas in turn. I’ll start with endpoint selection. Consistent with our expectations both agencies recommend focusing on end points that are clinically meaningful. Based on our own work and other publications in the field, we know the 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 and hours of ventilatory support overtime through week 24 post treatment.

Both the FDA and EMA have agreed that this is the 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 2019 ASPIRO data analysis, we saw sustained and meaningful reductions in ventilator support in all nine patients treated with four patients successfully completely weaned off of mechanical ventilation. So, we believe we’re on follow up footing for the primary efficacy analysis.

Now, let’s turn to the second main area focus study design. We’ve designed the ASPIRO pivotal expansion cohort to enroll eight patients consisting of four aged 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 AT122 3x1014 vector genomes per kilogram and the other will serve as a delayed treatment control.

Delayed treatment control patients will be administered AT132 once a 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 biopsy uncontrolled 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 as the efficacy assessment. First, we've gone from a 3 to 1 randomization in the dose escalation Cohorts to a 1 to 1 randomization, which amplifies the overall power to assess the treatment effect.

Secondly, with age match of 1 to 1 randomized pairs, to control for any motor our respiratory functional changes that could be attributed to subject age. And thirdly, the ventilator weaning protocol now includes a blinded review of all respiratory functional data by an independent panel of pulmonologist to approve all ventilator support reductions.

This third point in particular review as critical is it enables blinding of the primary endpoint without requiring the placebo control. We are confident at 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 lower the follow-up the better. The key question is when is the optimal time point to perform the data to support a filing. Here, not surprisingly, the FDA guided towards 48-week follow-up.

As we have previously shared, all patients in ASPIRO will be followed for safety and efficacy for five 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 for 48 weeks or longer, which we believe will strongly support the durability of benefit with AT132.

So in summary, we believe we've 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 a 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 and now I'll touch on in a moment.

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

With that, I'll turn the call over to Natalie to talk us 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 have made tremendous progress on 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 towards an IND filing later this quarter.

We now completed our dose ranging and GLP toxicology studies in both Pompe Mouth and NHP respectively and are in the process of finalizing study reports and preparing the IND submissions with an eye toward initiating clinical studies early next year.

Our expertise in systemic administration of AT845 to drive broad muscle tissue transduction and transgene expressions provides us with a highly differentiated approach in Pompe disease. We believe AT845 is the only gene therapy and development today which is delivering and 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 uptick mechanism of GAA from plasmid to deliver the enzyme to its intercellular site of action.

As such, we avoid the need to engineer the GAA transgene to optimize for exon stability or cell surface receptor binding affinity with this approach. We’re excited to bring this program through the IND submission as we believe it has transformative potential for the treatment of Pompe Disease.

Turning now to our Duchenne muscular dystrophy program, 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 help the potential to address more than 25% 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 was manufactured at their facility.

We expect Nationwide to dose one to two patients prior to the clinical program transition to our contrast and clinical material early next year. In parallel with the NCH work, we’ve successfully completed work to transition to and manufacture our AT702 construct in-house. Dose ranging and toxicology studies are underway to support a 90 filing for Audentes products 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 contract because we intend to use the background as a platform for rapid expansion of our vectorized exon skipping approach into additional DMD genotypes and to get affect.

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 position to rapidly advance appropriate clinical work on AT751 and AT753, our additional product candidates designed to treat DMD patients with genotypes amenable to skipping of exons 51 and 53. We expect to provide more refined timelines for moving these programs into the clinic and our coming update.

In myotonic dystrophy, vector screening studies for AT466 are underway and we plan to submit an IND in 2020. Well 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 exons skipping approaches, each of which have been mechanistically validated to block these stimulation of toxic RNA in effective cells, the key pathologic mechanism in DM-1.

We believe that by combining antisense with the delivery in tissue transduction power of AAV, we overcome the recognized limitations and make it antisense and create the potential to provide transformational impact on the devastating disease, which affects more than a 100,000 people in the U.S., Europe and Japan. So, more to come here and we are certainly pleased with the early progress.

Turning to manufacturing, we continue to view our investment in our owned internal large scale cGMP manufacturing operation as a key strategic value driver for the Company. It has enabled our rapid progress through clinical development towards BLA and MAA filings for AT132 as Matt shared earlier and more recently has allowed for accelerated pre-clinical development of our Pompe, Duchenne, and myotonic dystrophy program.

Our current operation utilizing of a 1 million serum-free suspension culture production process at a 1,000 meter scale is expected to meet the anticipated global commercial demand for AT132 and the near-term development needs for other product candidates. Also in April, we were pleased to announce our new state-of-the-art CGMP placid manufacturing facility.

We brought placid manufacturing in for reasons similar to our early decision to bring in vector production, to improve control over our supply chain, reduced costs and accelerate production timeline for this key starting material.

We expected internal capability to take month off development timelines across the pipeline overtime. Leveraging all aspects of our AAV manufacturing leadership for muscular diseases will continue to be a cornerstone of our strategy from 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 30th 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.

[Operator]

[Operator Instructions] And our first question comes from Anupam Rama with JP Morgan. Your line is now open.

[Anupam Rama, JP Morgan]

Hey, guys. Thanks for taking the question and congratulation on all the progress. Just two quick ones from me. For the eight patients in the pivotal ASPIRO cohort, have these patients all been identified? I think you said enrollment will complete this call. And then second question for the world muscle update later in the year. What additional analysis to be presented beyond kind of end point we already know? And can you remind us the duration of follow-up will get at the conference? Thanks so much.

[Matt Patterson, Chairman and Chief Executive Officer]

Hey, Anupam. This is Matt. Thanks for your question. Those are pretty quick ones. Eight patients indeed are identified I can remind people that we have been continuing INCEPTUS natural history of run-in study in the background alongside ASPIRO all long and so, we've maintained a pool of patients that might be candidates for ASPIRO should be need additional enrollment, and so our patients are 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 a lot sort of get to the BLA in the next year. WMS, it’s a little fluid as we understand. So, we certainly will have the data update, but I'm not in a position today to articulate exactly how much additional data and 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 study and BLA preparation activity et cetera.

So, we’ll have a little more color on that as best as we can herein the coming weeks, but I would say that I don’t expect it’s going to be quite as much of the 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 with the ASGCT. That’s my initial read on it.

[Operator]

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

[Nicole Gabreski, Piper Jaffray]

Hi, this is Nicole Gabreski on for Chris. Thanks for taking the question. I guess we 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 preclinical IND enabling work all the way now, almost the 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’s certainty you need to show FDA to confirm that you have an equivalent product when you switch to product that needed a new production site. And then just lastly does this have any impact on BLA filing time it offers for the MTM program?

[Matt Patterson, 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 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’s 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 BLA filing. And if some reason, we need to do a little bit more work, we would file as oppose to approval change. We’re in a position to be able to be flexible in that regard. So, certainly, we’ll do our best get done and leverage it as much as we plan to, but we won’t let it delay any BLA filing.

[Operator]

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

[Dae Ha, SVB Leerink]

Great good afternoon and thanks for taking the question. This is Dae Ha dialing in for Joe and congrats on all the progress. So Matt just two questions from me, one on AT132 and the second question on DMD, apologies if there are kind of the question is multiple questions. But I guess starting with the 132, just wanted to get your take on sort of that eight patient number? I think you previously talked about enroll -- expansion cohort enrolling three to five patients and you now have eight. I understand that it’s now randomized one-to-one, so maybe it is just to semantics kind of a thing where what patients does fit in with the 325 guidance you provided previously. So any color there will be good?

Second question is on DMD so you mentioned that 702 will enter the clinical trial and one or two patients using the NCH base material. I'm assuming that the material based system and you’re working through the conversions to suspension base. So how many patients are you thinking in terms of Phase 1, 2? And as we think about your subsequent programs and 51 and 53, any chance you could run a basket trial especially since the 53 patients are somewhat of a small underrepresented genotype amongst the DMD population? Thanks.

[Matt Patterson, Chairman and Chief Executive Officer]

Thanks. I took some notes. Hopefully, I get this right, but tell me if I don't. So, regarding AT132, yes, so, I'll try to say it in the script but let me just restate the patients numbers so to 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, first we treated 3 patients and we had an un-treated control and then we announced that we are going to expand that to enroll another 3 to 5.

Today, we are announcing that we did control additionally those three patients into that Cohort so that done. That is in fact distinct and separate from the pivotal expansion cohort which is 8 patients, 4 treated and 4 delayed. So, hopefully clear and that gets me those numbers I mentioned in the script which is that in the end the BLA would be filed on 22 total number of patients, 18 been treated, 12 of them have been treated at the proposed commercial dose of three 3x1014 so hope that that makes sense.

And then on the DMD side, so yes, look, the program earlier search as everyone knows started nationwide. There are partners on this and they have done additional work to answer FDA's questions and get a trial started, but indeed you are right. It looks like they'll get started with may be one or two patients with the material they have made it nationwide with their version of a construct and that's on track to start here later this year as previously guided to.

I believe also chosen to optimized to constructs, we're switching to AAV construct which of course is where we use in our other programs and as Natalie mentioned, we're pleased with how that is has gone and that has kind of result in our own are distinct IND that we're going to file in Q1, which is for that optimize construct manufactured by our same in-house large-scale to increase suspension culture system.

So that's a plan. So, the vast majority of the clinical work will be from the Audentes products and starting first half of next year. NCH will get started with usually start with a couple patients and will what we learn from that as part of the program. And then finally, but as far as the specifics of the clinical protocols for that Audentes IND in Q1 and the number of patients and specific end point, don't have the details to go into today but I expect will have that information and more color to provide their leader in the year.

It won't come as a surprise that we expect to evaluate. There is a lot of the same assessments both tissue and clinical assessments that have been seen today in the Duchenne community, which will probably also translate over to what we end up doing in a clinic for 51 and 53. And finally your question about a basket IND, a little early to say that we are engaging with the 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 construct in each case, but for specific antisense sequence for each exon. And so, one can envision a scenario that's very logical and credible where you can rapidly move through preclinical development for future axons and even clinical, if you can find ways to be creative and leverage experience with various end points and design to the whole thing quickly -- so, but we expect to engage with the FDA in that sort of created 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]

Hey guys thanks for taking the question. On the pivotal cohort, what are your powering assumptions around the one-to-one? Is it the eight patients randomized one-to-one? You mentioned the primary endpoint is reduction in hours of ventilator support through 24 weeks. What is your powering? And what are your placebo assumptions, not placebo -- sorry, delayed treatment control assumptions for what’s going to happen to their ventilator support?

[Matt Patterson, Chairman and Chief Executive Officer]

Well, no surprise the team has done a thoughtful analysis of this and reviewed all of that, thanks for two -- sorry for the question. No surprise, the team has done a thoughtful review of all the data we have today and has gotten quite comfortable that eight will power the study adequately to take the script to determinate statistically significant difference.

And as far as the controls I mean we have the benefit of having monitor that 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 ventilator status in to control patients so of course it’s logical that one would expect the same in the controlled patients in the study so…

And so, there’s a lot of high degree of confidence about eight 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]

Was that placebo delay treatment assumption? Was that powered it all by some of the infective patients or just the two patients in ASPIRO?

[Matt Patterson, Chairman and Chief Executive Officer]

I don’t actually know the answer of that off the top of my head, but I'm not -- I'm certainly happy to follow up and double check, but yes so yes rather than speculate I guess I’ll confirm upon it, but there’s no data in any of our work whether it’s in INCEPTUS or even RECENSUS or natural history or medical record review, We did a while back or of course the ASPIRO did in those two control patients to suggest that any patient would have untreated without any other outcome acceptance remaining on ventilator support the whole time from base line only.

[Ritu Baral, Cowen]

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

[Matt Patterson, Chairman and Chief Executive Officer]

Sure, it is 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 on once the IND is in and cleared and we have any agency feedback. So -- but that being said, it’s reasonable to assume that this will be a study that more likely the knot 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 needs, but we have a lot of experience in Pompe around the table. So, we have some thoughts and how to do that.

But I think starting in adults and no surprise end points are likely to include both biopsy-based assessments or looking at protein expression, GAA in this question, and glycogen levels, as well as relevant clinical endpoints, which are recently well established in the Pompe community from various clinical studies that have been overtime, a little bit distinct obviously between what one measures in the adult population versus infantile course. And that's why those may very well be appropriately studied in separate protocols 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.

[Operator]

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

[Whitney Ijem, Guggenheim]

First question is just on DMD given the vector, so I guess wondering, what if any read through or how you guys are thinking about the read through of first two NCH patients that will treated depending on what's the research and data you will get there as we think about those data from your program? And then second question is just on going back to plasmid manufacturing, can you just remind us the benefits there other than obviously having controlled around supply there any financial kind of benefits as we think about COGS?

[Matt Patterson, Chairman and Chief Executive Officer]

Sure. Hi, Whitney, I would say how we think about the MCH versus our product is that the MCH data will be interesting and certainly will 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 one or two patients. And as Natalie articulated, we've made what we feel are powerful improvements to the constructs or product quality and productivity in the manufacturing system sets us up for this template approach for future program.

So, I would encourage people to think like we do, which is the key data to begin interpreting the data from patients treated with Audentes product over the over the course of next year. If there's something interesting to be green from the first couple of of patients that nationwide so we'll talk about it. But, it feels a bit unlike that given the low and some of the product differences.

Sorry. Second half of the question on placid side, so again no question that its multifaceted positive and remember this is particularly critical when you work in neuromuscular diseases and working with the larger doses of AAV and of course as we expand in the addition and -- we are beginning to work with larger patient populations and patients who are heavier with particular dosing.

So, the plasmid manufacturing is absolutely about control and we have seen some examples, setbacks for programs because there's been a quality question related to the raw material, but it actually also about costs and we believe this operations 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 spaces CMO for manufacturing a product and preserving a suite and spending money up front and then hoping everything tracks okay and that it works out. In this case, it gives us much more certainty over our timelines and ability to hit our program development milestone. So, it's really three things, quality, costs 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.

[Steve Seedhouse, Raymond James]

Good afternoon 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, enzyme details and duration to follow up. I apologize if I missed this, but I didn’t hear what then was the FDA’s response or receptivity to your ultimate study design subsequent to the initial exchange? You have a written agreement on the final protocol or what your level of confidence with the FDA’s amendable to the trial design detail that you laid out?

[Matt Patterson, 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. The Europeans are largely in the context of scientific advice procedure, but of both written in verbal exchanges that sort of guided us to where we landed. I would say that not surprising to us FDA is sort of final agreement that one can file with BLA is something that’s a deferred to the time when they have the full data set. And there’s nothing surprising about that to us that’s standard course of business for rare disease drug development.

And particularly we 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 plans. And that was part of what I was hopefully able to articulate in the script conversation there, our written remarks that when you really dig in, you try to evaluate what the agency is looking for with the request and it really it doesn’t end up coming down to getting some additional data that does studying meaningful clinical endpoint, collecting data in just a reliable meaningful way. So, they can believe that it’s real and accurate and of course they always said, it's like as much as possible.

So we really work very hard to commute all those and so through all that 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 positive benefit risk ratio, which is another important perspective to keep in mind. This is X-linked myotubular myopathy 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.

[Steve Seedhouse, Raymond James]

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 and SMA, so genes much showing that you can target with AAV and SMA pretty effectively and preclinical data that shows vectorized exon inclusion in SMA is possible. You’re already collaborating with the NCH as a good is, SMA and appealing indication clinically through you and would there even be freedom to operate with vectorized exon inclusion approach there we’re interested in?

[Matt Patterson, Chairman and Chief Executive Officer]

We’re certainly excited to go into vectorized exon skipping and in addition to standard replacement as we’ve done historically, and we find that there is wealth of opportunities out there that are interesting. But for now, I would say that our focus and the near term remains on the pipeline that we’ve recently announced and executing on Pompe and Duchenne myotonic, there’s tremendous amount of opportunity in front of us the pipeline we established.

That being said, the vision of the Company will be to continue to add interesting programs overtime. And if we think, it’s something with good medical need and strong scientific rationale and a good strategic fit for us, you can bet well 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 are really setting up for a very exciting 2020 in particular with the BLA filing and MTM and potential for proof-of-concept data and Pompe and Duchenne and IND and myotonic, so, plenty of work to do.

[Operator]

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

[Debjit Chattopadhyay, H.C. Wainwright]

Hey. Good afternoon. Thank you for taking my questions. I have got a couple, so just could you walk us through your updated comps from 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 traction of patients alive over the age of 5? Thanks so much.

[Matt Patterson, Chairman and Chief Executive Officer]

Sure. Thanks for the question. No meaningful changes from our previously stated commercial guidance. We think that the recent publication MTM instance and prevalence as well as our own data still guide us to place where we believe that there is an incident population of a several hundred patients in the markets we would expect to pursue and a prevalent population of two or three of times.

And indeed you're right that we're focused on enrolling patients who are less than 5 years of age, but 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 treatment access for all patients with MTM. And so, we're evaluating additional opportunities to collect any data and slightly older patients that would be helpful to payers.

So, while we don't have a set plan today, but something certainly we are interested in. That you bet 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 stories key to us. As you know, we have 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 are demonstrating with a 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]

And then on the AT702 program, I understand it's on the clinical yet, but based on the preclinical data, where do you think this sort of expression should line up for you guys? And given the relatively smaller opportunity the first program, the regulatory path forward, does that mimic the axons skipping approach in terms of a dystrophin expression based filing or the microdystrophin gene therapy approach is better to more functional data? Thanks.

[Matt Patterson, Chairman and Chief Executive Officer]

Well, with 702 program as we e 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 the range of muscle tissue 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% size truncated form of dystrophin which is what one makes with the microsdystrophin programs.

And that of course is the products that why we believe we have the potential to be superior safety and efficacy profile overtime that our approach produces a full length or near full length version of the missing protein. So, we believe the preclinical data track very positively and that we look forward to setting out in biopsies in clinical program as well and sharing that information as soon as we can.

As far as the regulatory approach and the template for future programs, I mentioned earlier we think we can be 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 everyone else reads, but I think it remain 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 and I think program to program depending on medical need even within given exons. So, we’ll see about that. So it's so difficult to know, but right now we’re just intent on finalizing our clinical plan and coming up with this thoughtful approach to generating positive safety and efficacy data and differentiating our program overtime as we do.

[Operator]

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

[Unidentified Analyst]

Hi there guys this is Sammy on for Raj, congrats on all the progress. I had a question something on the commercialization strategy AT132. Are you guys looking to partner with any kind of specialist centers in order to recruit patients?

[Matt Patterson, Chairman and Chief Executive Officer]

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

[Unidentified Analyst]

To support commercialization.

[Matt Patterson, Chairman and Chief Executive Officer]

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

[Unidentified Analyst]

Thanks and then just one more to 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 maintenance of what has been seen previously with a great number of patients?

[Matt Patterson, Chairman and Chief Executive Officer]

I think that’s a fair conclusion. I mean certainly you wouldn’t have gotten RMAT and PRIME designations as we did as 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, but they see the potential, they’re very engaged, responsive.

And -- but in the end, absolutely, as we’ve said in this call and 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’re all agree as clinically meaningful in gathering those data as robust a manner as possible and kind of that is surprise. And so, we put together a good plan to accommodate that all and we are confident that it's going to result like to mid next year as we said. So, hope that out.

[Operator]

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

[Matthew Luchini, BMO Capital Market]

Hey, guys. Great. Thanks for taking the questions. A couple from me if I may, so first on MTM, we have obviously heard a lot about the primary analysis for the pivotal extension cohort. And I was just wondering, if there had been any addition or change to any of the secondary endpoints that maybe worth noting at this point?

And then second question will be on Pompe, given that you are going to be filing the IND this quarter, can you talk to us a little 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 will be helpful.

And then, last question would be just as a point of clarification, Matt, since it sound a little bit like you are hedging. With regards to the DMD patients that are treated with the MCH contract is the plan to share those data not share those data or only share if there is something I guess unexpected on toward that you come out of them? Thank you.

[Matt Patterson, Chairman and Chief Executive Officer]

Sure. Hi, Matthew. Thanks for the questions. Yes, glad you asked about the secondary endpoint question on MTM. So, through our conversations, I would say that the both authorities observed in both the ventilator, time on vent as a key clinical end point and obviously we land on that as our primary endpoint. But they are also really enthusiastic about our achievement of key motor milestones, which is something that we heard and observed is important also in SMA clinical -- gene therapy clinical trial. 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 on assisted for 30 seconds, which is obviously a basic and really important motor milestone for kids these days. So, that is in fact the secondary endpoint, it's something that we had a lot of success achieving in the patient's the earlier studies. So again, it's something we feel very confident we can meet and we believe will be strongly supportive.

We also certainly believe in the biopsy data as strong as supportive everyone is familiar with the fact that we have high evidence of VCM 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 extension cohort study plan.

So, as far as Pompe, yes, very active on trial preparation, again, the multiple members of team here worked on Pompe in in different forms and we know the community. So, we've been engaged with KOLs for quite some time actually. They have been in the background guiding some of our work in the program. And so, we feel good about that and look forward to sharing more details about our, not just a protocol, but also operational details, but I believe we will be able to get up and running efficiently.

And then finally on Duchenne, yes, I certainly didn't mean to sound hedging. I was just trying to be realistic that I think data from one patient with a one or two patients with products that's going to be outdated quickly just want to ensure, how much we'll be able to reply 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'll share it.

But I just want to be straight forward about I think how to think about the program, more realistically and it’s likely that the data from our products and 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.

[Operator]

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

[Difei Yang, Mizuho Securities]

Good afternoon and thanks for my 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 point of treatment? And then secondarily with regards to offset of actions with the higher dose, do you expect an acceleration onset of seeing this reduction of ventilator use?

[Matt Patterson, Chairman and Chief Executive Officer]

Sure, hi, thanks for the questions. You know when one reviews the data from the study to-date, we see evidence of improvement in respiratory function very rapidly, first and foremost in a matter of weeks through first patient stability to control their airway on their own to then improvements in the maximum inspiratory pressure test that we’ve been doing for some time and then that turn leave investigators to get comfortable reducing time on event.

So there’s plenty of evidence from a number of patients that you see improvements and reductions in time of ventilator over the course of the first of all the 24 weeks of the study. And so, that’s why when you look at the data, we’re very comfortable that 24 weeks we're likely to ht this endpoints and it's really distinguish us statistically significant difference from the controls who are as we said earlier, extremely unlikely to change it all from baseline and the requirement that all patients have a baseline, which is to be mechanically supporting ventilated for a 20-24 hours a day.

So as reason to be very optimistic a 24 weeks we’ll have that in plan. As far as the higher dose and the faster onset, what we've observed and it was part of the decision making process for choosing 314. We did not see a meaningful difference in the safety profile with two doses nor the efficacy profile when 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 a big higher level 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 seemed to happen a bit faster.

And so, that’s the only area where I thought we were able to distinguish the difference between the two doses and can certainly contributed to our decision to go at 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 if that’s practical with that endpoint, but anyway we feel really good about the high gross for all the reasons that I think we talked about before. And of course, it also has a little bit of an eye towards long term durability of effect and that’s a goal we all had as well. So, I hope that helps.

[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.

[Matt Patterson, Chairman and Chief Executive Officer]

Okay, thank you again everyone for your participation and for the opportunity to sharing our updates. Looking forward to a busy remainder of 2019 and updating you on our progress again soon, operator that concludes our call today.

[Operator]

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone have a great day.