Audentes Therapeutics, Inc. (BOLD) Q4 2018 Earnings Conference Call Transcript

BOLD earnings call for the period ending December 31, 2018.

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Audentes Therapeutics, Inc.  (NASDAQ:BOLD)
Q4 2018 Earnings Conference Call
Feb. 27, 2019, 4:30 p.m. ET

Contents:

Prepared Remarks:

Operator

Good afternoon, ladies and gentlemen. And welcome to the Audentes Therapeutics Fourth Quarter and Full Year 2018 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. (Operator Instructions) As a reminder, this conference call is being recorded.

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

Andrew H. Chang -- Director 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 fourth quarter and full year 2018. 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, Chief Financial Officer.

Before we begin with prepared comments from our team, 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, February 27, 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 -- Chairman and Chief Executive Officer

Thank you, Andrew, and good afternoon, everyone. I'm pleased today to recap the significant accomplishments of our team over the course of an outstanding 2018, as well as to share with you the important milestones we are looking forward to this coming year. For Audentes, the last 12 months have been transformational. It was in January of 2018 that we first shared the earliest data from ASPIRO, the Phase 1/2 clinical study of AT132 our lead product candidate being developed to treat XLMTM.

Since that time, results from ASPIRO continued to exceed expectations. The latest data set, which was presented at the Annual Congress of the World Muscle Society in October 2018 demonstrated that all six treated patients in Cohort 1 and the sentinel patient in Cohort 2, showed meaningful improvements in neuromuscular and respiratory function, with follow-up ranging from 4 to 48 weeks. We are particularly pleased that three of our Cohort 1 patients have achieved ventilator independence and unprecedented result for children with congenital myopathy, who have been ventilated since birth. Additionally, week 24 muscle biopsy data for the first four treated patients showed robust tissue transduction, protein expression and histological improvement. And importantly, AT132 continues to be generally well-tolerated at doses up to 3x1014 vector genomes per kilogram.

In the fall, we completed dosing of Cohort 2 for the original protocol, which included three patients and one delayed treatment control. And as we recently announced, we plan to dose an additional three to five patients, as part of the Cohort 2 expansion, which is ongoing. Our next clinical data update for AT132 is scheduled to occur at the 2019 Annual Meeting of the American Society of Gene and Cell Therapy, starting in late April in Washington, D.C. 2018 also brought significant progress with regulatory agencies for AT132, including the receipt of RMAT designation from the FDA, PRIME designation from the EMA, each of which are awarded to products intended to treat serious or life-threatening diseases, where preliminary clinical evidence indicates a potential to address significant unmet medical need.

In the fourth quarter of 2018, we completed a productive meeting with the FDA. And recently we completed a meeting with the Scientific Advice Working Party of the EMA, interactions with both agencies were productive and provided a potential path toward BLA and MAA submissions, respectively. As a reminder, we plan to select the optimal dose in the second quarter of 2019, after the evaluation of the six-month biopsy results from the first three patients dosed in Cohort 2. After determining the optimal dose, we plan to provide an updated data package to regulators to facilitate final agreement on license application pathways in the third quarter.

Turning to manufacturing. As a reminder, we began our ASPIRO program with our planned commercial manufacturing process for all AT132 clinical material, a first within the neuromuscular gene therapy field. This combined with the significant investments we've made in process and analytical development, fill-finish and QC testing, means that we are uniquely well-situated to be BLA ready on timelines consistent with our clinical progress. Our facility has been designed and commission to support global licensure and thinking ahead toward global launch, we are reproducibly generating excellent yields, providing us with confidence in our capacity and utilization projections, as well as our eventual commercial cost of goods. Our AAV manufacturing leadership position continues to be the foundation of our strategy for long-term value creation.

As we look -- look ahead toward commercialization of AT132, we recently expanded our leadership team with the addition of Eric Mosbrooker, our Senior Vice President and Chief Commercial Officer. Eric has a demonstrated track record of building global commercial organizations and successfully launching rare disease products. He most recently joined us from Origin Biosciences after serving in commercial leadership roles at Jazz, Onyx, Enobia, Alexion, Raptor and Horizon. We look forward to introducing Eric to the broader investor community as his work progresses.

Before we leave AT132, I'd like to take a moment to thank our internal team, medical and scientific collaborators, and most importantly, the patients and families that have supported and participated in INCEPTUS and ASPIRO for the years of effort that have gone into advancing the program to this point. We are privileged to be working with and alongside with the XLMTM community and remain single mindedly focused on advancing this important therapy to market as rapidly as possible. We look forward to collaborating with regulators in the coming months to reach final agreement on the license application pathways and to updating all of our important stakeholders as the program advances.

Turning now to our Pompe disease program, we remain highly encouraged by the progress of our ongoing preclinical studies and continue to guide to an IND submission for our optimized construct AT845 in the third quarter of this year. Importantly, we continue to believe that our differentiated approach of utilizing AAV to transect and express GAA directly in tissue affected by the disease, including skeletal muscle, heart and the CNS is best-in-class, which can be contrasted with enzyme replacement therapies and liver directed gene therapy candidates that rely on uptake of GAA from plasma. We look forward to sharing the continued progress in our Pompe disease program over the coming months.

Moving on to AT342 for Crigler-Najjar Syndrome. During 2018, we established initial proof-of-concept in the sentinel patient of VALENS and made the decision to dose escalate for the treatment of subsequent patients. In late 2018, as shared in previous updates, we experienced unexpected screen failures in several patients. And to-date we have not yet dosed a new patient. While we are disappointed in these delays, we continue to believe that Crigler-Najjar Syndrome remains a highly promising target for AAV gene therapy and expect to provide the next program update in the second quarter.

Finally, a key priority for Audentes is to leverage our development expertise in neuromuscular diseases and our industry-leading AAV science and manufacturing capabilities to expand our pipeline into additional neuromuscular indications that provide the potential for our work to make a broader impact for patients. To that end, we are encouraged by progress with our new program candidate, AT720 and are on track to provide a program overview in the second quarter of 2019.

Additionally, our plans extend beyond AT720 to enable our vision of becoming a global leader in AAV based genetic medicines for neuromuscular diseases, we continue to work internally on new and differentiated approaches to challenging disease targets and externally with collaborators for accelerating our understanding of the field of genetic medicines. We're tremendously excited by the breadth and depth of our pipeline expansion efforts and look forward to sharing further news as our work progresses.

In closing, our ability to meet these important upcoming milestones is supported by a strong balance sheet. Our year end 2018 cash position of $418 million is expected to fund operations into 2021. And with over two years of cash runway, we are well-positioned to make meaningful progress toward our goal of providing transformative therapies to patients living with devastating neuromuscular diseases. We are excited by the multiple 2019 milestones ahead and look forward to sharing these updates with you over the course of the year.

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

Questions and Answers:

Operator

Thank you. (Operator Instructions) Our first question will come from Ritu Baral with Cowen. Your line is open.

Subbu Nambi -- Cowen & Company -- Analyst

Hi. This is Subbu Nambi on for Ritu Baral. Thanks for taking my question. I had one basic question, what is the quantification method you use to measure vector copies? And I have a follow-up.

Matthew R. Patterson -- Chairman and Chief Executive Officer

The quantification method for vector copy number, to make sure that's an accurate response, I wanted to make sure we -- I get the right people on the line and they don't -- they aren't on the line today, so I apologize for that, but I don't want to misspeak. So we will be happy to follow-up with you just after the call with the answer.

Subbu Nambi -- Cowen & Company -- Analyst

Okay. Sounds good. And with the hiring of Eric, can you provide any high level color on commercial effort you are undertaking for XLMTM? Any market research you have done so far?

Matthew R. Patterson -- Chairman and Chief Executive Officer

Well, there's a range of activities that have actually been ongoing for some time. Prior to Eric joining, which have the -- have been focused on characterization of the burden of MTM as a disease on patients and families, and the healthcare system, largely with the vision of developing a very thorough analysis for future conversations with payers. And then, not surprisingly, we've also put in a significant amount of effort to begin patient identification efforts. And with Eric joining, those efforts will ramp-up significantly, and of course, Eric will be hiring a team of leaders to help advance that work, specifically. So I'm looking forward to investing further in that area of the business as the regulatory discussions progress.

Subbu Nambi -- Cowen & Company -- Analyst

Got it. Thank you.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Thank you.

Operator

Our next question comes from Anupam Rama with JPMorgan. Your line is open.

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

Hey, guys. Thanks for taking the question and congrats on all the progress. Maybe just quick two quick questions here. Maybe what are sort of the final gating factors on the preclinical side for the Pompe program to get to that IND filing? And then second question, maybe can you talk about what would be like your ideal scope of the update for Crigler-Najjar Syndrome in 2Q with some of the enrollment dynamics that you kind of outlined? Thanks so much.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Sure. Thanks, Anupam. So on the Pompe preclinical, we are in the process of finishing robust set of activities in the mouse model and that analysis is particularly valuable given the more informed perspective we have on the disease and this approach to treating Pompe based on our experience in 2018, which is of course, why we're filled with confidence about next steps. Specific next steps will include going ahead and manufacturing the AT845 at the large scale and performing our non-human primate toxicology study as the final piece of the puzzle for the IND filing and we expect that's a 12-week study and allowing time for full analysis and paperwork and filing preparation that it gets us into the Q3 timeline comfortably.

For the second question, difficult to answer that with too much specificity. As we made it clear in my opening remarks, of course, we're disappointed by some of the delays we've seen in enrollment in the study, but study operations are ongoing and we're looking forward to seeing how things progress and so we'll just -- we'll give us fulsome and update us makes sense at the time. I don't really know how to predict it much more than that at this time.

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

Thanks for taking my questions.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Sure.

Operator

The next question comes from Ying Huang with Bank of America Merrill Lynch. Your line is open.

Aspen Mori -- Bank of America Merrill Lynch -- Analyst

Hi. It's Aspen on for Ying. Thanks for taking my questions. First on XLMTM, can you guys talk maybe broadly on what some of the biopsy metrics look like in the Cohort 2 beyond that first patient. I guess, are you seeing a higher rates of improvement in neuromuscular or higher -- better improvement rather in neuromuscular and respiratory function? And then on Crigler-Najjar, could you just remind us again what's driving some of these failures. Yeah, thank you?

Matthew R. Patterson -- Chairman and Chief Executive Officer

So in MTM your question starts to get to what will be included in our next data update. So let me just remind people, as we said in the release and opening remarks, back in October, we shared data that included out to 48 weeks in Cohort 1 and just four weeks in the first patient enrolled in Cohort 2 with the higher dose. And the next data update will be at ASGCT and that data update will be very robust. It will include longer-term data in all patients and that will include out to full-year data in all patients in Cohort 1, as well as much data as we can get in Cohort 2 patients, which we hope will be full 24-week data, but it's very tight on the biopsy timeline in particular. So we'll see how that progresses, we're hopeful. We can get those data is included in the update. But I won't be able to answer your question about how things are going in the first patient Cohort 2 at longer time points or the additional recent treated patients until that time.

And on the Crigler-Najjar, the -- as I mentioned, the challenge that we observed in Q4 with the screen failures was a surprise. That was a surprise to us and even to Crigler experts given that there wasn't a belief that there was much liver damage in patients over the years. But when we tried to enroll several patients who were a bit on the older side in their teenage years in a screening process we found evidence of some baseline liver damage. Now, to be clear, we think those patients would probably benefit greatly from this treatment. But we also feel strongly that they're not appropriate to be the first patients treated in a Phase 1/2 clinical trials. So our entry criteria are strict for that -- for a reason and so we stick with that. So that's why those patients weren't eligible and those were disappointing delays. But as I said operations are ongoing and we still remained very upbeat about the potential for AAV gene therapy for Crigler.

Aspen Mori -- Bank of America Merrill Lynch -- Analyst

Thanks.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Sure.

Operator

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

Chris Raymond -- Piper Jaffray -- Analyst

Thanks. Just to clarify that to keep hitting on the Crigler program, but I think last month, your guidance was for a Q1 update. Just to be clear and just to clarify, is that delayed to Q2, is that all around patient identification or is there some other aspect to the program, that's sort of driving that? And then also on Pompe, you mentioned a pretty decent body of preclinical data that you guys are generating. Is there a publication plan or some idea that maybe you would get that in front of us, either as you work toward filing or after you file? Thanks.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Sure. Hi, Chris. Thanks for the questions. Look, there's a lot of details that go into advancing the clinical protocols and Crigler is no difference in that. We didn't expect much would happen in way of enrollment over the holidays. And there's quite a few steps involved with that process whether it's identification of patients, which we feel good about the scheduling and screening and all the things that go into that.

So, we weren't sure how things have progressed in the first few weeks of the year and we're not there as we maybe hope just yet with another patient treated, but that's OK, the program is moving along and we will promise to continue to keep everyone updated. Certainly, as we said, we're frustrated by those delays. We appreciate frustration from others. But like I said, we still believe in this approach in Crigler. So we'll do our best to execute and keep everyone posted.

As far as Pompe, as we've talked about earlier in the year, we are sensitive to the very interesting competitive dynamic that's developed in Pompe gene therapy. And to that end, we feel, it's best that we don't over-share on what we've learned, because we do feel that it's really important and strategic and gives us an advantage in that program going forward. So -- but we certainly appreciate also the value and importance of providing some information to investors and the science community when possible. So, I don't have perfect answer for you on when we will share additional details. I do think that we will share information when we do -- then we'll share information that's most relevant to our program or our product AT845 that's advancing into the clinic, rather than looking backwards too much, but I feel like the backward stuff might be what really educate others.

And so I would hope that we'll get to that point sooner rather than later, that we can share that information and it may very well be that the fall is the right time for that as the idea get us in and we're in relevant scientific conferences.

Chris Raymond -- Piper Jaffray -- Analyst

Great. Thank you.

Operator

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

Dae Gon Ha -- Leerink Partners -- Analyst

Hi. Good afternoon. Thanks for taking my questions. This is Dae Gon dialing in for Joe. So, Matt, just a couple of questions on MTM program. So, you mentioned that dose selections are coming up in 2Q, after you see the biopsy data. So I just wanted to know, can you frame for us your internal expectations on that particular biopsy data that may or may not be presented at the ASGCT conference. So if we go back to I think 2Q, you previously stated normalization as sort of the intention behind the higher dose. Is that still the bar or is anything greater than 1E14 but enough given that functional data were already strong on the respiratory and CHOP-INTEND?

And the second part to MTM question is, since reviewing the meeting minutes, I'm guessing that's where you got the update since the early Jan update you provided to the community. Just wondering have the regulators set any expectations either CHOP-INTEND or pulmonary function improvements they would like to see for our gene therapy?

Matthew R. Patterson -- Chairman and Chief Executive Officer

Okay. Thanks for the questions. So -- yes, so on MTM biopsy expectations, I mean, as you recall, and you just said it, in the 1E14 dose group, we were thrilled to see, not just the results across the various endpoint -- clinical endpoints, but also the biopsy data that showed a significant improvement in the histology along with of course robust protein expression and vector copy number, in fact approaching normal in all patients, but not quite normal. And I do want to be clear that, it was never our intention to try to get all the way to normal, I mean, that is a remarkable bar to hold yourself to and that was never our intent, but when we got those data and we appreciated the importance of doing what we felt was best for patients, which is to see, if we could get closer to normal if possible.

But also, as I said before, recognizing the value of evaluating more than one dose in the clinical protocol and how we believe strongly that that will and already is resonating with regulatory authorities as a part of our strong program. We chose to go up and dose. And so we'll see, we don't have the data in hand to answer that question today. As I mentioned, we're hopeful that we'll get to that data in time for ASGCT. But even if we don't have it for the conference we will have it shortly right around that time and we'll wrap, we will do the analysis and see, did the higher dose actually have any impact on the histology or not. And what is the totality of the data tell us about what's the better of the two doses to propose for our BLA. So we'll see. We're looking forward to those data as much as everyone else.

As far as the regulatory conversations, these first interactions with both the year -- the FDA and the European's, as I mentioned, were highly productive in different ways. I suppose the two most interesting areas of discussion, included discussion around endpoints and emphasis on certain endpoints. And then, secondly, of course, the ever interesting topic of how many patients should be treated at the optimal dose and for how long should one monitor them before filing a BLA.

And with regard to the first category and the endpoints, it's clear to us that the authorities appreciate all the different endpoints that we've evaluated. But when it comes to neuromuscular function they seem a little more interested in motor milestone achievement than CHOP-INTEND and so their suggestion was to emphasize that aspect of efficacy a bit more in our statistical analysis plan.

And on the respiratory side, not as surprise to us, they were really pleased to see the reduction in mechanical ventilatory requirements for the kids and they suggested that we emphasize that change in their care over maximum inspiratory pressure or MIP. So, that wasn't surprising feedback to us, especially knowing some of the history of other programs in our space and we are totally comfortable with that feedback, because thankfully, we have robust results across all those endpoints and so it's really a matter of emphasis and positioning an analysis for the eventual BLA.

Just with regards to the other -- with regards to the other point that I made, of course, everyone is interested as we are to hear a final agreement on patient numbers and how much time you need. And while we were encouraged by the discussion around that part of the story, that's the part that's not final, and we expect will be final once we have the updated data set and come back to the authorities to share that and reach that final agreement. So now that's the piece of the puzzle, along with the choice of dose that I think will be most interesting to all of us and that will come in the Q3 timeframe.

Dae Gon Ha -- Leerink Partners -- Analyst

Great. Matt, if I can just squeeze in one more question, given the advancement of your gene therapy programs. Can you maybe remind us what are your plans for scaling up your current capacity given that MTM is edging closer to potentially regulatory filing. But also you now have 845 IND filing in 3Q, which is pretty sizable population and then 720 update in 2Q. That could also be pretty sizable. So any thoughts you can provide there/? Thank you.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Sure. We feel extremely well-positioned on the manufacturing side. Our current capacity of a 1000 liter scale is enough to meet the global commercial demand for MTM, no matter what the dose. And in addition, in parallel with launching that drug globally, the same capacity is enough to support the ongoing clinical development of our lead programs. Now, if those larger indications of course progress, then we will eventually want to add capacity and thankfully we have the space and ability to do that in our existing facility. We just need to decide when the time is right to invest in that expansion.

So we're very well-positioned based on all the work we've done in process, development, in particular over time and reaching the productivity and yields that we have today. So manufacturing is in excellent shape for both in terms of MTM supply, but also the regulatory process, as I mentioned, and continuing to supply the timelines we have in mind for Pompe and AT720, and other things in mind that we hope for in the future.

Dae Gon Ha -- Leerink Partners -- Analyst

Great. Thanks, Matt, and congrats on all the progress.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Thank you.

Operator

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

Evan Wang -- Guggenheim Securities -- Analyst

Hi. This is Evan Wang on for Whitney Ijem. First question I have is, can you compare and contrast your current capabilities in terms of manufacturing process and scale of Spark especially given you guys are both using mammalian?

Matthew R. Patterson -- Chairman and Chief Executive Officer

A little bit difficult to do that, because you don't know the intimate details of each other's work only what other companies have shared publicly, but what I can say is that I believe unless my recollection is incorrect that Spark uses a very similar system to ours, as far as using 29 -- mammalian cell system 293 cells with transient transfection. I don't know for sure whether they were still using an adherent HYPERStack, which would be perfectly reasonable for ophthalmology or if they'd converted to what we are, which is a serum free suspension culture system, which of course is very robust and more scalable, and all the more appropriate, if you need large quantities materialize, as one would and larger hemophilia indications are certainly neuromuscular disease. So I think the answer is to our knowledge there is significant similarities in the basics of the approaches certainly differences in scale though given that we're at a 1000 meter scale,

Evan Wang -- Guggenheim Securities -- Analyst

Thanks. And...

Matthew R. Patterson -- Chairman and Chief Executive Officer

Fully serum free suspension.

Evan Wang -- Guggenheim Securities -- Analyst

Thanks. And then I had one follow-up. I guess, can you provide a more detail on your interactions with EMA and is that regulatory package is expected to be similar to the FDA?

Matthew R. Patterson -- Chairman and Chief Executive Officer

Yeah. Good question. We, as I mentioned in the script, we recently had our meeting with the scientific working groups, scientific advise working group and we were pleased with that discussion in that process and the initial feedback we received. We were interested to learn that their feedback was in many ways consistent with that of FDA. So that's particularly comforting because we believe it's likely that we can move forward with the regulatory process for both regions, with the same basic set of information. I mean we'll see how it progresses to final form, but we're optimistic today at the same fundamental data package could be satisfactory for both regions, when the time is right, and that's a very good thing, especially in rare disease drug development to be able to accomplish that rather than have to have different trials and somewhat different programs for each region. So we don't have the final minutes in hand from that meeting, but we've feel reasonable enough saying what I'm saying based on the verbal discussion that we completed a couple weeks ago.

Evan Wang -- Guggenheim Securities -- Analyst

Great. Thank you.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Thank you.

Operator

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

Raju Prasad -- William Blair -- Analyst

Thanks for taking the question. Just a quick follow-up on 132. Can you give a sense on (ph) discussions with FDA and EMA, if either agency has any opinions on the number of patients that need to be treated in that country or those -- or that jurisdiction?

Matthew R. Patterson -- Chairman and Chief Executive Officer

That has not come up in our conversations, we have a multi-center trial in the US and Europe in MTM, so to some degree we appreciate that there's value in having patients treated locally in the region and how that may be helpful in the regulatory process, but I think there's still flexibility in those regions as to where you do your clinical trials and those data supporting approval, it's my impression anyway. But in our case, we have multiple centers in the US, Europe and Canada, so we hope that that is helpful. If it matters to them, but it hasn't come up in specific discussion in those meetings.

Raju Prasad -- William Blair -- Analyst

Great. Thanks. And can you give us a range of the approximate number of patients that the 1000 liter scale would be able to support, Is in the 10s, or is it 100s?

Matthew R. Patterson -- Chairman and Chief Executive Officer

I'm sorry, I cannot give you that answer without talking in greater level of detail than we care to about our proprietary manufacturing operations. But I'm still hopeful that you hear and others here, our confidence in the fact that we can produce -- easily produce enough material with our current capacity to serve the global market at a acceptable -- very acceptable commercial cost of goods and continued clinical development of other programs.

Raju Prasad -- William Blair -- Analyst

Okay. Fair enough. And then just one quick one on 845, with the third quarter IND guidance, will that include a monkey study or will those just be ongoing by the time the IND is filed and it will be mainly kind of preclinical mouse models?

Matthew R. Patterson -- Chairman and Chief Executive Officer

I assume we're talking about AT845 for Pompe for the IND in Q3.

Raju Prasad -- William Blair -- Analyst

Yeah. Yeah.

Matthew R. Patterson -- Chairman and Chief Executive Officer

No. I certainly expect we will complete a non-human primate toxicology study prior to the filing of the IND. So completing mouse work as we speak moving rapidly into the 12-week primate study plus histopathology and other analysis and the paper work for the IND that's what gets into Q3.

Raju Prasad -- William Blair -- Analyst

Great. Any expectation on when you might be presenting data -- updated data from that product?

Matthew R. Patterson -- Chairman and Chief Executive Officer

As I mentioned on Chris' question, we don't have a set vision for that just yet. As I have said before, we are sensitive to balancing the goal of sharing information about the program that's helpful to everyone in the community, but also not sharing too much that helps provide that gives help to our competitors, of which there now are quite a few in Pompe. So but I'm optimistic that we'll be able to do that reasonably soon and I'm hopeful that later this year even will be an opportunity to share some of our data from the preclinical work with AT845 in particular and then from their, of course, as the clinical work progresses.

Raju Prasad -- William Blair -- Analyst

Great. Thanks, Matt.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Yeah. Thanks, Raju.

Operator

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

Matthew Luchini -- BMO Capital Markets -- Analyst

Hi. When do we expect to start seeing some preclinical Pompe data. Can we get some update on that?

Matthew R. Patterson -- Chairman and Chief Executive Officer

Yeah. As I just mentioned, I think our plan is still coming together on when we will share information from the ongoing preclinical work, but I'm hopeful that we'll be in a position to do that this fall, in general, consistent therefore with the submission of the IND in Q3. But like I said, we're trying to strike a good balance between sharing information with the community, but also not empowering our competitors. So we'll be certain to provide additional thoughts on that as the year progresses, and of course, keep everyone updated on the milestone achievements. But as the year progresses, we should have better clarity on that, when we will have a scientific presentation of interest and no doubt that we'll be in the context of an appropriate conference or meeting.

Matthew Luchini -- BMO Capital Markets -- Analyst

And one more follow-up on Crigler, of the estimated 12 participants you hope to enroll. How many have you dosed so far, if you can say anything on that?

Matthew R. Patterson -- Chairman and Chief Executive Officer

Yeah. As we shared in the update, we dosed one patient last year, which established initial proof-of-concept for the approach, but we chose based on those -- that patients results to go immediately up in dose. Late in the year, we had several screen failures, which we've talked about in the past. And in today's update, we're sharing that well study operations are ongoing that we have not yet dosed additional patient.

Matthew Luchini -- BMO Capital Markets -- Analyst

Okay. Thank you.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Sure.

Operator

Our next question comes from Mohit Bansal with Citi. Your line is open.

Mohit Bansal -- Citi -- Analyst

Great. Thanks for taking my question and congratulations on all the progress. Also I wanted to extend a warm welcome to Eric. In this period I mean a commercial question I'll ask. is there a Medicaid component in this XLMTM market similar to SMA we should know about. And also the follow-up would be, how do you think about the Spark has come up with this idea about -- this annuity-based model where 50% of current and then 25% each at different time point, would love to get your thoughts on that in the gene therapy paradigm? Thank you.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Sure. So already forgetting the beginning of the question.

Tom Soloway -- Senior Vice President and Chief Financial Officer

Medicaid.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Medicaid.

Mohit Bansal -- Citi -- Analyst

I can repeat it, if you want.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Yeah. No. It's totally fine. I heard it, sorry. Medicaid is an important part of this community. These children are severely disabled and so Medicaid does play an important part of their healthcare support. And so that is relevant for our commercialization plans, as it truly is with the SMA population as well. So we have a very -- so we'll be very focused on ensuring that part of our commercial planning goes well. I am sorry, I can't remember (ph) the second part of the question.

Mohit Bansal -- Citi -- Analyst

The pricing mechanism -- different pricing mechanism, yeah.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Yeah. This is an evolving subject. I can tell you that we've worked very hard for a number of years already to build the background data story to ensure that when the time comes, we have a robust discussion with payers. As far as, Spark or others in the community, what I appreciate about the efforts being made by those companies is the effort to be creative with new approaches and to enter into dialog with various parties, to try to come up with a new and improved ways of ensuring market access to these products. We simply don't live today in a world that's designed for single-time -- one time curative therapies. And so there's many steps to take to try to improve the system we use for pricing and reimbursement, in particular in the United States.

The good news is, a lot of those conversations are happening both in Washington and in private settings. And so I admire those companies for taking creative steps and we're certainly paying close attention and thinking a lot about these issues as well. I personally, I'm a strong advocate for coming up with a payment over-time option for one-time therapies. Because I do believe that will increase market access for patients in particular so and we'll see how things progress for our work in particular.

Mohit Bansal -- Citi -- Analyst

Great. And then, do we know exactly what percentage is Medicaid at this point for XLMTM?

Matthew R. Patterson -- Chairman and Chief Executive Officer

I don't have the answer to that off to top of my head today. But we'd be happy to follow-up with you at a later point and talk more about it Mohit.

Mohit Bansal -- Citi -- Analyst

Great. Thank you very much.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Thank you.

Operator

Our next question comes from Debjit Chattopadhyay with H.C. Wainwright. Your line is open.

Earl DeSouza -- H.C. Wainwright -- Analyst

Hey, guys. This is Earl DeSouza in for Debjit. So we just had two questions on our end. The first is on the Crigler-Najjar program. I know you touched on this a bit and is there a particular maybe number or rough number or estimate of the patients that experience the screening failure? And our second question is on Pompe. Can you address both CNS and musculoskeletal manifestations of the disease via liver directly gene therapy. And what percent of the administered construct needs to get across the blood-brain barrier to deliver a meaningful effect? Thank you.

Matthew R. Patterson -- Chairman and Chief Executive Officer

As I mentioned in our previous Crigler updates, we saw three screen failures -- several screen failures later in the year, so no more to report beyond those. And with regard to your question, I just want to make sure we're clear with regard to our approach to Pompe. And that is, that we -- through systemic administration of our AAV product intend to transect and express the protein directly in muscle and CNS, and we've shown the ability to do that with MTM and in our preclinical work. This can be contrasted with deliver-directed approaches, which attempt to use the liver as a pump, if you will, and then hope that GAA gets taken up from the plasma into those tissues that are actually affected by the disease. So our approach, we believe will be superior in terms of safety and efficacy in the long run. And so we look forward to advancing that program and that approach specifically.

As far as, I think your question was, what percentage might get into those tissues? I think we're feeling very optimistic about our ability to transduce those tissues based on our preclinical and clinical work in MTM. And particular the biopsy data that we've shared publicly and in our preclinical work in Pompe, where we've done a robust amount of evaluation in both mouse and non-human primates.

Earl DeSouza -- H.C. Wainwright -- Analyst

Appreciate that. Thanks.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Thank you.

Operator

Thank you. Our last question comes from Difei Yang with Mizuho Securities. Your line is open.

Difei Yang -- Mizuho Securities -- Analyst

Hi. Good afternoon and thanks for taking my question. Just two quick ones. The first question is with regards to the manufacturing facility. So you have been talking about a new neuromuscular indication. So to -- for that particular program, I'm just wondering from manufacturing perspective, how much changes would you need to do to the process? Is it a certain of change or is it a process development from scratch? I guess really what I'm trying to get to is that how much of the expertise that you already have in-house can be leverageable when you move from program to program?

Matthew R. Patterson -- Chairman and Chief Executive Officer

Yes. I'm happy to say that the knowledge we have from the MTM program and manufacturing at large scale is completely applicable and will be relevant for these other programs. That's one of the beauties of what we've established is that we believe our process can be applied across multiple programs and we have shown that internally with our work all the way up to the 1,000 liter scale. So it's basically the same system. It will just be a slightly different product. And so no fundamental changes will be necessary in the approach that we use for these programs. So our approach in MTM will be replicated to a significant degree for Pompe and for AT720 and future programs.

We also believe that this process can be -- and capacity can be increased either by increasing the number of bioreactors with our existing system and scale or scaling higher, which is certainly a option for us as well. But even that would not involve any significant changes in our technical approach. So this is a huge strategic advantage for the company and it's a fundamental reason why it's more straightforward for us to establish new programs and move them forward rapidly. That is one of the great strategic advantages of owning manufacturing at a scale in-house, is that we can do something like add AT720 and do it rapidly and continue to build from there. So I hope that helps.

Difei Yang -- Mizuho Securities -- Analyst

Yeah. Thank you Matt for sharing your thoughts. Then a quick follow-up on the ASGCT presentation. Can we expect, I know you talked about biopsy data for Cohort 2, can we at lease expect to see some level of biopsy data there or maybe we'll see none?

Matthew R. Patterson -- Chairman and Chief Executive Officer

Oh! No. You'll certainly have some biopsy data. Recall that the patients get biopsy at 48 weeks in addition to 24 weeks in our study. So when it comes to the Cohort 1 data, which will extend out to 48 weeks, we expect that will have the option of sharing biopsy data from those patients, which will be interesting and informative. As far as the Cohort 2 higher dose patients, as I said, we're doing everything we can to get as much biopsy data as possible. I am optimistic that we'll have data from at least the first patient treated in that Cohort, given that he was treated a bit earlier, and we'll hit the 24 week time frame for that patient. For the others it's very tight and we'll do our very best.

Difei Yang -- Mizuho Securities -- Analyst

Thank you for taking my question.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Thank you.

Operator

Thank you. And this concludes today's question-and-answer session. I would now like to turn the call back over to Matt Patterson for any closing remarks.

Matthew R. Patterson -- Chairman and Chief Executive Officer

Great. Thank you again for your participation this afternoon everyone. We've appreciated the opportunity to share our updates with you and look forward to providing more information throughout what promises to be an exciting 2019. Thanks very much for your time. Talk to you soon. Operator, that concludes our call.

Operator

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program and you may all disconnect. Everyone have a wonderful day.

Duration: 46 minutes

Call participants:

Andrew H. Chang -- Director of Investor Relations

Matthew R. Patterson -- Chairman and Chief Executive Officer

Subbu Nambi -- Cowen & Company -- Analyst

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

Aspen Mori -- Bank of America Merrill Lynch -- Analyst

Chris Raymond -- Piper Jaffray -- Analyst

Dae Gon Ha -- Leerink Partners -- Analyst

Evan Wang -- Guggenheim Securities -- Analyst

Raju Prasad -- William Blair -- Analyst

Matthew Luchini -- BMO Capital Markets -- Analyst

Mohit Bansal -- Citi -- Analyst

Tom Soloway -- Senior Vice President and Chief Financial Officer

Earl DeSouza -- H.C. Wainwright -- Analyst

Difei Yang -- Mizuho Securities -- Analyst

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