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Audentes Therapeutics, Inc. (NASDAQ:BOLD)
Q1 2019 Earnings Call
May. 7, 2019, 4:30 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good afternoon, ladies and gentlemen, and welcome to the Audentes Therapeutics First Quarter 2019 Earnings Conference Call. (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 H. Chang -- Director of Investor Relation

Thank you, operator. And good afternoon, everyone. Just after market closed today, we issued a press release with earnings and operating results for the first 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 from our team, I'd like to remind callers that the information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. I caution listeners that the company's management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by 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, May 7, 2019. Audentes undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of today's call, except as required by law.

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

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

Thank you, Andrew. And good afternoon, everyone. 2019 has already been a year of meaningful accomplishment for Audentes, and I'm very pleased today to highlight the progress we have made across our pipeline and to share with you the important milestones we anticipate for the remainder of the year. Starting with AT132, our lead product candidate for the treatment of XLMTM. Just last week, we shared a positive clinical data update at the 22nd Annual Meeting of the American Society of Gene & Cell Therapy in Washington, D.C.

The latest safety and efficacy data from ASPIRO concluded 48 weeks of follow-up for all patients in dose Cohort 1 at the 1x10^14 vector genomes per kilogram dose and 24 weeks for all treated patients in dose Cohort 2 treated at the 3x10^14 vector genomes per kilo. The data show progressive and sustained improvements in neuromuscular function in both dose cohorts, with continued corresponding achievement of clinically meaningful motor milestones.

Respiratory outcomes are significantly improved in all patients, and most notably, 4 patients are completely weaned off of mechanical ventilatory support, with all other treated patients demonstrating clinically meaningful reductions in ventilator use. Muscle biopsy data show evidence of robust dose-dependent transduction, transcription and protein expression across both dose cohorts. All biopsies also show marked improvement in histopathological markers of disease with a trend toward continued improvement in the Cohort 1 patient samples from 24- to 48-week time points and evidence of more rapid pathological improvement by week 24 in the Cohort 2 biopsy samples.

And importantly, AT132 continues to be generally well tolerated across both dose cohorts, with no clinically meaningful safety differences between doses to date. All reported serious adverse events were successfully managed, and patients have shown no evidence of clinical compromise. As we announced earlier this year, our plan is to dose an additional 3 to 5 patients as part of a Cohort 2 expansion. Enrollment is ongoing, and we plan our next clinical update to occur at the World Muscle Society annual meeting in early October in Copenhagen, Denmark.

As it relates to the next steps for the development of AT132, we plan to provide an updated data package to the FDA, including a recommendation on optimal dose in the coming weeks, and we are on track to provide an update on license application submission plans for AT132 in the third quarter of 2019. Turning to the important subject of manufacturing. As many of you know, we invested over 4 years ago in our own internal, large-scale cGMP manufacturing operation. Importantly, since the beginning of the AT132 clinical program, we have used the same process and scale of manufacturing that we now propose for commercialization, 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 for our CMC package to be BLA-ready on time lines consistent with our clinical progress. We were also pleased to announce just a few weeks ago the launch of a new state-of-the-art internal cGMP plasmid manufacturing facility to improve control over our supply chain, reduce cost and production time lines for this key starting material and accelerate the rapid advancement of our neuromuscular programs from preclinical development through commercialization.

Leveraging our AAV manufacturing leadership for rare neuromuscular diseases continues to be a cornerstone of our strategy for long-term value creation. And as a final, important comment on the AT132 program, I would like to recognize and thank our internal team, medical and scientific collaborators and, most importantly, the patients and the 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 the XLMTM community and remain single-mindedly focused on advancing this important therapy to market as rapidly as possible.

Turning now to our Pompe disease program. We are very pleased with our continued progress toward a Q3 IND filing for AT845. Importantly, we have recently successfully completed a non-GLP NHP study in which AT845 demonstrated a clean safety profile. Based on these encouraging results, GLP NHP toxicology and miles -- dose-ranging studies are both under way, and IND preparations are on track. We continue to believe that leveraging our deep expertise in systemic administration of AAV8 to drive broad tissue transduction and expression provides us with a highly differentiated approach.

We believe AT845 is the only Pompe gene therapy in 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 uptake mechanism of GAA from plasma to deliver the enzyme to its site of action. We are encouraged by the recent progress in our Pompe program and look forward to keeping you apprised of our continued progress in the coming months.

Turning now to our Crigler-Najjar and CASQ2-CPVT programs. Subsequent to the announcement of our recent pipeline expansion, we have completed a strategic review of our product candidates, with the goal of focusing internal efforts and resources on those programs that have the potential to provide the greatest long-term value for patients and shareholders. While we continue to believe that both programs remain excellent targets for gene therapy, we have made the decision to focus future efforts on our expanding pipeline in neuromuscular diseases and plan to explore outlicensing opportunities to advance the important work we have completed to date in Crigler and CPVT.

With that forward view toward our focus on neuromuscular diseases, last month, we were pleased to announce the expansion of our AAV technology platform and pipeline and a new collaboration with Nationwide Children's Hospital to develop treatments for Duchenne muscular dystrophy and myotonic dystrophy type 1. This new work advances beyond traditional gene replacement, combining the delivery power of AAV with the mechanistic precision of antisense oligonucleotides to develop best-in-class genetic medicines for these devastating diseases. In DMD, we are advancing 3 vectorized exon skipping product candidates, which, together, have the potential to advance more than -- address more than 25% of the DMD patient population.

We anticipate commencing a Phase I/II clinical study for the most advance of these product candidates, AT702, in the fourth quarter of this year and plan to utilize the same vector backbone for the subsequent programs, which we believe will enable accelerated preclinical development time lines for AT751 and AT753 as well as future products. And in myotonic dystrophy, we are evaluating both vectorized RNA knockdown and vectorized exon skipping approaches, each of which have been mechanistically validated to block the accumulation of toxic RNA in affected cells. We expect an IND for our product candidate AT466 to be filed in 2020.

And importantly, we should note that we maintain global commercial rights to these programs, as is the case across our entire portfolio of product candidates. Finally, we continue to maintain a strong balance sheet with $375 million of cash, cash equivalents and marketable securities at March 31, which is expected to fund operations into 2021 and positions us to make meaningful progress toward our goal of providing transformative AAV-based genetic medicines to patients living with serious rare neuromuscular diseases. We are excited by the multiple upcoming milestones for Audentes and look forward to sharing these updates in the coming months.

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

Questions and Answers:

Operator

Yes sir. (Operator Instructions) Our first question or comment comes from the line of Anupam Rama from JPMorgan. Your line is open.

Anupam Rama -- JPMorgan -- Analyst

Hey guys thanks for taking my question. And Congrats on all the progress. I was just wondering on the Crigler-Najjar program specifically. Could you walk us through some of the key leverage and the decision to sort of outlicense that program?

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

I think -- Anupam, thanks for the question, first of all. And look, I think with time, we have grown in confidence and appreciation of the knowledge and experience we've got in the neuromuscular gene therapy space. The experience of the MTM program on clinical execution and now on regulatory issues as we approach license applications is extremely powerful.

And when you combine that with the investment we've made in manufacturing, but not just manufacturing, but the entire technical operations required to manufacture products of the highest quality and to do so in particular at, I mean, high quantities necessary for neuromuscular diseases, we just realized that, that is the source of greatest potential impact for us to have on patients and for value for our shareholders. So it wasn't an easy decision. Because as we said just a minute ago, we still believe strongly that Crigler has great potential.

But it simply comes down to focusing the resources of our team and our shareholders, and we feel that we can have the maximum impact with a focus on neuromuscular. And that's what we're going to do. In the meantime, we will work to ensure that we get as much financial benefit out of an agreement with other parties on those programs as possible so that we can recuperate our investment and then some and ensure that we work with someone who's going to help make those products available to patients because we do believe that they will benefit from those products in the future.

Anupam Rama -- JPMorgan -- Analyst

Great. Thanks so much for taking my questions

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

Yeah thanks.

Operator

Thank you. Our next question or comment comes from the line of Chris Raymond from Piper Jaffray. Your line is open.

Nicole Gabreski -- Piper Jaffray -- Analyst

Hey thanks. It's Nicole Gabreski on for Chris. So just 2 quick questions. One on AT466. So here, you're evaluating 2 approaches for DM1. Can you just remind us of the potential that you use both of these modalities into the clinic? And then just second, following up on the BLA readiness for XLMTM. Maybe just help us understand where you're adding the -- at this point the manufacturing process and what gives you confidence that this won't be a rate limiting factor for regulatory filing.

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

Sure. Thanks, Nicole. So I think the vision -- right, it's a little early to say definitively, but our current version is that we will research both approaches in myotonic and end up choosing the approach that we feel has the greatest potential as the one to advance into the clinic. I suppose it's theoretically possible that we could be so intrigued by both that we would consider clinical development for both, but I think that's unlikely.

So that's our current state of mind on it, and we're looking forward to continue to research to evaluate both, and we'll see what looks the most promising. And -- but in either case, with either approach, we feel very good about the guidance be at an IND in 2020. As far as AT132 for MTM and BLA readiness, I think our confidence on this is simply driven by a few factors. First and foremost, what I mentioned earlier, which is the fact that we've used the same process, same scale, same facility here internally all along to make our material.

And we've invested heavily in all these other aspects of tech ops, including all the analytical methods, for example. And so that gives us great confidence. The fact that we own all of it internally and that we can work on it together as a team every single day internally is a huge source of confidence as well. So of course, we did have an interaction. We've started interacting with the agency late last year after the RMAT designation. And we had our first interaction, which has led to additional interactions, which have included some opportunity to have dialogue around CMC issues. Certainly not a complete conversation yet.

It's an iterative process with some back and forth, just like on the clinical. But we feel quite good about where that stands today, both in the context of the United States feedback as well as that of the European authorities. So hopefully, that gives you a little color. I should also say with optimism toward our clinical progress over the course of this year, we began investing in the process validation and facility validation activities Q4 of last year. And it was a driver for why we wanted to raise money last fall, was to be in a position to begin investing in commercial-oriented activities like that. So for all those reasons, we're comfortable with where we stand today.

Nicole Gabreski -- Piper Jaffray -- Analyst

Thank you.

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

Sure.

Operator

Our next question or comment comes from the line of Ying Huang from Bank of America Merrill Lynch. Your line is open.

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

Hi guys. Thanks for taking my questions. It's Aspen on for Ying. Just one on MTM and one on DMD. So could you maybe discuss the disconnect you may be seeing between the superior biopsy data from Cohort 2 and some of the, I guess, more comparable functional scores that you're seeing compared to Cohort 1 for MTM? And then for DMD, what's the -- can you just discuss kind of broadly what the strategy is behind for the product given that it's likely not to be the first to market? Thank you.

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

Sure. Thanks for the questions. With regards to AT132, I mean, look, we're thrilled with the profile of the product at both doses, safety and efficacy and in the biopsy. The biopsy differences are really interesting. The higher dose -- as you know, we see even higher copy number and higher levels of protein expression, and it appears possibly an even faster rate of correction at the tissue and histology after 6 months compared to the first cohort. As far as translating that to the clinical measures, look, the clinical measures are outstanding measures, but there's some inherent variability that is always a factor in those tools.

And in particular when you're pushing into the normal ranges for these kids in both cohorts, it's difficult to detect the differences between the doses. But the good news is that the data produce extremely clinically meaningful changes at both doses according to all those different measures, including the CHOP INTEND, the motor milestones on the neuromuscular side as well the NIP and ventilator requirement on the respiratory side. So I wouldn't read into that too much. I think it's interesting, the biopsy data. And for those reasons -- those results, we do lean a bit more toward the 3E14 dose today as the dose of choice for the future.

But we're still finishing that conversation and want to provide our final recommendation to the agency in the coming weeks, as I said. And so we'll be able to share that and more final decision for them soon, probably in the context of sharing our Q3 update on our plans for next steps prior to BLA and MAA filings. On the DMD side, look, we feel strongly that our approach has the potential to be best in class and to produce the best safety and efficacy for patients with Duchenne over time. And that is driven by the fact that in our approach, we are replacing a near -- or normal or near normal form of the dystrophin protein, and that can be contrasted with the microdystrophin approaches, which are producing a protein that's about 30% of the size of normal dystrophin.

And while the initial data from those programs are interesting, we believe it's also early and that time will tell as more clinical data and safety data are evaluated in a wider range of patients with Duchenne. So we feel very strongly about our approach and its potential. As far as execution, we feel very good about our ability to execute rapidly given our experience in MTM, our manufacturing capability in particular. And the fact that, as we -- as I've mentioned a couple of times, we do feel we can take a very template approach to Duchenne. As I mentioned in the call, it's really fascinating to think about.

But you're really using the same basic construct in each product, meaning AAV8 with the same promoter, the same small nuclear RNA sequence. You're just simply changing the antisense sequence that you're specifically required to use for whatever exon you're skipping, and so it's a very modest difference. And so with that template approach, we believe we can very efficiently perform preclinical development activities and thus get to IND and get into the clinic rapidly in each of these programs. So in the end, well, time will tell. We feel the differences in the time lines potentially getting to market. Our -- and maybe not as great as people may think, and we're looking forward to next steps on the program.

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

Thank you.

Operator

Thank you. Our next question or comment comes from the line of Joseph Schwartz from SVB Leerink. Your line is open.

Dae Gon -- SVB Leerink. -- Analyst

Hi. Good afternoon guys. Thanks for taking the questions. This is Dae Gon dialing in for Joe. So belated congrats on the data last week at ASGCT. Now looking forward to the next update, Matt, you were just talking about the data package submission in second quarter and meeting with regulators in the third quarter and then the WMS update in October. So can you set the stage for what investors should expect at the World Muscle Society conference? And when you meet with the regulators in third quarter, what data will they see given that World Muscle is in fourth quarter? And then I've got a follow-up.

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

Sure. So let's see. I'll try to take them in order. So I don't have a specific answer today on what exact data we'll have at World Muscle Society. Obviously, it'll be longer-term data in all the patients treated to date, and by then we may have data from the new patients being enrolled today into that Cohort 2 expansion. But as far as the exact number of weeks, et cetera, we're just going to have to defer and share that later when it's clear when we'll have the data cuts complete.

As far as next steps with FDA in particular, yes, so our vision is to internally with our experts choose which of the 2 doses we feel is optimal and to submit that information with all the updated data that was just presented last week to the agency. As a reminder, the last data update that the agency saw was from the World Muscle Society update in October last year. That was what we had in the time, and you're requesting the meeting. And of course, the way this works is you submit the information with a request for a meeting, and that meeting gets scheduled usually within a couple of months.

And that's how -- and you get to the discussion, and that's that. And so it's not real time as far as providing data updates to the agency as much as one might think. So in this case, we will provide the updated data from last week to the agency in the coming weeks, along with that dose recommendation. It's a substantial amount of new data, of course, since last fall. So we're looking forward to sharing that, and we believe that will facilitate some further discussion with them about plans for next steps on the program and specifically what makes sense for additional work prior to a BLA filing.

And that's -- we had a good first conversation in that regard earlier this year, and we're looking forward to further interactions with them. And we feel good about our guidance that in Q3, we will provide an update to everyone with our plans and what we feel will be necessary prior to a BLA filing. I do expect for clarity for people that that's likely to be a press release of its own and a conference call where we can answer questions. So that's our current working hypothesis anyway. Hopefully, that helps.

Dae Gon -- SVB Leerink. -- Analyst

Great. Yes, it's very helpful. And next question is sort of shifting gears to manufacturing. So at ASGCT, I noticed that there was quite a significant interest in the actual manufacturing procedures and the vendors. So you mentioned earlier in the call the strategy and the force that you had to internally invest for AT132 development. But now that your setting your sights on larger, less rare indications in the neuromuscular space, 2-part question, how are you thinking about scaling up? And briefly, remind us where you are now and when is it appropriate to implement a scale-up. And to that effect, Tom, Ultragenyx last night spoke of a CapEx commitment to an in-house manufacturing facility. You already have that obviously, but any near to midterm CapEx that you guys are thinking about committing to accommodate these multiples assets?

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

Sure. Good questions. Thanks. So for a reminder on manufacturing, where we are today is that we manufacture in a mammalian system with 293 cells specifically in a serum-free suspension culture, which we believe to be extremely robust and producing material of outstanding quality, which we believe you see reflected in our clinical data and the biopsies in particular.

And we manufacture in 2 500-liter bioreactors, and so that's our current facility and capacity. Specifically though, that capacity translates to -- enough to meet the global commercial demands for MTM as well as the near-term clinical needs for the other pipeline programs. So we're in good shape as to where we stand today, and that's a reminder of our current scale. As far as the future, it's a hot topic around here. We're very optimistic about the new programs. And so -- and certainly, especially as we go toward commercial with MTM, we're going to be very thoughtful about supply.

The good news is that within our current existing facility, we have the ability to add 8,000 liters of additional capacity in our existing lease footprint, and so that is an opportunity that sits right in front of us. But among -- but in addition to that, we're bound to be looking at options for future redundancies and manufacturing to ensure appropriate management of commercial success. And so -- but that's a moving subject right now.

I don't think we have real clarity to provide you today, but it's certainly something that's on our mind, and we're looking forward to sharing updates over the course of the year. Not sure, Tom, on the CapEx. I don't think there's anything to say today on CapEx. Certainly, there would be some CapEx spending when we get to the point of pulling the trigger on either the expansion in our current facility or adding a second site in support of our commercial efforts, but we don't have information to share and immediate plan for that for you today.

Dae Gon -- SVB Leerink. -- Analyst

Great. Thanks for answering the questions and congrats on all the progress.

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

Thank you.

Operator

Thank you. Our next question or comment comes from the line of Ritu Baral from Cowen. Your line is open.

Ritu Baral -- Cowen -- Analyst

Good afternoon guys. Thanks for taking the question. My first question is on the Pompe program. And specifically, can you explain to us the difference between, I guess, the GLP mouse data that was done in new construct? I believe it was the non-GLP monthly and then the upcoming GLP dose-ranging study in mouse that still remains to be done. But what are the differences between GLP and non-GLP in that context?

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

Sure. Thanks for the questions, Ritu. And yes, this is an important piece of new information for the Pompe program. So what we did is an initial study in primates that involved not as many animals as in a full GLP toxicology study. It also -- the difference between GLP and non-GLP option just comes to -- option comes down to paperwork and documentation and quality assurance oversight, but from a data analysis perspective is very similar.

And so in this case, the importance here, of course, for those that know the Pompe story well, is that last year, when we ran into a challenge with our previous construct, it was in the primates where we saw safety signal that give us concern. And of course, as we talked about over the course of the year, we made a change to the products and we were -- have been encouraged over the course of the year by our work, in particular in the mouse model, which we did with an eye toward the potential safety signal.

But now that we've got primate data, it's -- we're very encouraged to meet that milestone and to be able to basically go into our final toxicology work with -- and even higher degree of confidence that, that study is going to be clean and supportive and that, therefore, we're well on track for the IND. So it's another very encouraging step forward for the program and our approach specifically to Pompe. So hopefully that helps.

Ritu Baral -- Cowen -- Analyst

It does. So you have GLP mouse left to do. Do you have any more primate studies, GLP primate studies to do before you start -- before you file the IND?

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

Sorry, yes. So there's 2 final studies that are ongoing in parallel. One is the GLP toxicology study in primates, and the other is a final dose-ranging in the mouse model. And those have already been initiated and are ongoing, and those will be the final pieces required for the IND. The non-GLP primate study that we referred to is something that we did this spring and completed recently and we thought was important to share with the community today.

Ritu Baral -- Cowen -- Analyst

Got it. And will you be presenting on any of this GLP mouse or primate data at World Muscle or any meeting going forward?

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

No current plan to share data from either the primate studies or the mouse studies. That certainly could change. But as of today, no plans to present at World Muscle Society in this fall.

Ritu Baral -- Cowen -- Analyst

Got it. And then moving to manufacturing of the Pompe product. In -- I think your answer to Dae Gon's question, I think -- I at least infer that you don't currently have capacity to manufacture commercial sales product to Pompe at the time that you might start dosing early next year. What are your options as far as switching studies or scale up for the Pompe commercial products as you look at your current capacity?

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

Well, yes, so we have the current capacity, as I said, meets the global need for MTM and the near-term clinical needs for Pompe, Duchenne, myotonic. And -- but certainly, as we see those programs progress and especially with initial data in hand, we'll be very happy to invest in additional capacity. And as I said, that could very well be just adding within the existing lease footprint of our current facility in South San Francisco or a separate location, which also could serve as redundant manufacturing for commercialization for all of our programs.

As far as the scale, well, I don't envision a change in the process. We're very happy with the process. So -- and as far as scale, we are going to evaluate the potential for going to larger scale from the current 500 liter. But it's certainly also possible that we will stay at the 500 and at 500-liter bioreactors as our first step into adding capacity, which would require no comparability or any other fundamental work to address changes in manufacturing. So we're very well positioned and have optionality there to add that capacity when the time is right and to do so in a manner that doesn't give us a regulatory headache.

Ritu Baral -- Cowen -- Analyst

Got it. Thanks for taking questions.

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

Sure.

Thank you. Our next question or comment comes from the line of Whitney Ijem from Guggenheim Securities. Your line is open.

Whitney Ijem -- Guggenheim Securities -- Analyst

Hey guys thanks for taking the question. Wanted to go back to the ASGCT XLMTM update and see if you -- can you provide mean protein expression numbers for the biopsies from Cohort 1 at 24 and 48 weeks? I think median was presented at ASGCT. And then as a follow-up, wondering if you can help us understand how should we be thinking about the variability of protein expression across different muscles maybe and over time and asking in the context of what looks like a drop maybe in terms of protein expression from about 50% at 24 weeks to maybe 5% or 10% at 48 weeks in a couple patients. So just trying to get more color there.

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

Thanks, Whitney, for the question. Certainly, for new numbers that were not in the presentation for the last week, I'll have to -- we'll have to get back to you on that. I don't have that sort of information at my fingertips here. As far as the variability between different muscles, that's something important for everyone to note, is that biopsy is an inherently variable assessment. And you're taking in this case a sizable amount of tissue from the patient.

And so in little kids, of course, you need to do that from different locations. We do a baseline, a week-24 and a week-48 biopsy, so we're doing that from different location in each case, which is just the simple practical reality of it. And so it's inevitable that there'll be some variability between muscle groups -- and we reviewed the data of the vector copy number, mRNA and protein expression in great detail with our outside experts, including my father who you met last week. But we have an entire team of muscle pathologists who read these things in a blinded fashion and look at those data with us.

And their interpretation was that there is no meaningful differences like the ones that you're sort of speculating on there. And that protein number, that doesn't resonate with me, the one -- the specific one you mentioned. So I'll have to follow up and talk about exactly what you're looking at there. But we received, universally, a positive feedback from the experts about the data we were seeing and then of course how to translate to clinical outcomes. So we feel really great about the biopsies and especially learning from those experts and their interpretation of it. So -- but we'll be happy to follow up with you after today's call to try to answer some of the other questions that you mentioned.

Whitney Ijem -- Guggenheim Securities -- Analyst

Great. Thank you.

Operator

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

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

Hey good afternoon. Thank you for taking the questions. So on the Pompe program, is the understanding currently that you could overcome, especially in older patients, the anti-GAA antibodies, a bit of high enough expression of the protein in the liver with a very strong liver specific promoter?

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

Sorry, overcome anti-GAA antibodies in older patients and -- can you say the question one more time, make sure I understood it?

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

Yes. So antibodies to enzyme replacement therapies are pretty common in Pompe, right? So I'm just wondering if you've eventually ventured into all the patients as opposed to infantile onset Pompe disease. And I believe you have a dual promoter strategy. So I believe then the one promoter is probably very liver specific to drive very high expression on GAA in the liver. Is that the -- is the thinking behind it very high expression with a very strong promoter can overcome that antibodies to GAA?

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

So I just want to caution you, I think you may recall 2018, we talked about a dual promoter approach that included a muscle specific promoter but one with a liver enhancer element, which, at the time, we theorize would be a good option to go forward. And it was with that construct that we ran into challenges with the safety signal in the nonhuman primates. Now we haven't elaborated on exactly what aspect of that product we believe caused that safety signal, but we did change the promoter with the new construct.

So I cannot confirm for you that there's any liver directed expression with the new construct. And I would highlight for you what we've said consistently, which is that our focus is to use systemic administration to transduce muscle and neuronal tissue and express the GAA directly in those tissues. We do not believe that a majority of GAA expression from the liver is likely to produced the optimal outcome in patients.

So hopefully, that's some clarity or some -- I hope that's helpful with regards to the product just to make sure you recall the history. And then otherwise, as far as the patient population, we certainly are very familiar with the State of the Union in Pompe disease and patients who have been on ERT. We are not significantly concerned about the ability of our approach to be effective and safe in patients who have some pre-existing antibody levels.

The exact entry criteria we use for our clinical trial is still something that's being finalized with our experts. So that may get factored in to some degree, but right now, we're not overly concerned about that aspect of it. And also, for clarity, I do expect that our initial clinical efforts are more likely to start in older Pompe patients and transition to include the very young Pompe patients who are severely affected over time. So hopefully, I've done OK answering your questions there.

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

Thank you so much sir.

Operator

Thank you. Our next question or comment comes from the line of Raju Prasad from William Blair. Your line is open.

Raju Prasad -- William Blair -- Analyst

Thanks for the question. I just want to follow up on 845. Do you evaluate multiple doses in the non-GLP tox study? And if so, how do those kind of correlate kind of on a general basis with the doses that you use for the previous construct?

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

Yes. Thanks, Raj, for the prior question. We did evaluate multiple doses in the non-GLP safety study. And while we're choosing to not go into what exact doses those were, they certainly were relevant to the expected ranges that we would expect to go into and in both our toxicology study and then, of course, supportive of our vision for the clinical trial. So yes, so I think that was the question. Hopefully, that answered it.

Raju Prasad -- William Blair -- Analyst

Great, yes. And then I apologize, I may have missed it in the prepared remarks, but can you just mention what's the strategic review on CASQ2-CPVT, that program, and your thoughts there moving forward?

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

Sure. CPVT, we haven't spoken much about it as a group in a while. But for those that know the history of it, it was a very compelling preclinical dataset. IND was filed and cleared last year, but we chose to not advance rapidly into a clinical trial. Because as we researched the indication further, we struggled to identify as many patients living with the disease as we expected, which was very surprising given that usually it's the other way around, where you end up finding more patients over time with a rare disease than what was initially speculated on in the limited literature that exists.

So while that was of course very disappointing, it was the reality. And in parallel with that assessment, we were evaluating new and interesting opportunities. And over time, they just became a more compelling area of focus for the company. And so in that regards, it's sort of similar to the Crigler decision in that based on the experience and expertise we have in place on the neuromuscular space and the capabilities on manufacturing in particular, we just feel it's better to focus on those indications, and that's why we're talking about Duchenne and Myotonic and Pompe as our next clinical programs instead of Crigler and CPVT.

And we think that's going to benefit the broadest number of patients and our shareholders, and so we're looking forward to that. And like I said, we'll work hard to find good homes for Crigler and CPVT because we think they have a very good potential as gene therapy products.

Raju Prasad -- William Blair -- Analyst

Good. And then just one last one, you've obviously talked about bringing plasmid manufacturing in house. You might be one of the first companies that's done that so far. Do you have any kind of general numbers you can put around how much you might be able to save, say, on a per batch basis or per patient basis based on bringing plasmid GMP manufacturing in house versus using your CRRC DML?

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

Probably not surprisingly, no. I don't have specific numbers of that regard that I can share with you. But I can assure you and everyone else that we feel this is a very powerful investment and capability for the company, especially working in the neuromuscular diseases. The amount of plasma required to be successful in these indications is striking. And the costs of that and the time lines associated with getting that from what has historically been largely a single supplier is just a risk profile that we were no longer willing to accept for the longer-term success of the business.

So we're really thrilled to take more control over that aspect of our work and feel a little end up resulting in a better chance to hit our time lines, to move the whole pipeline forward, to keep costs down and maintain quality of our products. And so I think that's going to be a powerful investment over time. And I should say I think it's going to pay for itself very rapidly, very rapidly. So...

Raju Prasad -- William Blair -- Analyst

Great. Yes, agreed on that aspect. Just for my understanding, plasmid was or is the most expensive part of a gene therapy. Is that -- that's fair to say?

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

Yes, as a raw material, there is no question, it is the most expensive.

Raju Prasad -- William Blair -- Analyst

Great Thank you.

Thank you. Our next question or comment comes from the line of Matthew Luchini from BMO. Your line is open.

Na Sun -- BMO -- Analyst

Hi, This is Na Sun on for Matthew. Just 2 questions. For Crigler-Najjar, have you had any interests in the product? And did that help you push toward the outlicensing decision? And the second one is on AT466. I know it's early, but given that there's a wide range of disease severity for DM1, can you discuss your thoughts on patient selection? Is there like a portion of patients too sick for the therapy or not sick enough?

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

Sure. Thanks for the question. I would say we believe there are parties interested in the Crigler program, but we've only very recently made that decision official. Obviously, sharing it publicly today. So those conversations are a bit early, but I have optimism that there'll be multiple interested parties. Because like I said, I think it has great potential, and we've identified patients. And so while it may not be the perfect strategic fit for us as a company, I believe it will be for another party.

So we look forward to those discussions. The second question is difficult to answer today. I think we don't yet have a refined clinical vision for our first trial in myotonic. Your point is well taken about the disease, but we really need some additional data from our preclinical work to first guide our understanding of our approach and where we can have the most impact and then have the right pre-IND discussions with the authorities to confirm that they're supportive of our initial vision. So don't have an answer for you today, but certainly look forward to that conversation as the year progresses and we get closer to an IND next year.

Na Sun -- BMO -- Analyst

Thank you.

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

Sure.

Thank you. (Operator Instructions) Our next question or comment comes from the line of Difei Yang from Mizuho. Your line is open.

Alexander Lim -- Mizuho -- Analyst

Hi. Good afternoon guys. This is Alex on for Difei. I have a question on Pompe. Could you maybe comment on how an AAV approach might be differentiated from a lentiviral approach?

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

Sure. So it's -- AAV approach, in this case, involves a single, approximately 1-hour intravenous infusion, which we believe will result in transduction of the key issues affected by the disease, muscle in particular, and the production of the GAA protein in that tissue, where we believe will have a maximum impact, and these are the tissues affected by Pompe disease. And we've shown, with our work in MTM, that that's a highly credible approach. So we're very optimistic about that in Pompe disease. A lentiviral approach is ex vivo gene therapy in this case, so we're extracting cells from the patient.

And with some conditioning ex vivo and the use of the lentiviral vector, you're inserting the GAA gene and then you're reimplanting those cells in essentially a bone marrow transplant procedure. So certainly a lot of interesting and exciting data in ex vivo gene therapy for multiple indications in development and approaching commercialization, and we wish our colleague companies well in that regard. But in the case of Pompe disease, we feel that the AAV approach is likely to be the superior approach, and so that's why we're focused on it.

Alexander Lim -- Mizuho -- Analyst

Okay. And then just related to your strategy in DMD. Are you aware of any other vectorized exon skipping approaches being developed not in DMD but in other gene therapy indications?

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

Other vectorized exon skipping I am not aware specifically. There are other vectorized antisense generally using different forms of RNA to produce clinical benefit and indications. Where there's research happening in that regard include, off the top of my head, Huntington's disease and certain forms of ALS in particular. So we will watch those programs with interest because there's obviously some scientific similarities but also meaningful differences between those targets and the specifics of those constructs and what we're proposing. But specific to exon skipping, not to my knowledge, vectorized exon skipping.

Alexander Lim -- Mizuho -- Analyst

Ok great. Thank you.

Operator

Thank you. I'm showing no additional questions in the queue at this time. I would like to turn the conference back over to Mr. Matt Patterson for any closing remarks.

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

Great. Thank you again, everyone, for your participation. I appreciate the opportunity to share our updates and look forward to talking again soon. Thank you very much, operator. That concludes our call for today.

Operator

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day.

Duration: 51 minutes

Call participants:

Andrew H. Chang -- Director of Investor Relation

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

Anupam Rama -- JPMorgan -- Analyst

Nicole Gabreski -- Piper Jaffray -- Analyst

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

Dae Gon -- SVB Leerink. -- Analyst

Ritu Baral -- Cowen -- Analyst

Whitney Ijem -- Guggenheim Securities -- Analyst

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

Raju Prasad -- William Blair -- Analyst

Na Sun -- BMO -- Analyst

Alexander Lim -- Mizuho -- Analyst

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