Good day, ladies and gentlemen, and welcome to the Sharpta Therapeutics Second Quarter 2019 Earnings Call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will be given at that time. As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program.
Ian Esteban, Senior Vice President, Chief of Staff And Corporate Affairs. Please go ahead.
Thank you, Tamisha, and thank you all for joining today's call. Earlier today, we released our financial results for the second quarter 2019. The press release is available on our website at www.sarepta.com and our 10 Q was filed with the SEC earlier this afternoon. Joining us on the call today are Doug Ingram, Sandy Mahatme, Bo Cumbo, Doctor. Gilmore O'Neill and Doctor.
Luis Rodino Klapac. After our formal remarks, we'll open up the call for Q And A. I'd like to note that during this call, we will be making a number of forward looking statements. Please take a moment to review our slide on the webcast, which contained our forward looking statements. Forward looking statements involve risks and uncertainty, any of which are beyond certain control.
Actual results could materially differ from these forward looking statements and any such risks can materially and adversely affect the business, the results of operation and the trading prices for Sarepta's common stock. For a detailed description of applicable risks and uncertainty, we encourage you to review the company's most recent quarterly report on Form 10 Q filed with the Securities And Exchange Commission as well as the company's other SEC filings. The company does not undertake any obligation to publicly update forward looking statements including any financial projections provided today based on subsequent events or circumstances. And with that, let me turn the call over to our CEO, Doug Ingram, who will provide an over view of our recent progress.
Doug? Thank you, Ian. Good afternoon, and thank you all for joining us for Sarepta Therapeutics Second Quarter of 2019 Results and Corporate Update Conference Call. As we pass through year, let us linger for a moment on our progress to date. As we entered 2019, we set an ambitious path requiring significant execution and with much still to prove, for the RNA platform, could we continue to drive the EXONDYS performance?
Could we consistently create new PMO constructs for other populations of Duchenne and have we truly forged with the FDA an efficient pathway for approval of efficacious new RNA therapies, one that could bring new treatments to the community rapidly and without unnecessary controversy and contention. For the gene therapy platform, with the stellar initial results that we've seen with our micro dystrophin gene therapy truly read through to any of the other 10 plus gene therapy programs that we possess. For microdystrophin gene therapy itself, can we quickly complete the dosing of the 24 patients in our placebo controlled trial for micro dystrophin. What would be the competitive landscape for micro dystrophin would we remain ahead of others both temporarily and qualitatively. And when we devote the resources, the talent, the energy necessary, to build out our commercial manufacturing process for gene therapy.
Well, over the course of 2019, the answers to these questions have been positive. In some ways, more positive than we could rightly have anticipated, as we entered the year. EXONDYS 51 continues to perform. The FDA accepted our filing for Golodirsen in the first quarter and we have a PDUFA date of August 19th. We also will not have an advisory committee meeting as a predicate to approval, which approval if we obtain it by August 19, will have been among the most efficient and rapid development and approval pathways in all of biotech.
Showing the consistency and precision of our RNA platform, we announced positive results for Casimersen in the first quarter, and we intend to submit for FDA review in 2019, further evidence that through our PMO platform and if it is successful, our next generation PMO platform, we have the ability to replicate our success and to treat greater and greater segments of the Duchenne population. And the landscape in our gene therapy platform has been no less positive. In the first quarter of 2019, we announced very positive results for the first cohort of our first limb girdle program, the 2E, our beta sarcoglycan gene therapy program. As many of our programs share the same promoter and the same vector. The consistency of these results further validated our gene therapy engine.
The exceptional work of Doctor. Luis Regina Klapac and the world class nature of our Chief Therapy Center of Excellence in Columbus, Ohio. As promised with our partner, Doctor. Jerry Mendell, at Nationwide Children's Hospital, We dosed all 24 patients in our placebo controlled trial in the first half of twenty nineteen. A remarkable feat when one considers that we only announced results left first proof of concept study in micro dystrophin about 1 year ago.
As we entered 20 team, we appeared to be in the lead, but with 2 other credible companies advancing micro dystrophin programs as well. Unfortunately, for those programs and more profoundly, unfortunately, for patients, initial results from both of those programs have been appointing in terms of both safety signals and resulting expression levels. And both programs have suffered delays as solid has announced that it intends to dose escalate Forex in an effort to show a quantifiable amount of expression. And Pfizer has recently disclosed that its program is on a protocol mandated hold. While an ethics committee reviews its initial results.
So as compared to the landscape at the start of 2019, Sarepta's micro dystrophin program appears to have further distance itself from others, in time, in substance, and it would appear at this early stage in probability of success. One of the risks of this changing landscape presents is that we might falsely believe that we no longer need to move with a sense of urgency, but such could not be further from the case. Indeed, while our leadership position does give us the opportunity to bolster our program, and we will discuss shortly how we will be doing this in both our current placebo trial and in manufacturing, it leaves Sarepta with an enhanced obligation to this community. As we have so often said, our only real competitor in this space is this disease itself, Duchenne muscular dystrophy. As you know, a relentless foe that every day lost tens of thousands of children of their muscle and then invariably of their life.
And we must now operate and make decisions with a very real possibility that we alone hope to hope for a transformative treatment that can battle this disease effective The decisions we make and the energy with which we work are fully informed by this responsibility. So with that, let's review performance in the quarter. Consider recent decisions that we've made, starting with our RNA franchise. In the second quarter, I saw this 51 continue to perform sales standing at $94,700,000 and quarter over same quarter last year growth of a very impressive 29%. For our other PMOs, the PDUFA date for Golodirsen, as I've mentioned, is August 19, 2019.
By the way, the brand name of Golodirsen is now by August 53. So I will often be using this name going forward. We will be ready to expected in the first half of twenty twenty. If we are successful, we will be by early 2020, one of a very rare group of biotechs which has developed and launched 3 or more internally developed therapies. But more than that, we will have more than double the number of patients living with Duchenne who have an available PMO therapy.
Our next generation RNA program, the PPMO, is proceeding having initiated dosing in our multi ascending dose study for SRP-five thousand and fifty one. Our goal is to obtain dosing and safety insight by the first half of twenty twenty. Now moving on to our gene therapy franchise, we have made significant progress this first half of the year in the second quarter. As noted earlier, through the impressive work of Doctor. Jerry Mendell, We have completed dosing of all 24 patients in this blinded placebo controlled trial, a trial that we call either Study 102 or I call Study 2.
As you may recall, the study is being conducted with clinical material from Nationwide Children's Hospital. Our internal statistical analysis review of our in one year. However, it is also the case that the study was dictated by the amount of study material available for Nationwide Children's Hospital. We are very pleased on that basis, we have amended the study protocol to increase the study in from 24 to 40 patients. Increasing the size of the study by nearly 70%.
This will also increase the study power to significantly over 90% confidence level. To aid in the rapid enrollment of these additional patients, we plan to open another U. S. Clinical trial site in the very near term, we believe, but between Doctor. Mendell and the additional site, we should be able to complete enrollment and dosing in the fourth quarter of this year.
With the increased N study 2 should still read out for the end of 2020. Now, the decision to increase the N was straightforward and from my perspective, at least, very compelling. NCH aesthetic material available, which will increase the power of this study to greater than 90%, and it is in the best interest of all patients to ensure that we have a robustly empowered trial as it's reasonably possible. We must also acknowledge that the external competitive environment has changed over the course of augment is pressured and would justify failing to take advantage of this clinical trial material. For avoidance of any doubt, there is nothing that has changed in our original powering assumptions.
And certainly, we have seen nothing at either study itself that changes our confidence. Avoided Study 101, as you know, continue to perform very well. Study 102 is blinded and we have either unblinded it nor have we performed any sort of unblinded analysis, we are simply taking advantage of an opportunity to increase the probability of success. In Study 2. In light of the increasing we had in Study 2, there was less pressure to commence Study 3 in 2 2019.
So instead, we will use the remainder of 2019 to continue optimizing process and analytical development for our commercial process supply we plan to commence the study in the first half of twenty twenty. As has been our goal, we still plan to have 3 month biopsy data from Study 3 by the readout of Study 2. To remind you, Study 3 is intended to be a study using our commercial process supply. On that topic, we continue to make very good progress on commercial process and on capacity. Our commercial facility in Lexington is just about complete.
Should be complete by the end of August and should be qualified by about October of this year. We have achieved very good yields in the Icellus unit the Icellus nano units, and we are in the process of scaling up and working to achieve optimized yields in the commercial Icellus 500 units that is going very well to date. We are making good progress on analytical development. Based on the work that we have done to date, we could reasonably have anticipated commencing study 3 with commercial supply by the end of 2019. But given the additional time available to us, it is simply not prudent to do so for a number of weeks.
As noted, the change in competitive landscape creates significant responsibility for Sarepta. We must plan for the increasingly likely possibility that we will be launching a microdystrophin gene therapy alone or at least at a very significant advantage. And this means for planning purposes, we must ensure that we have optimized yields in process to potentially satisfy alone the needs of the DMD community at launch. To that intent, to that end, we intend to continue to improve process and yields. If we artificially lock the process early to commence Study 3 and thereafter continue to improve process and yield, that would be our intention.
We would run the unnecessary risk of having to conduct yet another bridging study to show comparability between the Study 3 supply and the ultimate commercial supply, this is an unacceptable risk in light of the timelines and the competitive landscape today. Approach we are taking with our micro dystrophin program is informed by the external landscape, and most importantly, by our obligation to the communities of Alsepara. First, we are going to take advantage of additional study material to further improve the powering of our current placebo trial and to enhance the probability of success. We are going to take the time available to us to maximize yields and commercial process with the goal that when we are successful, we are in a position to satisfy alone the requirements of the DMD community that we serve. And we are building out a study 3 protocol that is designed with the goal of providing sufficient evidence to support rapid access for Duchenne patients, regardless of age, regardless of ambulatory status, regardless of mutation, and regardless of country citizenship.
So now let's move on to our other gene therapy programs. Following excellent results in our first limb girdle 2 ECO work, We will be using Nationwide Children Hospital Supply and dosing 1 additional 3 patient dose escalation cohort this year. To remind you, our prior cohort was 5 times E to 13th, and we obtained mean protein positive fibers of 51% 250% of the predefined milestone of success in the study. We also had mean intensity of an impressive 47% we had mean Western blot quantification of 36%. We will dose 1 additional 3 patient cohort for a full higher dose then based on the results, we'll choose between the 2 doses for our pivotal trial.
With our manufacturing partner Paragon, we'll also chart out a pathway for all buying of our limb girdle programs from Myonexus, and we'll report that back out to you early next year. Our partner LIFO gene, we have so far done 7 patients in our Phase IIIII gene therapy program to treat MPS IIIA also known as sanfilippo Syndrome, a devastating neurological disease that robs the life of children for the age of fifteen. And we are working to obtain material to commence dosing before the end of the year in our CMT or Charcot Marie Tooth program with Doctor. SANG at Nationwide Children's Hospital. We have also taken significant steps over the course of 2019 to ensure ensure that we are properly building our vision to become the world's leader in gene therapy and rare genetic disease.
Towards that end, Our team therapy team has secured an 80,000 square foot facility in Columbus, Ohio. We have also expanded our footprint in Andover, Massachusetts from 26 Acres to 36 acres. In addition to taking additional space in our Kendall Square facility, we have taken significant space in Burlington, Massachusetts, where we have some 10 Icellus units that we use solely for process and analytical developments activity. Brammer is near completion of our 75,000 square foot gene therapy facility in Lexington, Mass thesis. This will be a single use site dedicated to microdystrophin commercial supply.
We've also taken out additional capacity at Pericom, in fact, we have sufficient space at Paragon to more than double the capacity that we have at our Brammer, Lexington facility. We have also not been sitting idle for a business development perspective. We have entered into a number of important partnerships and in licenses for new technology and we will begin to discuss in more detail as we advance for preclinical into clinical focus. For instance, these include the following: We have entered into a partnership with the University of Massachusetts Medical School And Gene Therapy Leaders, Doctor. Guang PINGAL, Michael Green and Miguel Senes to advance a novel gene therapy to treat Rett syndrome, a rare and variable fatal brain disease that early exclusively affects girls.
We have also entered into an agreement with the University of Florida College of Medicine to advance Doctor. Lee Sweeney's gene therapy for the treatment of cardiomyopathies. Our gene therapy center of excellence in Columbus has built an innovative gene therapy said, to treat amory drive this muscular dystrophy type 1. A life limiting and often life ending rare neuromuscular disease that affects skeletal and cardiac muscle. We have entered into a collaboration with Columbia University at Doctor.
Howard Worman, the world's leader in the study of Emory drive this muscular dystrophy to assist us in rapidly advancing our Emory drive this program. And importantly, we have entered into a very exciting agreement and to advance Doctor. Brad Hoffman's innovative gene therapy to treat multiple sclerosis. The most common immune mediated disorder affecting the central nervous system. This is our first program outside of rare disease as MS affects some 2+1000000 people Worldwide and is responsible for about 20,000 deaths each and every year.
And while this may seem to venture beyond our core area of focus, I would remind you that our head of research and development, Doctor. Gilmore O'Neill has a rich and very successful background in the development and the approval of novel treatments for MS. We are also providing additional tools for our Gene Therapy Center of Excellence, For instance, we have entered into a collaboration with University of Massachusetts Medical School and the lab of Doctor. Guang Gao develop novel human derived vectors. And we've also entered into relationship with the Institute of Biology to assist in the exploration of the combination of our PPMOs and micro dystrophin.
And we have the resources to execute our plans And I joined Sarepta, we were about 200 employees. Today, we are nearly 700 and we are tracking to approximately 900 employees by the end of this year. It is a dedicated seasoned group in genetic medicine today. As of the end of Q2, we are also well resourced with about $1,100,000,000 in cash. Although things have gone well in the first half of the year, we have much to do in 2019 2020, and we cannot take our leadership position for granted.
We're take our foot off the accelerator, and we will not. For the remainder of 2019, we must continue to serve the community ASONDYS 51 and it's approved this month by August 53. We must submit for casimersen this year. Must rapidly enroll and dose the remainder of our increased study too. We must continue our yield optimization process development and analytical development work and be in a position to commence dosing of Study 3 in the first half of twenty twenty.
We must dose our next cohort of 2E and build out our plans for all of our limb girdle gene therapy programs. We must dose our 1st cohort of Charcot Marie 2 for CMT, and we must continue to build out our gene therapy engine and advance the remainder of our ever increasing. Genetic medicine pipeline. I would like to take this opportunity to thank all of the hardworking employees at Sarepta for their dedication and for their passion. To this mission.
I would also like to thank our collaboration partners for their dedication to this mission with a very special mention to Doctor. Jerry Mendell, who is working tirelessly to advance our micro dystrophin program in the clinic. And I would also like to thank the families with rare disease who believe in us and who have taken the step of participating in clinical trials with Sarepta. It is easy to look upon those in our studies as the lucky few make no mistake about it. Participating a trial for another approved therapy requires courage and it requires dedication.
Dedication. Much is asked of the children and their families in our trials. And it is through your participation families who send us through dystrophy in our trials that we advance promising programs, ultimately to the benefit of tens of 1000 perhaps even hundreds of thousands of families around the world living with rare diseases that we're fighting. With that, I will turn the call over to Sandy to provide an update on our financials. Sandy?
Thanks, Darren. Good afternoon, everyone. Let me start by saying that we had another strong quarter. Revenues continuing to grow well with Q2 net revenue at $94,700,000. From a business development perspective, as Doug mentioned in the call, we continue to selectively add to our pipeline and capabilities via external alliances.
Year to date activity, including the acquisition of Mine Xs, has significantly bolstered our pipeline and further positions Director for long term growth. While we remain selective, we are continuing to find opportunities to partner with the best in the field to bolster our pipeline. And agile capabilities and expand our overall network in gene therapy and RNA Technologies. Partnering with leading organizations and researchers allows us to maintain our focus on the near term value of our GMV pipeline while assisting our collaborators in advancing their programs. And simultaneously giving us the flexibility in determining whether to bring these programs in house as they become derisked.
As our gene therapy program in multiple sclerosis demonstrates, for the right technology, we are willing to make targeted investments beyond rare monogenic diseases. We expect to continue to invest in building our pipeline and in adding technologies in area currently in our pipeline. As a DMD and continue to compete against ourselves to deliver better and better therapies to patients in need. Now moving to the financials. This afternoon's press release provides details for the second quarter of 2019 on a non GAAP basis as well as a GAAP basis.
The press release is available on the on Sarepta's websites. Please refer to our press release for a full reconciliation of GAAP to non GAAP. I'd like to add a quick reminder here that our 2019 non GAAP financials exclude net interest expense and depreciation and amortization expense in addition to one time expenses and stock based compensation. Net product revenue for the second quarter of 2019 was 94 point $7,000,000 compared to $73,500,000 for the same period in 2018. The increase primarily reflects higher Dematrix 51 in the U.
S. We reported a non GAAP net loss of $61,200,000 or $0.83 per share, compared to a non GAAP net loss of $28,000,000 or $0.43 per share in the second quarter of 2018. In the second quarter of 2019, recorded approximately $15,900,000 in cost of sales compared to $6,700,000 in the same period in 2018. The increase was driven by inventory costs related to higher demand for EXONDYS 51 during 2019. Depletion of previously expensed material as well as accrued royalty payments to BioMarin and the U.
S. To Western Australia. On a GAAP basis, we recorded $286,500,000 $122,800,000 of R and D expenses the second quarter of 2019 2018, respectively, which is a year over year increase of $163,700,000. This increase is primarily related to $173,000,000 payment and accrued expenses related to Minexus. I'll note here that our 10 Q breaks out this trigger as acquired in process research and development costs.
In addition to the mine access costs, was an additional $15,100,000 in R and D expenses were $87,500,000 for the second quarter of 2019 compared to $57,000,000 for the same period in 2018, an increase of $30,600,000. The year over year growth in non PMO and micro dystrophin clinical trials, ramp up of manufacturing activities related to our gene therapy platform, as well as continued of internal research and development within Sarepta. Turning to SG And A. On a GAAP basis, we recorded $7,400,000 $47,200,000 of expenses for the 2nd quarters of 2019 2018, respectively. A year over year increase of $20,200,000.
On a non GAAP basis, SG and A expenses were $52,300,000 for the second quarter of this year. Compared to $37,300,000 in the same period last year, an increase of $14,900,000. The year over year increase primarily driven by significant organizational growth and continued expansion to support our commercial launch plans globally. Well as almost 30 therapies in various stages of development across several therapeutic modalities. On a GAAP basis, recorded $900,000 in other expenses for the second quarter of 2019 compared to $5,200,000 other expenses for the same period last year.
The favorable change is primarily driven by the payoff of certain debt instruments during the fourth quarter of 2018, as well as the higher turn on investments in the second quarter of this year. We had approximately $1,100,000,000 in cash, cash equivalents and investments as of June 30, 2019. With that, I'd like to turn the call over to Bo for a commercial update. Bo?
Thank you, Sandy. Afternoon, everyone. At midyear, I'm pleased to report that the commercial organization has continued to execute on our 2019 goals, and is on track $7,000,000. We expect continued interest in EXONDYS 51, driven by our ongoing efforts to ensure existing patients remain on therapy. Assist those who may be facing unnecessary access and reimbursement hurdles and identify new patients who could benefit from McDonald's 51.
We are pleased with the success of EXONDYS 51 as we are in the final months of completing 3 full years post FDA approval. Our commitment to the Duchenne community rests on our goal or that goal, we are fully prepared to launch our next RNA-one product should the FDA grant by August 53 or no Duroson for marketing clearance. We have an operational plan in place for compendium contracting distribution and we're reporting requirements within 24 hours of approval. We will leverage our current distribution partners and our Sarepta Sys network to help get patients 53 label immediately so that we can have important conversations with KOLs. Rapid execution on market access initiatives will be essential, and we are prepared.
Our goal is to reach patients as soon as possible following approval. We expect commercial plans to provide faster access than government payers, such as state Medicaid plans, but both types of payers will follow normal new drug approval or new NDC processes for each planstate. We also the commercial to Medicaid patient mix to be similar to that of EXONDYS 51, which is roughly fifty-fifty. If approved, we expect most patients will start therapy in the hospital and transition to home infusion at a similar rate as we've seen with EXONDYS 51. The knowledge we have gained over the past 3 years with the approval and launch of EXONDYS 51, potentially one of the most successful ultrarare disease launches in history has informed the new the strategies we now have in place for Bion's 53.
My Office 53 is a phospho diamide for Paulino Waldimer, or PMO, engineered to treat those individuals with Duchenne, have genetic mutations amenable to skipping EXOND 53 of the dystrophin gene. As a reminder, EXONDYS 51 treats approximately 13% of the Duchenne population. And if approved by August 53, we'll potentially treat up to submit our NDA for casimersen this year with a target approval decision by the first half of twenty twenty. If approved casimersen will treat patients with minimal skipping ex 45, which is approximately an additional 8% of the Duchenne community. What this means is that by mid-twenty 20, we could have reapproved drugs born out of our RNA platform, doubling our BMO based opportunity in the United States.
Again, we will apply strategic important learnings from the EXONDYS 51 and Vionic 53 launches to place casimersen in a position of strength at launch, if approved. We will have teams preparing for launch operations immediately for Exxon 45, if the FDA approves by on this 53. As for gene therapy, preparing for the required execution and operational excellence needed for a global gene therapy launch of this magnitude is not a team, but we have a seasoned team in place, experienced in navigating and preparing for what could be one of the most transformative therapies in medicine. We will ask the right question, challenge convention, prepare well, and be ready for the opportunities and challenges for us. In doing so, we will be prepared for launching what could be the 1st gene therapy to serve the Duchenne community and pave the way for us reptiv's many other gene therapy pipeline products.
Reaching the regulatory finish line is just the beginning of what we need to accomplish. We are now focusing keep payers on pricing. And again, held multiple meetings with payers across the U. S. Over the last quarter on topics regarding gene therapy access and finding ways to partner together so that all patients will have access to life altering therapies as quickly as possible.
At Sarepta, we can make quick decisions that are best for patients. We have an extensive gene therapy portfolio with microdystrophin, Lim Girl, CMT, MPS IIIA, as well as additional programs. And we will adapt, grow and reflect our lessons learned and insights we've gained along the way so we can refine our strategies, importantly. Outside of the U S, we are thoughtfully and strategically expanding globally into key markets. While there's no single key to unlock the market access, tackling common barriers at the country level is a good place to start, and we're building towards this goal.
We've hired the right people, individuals who know the importance of pursuing and partnering with the best opinion leaders globally. Who we will continue to work commercial medical affairs teams are focused on operational excellence, and we will be ready for future potential launch We are committed to improving the lives of those suffering from rare neuromuscular and CNS diseases. From RNA, gene therapy, gene editing, and other potential modalities, we remain focused on patients, keeping them at the center of all conversations from discovery to global commercialization. And with that, I'll turn the call back over to Don.
Thank you, Bob. Vineethu, let's open the call for questions. Thank
And our first question comes Olivia Young with Cantor Fitzgerald. You may proceed.
Hey guys, thanks for taking my question. Congrats on all the progress. Far, two questions for you, sorry. 1, I just wanted to know kind of what went to your decision around increasing the sample size for study 102 now? Like was there anything incremental color that you can give us?
And then the second question, I was just curious on what the status is around the confirmatory trial for a Teferson thing.
Sure. This is no, thanks a lot for this question, Olivia. So I mean, the sample size, as I said before, we were comfortable with the size of the trial before. And our analysis gave us some comfort around it. And certainly that there cowork gave us some comfort, but it is not it doesn't, require a lot of imagination to realize that 24 patients is a relatively modest trial and it was, in fact, limited by the fact that we had 12 doses from Nationwide Children's Hospital at the time.
So we now have an opportunity nationwide has a material available for us. As we consider that material earlier in the year, We were in a different landscape competitively than we are today, for a host of reasons. And so obviously, given what we've seen from the other programs with solids and Pfizer, we are confident that the right decision is to increase the probability of success. We're very confident in the therapy. We want to make sure that in a 12 month period, we'll be able to see a difference between the Acton group in the placebo group.
So increasing the trial from 24 to 40. From my perspective, it just makes brilliant sense from a risk perspective. Beyond that, you know, there would have been a question about what else we could use in that material for. One might have imagined a scenario in what and which one would want to, for instance, dose escrow But the issue on that is the civil work. Our preclinical data did not, suggest to us that we that was escalate.
The dose we have right now, which is using super coiled method 2 times E to 14 would give us the best, answer without creating undue burden on the kids. And certainly the first four children in our first cohort, so forwarded that conclusion. Now it does turn out that there was another company that was running an experiment essentially for us. Pfizer was at a very a significantly higher dose than ours. And while they use a different titering method than we do, they dose escalated to something that was multiples higher than ours.
It made sense for us to look and see what that looked like. And of course, what we saw there was, in addition to an issue is organic to, Pfizer's program, and both from an A. E. Perspective and from an expression perspective, we didn't any significant, benefit from dose escalation. We didn't see much of a dose response.
I think using theirs. They had about 700 femtivolors and they went to, the next level and it was, it was, 900 femtromolars at multiples higher, 3 times higher than their progress. So from our perspective, the best use of that material was clearly to increase the end of this trial. Doesn't create an enormous amount of additional time in the study at all, and I think it increases the probability of success. The avoidance of any doubt, I'm going to make sure I remind you, once again, what I said in the, in the script, which is we haven't seen anything in the study that's changed our confidence around the trial.
This is an opportunity. Nationwide Children's Hospital has to it would allow us to go to 40 patients and increase the probability of success. It gets us to a confidence level, powering level at well over 90%. And I think the best answer for the patients as well. On the confirmatory trial, I'll turn that over to Doctor.
O'Neill who can talk about status of our confirmatory trial for levels.
So the confirmatory trial is actually, moving well. We have our protocol is very well developed. We are in discussions with regulatory authorities around the world about it. And, And, we are actually on track with regard to, site identification regulatory dialogues, etcetera. So we're very confident that we are in a good position to be able to execute, as soon as possible.
One of the things that people understand. It's not as if there has been work done. Confirmatory trial for a teplorsen is, is unusual. It is not a simple trial versus a placebo. The confirmatory trial for a teplorsen.
Excuse me.
So I answered my question. I was answering
her from Charles Burke. Oh, I apologize. I think I can confirm to Charles for I am so sorry. On a Tuverson real quick, the request from the agency has been to test the current dose of a Tuverson versus a higher dose of a teperson. So it's a little unusual in the sense that we have to first do a study in healthy human volunteers to ensure that consistent with the preclinical data that would suggest that it's safe, that we're safe for these doses.
We've actually completed all of the all of the enrollment from that study, the readout on that study will be September. And assuming everything goes well and it will, I think have I'm sure that we don't go well based on all the stuff we have so far. We'll start the confirmatory trial before the end of this year.
Yes. And we are, I'd say from I'm forgive me friends on our question. I just heard your I apologize. We're actually initiating sites now, etcetera. So we'll be ready to execute
That was my fault because I feel a buzzer in the first question. And our next question
comes from Tazeen Ahmad with Bank of America Merrill Lynch. You may
Hi, good afternoon. Thanks for taking my questions. Doug, I'm sorry if you've already said this, just want to be clear that I understand all of this correctly. Can you remind us what data you expect to be in this package for D and D gene therapy? So what time points do you need from Study 3 to get approval?
And when should we expect that data? And maybe to follow-up on that, what, if any, interaction have you had with FDA since Pfizer might have shown its data at PPMD and did FDA influence your decision to size your study? Thanks.
So let's start with the last question first. No, the FDA didn't play a role in upsizing. Study. This is literally a decision that they would be perfectly fine with the size of the study that we had. We simply looked at the opportunity in front of us realized that it made the most sense for patients.
I mean, when we think about it, nothing would be more tragic than, to find that you have a very cases therapy, but you missed that cig by, by some small marks because you
didn't take the time to
make sure that the study was was, dose. It was a really easy decision when we had 12 doses, but now we have more doses. It certainly makes brilliant sense to make sure we can upsize this. Toward it. And now let's talk about the timelines because it's important to consider timelines and now you'll see why it makes so much sense to upsize it because let's start with Study 2 itself.
We will be done certainly in the 4th quarter dosing the entire study. Doctor. Jerry Mendell did a really good job earlier this year in dosing those first 24 patients. I will remind us, you know, the 4 of the patients was, was analyzed in that 1st cohort and was, at the was either October or November, forgetting now when we had the Argentina meeting. But, it was October.
October. So it was in the last October. And from there, we literally designed, got blessing on the ancient started a placebo controlled trial and Doctor. Mendel did all of those patients do. So we will, between Doctor.
Mendel and Weben, we sign up and running very shortly. We only have all of the next coworker patients make it to 40 does before the end of this year, which means Study 2 will readout before the end of 2020. So we really haven't taken any significant delay by increasing the end. We've only increased the probability of success. Now to Study 3, our goal is to start, as early as possible in 2020, study 3.
And then we'll have a cohort. One of the goals right now that we have is to have a subset 93 that we are going to look at for expression at the 3 month level from a biopsy perspective. And our goal is to have that available the time study 2 would read out as well. That was our goal before that, still our goal. We think we're on track for that.
So before the end of 2020, our goal is to have 2 things. To have a number of things, to have Study 2 fully dosed before the end of this year, down 8 readout on function in Study 2 before the end of 2020 to have Study 3 up and running early next year have the subset of patients, with expression levels from a biopsies read out at the same time as Study 2 before the end of this year. And then our goal at least is to approach the agency with the with the, view assuming that we're successful. In all of these. And we would be able to submit on that basis in a payment approval on the basis that we have shown first that the construct that we have is functional and beneficial to children with Duchenne muscular dystrophy.
And then the commercial supply that we're using is profitable to the clinical supply. As far as what discussions we've had with the agents, we've had very good discussions with the agency around CMC and manufacturing issues. We're designing our study 3 and then we are very, we're essentially designed to study 3. And then we'll take that to the agency and talk through with the agent see, whether they accept all of that and feel confident to learn in the right direction. And then we'll start that study early next year.
Okay. So it seems like just so that timelines are clear, are you guiding to a start to the commercial setting first half of twenty twenty because it seems to be you seem to be giving yourself kind of a wide band on this. Is it the first half or is it early 2020?
It's well, we're giving ourselves a little bit of we're trying to get ourselves in breathing room, but we want to be as early in 2020 as as possible. There's a number of things we want to get done for that. We want to there's couple of things. One is of course site readiness getting the sites up and running. We can get that done before the end of this year.
So that won't be We always intended to do that. Finishing the design and study 3 and getting the blessing of the agents improve the agency on that, we can get that done before the end of, 2019. And getting the commercial process at the right place. And that, and that, from our perspective, we can get to a place before the end of the year where we could use commercial process supply and start the study. But as I mentioned in my script, Our goal is to really continue to improve.
We don't so improve yields thereafter that we find ourselves in a position that we have to do some additional bridging study for approval. So The short answer is, you know, our official word is obviously first half of twenty twenty that we would commence Study 3. It will not surprise you, both of those those who know Sarepta and our center urgency that is as early in 2020 and as reasonably possible. So we would like to do it as early in 2020 as possible, first quarter if possible.
And our next question comes from Brian Abrahams. You may proceed.
Hey, thanks very much for taking my question and congratulations on all the progress. Any comments you can make on the safety that you're seeing from the ongoing 24 patient study. I realize it's blinded, but just wondering if there's any sort of safety events that would be considered reportable, what would be a bar for stopping or what would have been a bar for stopping or pausing that study? And did that change over the course of time when the, your competitors talks issues became known to the FDA?
And I
had a quick follow-up.
So, as you well know, the study remains blinded. We do, as you quite rightly, inferred, have staffing rules and rigorous oversight of the study. We have not crossed the threshold for the stopping rules. You've not come close to that. The study continues And so, from that point of view, we are actually very happy with the ongoing study.
It is worth noting that in our 101 study, if you're well aware of this, that we had, no evidence of significant, adverse or serious adverse events. And so we actually are very happy with that. And, with regard to the readout from the other companies, Pfizer and Solid, we have not seen what they have described. But I want to reinstate one thing, which is that we have not, but we do have stopping rules. We have not hit the stopping rules, and 102 is progressing well, and remains fully blinded.
One of the things I will also add is that obviously, and really all kudos to Doctor. Jerry Mendell for this the study is going very well. It's progressed well. We've got a good inventory of patients, and that gave us a lot of confidence to increase of the study from 24 to 40s and still, ensure ourselves that we'll be able to comfortably finish the dosing of the study for the end of this year, not creating kind of significant delays in our timelines.
That's really helpful. And then secondly, as you work to optimize yields and margins, curious what shapes your confidence that you will be able to ultimately get to a point that you could potentially supply the whole DMD market and with material that is indeed comparable to the NCH product?
And I'll hop back in the queue. Thanks.
Thank you. There's a lot of things that give us confidence. We've got a lot good data in front of us now. We're doing a lot of work. So there are 3 groups right now working on the process development and then also the analytical development and deal optimization.
We've got process development experts at Brammer, got that process development experts at Perrigo, and we've got our own process development experts. In fact, we've got probably one of the world's leaders not the single world leader in process development. Doctor. Reeve Clark, who I think, you know, or anyone who's on diligence and gene therapy will find this probably the most renowned and AAD biology and process development that exists right now. So we're doing a lot of good work.
We will get there. We are putting the so we've got the talents. Let's start there. We've got the talent of the external internal to get it done. We got the resources where, as I said before, we will spend a good $6,000,000 to $650,000,000 in the next 15 months or so.
You, sir, that we not only get process and analytical development done right, but then we get the capacity necessary to fully serve this community. And we've made good progress today. We have very good, results from the Isellus Nanos, the Isellus Nano units. We've scaled up a ready to Icellus 500s. And we are in the process of optimizing deals at Icellus 500s.
We still have much more to do there, but that it's just a matter of time from our perspective. We're getting every time we do runs and optimize, we're getting better results. So we do feel very confident we're going to get to a place where we're going to be able to serve the community. We had always envisioned a world in which it might be the case that we would need to serve this community alone. But today, I mean, to be direct, and these are early days, but to be directed, we believe there is a very enhanced probability that when we launch this product, we are going to be launching this product and have service entire community from day 1 and for probably a very long time thereafter alone.
And so we have to take very seriously the issue that we have to have the capacity available to us, which means we have to have the right yields, the right investment, the right capital, the right manufacturing facilities. We're doing all of those, even as we speak, process development is going along. It's going well right now. The capacity issues are going well. We have the Lexington facility, which will be complete, as I mentioned, sometime probably in the next 30 days or so, and will be qualified certainly before the end of this year.
At Brammer, in Lexington, that's a single use facility, about 75,000 square feet, at Perriga actually, we have taken out sufficient space to more than double that amount of capacity at Perrigo. We can use that space both for microdystrophin as well as our limb girdle programs. So we are very confident about the, the process right now and about the Black of the app for additional to satisfy the community, assuming that our trials work out.
And our next question comes from Martin Auster with Credit Suisse. You may proceed.
Hi, this is Mark on for Marty. Thanks for taking my questions. I guess first question is you announced that you're expanding your gene therapy pipeline by exploring RAT cardiomyopathy, another muscular dystrophy program and multiple sclerosis. I'm sure you looked at multiple targets. I guess I'm just curious how you settled on these specific programs.
And if there were any unifying themes that made these indications particularly attractive? And then my second question is, is with WMS less than 2 months away, I'm curious what data, if any, you plan on presenting at that conference? Thank
you. Sure. So on the first one, I'm going to take been a question on these new research programs from, Doctor. O'Neal and Doctor. You know, Clayton only because I don't want to spend a ton going into the underlying programs themselves.
They're in research stages right now. I really want to focus on our clinical programs for the time being. We're very excited about these programs, and we're not done. Know, as we said for a while, we're going to continue to do program, transactions like this to bolster our pipeline. There are a number of things about these programs that excitis.
First of
all, they're all very serious diseases. We are a company focused on the use of genetic medicine, both RNA and gene therapy to bring a better life people who are suffering from and dying with serious diseases, either storage focused on rare diseases, that certainly is a big part of us. But MS, while it is not a rare disease, it's a serious disease. And we have the expertise internally with our Doctor. Gilmore O'Neill to, progress that.
So we're excited about the seriousness of these diseases is part that the elegance of the constructs is in these various programs. We're not going into much detail the elegance of the approach and the elegance of the constructs is something that's given us a lot of, excitement and they sense to, to pursue. So we're very excited about the, these, the approach that's being taken in these EMEA line. We're of the ideas that we have in that release that our team has about the approach to genetic medicine. They, they, and then the beyond that, we have the opportunity in all of these programs to work with some of the best and brightest in gene therapy genetic medicine.
The, as I'm listed in the text of my, of my initial comments, the gene therapy leaders that are running many of these programs are who's who in gene therapy, of luminaries in this area. So it's all of those together that excite us. I'd say HMS is a really interesting concept and it does take us into a place that is different than rare disease. I get that. And we will be continuing to look at things like that over time.
We are a number of things at the same time. 1st and foremost, we are a genetic medicine company. So we are focused on genetic medicine, RNA and gene therapy. We are to date a neuromuscular and neuroling rare disease company, but we are a gene therapy leader. We are, as we stand here today, almost certainly the world's leader in gene therapy.
And so we are going to and there is a lot of opportunity in there to do good. And we're going to take gene therapy as far as it can go. And that means we going to without busting our, balance sheet. We are going to do interesting things that explore all of the meats and bounds of where genetic in gene therapy can take us. And this program with Doctor.
Brad Hoffman, for MS is a very, very interesting one. It's a research program right now. Free clinical. We're not in humans yet, but we're very excited about it as we are excited about our rep program, as we are excited about our amyloid driver's program, which Doctor. Release Rodino Klapacanchor team develops themselves, except for us.
So we're excited about these pipeline programs. And we think they align with our strategy, particularly the strategy that we have about building an enduring gene therapy engine can do good in the world and be successful for investors at this time.
And our next question comes from Christopher Morey with Nomura. You may proceed.
Hi. Thanks for taking the question. Just a couple here on, the new study to size and your powering assumptions, could you maybe talk about some of the effect size you're expecting to see there, numbers that went into that powering assumption. And then on Study 3, thinking about the subset that you're going to look at the 3 month biopsy. What biopsy data will you specifically be looking at?
And then when we think about the size of that subset, Is it sort of 3 patients, 32 patients sort of like your current or your new study 2 size? How should we think about that? And then just because it wasn't answered on the last question, do we expect any like Limb girdle data or anything else at World Muscle? Even safety data on a program like that or CK? Thank you.
Yes. Let me answer the last question first because I failed to answer the world muscle question from the last question. And that was just an error on my part. And thank you for mentioning Limb girdle because that is likely the thing that would be tenant at World Muscle. So one of the things we're looking at right now is the following Doctor.
Mendell is very interested and excited about the possibility of presenting data on the first cohort of functional data on the first cohort of limb girdle 2E that we, announced the expression results and safety results for earlier in the year, And, while it hasn't been nailed down right now, I would suspect that that is going to be something that's going to be, presented at World Muscle, if Doctor. Mendell is available and and have the data available in an appropriate place by then. With that, I'll turn it over to Doctor. O'Neal to talk about the powering.
Great. Thanks very much for that question, but powering a Gilmore here. So, I think you understand that for many reasons competitive or other that we've hoped to disclose the specifics and details of our power assumptions, particularly the effect side. What I will say is that the assumptions around variance, etcetera, are strong. They haven't changed, since our original calculations And they are backed by a very strong data set of raw data, both internally generation generally generated from various registries.
So I think what I can say is that we're very confident about the strength of our calculations there and forgive me for not just going to the effect size, there are obvious reasons for that. Then with regard to these sub cohort in Study 3 from which we would do the muscle biopsies. Those muscle biopsies will be skeletal muscle. They are a limb, and, thinking right now is that they are just still lower extremity, you know, gas drops. With regard to the size of the cohort, as you can imagine, based on the, the strength of the expression data we see to date, we don't believe that need a large number.
But I think that final number is going to be a matter of discussions with, regulatory agencies and what they want to see. But we believe that that number will be small and represent really a small fraction of the global population that we're enrolling in multiple countries in that study. I think then go to the
3rd question.
And our next question comes from Matthew Harrison with Morgan Stanley. You may proceed.
Hi. This is Max Gore on for Matthew Harrison. Regarding the PPMO program, could you talk about the safety profile with single doses how we should think about your ability to release data from the multi dose study? When will you be taking muscle biopsies and will you wait for all patients? Thank you very much.
So I'll give you the broad strokes on it. The the our goal is to get insight from the PPMO program and the MAD study by early next year. So that is our goal. What we know from preclinical work is that if we get to good dose levels with our program, that we should get significantly enhanced expression versus PML, in fact, in animal models, we get an order of magnitude, greater expressions. So we're very excited about that.
But the issue that you that we're talking about here is the issue of the safety profile. And that's what we're going to find out over the course of this year into, early next year. Have gone very well so far. We've been in a single ascending dose study. We're, we're, you know, getting great results so far, and we started dosing the multi ascending dose study, and we're getting great results there as well.
But I'm one of the cautious that it's too early to say that because we're not at the dose levels that we really want to get to to be correlated with brand expression. So this is still, in a very real sense, too early to declare victory. We are, we started, I think, the NASH study is, where we started 5 mgs per day for at 4 mgs per kg and we're going to continue to dose net out. So things are going very well in the NASH study. If not a little slower than I would have anticipated a year ago.
Doctor. And Doctor. O'Neil has come on board and she's got that in order. And we'll know by early next year, if what we've seen in preclinical models cares out with these kids. And so far, things are looking very good.
So we'll give you a good update on it early next year.
And our next question comes from Anupam Rama with JP Morgan. You may proceed.
Hey guys, this is Matt on for Anupam. Thanks so much for taking our question and congrats on the progress. So just some higher level questions from us. You mentioned that you'll be nearing 900 employees by year end. So kind of just as you expand your processes and potentially you treat geographical reach, where do you see this number going over the next few years?
And then on your gene therapy factoring efforts. Can you just remind us of how much cash you've earmarked on this front, kind of in the same timeframe? Thanks so much.
Yes, it's a good question. It's great questions actually. So we're going to end the year at around 900, maybe a little shy of 900 employees worldwide. We are going to begin to moderate the growth of our employee base. We already are over the course of this year.
For most of reasons. The reason that we grew, we didn't grow from 200 to 700 simply because we have the ability to. We have the need to. We've really expanded our ambition. We have probably going on now with programs, both disclosed and undisclosed.
We're probably well over 30 programs in RNA and gene therapy together right now. So we've needed to really bolster in all areas of the company, but specifically in the research and development and manufacturing tech ops CMC areas. But we're getting to a place now where we're comfortably, we're getting to a very comfortable place from an employee perspective, both quantitatively and qualitative, we've got great people here right now. We are a magnet for good people right now. I'm proud to say, and we'll start moderating that growth.
So we'll have growth next year over the 900 that we have this year. But we will be doing what we did this year. We don't imagine that we're going to double it again in a year, the size of this. We'll start moving more to a rational growth rate on employees, after this year, otherwise, we're going to get, we're going to have too many fixed costs as we move forward. You've executed your place where we're comfortable with the number of employees in the quality of the employees that we have.
With respect to gene therapy, as I said before in broad strokes, between milestones, capital, I don't know, expense and prepaid cost of goods. So we're actually benefiting from a lot of these expenses there. They're not simply capital or direct expenses. We'll spend something where we're like $600,000,000 over the next, but for the concluding what we've already spent this year, into the end of next year and kind of into the little bit of the follow-up here in the $600,000,000 range. Do you agree with that, Sam?
Yes, I would agree. And slowly, we'll be starting to ramp up our goods that will effectively be going to inventory. So some portion of that will be cost of goods, if you will.
And our next question comes from Gena Wang with Barclays. You may proceed.
Hi. This
is Peter for Gena Wang. Thanks taking a question. Just a couple from us, Simeon. I guess, first is, I think this has been asked before, but to make sure. Were there any, like, measurements from Study 2 that prompted the expansion?
And would would you be able to measure anything that may inform the pivotal study design at all? Or is that does that is it completely independent?
So thank you for giving me an opportunity to get it. Answer this question again, actually, I really do appreciate it, Peter. So let me be very clear so there's no avoidance of any doubt. There's nothing in the analysis blinded or unblinded or otherwise out of study 2 that motivated the increase in at all. In fact, the only data that we've had is the data from the first four patients in study 1, and that's given us tons of confidence in where we are.
The reason that we've increased the end is quite simply because we have opportunity in front of us. And I think it is a small price temporarily to pay, you know, literally measured in the in weeks and maybe, you know, months couple of months to be in a position to feel that we have a study that's really robustly power powered at over 90% now, which increases the probability of success and gives us, gives us really comfortable with study too as we plan for study 3. And, you know, there's just, you know, to say something that is obvious without being overly starkey about it, there's no erogenous reason why we to do this right now. We are the race that we're in right now is a race against the disease itself. It's not a race against other company as it stands right now.
We are, I think, significantly in the lead versus others around us, both importantly, but for we maybe even more importantly qualitatively. And so we really need to think about these families and these patients 1st and foremost. And while it may delay us, you know, by some number of weeks or maybe even a month or 2 to ensure that we have the right power of this study, it increases the probability that we don't have additional delays in the back end
because we
powered the study at the right level. So it's the best answer for The program is more important than all of that, the best answers for the families around the world who are waiting for a transformative therapy in Duchenne muscular So we really, I'll just be really direct about it. We feel really, really good about this opportunity to increase demand And we think it's a real opportunity for the program and a real opportunity for families.
And our next question comes from Vincent Chen with Bernstein. You may proceed. Congrats on
the progress and thanks for taking the questions. A couple of specific ones on Study 2. First, about your statistical assumptions, how would you expect the mean effect size from the gene therapy to compare to the likely standard deviation, because just in ballpark numbers, would you say that's roughly about the same size, would you say it's likely to be larger, smaller And then, the second question would be, if you had wanted to, could you have increased the study size for study 2 even further than 40 patients how much longer would the trial have been extended, for example, if you decided to increase to say 50 or 60 patients?
I'll answer the last question and then I'll turn it over to Doctor. Any other questions? Use this you see here, no, no, we could have modestly increased the size of the study even greater than we did with the JL available. We are very comfortable with, 40 patients study. It's the right, right, level for us.
And we don't, and we weren't, we didn't not a compromise issue. It wasn't a temp timing issue. We feel we felt good about the end of 24. We felt good about the end of 24. The and frankly, the data evolved in Study 101, as you know, we got 9 month data from the kids in the study 101, and it only confirmed even more that we were feeling very good about the assumptions we were making in the power and we had for study too.
But 40 patients in getting to significantly over 90%, power just gives us even more confidence that we're doing the right thing these families. And then, Vincent, thanks for the
other question. Again, I'm not going to go into specifics of our assumptions around that size. And standard deviations. I mean, the only thing I can sort of tell you about gender deviations is that, you know, based on our raw data, the standard deviations that are published in literature are, you know, in the ballpark of what we're seeing, for the North Star etcetera. But forgive me for, again, not going into the effects side if you feel that's something that we just want to keep internal right I see.
Well, maybe one follow-up then. You mentioned that the data you're seeing from the initial study kind of corroborated what you had expected in terms of, you're powering the effect sizes and so forth. Is it fair to say that the data you've seen from the first four patients is pretty much in line with what you would have expected in terms of the likely gene therapy effect size?
It's, I would say a couple of things on that. 1, we were one, I would say we took the we've taken the results from the 1st study, what we've And then we've been more conservative. Just I will give you the qualitative answer. We've been more conservative in our power assumptions, okay? So we're not taking We're not meeting all of our assumptions in an aggressive direction, just so you know, I don't want you to get price to never fooling ourselves into our power calculations.
Native job is given a very increased demand for things like that. And if you want to know what our view is, it's hard to say what one should have anticipated. Pated from a study going into it because frankly in the history of all Duchenne muscular dystrophy, no one has ever seen these kinds of transformative results, before. So I think, you know, probably people may have different views. I think broadly speaking, the results we saw from the 1st cohort of kids was pretty shockingly positive.
It was probably greater than one could have normally anticipated. We're used to dealing with therapies that tease out differences from background over a long period of time. And what we saw with these kids was a fairly dramatic benefit. Open label for kids, please understand. I understand that as well.
But early days, both quantitatively and qualitatively saw a fairly dramatic change in these kids. I'd say the preclinical models generally that same kind of concept. If you've ever looked at the gene therapy micro dystrophin, golden retriever, you know, models and video, you would, you might have anticipated this kind of transformative effect, but, we were very pleased with very pleased with what we saw in Study 1, still took a very conservative approach in powering Study 2 and now we're taking a, I think, an appropriate, not overly conservative approach to increase that that end to increase the powering of that study and to increase the chance that we did this therapy as fast as possible. But with the highest POS, to patients waiting around the world, frankly waiting and degenerating all their weight. So we really are making these decisions intelligently is important.
And our next question comes from Ritu Baron with Cowen. You may proceed.
Hey guys, thanks for taking the question. Going back to Study 3, Doug, is it still your idea to keep that a placebo controlled study? In that case, how would you handle, placebo biopsies in a study like that? And you mentioned that the biopsies are going to be taken from a subset of patients. How are you thinking about the other patients as part of Study 3 in your FDA negotiations, like who else are you going to include, age range, etcetera?
And then I've got a follow-up.
A couple of broad strokes, I guess, there's a lot to unpack. The question about the ability to take a subset of patients do a biopsy of them online to study, I can give you sort of some proof of it as possible. We just did it. So we did it with casimersen. So, So it is possible to do without unwinding the study.
Yes. So
since I actually, this is Gilmore,
I just want to actually
step in, with regard to the biopsy, Our intention is to biopsy all patients. Subsequently, what we're talking about is not a sub cohort of biopsy patients. It's just a cohort in time. That's the first thing I want to say. I think the second thing I want to say about perceived control is that we do anticipate things we've received with Crohn's study.
And I think to Doug's point, there are a couple of important lessons that work points gap, which is one that we actually have our successfully running placebo controlled studies with Duchenne patients in the context of our casimersen progress and in our study 2 protocols. So we're that we can actually execute on that. And of course, that really comes down to a very important thing that we have built in the kit that we its organization, which strong relationships with patients, strong relationships with investigators and a very good patient advocacy group, where we actually sit down and explain in detail the rational thinking and the importance of this work to patients and their families.
And the placebo controlled nature of the main study III as it was studied to is a difficult one. And it's one that takes, I mean, a lot of thought before one does, because there is a price to pay for these placebo trials. And I'm want to understand that we're mindful of that. But our goal, you know, one of the things I said in my text is, you may have noted, is our goal is to have such a robust set of evidence at the time that we lost this therapy that we can get kids of all ages EMV patients and status on therapy rapidly and to do it around the world, not simply in the United States. It's important to be United States is, to us and to our company and to our, to the families in the United States.
We want to create a program that is fit for purpose around the world. So we do believe this as difficult as that decision is to make a positive, a placebo trial, at least for the main trial. Is appropriate. And that main trial will very likely be the kids that will match the, the cohort that we're looking at right now in four to seven year old range. With respect to other cohorts, different age ranges, it's something we're still talking about, but as related to that main cohort of patients in the next study, will almost certainly be a placebo controlled trial.
Do you agree with that doctor?
And our next question comes from Brian Skorney with Baird. You may proceed.
Hey, good afternoon guys. Just a couple of quick ones from me. Just one getting a lot of questions with the FDA released yesterday about some data integrity issues with the Novartis of excess gene therapies, old gensma. And just wanted to know, given the similar origins, of that program in 9001 if you've looked into the issues there and what level of confidence you can give in your construct that these Zolgensma issues are specific to Zolgensma? And then as you talk about ramping up inventory with the competitors in therapy seemingly falling behind.
I think you had previously anticipated having a couple 1000 doses at launch and just wondering if kind of these new efforts to meet demand, if you're changing that to a higher number now or you think you can make it to a higher number and And should we expect to see the manufacturing costs of these doses effectively expensed into R&D over the next 2 years?
Yes. So a couple so let's go to the first question, the Abaxis Novartis issue that occurred yesterday. So we know not before then others now would be able to read the documents that currently exists. We've looked directly at the 483 So we're all on the same thing. There's nothing about that issue that reads through to anything that we're doing, at all.
Appears to be a very specific issue and then a very specific person or a couple of people at that company, on a particular data entry issue. It's nothing to do with us at all and nothing to do with any of our programs. So there is just so we're unequivocal about there's 0 beyond 0 read through in anything that may have occurred there to, to anything that we're doing. So there's nothing no toilet whatsoever at all. And then with respect to there's sort of two things I'll get yields right and the like.
One is the target we have for the number of doses available and the ability to treat the community. And the other is probability of success that we'll have that on a dose at the time. Getting the yields right does both. It gets us to a place where we feel confident, not only in the number of doses, the probability of success, but we can also make decisions around the amount of dosing. I still think the kind of a couple 1000 at launch is a good aspirational target for us, but we'll take a more careful look at that.
Over the next couple of months and we might make some additional decisions depending on what yields we achieve and we have lots of room for capacity as well. The short answer is that, you know, we want to be in a position if at all possible to fully service community 1st in the United States and then around the world at launches without any risk that patients will have to wait for our therapy. And that's why we're taking the time now that we have the time with Study 2 to ensure that we continue to to enhance our cross development and to enhance our yields before we would start. And
our next question comes from Danielle Brill with Piper Jaffray. You may proceed.
Hi guys. Thanks for the questions.
A quick follow-up to a previous one. When you decided to expand enrollment in Study 2, did you consider including other patients, older patients with signs of function decline and any specific reasons why you stuck with that 7 4 to 7 year age range? And then I think you mentioned you're planning to open an additional site. Is that also for study too? And I'm just curious from a safety perspective how do you get comfortable with someone other than Jerry administering the drug?
Thanks.
Well, I think that last question is a great one. He is fantastic, but you're going to have to we're going to have to have another site sometime So the good news is that Doctor. Macdowell is very committed to ensuring that we maintain consistent quality as we bring other sites along as well. In fact, we've had good detailed discussions about the fact that we need to have essentially amend those university around the way we approach gene therapy, the way we approach the executions and the like in Doctor. Mendellis, is very much on board for all of that.
So we're very confident about our end to sites that we're going to be, bringing our mind are going to be really top quality neuromuscular the sites with experience in gene therapy. As it relates to the study too, they will be in the 4 to 7 year old range. They will be exactly the same cohort. And they must they must be. And the reason they must be is because our goal is to increase the probability of success, increase the power we went to other age ranges, we would actually create, more standard deviation and we would reduce the power impact.
We couldn't do it because the instance, for instance, older non ambulatory kids, we'd have to use a different measure than NSA. We could use NSA. So, for this study, we have to narrow the focus and ensure that we have the same matched populations so that we have the same confidence around the powering. And as I said before, it's going to be 90%. Study 3, such will not be the case.
In Study 3, we are going to have, a number of different studies that they'll give you their 30 foot per hour. So that's what they're telling me when I call them one study. It'll be in 3a, it'll be a main cohort of stat of patients will have. Older non ambulatory patients in a separate, study as well, but we will cover larger age ranges and different measures in the next step.
And our next question comes from Joel Beatty with Citi. You may proceed.
Hi, this is Shawn Egan on for Joel.
Thank you for taking my question.
I have a few more specifically on yields and capacity. So first, have your initial iCellis lot tests satisfied your yield goals And at this point, is it the expectation that the extra yield optimization process time you described today will raise your maximum capacity estimate or help you reach your original estimates? And I have a follow on question as well.
Yes. So we have we've reached very good, yield in Astellas Nano. We are in the process of scaling Dietellas 500s right now. And the ISO 500, we are not at the optimized number yet, but we're getting, we're getting there. We'll get there.
The issue with and just to understand what that means, this process just takes time every time. If you do a run, you find opportunities to enhance that you make changes and then you do another run and a run takes somewhere in a month or more time frame. So it just takes some time. So short answer is we are getting very good yields in the hunt of what we want in the is nano. We scale to is 100s.
We've made a number of runs in my cell's 500s. We have made a number of improvements, significant improvements every time we do it. And we're very confident we're going to get to the same kinds of yields. We've got the Icels 900 and Icels 500 over time. And then, and there's sort of 2 targets.
There's kind of, there's sort of an optimized target that gets us where we want to go. And of course, if you can get even beyond that, fantastic to give us, which would give us both more capacity as well as lower cost of goods. So the goal here is to get to, as optimize that as possible, yield, really before we start 'seventy three if at all possible.
And our next question comes from Salveen with Goldman Sachs. You may proceed.
This is Ross on for Salveen. Doug, can you just elaborate a little bit further on the current manufacturing situation here? So like regardless of the competitive dynamics that you mentioned earlier, you would need to have your yields fully maximized and your process development optimized. So can you just define what this looks like today versus what it looked like previously? And then I have a follow-up.
I'm trying to, so we're kind of midway through a process. I'd say you know, we're midway through a very, so far a successful process. We're sort of a number of things to do from a manufacturing perspective in a place to launch the therapy. The first thing, of course, is just capacity itself. We've got, we're building a facility with Brammer.
We're just about done with that. That's in Lexington. The next issue, which we haven't talked much about today, we'll talk about it. Over time, there's analytical development, we're doing pretty good progress there. As I said, we've got Doctor.
Reed Clark on board. So we feel very confident that we have the talented place to get all the analytical developments done in a way that's effective. And then the final one is process development and yield optimization. And as I said, just sort of stepwise where we are is we first thing to do is work in smaller EBITDA, mycelis. We've done that.
We've gotten the good numbers there. Now we're moving up to the Icellis 500. We've done a number of, runs there. We're continuing to improve that. So we're kind of in the middle of the process.
Our goal, there's a number of things we have to get to before the the commercial trial. I don't want to suggest that there's not opportunities to continue to optimize after the trial. But we want to get as far along as possible before we start the trial so that even if as we're making additional improvements in yield, for instance, there's no reason would continue to do that. We don't want to find ourselves in a position that we still dramatically, increase yield that we, you know, we have an argument around a new product and we have to do a bridge yet again prove that we have the same product. So, we're in the middle of the process.
Things are going very well. We've got great partners. We've got a lot of folks working on it, a lot of really smart expert folks. We've got Amer joined the work we got Paragon Paragon, is fantastic frankly. They were behind a lot of the AveXis work, has come back to Baragon, but more than all that, we've got our own folks.
We've got Doctor. Reed Clark, we've got 10 icellis units. So we're doing very well. Going very well so far.
And our next question comes from Sam Lugo with William Blair. You may proceed.
And of the new gene therapy programs announced, during the quarter. Will any of those be in the clinic over the next year? And can you are you maybe deemphasizing some of the other previously announced pre clinical programs. And I might have missed it, but do you have a total number for gene therapy programs currently in the pipeline?
We'll have to, I can throw a number out on 2 therapy programs, but I fear I might be wrong. And we'll update our pipeline. We're well over probably a nearly 15 or more programs between preclinical and clinical. Actually, I think that should be a great looking at your life. Hopefully, it was inadequate in that number.
Tied. As I said before, I was going to make an error if I try to do that. We're over 15 and up. We're over the 50, yes, we didn't get it also is grow the 15 programs clinical and preclinical. We're not deemphasizing the preclinical programs that other the clinical programs that we have.
One of the things that we had suggested some time ago is that we're building an engine and we have an aspiration to continue to fuel that pipeline and we're going to continue to do that. So we're, we're, we're very excited about programs we have. We don't want to spend a lot of time talking about this in-depth right now. So that you get a preclinical, and we don't want to go really promotional with, we are currently really exciting cassettes, but research program But, you know, needless to say, these are great areas of focus. When great leaders behind them, we've got, regretted this in the leadership there in addition to the world's leader, Doctor.
Roman, on that. And we've got our own therapy center of excellence and Louise Rodino Klapac who's built the very cassette that we're working on there. We've got Rett Syndrome. We're very excited Red Syndrome as a focus. It aligns perfectly with what we're doing.
We've got a very exciting gene therapy program there. We're very excited about our cardio ability program with Doctor. Sweeny. He's obviously one of the big luminaries in gene therapy. So we're very excited about that.
And Cardiomyopathy is a sort of a natural extension. Of the areas that we've been in neuromuscular admit. And of course, it goes without saying, we are excited about MS. And we're very excited about working with Brad Hopin. It's got a very innovative approach.
It's still research, but it's a very innovative approach. We're going to lean that as well. So we're excited about our research programs and we're not done.
And our next question comes from Joseph Schwartz with SVB Leerink. You may proceed.
Great. Good afternoon. Thanks for squeezing us in. Just two quick questions from us. Doug, so just going back to an earlier question on Zolgensma and Revolution yesterday.
I guess given the numerous similarities, I was wondering, how do you see the Zolgensma revelation a the optimization work here. 2nd is, strategically speaking, as we look forward, you mentioned the status update on TPMO, the SRP 51. So congrats on that. But I guess there's growing competition in DMD with gene therapy, gene editing, as well as antibody conjugated ASO is emerging. So I guess as you think about your base business of antisense oligos, what are your strategies there given how PPMOs may have hit little bit of a delay with safety here and you only have fifty-fifty 1.
Do you have alternatives to maintain that base business? And if so, what would that be? Thanks.
Okay. Let's take this in order. So Zolgensma has 0 effect, 0 read through. And one of that I confident we'll have zero effect on the way the agency looks at other programs. If one looks past, what are really some malicious headlines about this deal largely.
And what one looks at when you go and actually look at the $483,000,000 is this is a very specific issue, not about gene therapy, but about, individuals who may have done something with data manipulation as that's the rate that's being used. With respect to a study. Something that didn't affect the integrity. Apparently, it didn't, for what we've read, didn't affect the integrity of the study, didn't affect the actual outcomes to APM next year, even the approvability of the program, but was concerning because I think what we read there was some question about intentionality in all of them. It was a very specific issue about specific human beings, specific company It does not relate in any way to our program nor do I believe that there's any reason to believe that they would change how the agency would approach other folks in this program.
I mean, it is because we're not saying, one has to be very thoughtful careful and follow, SOPs, good clinical practice in, in research and the data And that's the that was the same answer the day before yesterday. It's the same answer today. So I'm not, at all concerned that this impacts way the agency approaches programs, I mean, it's a very specific issue. The status of it as our T-five thousand and fifty one. And what I do want to make clear, we haven't hit any stats.
I'll say a few things are what brilliant. The issue that we've always had, the open issue with respect to The PPMO is can you get safely to a high dose? If you can get safely to an acceptably high dose, we are very confident mechanistically that we're going to see significant increases in dystrophin production over, our PMOs. In fact, as I said before, you know, it could have literally an order of magnitude better expression. There's a lot of reason to be excited about the PPMOs.
The only reason that we don't sort of promote that concept is I want to see how high we get in remotely ascending dose before we start declaring victory on there. As it relates to the base business and what that means from gene therapy and the like, I would say a couple of things there as well. So first, I would start with this issue about increasing competition. I actually think the competition has moderated over the last 6 to 9 months, frankly. The biggest competition to our PMO PPMO franchise is our own gene therapy.
And so, frankly, we think there is a real possibility that there is a room for both the PML or PPMO if it's successful on the one hand and adjunctively with gene therapy, our micro dystrophin program, on the other, and we're doing work right now. So look at that, we actually have a partnership looking at as well. And we'll have better information about that probably by the middle or so of next year. If it turns out in the long run that the gene therapy is so transformative, that there is a room for a PMO or PPMO thereafter, then so be it, the patient immunity is benefited from that. But we think it's a standard today.
There may very well be a good synergistic benefit of having a PMO or PDMO on one hand and our micro dystrophin program on the arabs. And we feel very confident about a little bit ago.
And our next question comes from Justin Kim with Oppenheimer. You may proceed.
Hi, thanks for taking the question
from Hartaj and me. Maybe just wanted to circle back on the excess gene therapy supply in DMD. Were there any thoughts to loosening the age criteria in order to establish a longer term safety experience in these older patients before a regulatory review?
I apologize. I'm not sure. Look, I'm not sure of the question. I couldn't do it in study too. Because in Study 2, we have to get the powering right.
We will be looking in older patients in Study 3 as well. So we will have evidence both from an efficacy perspective and a safety perspective on non ambulatory patients and older patients and heavier patients. In what I call Study 3 that Doctor. Phil O'Neill rightly noticed is actually a series of sub studies. Okay, got it.
And then is there a target goal of what proportion of the additional patients would come from a second clinical site?
We're going to, we're going to dose as fast as we can. So we're opening the second site to dose both as fast as possible. There's no target. We'll take them all from structure of Mandel if you get some of those from our nationwide, but we'll have a second site very, well repeated second side to assist in that dosing to make sure that there's no risk that we're not going to have at all dosing before we end this year.
And our next question comes from Robbie Raja with Evercore. You may proceed.
Have a dumb question, but
I just wanted to clarify the very specific functional endpoint for the 102 study from which increased the N number gives you great confidence empowering us and the trees, assuming the specific social line point is NSAA. Can you just confirm that? And can we presume that the same endpoint in SAA will be the same when used in 103 to primary functional endpoint. And then as a continuation for the 103 study, when will you be able to give a specific on the N number within the main cohorts of 4.7 and the additional cohorts? Thank you.
So there's a couple So first, on the first two, I can confirm both. It's NSAA in Study 2, and it will be the primary endpoint for Study 3 as well. And, given that we're going to start with Study 3 as early as this rash really possible, in 2020 that we'll certainly come back to, in early 2020 and give you an update with more particulars around with cost savings.
And our next question comes from Tim Chiang with ETIG. You may proceed.
Hi, thanks, Doug. I think you mentioned, that Doctor. Mendel might be presenting some limb girdle data at WMS. I mean, what the functional data would be, just the 3 patients that have been dosed that are or the data that you've shown in the 3 patients that were dosed, MY0101. Is that right?
It'll be the functional data, yes. So as you may recall, we asked data in the first quarter of this year on IIE program, we are very pleased with the results of an expression level and a safety perspective as well, given the size of these kids, one of the interesting. These are the largest kids that have ever been dosed, as far as I'm aware of the full infusion gene therapy there and thirteen year olds to have them. But we were, there was 2 we had just literally dosed the 3rd child, so we couldn't get functional data. So the goal at World Muscle would be to, to present functional data on those first three kids.
And our final question comes from Lisa Bayko with JMP Securities. You may proceed.
Hi, thanks for taking the question. It's squeezing me in.
Just to
clarify, study 2 will capture the functional endpoint that you'll use for filing in addition to studies 3 showing expression. And at that point when you get expression data combined with Study 2 functional, you'll file, you're not going to wait for the Functional data from Study 3. Is that correct?
That is our goal. Now one of the things we need to do when we build down Study 3 on plans, sit down with the agency, confer with the agency and get their, thereby into the approach that we're taking. But our current goal is to have, study 3, we'll have functional data as well eventually, but to have, in a sub cohort of Study 3 to look at the impression level and show comparability between clinical supply and commercial supply. Yes. And you know, Jeremy, I think that's we're talking about FDA issues right now that U S, that's the approach in the U S, assuming that the FDA agrees with the approach that we're taking.
And then of course, we'll have to consider what approach we take ex U. S, because as you, I'm sure you know, our goal is to bring this therapy to as many patients around the world as to benefit from it as rapidly as it's possible.
Okay, great. And then just to also, just how do we think about or how do you think about what is comparable? Because obviously there's variability in expression from patient to patient. And this is kind of not exactly like a bio equivalency study. So what, I guess, what is the tolerance around some of those things to say?
It's actually the same. I'm curious about how you think about that.
Well, that'll be obvious. It's subject to discussion with the agency, obviously, on business early days in gene therapy. So, we'll have a lot of to talk about. But there's a lot of different ways to look at measurements because potency, plus CFC related issues. And we also have what others would you have in a number of other programs, for instance, if you wouldn't have had it in SMA, we have buyouts.
So we do have a good way to triangulate on comparability between commercial supply and clinical supply. And then of course, we'll have to talk to the agency about what level of tolerance is, is, permissible between supply and commercial support.
Okay, great. Thanks a lot.
Thank you very much.
Ladies and gentlemen, this now concludes our Q And A today's call. I'd now like to turn the call back over to Doug Ingram, CEO, for closing remarks.
Well, thank you all very much for spending this evening with us as we updated for the second quarter, on our, our performance of the second quarter and our flight path forward, we have a lot to do in 2019. I hope I'm impressed upon everyone on our perspective on this. We have we are in a privileged position as an organization respect to some of our programs right now. We don't take that privilege position for granted. We don't intend to slow down as a result of that.
And we don't intend to develop any form of arrogance. In fact, we want to approach all of the work that we have in front of us with an enormous amount of humility. We have a lot to do this year. We have to continue to perform with EXONDYS 51. We have to bring forward Golodirsen's assuming that we are successful by August 19th.
We have to submit for casimersen. We have to continue to push forward our various gene therapy programs to at these case dosed in the micro dystrophin study 2, get our process development and capacity for our micro dystrophin gene therapy program, done by the end of this year. So we can start dosing patients in our Study 3, and we'll give you additional updates over the course of as we progress against our goals.
Today's conference. This does conclude the program and you may all disconnect. Everyone have a great day.