Sarepta Therapeutics, Inc. (NASDAQ:SRPT) Q3 2020 Results Conference Call November 5, 2020 4:30 PM ET
Mary Jenkins – Senior Manager, IR
Doug Ingram – President and CEO
Ian Estepan – SVP, Chief of Staff and Corporate Affairs
Dr. Gilmore O’Neill – EVP, R&D and Chief Medical Officer
Conference Call Participants
Jack Allen – Baird
Tazeen Ahmad – Bank of America
Emma Nealon – Cantor Fitzgerald
Anupam Rama – J.P. Morgan
Gena Wang – Barclays
Joseph Schwartz – SVB Leerink
Colin Bristow – UBS
Brian Abrahams – RBC Capital Markets
Ritu Baral – Cowen
Vincent Chen – Bernstein
Tyler Van Buren – Piper Sandler
Shawn Egan – Citi
Difei Yang – Mizuho Securities
Max Skor – Morgan Stanley
Matt Terwelp – Credit Suisse
Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics Third Quarter 2020 Earnings Call. At this time all participants’ lines are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions] As a reminder, today’s program is being recorded.
At this time, I’ll turn the call over to Mary Jenkins, Senior Manager, Investor Relations. Please go ahead.
Thank you, Catherine, and thank you all for joining today’s call. Earlier today, we released our financial results for the third quarter 2020. The press release is available on our website at sarepta.com, and our 10-Q was filed with the Securities & Exchange Commission earlier this afternoon.
Joining us on the call today are Doug Ingram, Ian Estepan, Dr. Gilmore O’Neill, and Dr. Louise Rodino-Klapac. After our formal remarks, we’ll open up the call for Q&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 slides on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta’s 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 operations and trading prices for Sarepta’s common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the Company’s most recent annual report on Form 10-K and most recent quarterly report on Form 10-Q filed with the SEC as well as the Company’s other SEC filings. The Company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today, based on subsequent events or circumstances.
With that, let me turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?
Thank you, Mary. Good afternoon, everyone. And thank you for joining Sarepta Therapeutics third quarter 2020 investor conference call. Tonight, I’m very proud to share with you the progress we have made this quarter, including our performance and serving the Duchenne community with EXONDYS 51 and VYONDYS 53, our progress with respect to our RNA platform and the strides we’ve made in building out our enduring gene therapy engine. But, I’m going to take things a bit out of order this evening. I’m going to commence to this call by discussing an important milestone for Sarepta and for the Duchenne patient community. As you will have read in our press release today, having worked with the FDA, we now anticipate dosing a trial with commercial process material this year.
Let me provide some background and context. As you will know, SRP-9001 is our gene therapy, and the goal is to treat Duchenne muscular dystrophy by safely delivering the skeletal, diaphragm and cardiac muscle, a gene that robustly codes for a truncated functional form of the structural protein dystrophin that we call micro-dystrophin.
Children with DMD make essentially no dystrophin, which results in rapid degeneration and inevitable death, and the goal is to arrest this degeneration by giving them back a properly localized, functional form of that structural protein.
After many years of design and preclinical testing by doctors, Jerry Mendell and Louise Rodino-Klapac, we commenced and completed a small four-patient proof-of-concept study, Study 101, that was positive and very encouraging. The therapy was well-tolerated; the gene was indeed robustly delivered to the target muscles, about 3.3 genome copies per nucleus. The expression of the protein approached nearly normal levels, and on all functional measures the children continued to improve in ways that cannot be explained by natural history.
Based on this proof-of-concept study, we commenced a randomized blinded placebo-controlled trial, we recall that as Study 102. Study 102 is intended to show a well-controlled trial of SRP-9001 is safe and effective in children with DMD. The last one year visit will occur in December, and we plan to release results from Study 102 in the first quarter of 2021.
Now, the material for Study 101 and 102 was manufactured by our partner, Nationwide Children’s Hospital, pursuant to a process that will not scale for large commercial purposes. Over the last two years or so, we have developed a commercial process, and we’ve built significant manufacturing capacity. Assuming SRP-9001 proves effective, these efforts are expected to provide us capability to produce and launch a commercial product to fully serve the community.
By early 2020, we completed our process development and analytical development, and we commenced our GMP runs for SRP-9001 commercial process material to use in future clinical studies.
In the summer of this year with GMP material in hands to conduct additional studies, we requested a meeting with OTAT. OTAT is the division of the FDA responsible for cell and gene therapy. And we did that to obtain their blessings to commence a commercial material validation study.
We originally contemplated a larger 70-patient blinded placebo-controlled trial called Study 301. However, in light of the likelihood of a second wave of COVID-19, which now may be coming to fruition, and the risks it poses to clinical trial participation and execution, in anticipation of our September Type C meeting, we proposed a leaner, open-label commercial material validation study, Study 103 in the same patient population, as Study 102, our ongoing with placebo-controlled trial.
The goal of Study 103 is to gain insight and validate the performance of our commercial process material on both micro-dystrophin expression and safety in up to 10 patients with the primary analysis or part one of the study conducted at 12 weeks, post infusion, in all treated patients. Our Type C meeting with the division which was conducted entirely in writing, occurred in September of this year. In its written response, the division raised concerns with the potency release assay approach that we had proposed.
As I stated, at the time, if it’s occurred, if we were to follow a formal process to resolve our issues with the division, it would have taken a minimum of a matter of months and could have extended into next year. However, I am pleased to report that the division was willing to work with us expeditiously and informally, to discuss the issues to provide guidance to us, and to provide us with a pathway to commence our commercial validation study this year. Indeed, the division moved quickly to meet with us in late September. And we’ve spent the time since then gathering the data necessary for our updated potency assay approach for Study 103 and finalizing the meeting minutes.
Based on those discussions, the status and the next steps of our program are these: First, after discussion and obtaining division guidance, we proposed and the division accepted a potency assay approach for Study 103. We have already completed the work and generated the data for the new potency assay approach for Study 103. Second, the division will permit us to commence Study 103 which we intend to do before the end of this year. And third, to remind you, Study 102 will have the last 12-month visits in December of this year, and we will report the results of Study 102 in the first quarter of 2021.
Depending on the external environment and the pandemic, we anticipate speaking with the division and starting our largest Study 301 in 2021, after we have data available from Study 103. We also intend to design and propose to the division for their review and input, additional studies including importantly, in older and non-ambulant patients.
I would like to thank OTAT for their responsiveness and their willingness to informally and rapidly meet with us on this extremely important program, even in the midst of a pandemic that has placed additional burden on an already overworked group of professionals at the FDA, so that we may embark on Study 103.
Now, staying with the build of our gene therapy engine, over the course of this quarter, we’ve had a number of very-positive updates. As you will recall, back in June, the one-year results for Study 101 were published in JAMA Neurology, reporting robust expression, good tolerability and safety, and functional improvements across all measures in the cohort of Duchenne boys in that study.
At the World Muscle Society Conference in the third quarter, we provided an update on Study 101, reporting not only continued safety and tolerability, but also durability of effect, with all boys continuing to show functional benefits of the gene therapy at two years.
At World Muscle as well, we also provided updates on our three-patient cohorts for SRP-9001 for the treatment of limb-girdle muscular dystrophy type 2E, or LGMD2E. Cohort 1 was dosed at 5 e to the 13th and Cohort 2 was dosed at 2 e to the 14th, same dose used in our studies for SRP-9001. As you will recall, both cohorts were generally well-tolerated with a significant dose dependent increase in expression in Cohort 2.
At World Muscle, we reported the 18-month results for Cohort 1, showing not merely stabilization, but a substantial improvement in function above baseline and above natural history. We also reported the early 6-month data for Cohort 2, where the children are already showing not near stabilization of function, but improvement in function, again, against both baseline and against natural history. We are particularly pleased with these LGMD2E results, and in particular, the safety, expression, biomarker and functional results of Cohort 2. And so that’s potential read through to our remaining LGMD portfolio and supportive confirmatory read through to our SRP-9001 program in DMD as the program shares the same vector, the same promoter, the same design approach, and then in case of Cohort 2, the same dose as well.
With respect to LGMD2E, we are completing manufacturing material for our next trial, and we’ll engage with the agency on the design for what we hope will be the pivotal study. We will provide an update on both of these matters, and our perspective on the development and regulatory pathway and timing for our entire LGMD portfolio in 2021.
We continue to build our gene therapy platform and gather technologies to improve and enhance gene therapy. Over the course of 2020, we have completed some 22 gene therapy-related transactions, 20 of which were completed since this pandemic sent us all to a largely work-from-home environment. We also have what is likely the largest pipeline of high-potential gene therapy candidates in biopharma today. We are considering an R&D Day in 2021, at which we can update on our entire pipeline of gene therapy and RNA, and we will provide more details on this early next year.
Moving on now to our RNA platform. Let me now discuss our commercial performance in the quarter. As you will recall, in light of the dynamic and unpredictable nature of the COVID-19 pandemic, we withdrew our guidance for 2020. Nevertheless, due to the collaborative work of our multidisciplinary team, I am pleased to once again report that we’ve been able to serve the Duchenne community with our approved therapies with only modest impact from the current pandemic.
For our PMO franchise, currently EXONDYS and VYONDYS, our net product revenue for the quarter is $121.4 million, and that represents a nearly 23% increase over the same quarter last year. As we have never taken a price increase on our therapies, our performance relates directly to our ability to serve the patient community.
We continue to monitor performance closely as we are indeed in uncertain times. It is important to our patient community that they have an uninterrupted supply of therapy. While challenging, we have been able to largely ensure that this is the case, in part due to great execution from the team and also due in part to the fact that the vast majority of our patients receive in-home infusions rather than having to go into a clinic or hospital, and also due to the fact that thus far, the majority of payers have responded positively in this pandemic and have shown flexibility in authorizations and re-authorizations for this vulnerable DMD patient community.
Now, moving to our PMO pipeline. The FDA has accepted our filing for our third Duchenne therapy, casimersen, a PMO therapy intended to treat those 8% of Duchenne patients, who are amenable to skipping exon 45. The brand name for casimersen will be AMONDYS 45. Our PDUFA date is February 25, 2021, and the review is going well. If we obtain approval for casimersen, we will have three approved therapies, capable together of treating nearly 30% of the DMD community. And as we have mentioned before, our RNA technology has the potential to bring therapies to as many as about 85% of patients living with DMD. So, we do have much left to do.
As you will know, we are also making progress on our next generation of the PMO, which if successfully, may profoundly improve the efficacy and convenience of our RNA technology. We are in our multi-ascending dose study, called the MOMENTUM study for our peptide-conjugated PMO or PPMO, and that’s candidate SRP-5051.
To remind you, we are using a proprietary positively charged peptide to increase penetration. In animal models, we have shown that if we can safely achieve appropriate dose levels, the PPMO greatly increases tissue exposure, in turn, greatly increasing exon skipping and thus dystrophin production.
Before the end of this year, we will provide an update on the safety — systemic exposure in exon skipping for our PPMO SRP-5051 candidate at 20 mgs per kg. And for us the most important measure of all of these, and I’ve said this many times in the past, will be safety. Consider the following. Our PMOs are safe and they’re precise. Their ultimate limitation, however, is that they are also mutually charged. They penetrate muscle cells passively, and they clear the body in about four hours. This will limit the amount of therapy that can get to the right place. And simply increasing the dose will not reverse this limitation.
Our PPMO technology, on the other hand, potentially addresses this limitation in a dose dependent way. Indeed, our preclinical models have consistently shown that if one can safely dose the PPMOs to a sufficiently high level, we should hit a point where we get a significant increase in cell exposure and a great increase in exon skipping and dystrophin production. And that should translate into a great increase in benefit to patients living with Duchenne muscular dystrophy.
Our most significant question in the MOMENTUM study has always been safety upon repeat dosing and maximum dose. We will present the 20 mg per kg results this year. So, we have already moved to 30 mgs per kg, and intend, if safety signals will permit, to continue to dose even up to 40 mgs per kg early next year, and ultimately potentially even higher than that, if we are able to do so.
While we can make some educated guesses from animal models, until we observe it in human clinical trials, we can’t know with any certainty, precisely where the inflection point on exposure and dystrophin will occur in patients, purely based on animal studies. But, what we are confident about is the PPMO’s mechanism of action, which means we are very confident that if we can safely achieve high enough doses, we should see a very-substantial increase in dystrophin production. So, not to belabor this point, but it is all about safety, safety signals and maximum tolerated dose, at this point.
In conclusion, notwithstanding the unusual external environment, the team continues to execute with an unrelenting purpose. And the third quarter of 2020 perfectly exemplified our culture of performance. Consistent with our message — our mission, apologies, we kept the patient front and center in everything we did, which gives me focused on the science, we continued to execute with a sense of urgency that our mission requires, and when faced with inevitable obstacles and roadblocks, we did not simply accept them or regressed to the mean, but we moved with rapidity and creativity to address them to remove them and to keep progressing towards our ultimate goal of intervening and saving the lives of as many children living with and dying from Duchenne, limb-girdle muscular dystrophy, and other rare diseases as science will make possible.
And with that, let me turn the call to Ian Estepan, who will update on the financials.
Thanks, Doug. Good afternoon, everyone.
This afternoon’s press release provided details for the third quarter of 2020 on a non-GAAP basis, as well as a GAAP basis. The press release is available on Sarepta’s website. Please refer to our press release for a full reconciliation of GAAP to non-GAAP financial results.
Now, starting with our net product revenue for the third quarter of 2020 from our products EXONDYS 51 and VYONDYS 53, was $121.4 million, compared to $99 million for EXONDYS 51 alone for the same period of 2019. The increase primarily reflects higher demand for our products.
In the quarter ended September 30, 2020, we recognized $22.5 million of collaboration revenue, which relates to our collaboration arrangement with Roche. The co-development costs under the Roche agreement totaled $16.9 million for the third quarter and are included as a reduction for our operating expenses.
On a GAAP basis, we reported a net loss of $196.5 million and $126.3 million or $2.50 and $1.70 per basic and diluted share for the third quarter of 2020 and 2019, respectively. We reported a non-GAAP net loss of $111.5 million or $1.42 per basic and diluted share in the third quarter of 2020, compared to a non-GAAP net loss of $84.4 million or $1.14 per basic and diluted share in the third quarter of 2019.
In the third quarter of 2020, we recorded approximately $15 million in cost of sales, compared to $13 million in the same period of 2019. The increase is primarily due to increasing demand for our products.
On a GAAP basis, we recorded $190.4 million and $133.9 million in R&D expenses for the third quarter of 2020 and 2019, respectively, which is a year-over-year increase of $56.5 million. This increase is primarily related to a $42.5 million increase in manufacturing expenses, primarily due to the continuing ramp up of our gene therapy programs. On a non-GAAP basis, R&D expenses were $159.9 million for the third quarter of 2020, compared to $110.5 million for the same period of 2019, an increase of $49.4 million. The year-over-year growth in non-GAAP R&D expenses was driven primarily due to a continuing ramp-up of our gene therapy.
We recorded approximately $75.4 million of expenses for both of the third quarters of 2020 and 2019. On a non-GAAP basis, the SG&A expenses were $57.2 million for the third quarter of 2020 compared to $59.6 million for the same period of 2019, a decrease of $2.4 million. The year-over-year decrease was driven by a decrease in professional services, primarily due to a decrease in reliance on third-party contractors as a result of an increase in hiring and headcount. On a GAAP basis, we recorded $14.3 million in other expenses net for the third quarter of 2020 compared to $2.5 million in other expenses net for the same period of 2019. The unfavorable change primarily reflects the interest expense on our debt facility we entered into in December of 2019.
And finally, we had approximately $1.8 billion in cash, cash equivalents and investments as of September 30, 2020.
And with that, I’ll turn the call over to Gilmore for an update on our research and development activities. Gilmore?
Dr. Gilmore O’Neill
Thank you, Ian, and good afternoon, everyone.
Doug has already shared the highlights from our most advanced gene therapy programs. I will therefore focus my remarks on Sarepta’s presentation at this year’s World Muscle Society Congress and the progress we’ve made in advancing our RNA portfolio. Let me start with the World Muscle highlights.
This year’s meeting used a virtual format because of the ongoing COVID-19 pandemic. Nevertheless, we were able to present 16 posters that described data across Sarepta’s RNA and gene therapy platforms.
From our gene therapy platform, the non-clinical and clinical data that we presented support the hypothesis that the rh74 MHCK7 construct we use generates durable gene positive expression and durable physiological benefits in skeletal muscle.
Dr. Rodino-Klapac’s lab demonstrates durable sarcoglycan expression, histological benefit and significantly increased resistance to contraction induced injury in the tibialis anterior muscle in AHS, [ph] alpha and beta sarcoglycan knockout mouse that has been treated, respectively with alpha sarcoglycan or beta sarcoglycan transgene containing rh74 construct.
Moving to clinical data. We announced positive two-year functional results in support of our lead gene therapy candidate, SRP-9001 in Duchenne patients. The results demonstrated that two years after a onetime infusion of SRP-9001, trial participants exhibited a mean 7.0 point improvement in the North Star Ambulatory Assessment or NSAA, as compared to baseline. Please note and remember that at one year post treatment, the mean increase was 5.5 points from baseline. Thus, this functional data reflect a mean 1.5 point NSAA improvement between years one and two post SRP-9001 infusion.
These data were generated from four ambulatory participants aged 4 to 7 in Sarepta’s open-label trial Study 101, and showed continued safety and tolerability of a onetime infusion of SRP-9001 at a dose of 2 to 14 viral genomes per kilogram.
We also announced positive clinical data for SRP-9003, our gene therapy candidate for limb-girdle muscular dystrophy type 2E. These results included 18-month functional data from three clinical trial participants in Cohort 1, the low-dose cohort and six-month functional data from three participants in Cohort 2, the high dose cohort, which was dosed at the same dose level we are using for SRP-9001 that is 2 to the 14 viral genomes per kilogram.
We demonstrated Cohort 1 that three participants continued to show improvements from baseline across all functional measures, including the North Star Assessment for Dysferlinopathies, otherwise, the NSAD in addition to time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk run test at 18 months. The mean NSAD improvement from baseline in Cohort 1 was 5.7 points at 18 months. In Cohort 2 at 6 months post infusion, all three participants demonstrated improvement from baseline across all functional measures. The mean NSAD improvement from baseline in Cohort 2 was 3.7 points. This compares to a 3.0-point change in Cohort 1 at six months. Based on the safety, expression and clinical results, we are moving to high dose cohort for future clinical development of SRP-9003.
To sum up these presentations, we are very pleased that both therapies seem to be well tolerated. The clinical data presented at World Muscle from the micro-dystrophin, SRP-9001, 101 Study and the limb-girdle muscular dystrophy 2E, SRP-9003, 101 Study, support durable functional outcome at the two-year and 18-month time points, respectively. This further supports our hypothesis that because muscle is a term differentiated [ph] tissue, it does enables a durable benefit following a single administration of the gene therapy.
As you know, we are developing six additional therapies or six different therapies for the treatment of six subtypes of limb-girdle muscular dystrophy. We also presented non-clinical data at WMS, supporting the transition of our next limb-girdle construct limb-girdle MD2C into the clinic.
Sarepta also presented data generated from its RNA platform. These included long-term safety data for golodirsen from the 4053 101 clinical study supporting a safety profile. PK/PD data for casimersen from the 4045 101 clinical trial, demonstrating dose proportion exposure and an interim analysis of casimersen treated patients in the essence pivotal study showing a statistically significant increase in skeletal muscle dystrophin expression from baseline to 48 weeks.
All in all, we were happy to be able to share so much data across our comprehensive portfolio with the academic, prescribing and patient communities. Beyond the data we shared at WMS risk, there have been numerous developments across our RNA platform. The FDA review of our NDA for our lead PMO candidate and AMONDYS 45 is ongoing and from all accounts going well. Our PDUFA date stands at February 25, 2021, and the FDA has indicated, it does not currently plan to hold an advisory committee meeting to discuss the application.
Moving to our post-marketing commitments study for EXONDYS 51, also known as the MISSION study, we are pleased that we have enrolled part 1 of the dose escalation arm, and we are in discussions with the agency about the timeline for the study.
Before I turn to our PPMO platform and the PPMO SRP-5051 program with DMD specifically, let me give you an update on the USAMRIID collaboration. In late April, we announced an early research collaboration with USAMRIID that would exploit our PPMO technology as a potential therapeutic for COVID-19. More recently, and based on our in vitro results, we are planning to initiate a proof-of-concept in vivo study in collaboration with USAMRIID.
Now, turning to our PPMO development programs for Duchenne muscular dystrophy. The key element of Sarepta’s R&D strategy is to enhance tissue or muscle penetration of our PMO chemistry and thus enhance efficacy by increasing dystrophin expression. We have a number of research programs that support this strategy. To remind you, our PPMO platform uses a cell-penetrating peptide, or CPP, to a PMO to enhance cellular and nuclear penetration. Our most advanced PPMO program is SRP-5051. Our ongoing SRP-5051 201 multi-ascending dose trial named MOMENTUM is advancing.
We are pleased to say that we continue to escalate doses to levels higher than was originally planned at the initiation of this program. This is because to date, we have not seen clinical metro toxicity in our PPMO clinical trials, and no new safety signals have been observed across all studies, thus enabling us to keep escalation doses in the MOMENTUM trial. We have now commenced dosing SRP-5051 in the 30-milligram per kilogram cohort. This year, we will be reviewing 12-week data from our 20-mg per kg cohort in Duchenne patients treated with our PPMO candidate, SRP-5051. We will be examining systemic PK, tissue penetration, safety and exon skipping efficiency data.
I remind you that our preclinical in vitro and in vivo models have demonstrated a robust correlation between the amount of exon skipping efficiency and the amount of dystrophin production. We presented SRP-5051 preclinical data at the OTS meeting in late September, in which the PK/PD of SRP-5051 was evaluated in non-dystrophic nonhuman primates. A single dose of SRP-5051 resulted in sustained exon 51 skipping that was maintained for at least 28 days. This sustained exon skipping supports the Q4 week dosing regime currently being studied in the clinic. We also observed repeat at Q4 week dosing of SRP-5051 for 12 weeks, demonstrating a cumulative exon skipping effect that increased after each infusion.
For SRP-5051, we will measure exon skipping efficiency by digital drop PCR or DDPCR, allowing us to directly compare the efficacy of our PMO and PPMO candidates. Now, it is important to note that while 12 weeks is an early time point to assess exon skipping, we are confident that this is an appropriate time point to demonstrate proof-of-concept that the CPP or cell penetrant peptide enhances muscle tissue exposures and thus enhances downstream exon skipping efficiency.
So, although the data we generate will not be representative of steady stage efficacy for SRP-5051, it will determine if we should move this technology forward with the urgency necessary to meet the needs of patients with Duchenne. Now, whereas we are examining 12-week time points in the dose escalation part of the mentioned study, we will be using legacy 24-week data from PMO versus comparison. That will remind you that dystrophin accumulates over time. And so, based on observations and prior PMO studies, we will expect to see higher levels of dystrophin at a later time point if the therapy is successful. Indeed, muscle biopsies at later time points are planned in the latter part of the MOMENTUM study once we have selected our final dose for SRP-5051.
Finally, I want to thank all of the patients, their families, study sites and coordinators, my R&D colleagues and our partners who have done so much work under incredibly difficult circumstances to maintain our urgent mission to deliver new, highly effective therapies to people with rare diseases within the context of the ongoing COVID-19 pandemic.
Now I will hand back to Doug for Q&A. Doug?
Thank you very much, Dr. O’Neill. Catherine, let’s open the lines for Q&A.
Thank you. [Operator Instructions] And our first question comes from Brian Skorney with Baird.
Hi. Thank you. This is Jack dialing in for Brian. So, just one question really from us. What do you expect to see from the 10-person clinical trial you’re expecting to initiate? And will the data be strong enough to show its effect compared to the data that you have in Study 102? We know there’s significant variability within the first four patients of data looking at the Phase 1 trials for the DMD product. And we’re just wondering what the lower and upper bound of confidence are with respect to the dystrophin measurements that you’re looking at for this new planned clinical trial? Thank you.
So, first, let me answer the latter part of the question first. 10 patients is very sufficiently powered to obtain the data that we’re interested in obtaining. Let me explain what this is about. So, let’s go back. Remember, for some time, we had been thinking about a larger placebo-controlled trial using commercial material, and we’ll still do that at some point as well. There was a number of reasons for that study, which is called Study 301, of course. One is global purposes. The other is additional confirmatory data. Remember, we’re going to have Study 102 that’s going to read out at the beginning of next year. So we’re already going to have results from Study 102, both on safety and function of the construct. But the other thing that we would get out of Study 301 is larger study and acutely the thing that we are most interested in to get as quickly as possible is validation of that commercial material. This is the same construct, but generated using a different process and a different manufacturing process, as you know, and I saw those units.
And so, what we had planned with respect to 301 is to get what we really are most interested in right now. We would do an interim analysis of a subset of those patients around the same subset is what we’re actually going to do with 103 early next year. So, we would start that study, but we would actually get the real data that we’re curious — we’re most interested in right now, which is the validation of our commercial material, both on expression and on safety early next year. And then, of course, in the summer, as we thought this through, we watch the external environment, we thought about the risks associated with a larger study, the potential risk to patients for another placebo-controlled study as one example in the midst of a pandemic and exposure from the pandemic, as well as just the risk of the program and the execution of the program, it dawned on us that there is a far more efficient way in the mix of this pandemic to get exactly the same information, and that’s where we revise the concept of Study 103. So, there is no reason to do a placebo-controlled trial for the expression that we’re looking for in for the safety that we’re looking for, and we’ve always known we only needed about 10 patients or so, 8 to 10 patients to get that information.
And so, rather than getting that information out of a larger study, large multi-center, multi-country study, we should also propose a leaner approach, which is Study 103, and that’ exactly what we did. And as you know, we went to the agency in writing in September with this proposal, the big issue that occurred, of course, in the September meeting, which is, I think we all know, was all on written record was that the agency had questions and ultimately had issues with the approach that we were taking to release assets for Study 103. That could have taken us a long time to resolve, frankly. It could have taken us somewhere between 2, 3, maybe 4, 6 months, just to get an answer from it. I’m really pleased to say that — the vision was really to meet with us informally. They met with us in September. So, we’re very clear about that. We came to an alignment in September. They agreed to our updated approach on potency assay. We spent the time since late September doing two things at the same time, of course, finalizing the meeting minutes of that discussion with the agency, but also gathering the data for our alternative approach to the potency assay. And as we sit here today that data is all done, the minutes are done, and we should be able to start 103 by the end of this year, which means sometime in 2021, really on the earlier side of 2021, hopefully, fairly close to one another, we should have both, a readout of Study 102, which will show us both, the efficacy, the functional benefits in a well-controlled placebo-controlled trial, blinded trial from 102 with respect to SRP-9001, we’ll have safety readout from that study as well, and we’ll have the commercial validation results from Study 103, which will have micro-dystrophin expression results, will have safety results out of that study at the 12-week time point as well, which of course, is a crucial time point from a safety perspective.
We also will have a wealth of additional CMC related information, much of which we’ve already gathered. And at that point, of course, we will sit down with the agency and talk about the steps forward. The one thing we all know, of course, all of us are well aware that in the United States and then around the world, every single day, thousands and thousands of children wake up in the morning with Duchenne muscular dystrophy. And throughout that day, they degenerate. And unfortunately, every week and every month some percentage of those kids die. So with all of that information available to us, we’ll sit down with the agency and figure out what is the fastest approach to getting this therapy to the kids that are waiting. And hopefully, at the time we have that and of course, studies have the scientist to cooperate and studies have to come out the right way. We should be able to sit down with them armed with the information that shows, if we’re successful, that SRP-9001 is the safe and effective, and then the commercial material has been validated along with the clinical performance that we’ll see out of Study 102.
So, thank you for your question.
Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.
Doug, just to stay on topic with Study 103. So I just want to make sure I understand this. You were not doing a specific potency assay, but you are using Study 103 in lieu of a specific potency assay. Just want to confirm that. And then, secondly, do you still have to do Study 301? Is it still part of your assumption that you will need to submit study 2 plus now Study 103 and some data from 301, or is it your plan to go talk to FDA to see if you can apply, assuming that the study 2 and 103 show what you want those to show and not necessarily have to do 301?
Thank you for the questions. Let me clarify something that I might have created to confuse you about. Now Study — we have come to an understanding with the agency on the assay approach to Study 103. As you may recall, as we said at the time that we had the Type C meeting, we had an approach that we thought was appropriate with respect to the potency release assay for Study 103. The division had questions and disagreed with the approach that we were taking. We didn’t have clarity on precisely what that — those issues were. And if we had gone through a formal process, it could literally have taken 2 to 6 months to ultimately have enough clarity to know where to go. By the end of September, we had an informal meeting with the agency, we understood much better what their issues were, and we were able to quickly propose essentially a new potency approach that they found acceptable. We then gathered the data for that. That’s already done and completed. And so, we have the potency approach now for Study 103, and that allows us of course to start Study 103.
With respect to Study 301. So — and Study 103 will get us exactly what we wanted out of an interim analysis from Study 301. So, really, it is a very thoughtful approach to a pandemic, to gather the information through Study 103 and get the most salient information in the near-term when we get 102 read out, which is that in patients and in biopsies we could show that as we would predict from all of our CMC work, the material and Study 103 from a commercial material perspective will perform in a similar way, both from micro-dystrophin expression and also from a safety perspective.
With respect to Study 301, there’s still lots of reasons to conduct Study 301. First and foremost, that is a global study. We have global ambitions. It is our goal to get approvals around the world. And of course, Study 301 will provide us with that opportunity. The second thing to know, of course is that it will be additional confirmatory evidence that regardless of the pathway forward in the United States or anywhere else around the world would be additional information, would be valuable as we were bringing this therapy out to patients. And the third, of course, is we need to — I don’t want to — I want to be very clear about something that I think I’ve said many, many times before, which is that we are going to sit down with the agency and talk about the pathway from a regulatory and development perspective, once we have the readout from Study 102, and now the readout from this commercial material validation Study 103. And we’ve been very clear about this. I remain resolute that this is the right approach. We explicitly said we weren’t going to discuss this with in advance of the Type C meeting and after the Type C meeting. So, we’ll get into next year, we’ll get the results of 102. If it’s successful, we’ll have shown in a well-controlled trial, but our therapy has created functional benefits, and it’s doing a lot of good for these kids and that it’s safe. We’ll have the commercial validation material out of Study 103, hopefully not far after that. And then, with all of that, armed with that, we will sit down with the U.S. FDA and the division and talk about what — in light of the quality of the data and the data that we have, what is the most appropriate and the fastest way to get this therapy if it’s safe and efficacious to kids that are waiting for in the U.S. That’s a conversation, obviously, we’ll have after we get the data in hand.
And our next question comes from Alethia Young with Cantor Fitzgerald. Your line is open.
This is Emma on for Alethia. So, given the agreement here with the FDA on Study 103 is kind of a leaner approach for getting the most important information for 9001 in the midst of COVID. Is there — do you expect kind of similar flexibility for 003 in LGMD to support a streamlined pivotal program?
We won’t know that until we have conversations with them, obviously. So, I don’t want to make any presumptions. One of the things that we said is that we need to do a couple of things with respect to — this is for limb-girdle, I assume you’re saying 9003. We have to do it to get the GMP material completed and released. We’re still working on that. We’ve actually got the process development done, and we’re running a process development run. We have a lot of analytical work to do as well. Obviously, the work that we’ve done recently with the agency is going to be very helpful to 9003. And then, with that in hand, we want to sit down with the agency and talk about the next trial and hopefully, what we would like to believe will be our pivotal trial for 9003. But, we’ll give an update on that early next year once we have that framed out. Obviously, as we’ve seen, given the pandemic in [indiscernible] the agency is the opportunities to have discussions with the agency are formal, and we’ve got to be very thoughtful about that. So, I want to make sure we have the right kind of information in hand when we have those discussions. And then, we can give a better view on what the pathway forward is for 9003.
Our next question comes from Anupam Rama with J.P. Morgan.
I’m sorry. I’m just a little bit confused. So, for Study 103, looking at safety and some of the assay comparability work, right, and I think that’s at 12 weeks, and you called that part one. So, are there additional parts of the study where you’ll be looking at more functional type of measures? And as the FDA indicated any sort of interest in seeing that before you have some of the regulatory discussions, right?
Yes. It’s a great question. No. Look, this is an open label study. The goal of SRP — goal of Study 103 is to get essentially exactly what we would have gotten out of an interim analysis for 301. It is essentially precisely the same thing. The reason I mentioned that is part one is, of course in these studies, you’ll have longer term safety follow-up. And so, in a sense, the study maintained even after you get the primary readout from it. It’s the same with all of our studies. It’s the same with frankly Study 102. We’ll have Study 102, we’ll have the readout from a primary analysis, one year analysis that will be — with the kids crossed over, et cetera, and we’ll look at the results, and we’ll see if — as we have hypothesized, we’ll see a statistically significant and meaningful improvement in NSA versus placebo. And then, of course, that study will continue. Those kids will continue to be monitored from a safety perspective. So, that’s what we mean when we say part 1, part 2, but the real goal of Study 103 is essentially to get in a sort of a more straightforward, leaner way, the information that we were looking to get out of an interim analysis of Study 301, which was the previously proposed placebo-controlled trial.
Our next question comes from Gena Wang with Barclays.
So, maybe Doug, just wondering, what is the criteria for approval. Will Study 102 plus Study 103, would that be sufficient? And also, did the FDA already signed off the potency assay? And do you still need to do the release assay in order to get approval? And in the case you have to run Study 301, do you need to run another potency assay for Study 301?
So, the FDA signed off on our approach to the release assay for Study 103. I can’t tell you what the requirements will be precisely for an approval because as I think we’ve said a number of times in the past, talked about it, we’re not going to broach that issue and have those discussions with the agency until we have the data in hand. Let’s get through Study 102, let’s see how compelling the data looks from 102, let’s get through our commercial validation study, let’s see how compelling the micro-dystrophin expression and safety looks there, and then we’ll have that dialogue in telling the micro-dystrophin expression and safety looks there, and then we’ll have that dialogue with the agency and figure out what the appropriate pathway forward is. As you can imagine, we feel a great sense of duty and obligation to move as fast as possible. So, you would envision that we are going to certainly propose the leanest approach forward. But, that discussion will happen once we have the data available to us.
As it relates to the release out there — and this is the release out there. I want to be very clear, if I’m not making it clear. We haven’t approached the potency release assay. We’ve had the blessing of the agency on that approach. We have the data for that available and that’s — so that’s why we get to start the study, and that’s why we get to move forward. And we’ve been able to essentially unpause what was a pause part of this program. That approach could certainly — when we get around doing additional studies, 301 is only one of the other ones, we want to do a non-ambulant study as well. We could obviously very likely use the same potency release approach or we could use an updated one. As we’ve said many times in the past, one of the reasons we were so confident that — we weren’t confident on the timing at the time of when we would be able to get this issue resolved with the agency. We were always confident that we would get it resolved. And one of the reasons for that is that we have a number of assays that could be potency assay. So, we’ll use the most optimized one at the time that we start additional studies, but certainly, one of the possibilities is to use the potency assay that we’re using for Study 103 because we’ve obtained the concurrence from the agency on that one right now.
Our next question comes from Joseph Schwartz with SVB Leerink. Your line is open.
I was wondering, have the sites that you were going to use for 301, led — do they lead you to believe that it was going to be challenging to execute the trial? And, how do you feel about their ability to collect and evaluate data from 102 in this arm?
So, the short answer to that question would be, no. Sites were not coming back to us and saying that this will be challenging. But, to be honest, there is an extraordinarily high motivation from sites to participate in our studies for SRP-9001. It is certainly I think people are very excited about the potential for what this could mean for children with Duchenne muscular dystrophy. I think of situations where even in the raging portions of the pandemic, sites were — even when sites were currently shut down, they were suggesting they could start immediately. So, the truth is, we had to make an independent assessment of this issue. And it really was — this discussion really comes down to this. We want to start 301, we certainly do. We have a global ambition. It will be very important globally. And it will be good in the U.S. as well. I don’t think it’s just global. But, the thing that we really acutely need is that right after we have Study 102 results, we need to have results from a commercial material validation study that shows that in patients that we’re getting the same kinds of micro-dystrophin expression, and we have the same safety. We have a lot of CMC work done that tells us that should be the case, and we feel very good about it, but we need to confirm that. And as we thought about that, and we’ve thought about this in the summer time frankly, we realized that we could do this as an interim look in a larger study or we could simply adapt ourselves to the environment we’re in and really create a lean study that gets that information to validate the commercial material from an expression and safety perspective directly. Let’s just do it directly and start a study with the right number of patients and execute rapidly. And that’s how we kind of landed on where we were.
With respect to Study 102, we are very confident about where we are. The team has done a brilliant job. I want to give so much credit to a lot of people. Our clinical team, our clinical operations team have just done a bang up job of dealing with what certainly at the beginning we saw enormous challenges associated with this pandemic and how to adapt to it. I want to give also an enormous amount of kudos and congratulations and thanks to our clinical investigators, both at UCLA and then at Nationwide Children’s Hospital, I want to give just — I can’t begin to describe how much I’m thankful to Dr. Jerry Mendell, our principal investigator, who attacked this issue with an enormous passion to make sure that this study is staying on track, and these kids were able to still come in and get their functional readouts and the like and that the study is tracking forward. So, I stand here today, notwithstanding the pandemic and notwithstanding even the potential for the second wave, we’re very confident as it relates to Study 102 that we’ll have last patient, last visit in December, and we will have a readout in the first quarter of next year. I’m very confident about that. And it also relates to the fact that it is — while it’s a larger study than our Study 103, it is only two sites. And it certainly comes down significantly to the passion, hard work and commitment of Dr. Mendell and his entire team.
Thank you. And our next question comes from Colin Bristow with UBS.
So, first one, I understand the agency hasn’t fully blessed the faster market, but in terms of the willingness to accept this 8 to 10 patients is sufficient evidence of comparability between the commercial and clinical product. Have they signed off on that? And then, just quickly on the timing of Phase 3 initiation or 301, it seems like 103 is going to ring fence this commercial to clinical products question. And just, I guess, why not initiate the 301, either in parallel or as soon as you can get the results of the potency assay issue ironed out?
Yes, a couple of things. One, I want to be very clear about this. We have not had discussions with the agency about the sufficiency of evidence to support a BLA. We’ve been absolutely on purpose. And I think, I said long in advance of the Type C meeting that we explicitly don’t want to have those discussions until we have data available. I don’t want — with very busy agency, I don’t want to have those kinds of discussions, but at theoretic level I want to have it with data. And then, with respect to 103, 103 was designed originally because of the pandemic to get us the information we really need in the leanest way, without risk to the program and more importantly, without placing risk on children, including placebo kids, who would be having to go into doctors’ offices with the potential of being on placebo. So, there is a number of reasons why — we talked to the agency informally. We talked about the commencement of Study 103. The reason we are — we have proposed to the agency actually that we would consider a commencement of Study 301, once we had 103 in hand, and they concurred in that that concept.
There’s a lot of reasons for that. One, it’s the leanest way to get to the information we’re most interested in right now, and it allows us to focus on the information that we want most acutely, which is the validation of the commercial material, which will marry up with the results of Study 102 and then have discussions with the agency. Two, it reduces the risk to the program and to the patients along the way. And then, three, of course, we might learn stuff from 103 that could inform the way we designed 301. And so, it made sense to us to really focus on Study 103. That’s what we focused on in our informal discussion with the agency. And that’s what we got the blessing, the comments.
Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.
Hey, guys. Thanks for taking my questions. So, could you clarify, is FDA sign-off on the actual potency data that you’ve generated using the agreed upon approach dating for the start of Study 103 or for ultimate approval? And how do you view, I guess, the difference in potential risk, based on your discussions and any regulatory precedent, to seeking approval using open-label rather than placebo-controlled safety and expression data from commercial scale material? Thanks.
A couple of things. We have the data in hand. So, we feel very confident that we’re going to commence the study. We don’t — we don’t believe that we [indiscernible] gating items other than just getting it executed to commence Study 103, from our viewpoint, given what we’re looking at for the commercial validation study, the fact that it’s open label versus placebo really isn’t significantly relevant. We’re looking at expression. Obviously, you can’t placebo — you can’t get us a placebo effect on expression. And we’re looking at safety as well. So we don’t think that’s going to be a significant delta. But, we haven’t had the conversations about the pathway to approve. We’ll have those discussions at the appropriate time of the agency with data and that we’ll know when we know it.
Our next question comes from Ritu Baral with Cowen. Your line is open.
Doug, help me understand this. What assurance or I guess general messaging you have from FDA that the 10 patients that you’re thinking about the 103 is going to be large enough to capture the potential variance of the commercial product and the safety of the commercial product, just given what we’ve seen with the size of compound and complement in some patients and not others, what do you have in writing from the Type C meeting on the end of 10? And also, now that you have, it sounds like you have the potency assay settled, what you’re going to use, having it validated, do you have all the clinical product you need to potentially run 301? I want to make sure that you’re not going from 70 to 10 because of a lack of validated product?
Yes. That’s a really good question. Thank you for asking that. We do not have a material shortage problem. So, thank you. I hadn’t even considered that someone might have imagined that would be the case. We have done many GMP runs. We have sufficient material to start Study 103, 301 et cetera, non-ambulatory studies as well. So, none of this relates to the unavailability of material. So, thank you actually for giving me an opportunity to say that. I haven’t considered that someone might have worried about that.
The issues — the decision about the size of the study is us. It really isn’t the FDA. The division doesn’t essentially bless it or confirm that they agree with the analysis that we’re doing, and they haven’t, and we wouldn’t have asked them to do that because really, it’s — that is our decision. I mean, the risk around the size of the study is ours. I will note, however, that the size of this study is essentially exactly the size of what we would have envisioned in an interim analysis for Study 301. So, this is essentially the same thing we were going to do with Study 301 in the form of an interim analysis on a subset of patients. We were kind of looking at the 8% to 12% range, and that’s where we are now at 10 patients in this study. And that relies on our own evaluation. And we are confident about the size of the study, and we’re confident about the fact that we’ll get insight and validation around commercial material, both expression and safety out of it. You could touch on something, I just — you are well aware of this, but I’ll say it yet again. So, we’re absolutely clear. We have — I know that other programs have seen very troubling issues, for instance, completing [indiscernible] likely never seen those issues. And there’s no reason to believe that we would see anything like that in — out of our commercial process materially here. And so, we’re very confident about that. But, that’s never been an — that’s appeared with any of our rh74-driven programs.
Our next question comes from Vincent Chen with Bernstein. Your line is open.
A couple for me, largely following up and just clarifying some things that were asked before. First is really just to clarify, is there specific data you’re waiting for from Study 103 that gates the start of Study 301, or in a non-COVID world, could you go ahead and start Study 301, if you wanted to since the FDA sort of aligned on the potency assay? And then, I have a follow-up after that.
Yes. Thank you. I mean, we proposed Study 103 because of the COVID issues. And frankly, to be honest. It’s only — we proposed this in the summer, it’s only become more compelling recently. It does appear, unfortunately, certainly in the United States, and probably around the world right now that the second wave is upon us. So, it only becomes more compelling to us. When we met with the agency in our formal discussions at the end of September, we proposed and they concurred in the concept of the Study 103 and we actually proposed that we would start 301 after we had data from 103 and they concurred that. So, that’s the decision that we made in light of where we are. And we think it makes ton of sense. And there might be something that we learn out of 103 that could actually inform 301. But,, we’re very focused on getting the information that we’re most interested in right now, which is validating our commercial material, both in expression and safety in children with Duchenne muscular dystrophy, and having that information as soon after the readout of Study 102 and hopefully as close in time as is possible, so that we have together, at the same time, essentially three things. We have — from a placebo-controlled trial, we have the compelling evidence that the therapy is providing significant benefits to these kids, and believe for right, statistically significant and clinically meaningfully. And then we have safety data. And then, of course, with respect to the commercial material, we have commercial validation that we’re getting the kinds of expression we would expect out of the commercial material. We’re seeing the safety signs out of the commercial material that we will see out of the Study 102, at least, what we’ve seen certainly so far. So, we’re really focused on that. And then, we’ll have a discussion with the agency, and we’ll talk about the pathway to getting this therapy to these kids who are, as we all know, waiting, and time is not on their side. So, we’ll certainly meet with the agency as soon as we have that information on our books.
[Operator Instructions] Our next question comes from Tyler Van Buren with Piper Sandler. Your line is open.
Tyler Van Buren
I had a question on the MOMENTUM trial readout by year-end. I was just hoping you could refine expectations there. I think, you mentioned specifically, you’re going to compare digital drop PCR, the 12-week PPMO data to 24-week PMO data. So, is the ultimate goal at this initial readout to see skipping that is higher with the PPMO product at the early time point, or are you hoping to see several magnitudes higher of skipping, could you put a finer point on that? And are you dose-escalating because maybe the skipping is not where you would like to see it yet, and you think by getting to 30 or 40 you’ll be able to achieve that ultimate goal, even though it appears that you’re seeing great safety?
So, I would say, first of all, don’t read much into — don’t read anything into my comments about what we’ve seen because we haven’t — the reason we haven’t released the 20 mgs per kg data is that as we don’t have the data in hand right now. So, I’m going to turn this over to Dr. O’Neil to provide some color on what we’re going to look at between the two. I’d say a couple of things.
It would be nice to see some additional exon skipping, even though it’s in a different time point, between the PMO and the PPMO at 20 mgs per kg. But the reason that we’re dose-escalating is because it has always been our goal. The goal is to get to the highest possible dose we can get to before we see a dose-limiting toxicity, so that we know that we are creating the most exon skipping and dystrophin possible. And we’ve seen in the animal models that if you push the dose high enough and you can do so safely that at least — if the animal models bear out, you will see a very substantial — eventually, very substantial increase. Where that exactly is, it’s correlating between humans and animals is always difficult, is it [indiscernible] dosing is it late base dosing, is this a hybrid between the two. So, we don’t know yet, but we’re very confident in the mechanism of action.
And so, I will say, one more thing and then I’m going to turn it over to Dr. O’Neil to give more data-driven color on this. This is all about safety for us. We’re really — what we’re curious is one of the safety signals, the 20 mgs per kg, what’s the change we can go to 30 mgs per kg; if we go to 30 mgs per kg, what’s the chance we can go to 40 mgs per kg to make sure that we get to the optimal dose for these kids.
With that said, Dr. O’Neill, additional color on this?
Dr. Gilmore O’Neill
Yes. Thank you very much. So, I think, the key thing to say is that the MOMENTUM study has two objectives. The first is to test our hypothesis that the cell-penetrate peptide fused with the PMO significantly enhances tissue, cell and ultimately, nuclear penetration to enable higher levels of skipping and dystrophin expression, as we have seen in our nonclinical data. And the second objective, I think, this is what’s really driving your question, is that we want to maximize the benefit risk. And so, if we can continue, notwithstanding a proof of principle in the human of higher exposure, notwithstanding seeing that when we should see it, we would still want to push the dose as high as we can, considering the severity of the disease so that we can get a maximum tolerated dose and so maximize the benefit. So that is the key reason for dose escalation. I will reemphasize that what we will be examining is systemic PK, very importantly to the proof of principal tissue penetration in addition to ongoing safety as well as exon skipping data.
Our next question comes from Danielle Brill with Raymond James.
This is Anil [ph] on for Danielle Brill. Thank you for taking our question. Staying on the topic of PPMO. Good question in terms of dystrophin expression. As you’re dose-escalating, are you collecting the dystrophin expression data? And do you have any idea when you might be able to share that? Thank you.
We’re going to have an update on the 20 mgs per kg at 12 weeks. Dr. O’Neill, you’re going to correct me if I misdating anything. It’s 12 weeks with the PPMO. We’re actually going to compare it ironically to the PMO at 24 weeks. But, we’re going to have an update on exon skipping and tissue exposure at 12 weeks. We’re not looking for dystrophin right now for the simple reason that it is very early. You can get some lead of exon skipping in an early stage, but one of the things we know with certainty is that dystrophin builds over time, and 12 weeks is very early to start looking for dystrophin. We’ve seen with our PMOS and EXONDYS as an example, we’ve seen a significant difference in the amount of dystrophin that was produced, literally at four years versus one year so, nothing will be that long, but 12 weeks is a bit early to look at dystrophin. With that, Dr. O’Neill, do you want to add any additional color on that?
Dr. Gilmore O’Neill
I can confirm that what Doug has said is entirely accurate. And the only thing I will remind you of is that we have demonstrated non-clinically that there is a proportionality between exon skipping and dystrophin expression downstream. But, as Doug has said, 12 weeks data is very early for dystrophin expression. And as we have learned in the past with our PMO, dystrophin does accumulate over time. And so, that is the reason that from a proof-of-concept and a — proof-of-concept point of view, we are focusing on, first and foremost, tissue distribution or tissue concentration as well as exon skipping at 12 weeks.
Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.
This is Sonia [ph] on for Salveen. Where do you stand with longer term strategy on DMD with next-generation approaches using genomic medicine?
Dr. O’Neill — first of all, I’ll say this, we are, of course, in addition to our gene therapies, in addition to — both our PMOs right now and our next-generation PPMO, which we’ve just touched upon, and in addition to gene editing, and I should tell you, we have a gene editing innovation center in Durham, North Carolina, under Dr. Charlie Gersbach, that’s looking at a number of different things, including the potential for gene editing and Duchenne. I think that’s a bit out — a bit off in the distance. There are a number of other ideas that we’re looking at as well that I don’t think I come to fruition yet. But if you have any additional thoughts on that, Dr. O’Neill, let me know.
Dr. Gilmore O’Neill
I think you said it nicely. The key things are that we actually have a nice portfolio of platform approaches with gene delivery, gene editing and our antisense And I think that choice — certainly, when I think about gene delivery pending gene editing, further the revolution, and our antisense enables patients to make optimal choices we hope in the future. And obviously, they complement one another. And I think, as we’ve said before, you remember, we are even looking at the possibility of combinations of these therapies in the context of optimizing therapies for patients with Duchenne. And I will actually also highlight what Doug said earlier is that obviously, the other thing we want to do with our portfolio for Duchenne patients is ensure that we develop the data for patients at various stages of their disease, just to make sure we can maximize benefits for as many people as possible. Thank you.
Thank you. Our next question comes from Joel Beatty with Citi.
This is Sean Egan calling in for Joel. Circling back to 9001, it seems like not much has changed today in regards to what you guys hope to expect to eventually file that that being a positive 102 study and positive bridging results. But maybe can you confirm that there’s nothing new from the FDA discussions, which suggest that a positive 102 and positive bridging study alone would not support approval? And also, has blinded 102 data helped inform the design and scale of Study 103 in any way?
I’d say, Study 101 really has informed both 102 and 103. And again, just lingering for a moment, I want to make sure I’m very clear about the fact that we haven’t had no discussions with the agency, just solicit their views on what the data would be necessary for, for instance, the BLA side, I don’t want to mislead. But, I do agree with you that we are in the same position with our approach today as we would have been — as we were thinking about Study 301, which was an interim analysis. Probably the one difference — so two differences, one, if you roll the clock back of course, we were under the impression that the potency assay approach that we had as we tracked to the September meeting was appropriate, and that has caused us a couple of months delay as we sorted that out, got new data that difference. But, I must say, in fairness, and I really want to give tons of kudos, both to the teams and the willingness of OTAT, to talk to us, we were able to resolve those issues in advance of 103, as fast as I think it is possible to do. I think, in light of how busy that agency is and in light of pandemic and the ability to actually get up informal meeting with the division so soon after our Type C meeting and to come to a resolution, literally by the end of September, I think has said a lot about the team and its willingness to execute and its execution ability and it also said something about the division’s willingness to have conversations with us. And I really appreciate that.
I think, the one additional thing that I’d say between where we are and where we might have been before is that, I think 103 is — 103 is a much higher — will get us data much quicker, I think, than even with an interim analysis of 301. So, I think in many regards, we will get the information that will give us insight on the commercial material with a higher POS in the middle of a pandemic and faster than we would have done with the larger studies. So, other than that, I think, the approach is the same. If all goes well with maybe a 60-day delta between what we would have anticipated in the summer and where we are today, we should have both, the results from Study 102 that show the functional benefits of this therapy and safety and safety signals and tolerability, and we should also have the result of this commercial validation study, the same information we would have hoped to get out of the interim analysis for Study 301 on both micro-dystrophin expression as well as safety.
So, I think with the one caveat that we’re probably 60 days delayed versus where we were — where we thought we would have been, let’s say, in July of this year, we’re basically in the same position with the same kind of data by early next year.
Our next question comes from Hartaj Singh with Oppenheimer.
This is Jackie [ph] on for Hartaj. Thanks for squeezing us in. Maybe just a clarification question. Since you noted in your earlier prepared remarks that you’re going to pursue additional studies in older and non-ambulant boys, could you just clarify whether those will be separate from Study 301 or cohorts added to that study? Thank you.
There would be a separate study on non-ambulatory patients, at least that’s the way we envision it today.
Our next question comes from Difei Yang with Mizuho Securities. Your line is open.
So, just asking a clarifying historical question. So, back in the days, before all this discussion on potency test started, when the original plan was to go to the FDA with study — with results from 102 plus interim readout on 301, did agency — did the FDA ever confirm that will be enough to you form the basis for BLA submission, or was it at the point just enough to start the conversation about potential submission?
It’s always been our strategy, I think we’ve communicated this often that we will have those discussions with the division once we have data in hand, and that until we have that in hand, we won’t have discussions about the level of evidence necessary for a BLA. So the simple reason that I think it’s asking a lot of the agency in the middle of all how busy they are, the pandemic and the like to have theoretical discussions. We’ll get 102 executed. We’ll get the results of 102. We’ll get the material from our commercial validation study. And then, we’ll talk to the agency about the path forward with initial studies or a BLA or the like. I think, everyone knows what our goals are in that regard. But, we’ve been very consistent from that perspective.
Our next question comes from Matthew Harrison with Morgan Stanley.
This is Max Skor on for Matthew Harrison. Just a quick question. Is Study 103 gating at all for initiating discussions with the agency regarding the limb-girdle 2E trial with commercial material? More specifically, is there any read-through from one potency assay there?
I don’t think there’s any gating — there’s no gating item between Study 103 and the discussions with the agency about limb-girdle 2E. No. I think that there’s no doubt that the discussions we’ve had with the agency about the potency assay approach will inform the approach we take with limb-girdle 2E. So we’re in much better shape as a result of those discussions. We can apply those — that learning to the limb-girdle 2E to which without a doubt, the real gating item to have discussions with the agency limb-girdle 2E is getting the GMP material released. And that requires us to continue to do analytical work, and work that is well on the way, but not completed.
Our next question comes from Martin Auster with Credit Suisse.
Hi. This is Matt Terwelp on for Marty. Thank you for taking the questions. I just wanted to confirm the Study 103 is a single center study? Thanks a lot.
I believe it is, but I’m going to let Dr. O’Neill confirm that for us.
Dr. Gilmore O’Neill
The final number of sites will actually be determined as we execute the study. We have actually built in redundancy because as Doug had said, one of the things we did and the reason that we actually conceived of the 103 Study was to actually handle the — or deal with the consequences of the ongoing pandemic. And so, we have actually built in flexibility, so that we are able to enroll and execute the study as quickly as possible.
Thank you. There are no further questions in the queue. I’d like to turn the call back to management for any closing remarks.
Thank you all very much for joining us this evening. I will say, I’m very pleased with the team for continuing to execute during this pandemic, both in the performance of our proof therapies as well as our development programs. As it relates specifically to SRP-9001 is of course, the top of mind for Sarepta because it is such an important program for Duchenne muscular dystrophy boys that are waiting.
We did have a setback in September as one could expect to have it when you’re ambitious. We had hoped in September that we would have a blessing to commence Study 103 in September. But, I am very pleased to say that we executed consistent with our culture. We moved rapidly. We were able to get an informal meeting with the agency at the end of September. We were able to come to a meeting of the minds on the commencement of Study 103 and the potency release assay associated with Study 103. We could not have, I think, envisioned a faster resolution of this issue, so that we can commence with little delay the next commercial validation study in an extraordinarily important program. And so, I’ll continue to update people across the course of the year as we execute.
I want to give a lot of thanks to OTAT certainly for their willingness to engage with us and help us find the pathway forward. I want to thank the Sarepta team for their willingness to continue to execute fiercely across the organization and serve these patients. And I of course, want to thank the patients, both those who participate in our trials as well as those patients across all of our disease states, both Duchenne muscular dystrophy and currently limb-girdle muscular dystrophy for their commitment to the programs but also for staying with us as we continue to execute these programs. We have a single-minded goal as an organization.
Our success will come from our ability to intervene in the lines of patients who are suffering from these rare diseases in far, far too often with respect to Duchenne muscular dystrophy and these limb-girdles being stolen from their families by a shorter life because of these diseases. Again, we will work like mad to move as fast as possible. And I do believe that Study 103, which we proposed and was accepted by the agency is going to be an enormously important step forward in our ability to accelerate the therapy to patients that are waiting as soon as the science cooperates.
With that, have a lovely evening. And we will continue to update across the course of the year and into next year. Thank you.
Ladies and gentlemen, this concludes today’s conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.