Q3 2020 Sarepta Therapeutics Inc Earnings Call

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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: Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics 3rd Quarter 2020 Earnings Call. At this time, all lines are in a listen-only mode.

Operator: After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you'll need to press Star 1 on your telephone. 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.

To ask a question during the session you'll need to press star one on your telephone.

As a reminder, today's program is being recorded at this time I'll turn the call over to Mary taken senior manager Investor Relations. Please go ahead.

Mary Jenkins: Thank you, Catherine, and thank you all for joining today's call. Earlier today, we released our financial results for the third quarter of 2020. The press release is available on our website at Sarepta.com. And our 10 Q was filed with the Securities and Exchange Commission earlier this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dr. Gilmore O'Neill, and Dr. Louise Rodino-Klapack. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we'll be making a number of forward-looking statements. Please take a moment to review our slide 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.

Thank you Catherine and thank you all for joining todays call earlier today, we released our financial results for the third quarter 2020 that press release is available on our website asked about the dotcom and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon.

Joining us on the call today are Doug Ingram in at the time, Dr. Gilmore O'neil and doctors will be speaking I'm quite back after our formal remarks, we'll open the call for acuity.

I'd like to note that during this call well be making a number of forward looking statements. Please take a moment to review our slide on the webcast, which contains excellent looking statements. These forward looking statements involve risks and uncertainties many of which are beyond sarepta control actual results could materially differ from these forward looking statements and any such risks can materially and it materially.

And adversely affect the business results of operations and trading prices for Sarepta common stock.

Mary Jenkins: For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent and 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 floor booking 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.

A detailed description of a pickup of risk 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 FCC 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.

<unk> provided today based on subsequent events or circumstances with that let me turn the call over to our CEO does Ingram, who will provide an overview of our recent progress Doug.

Douglas S. Ingram: Thank you, Mary. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics' 3rd Quarter 2020 Investor Conference Call. Tonight, I'm very proud to share with you the progress we have made this quarter, including our performance in serving the Duchenne community with Exondys 51 and Biondys 53, our progress with respect to our RNA platform, and the strides we have made in building out our enduring gene therapy engine. But I'm going to take things a bit out of order this evening.

Thank you Mary good.

Good afternoon, everyone and thank you for joining Sarepta therapeutics third quarter each quarter 20.

Investor Conference call Tonight, I'm very proud to share with you. The progress we've made this quarter, including our performance in serving the Duchenne community with EXONDYS 51, and BYOD is 53.

Our progress with respect to our already platform and the strides we've made in building out our enduring gene therapy engine.

But I heard two things a bit out of order. This evening I'm going to commence this call by discussing an important milestone for sarepta and for the Duchenne patient community.

Douglas S. Ingram: I'm going to commence 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 starting a trial with commercial process material this year. Let me provide some background and context.

As you will have read in our press release today, we worked with the FDA, we now anticipate dosing trial.

Commercial process material.

This year.

Let me provide some background and context.

Douglas S. Ingram: As you will know, SRP9001 is our gene therapy, and the goal of it is to treat Duchenne muscular dystrophy by safely delivering to the skeletal diaphragm and cardiac muscle a gene that robustly codes for a truncated but functional form of the structural protein dystrophin that we call microdystrophy. 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 Drs. Jerry Mandela and Louise Rodino-Klipak, 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 on all functional measures. The children continue to improve in ways that cannot be explained by natural history.

As you will know EPS would be nine 001 is our gene therapy and the goal of this.

To treat duchenne muscular dystrophy by safely delivering to scold diaphragm cardiac muscle a gene that robustly codes were truncated, but functional form of the structural protein district that that we call micro disruptive children.

Douglas S. Ingram: Based on this proof-of-concept study, we commence the randomized, blinded, placebo-controlled trial. You'll recall that it's Study 102. Study 102 is intended to show in a well-controlled trial that 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 Studies 101 and 102 was manufactured by our partner, Nationwide Children's Hospital, pursuant to a process that will not scale for large commercial purposes. However, over the last two years or so, we have developed a commercial process, and we've built significant manufacturing capacity.

Douglas S. Ingram: Assuming SRP 9001 proves effective, these efforts are expected to provide us with the capability to produce and launch a commercial product that fully serves 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 hand to conduct additional studies, we requested a meeting with OTAT.

And political development and we commenced our G. M P runs.

The rest of our P. Nine 001 commercial processed material to use in future clinical studies and.

In the summer of this year with G. M. P material in hand to conduct additional studies, we requested a meeting with owe tax a cat is the division of the SDA responsible for cell and gene therapy, and we did that to obtain their blessing to commence a commercial material validation study, we originally contemplated a larger 70 patient blind.

Did placebo controlled trial called studies three O. One however in light of the likelihood of a second wave of Covid, 19, which now baby 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.

Douglas S. Ingram: OTAT is the division of the FDA responsible for cell and gene therapy, and we did that to obtain their blessing 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 placebo-controlled trial. The goal of study 103 is to gain insight and validate the performance Our Type C meeting with the division, which was conducted entirely in writing, occurred in September of this year.

We're open label commercial material validation study study one O three and the same patient population as steady one or two are ongoing placebo controlled trial.

The goal of study one O three is to gain insight invalidate the performance of our commercial process material on both micro dystrophin expression and safety and after 10 patients with the primary analysis or part one of the study conducted at 12 weeks boasting infusion and all treated patients are.

Type C meeting with the division, which was conducted entirely in writing occurred in September of this year.

It's written response the division raised concerns with the potency release assay approach that we had proposed.

Douglas S. Ingram: In its written response, the division raised concerns with the potency release assay approach that we had proposed. As I stated at the time that this 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, 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 have 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 for 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.

Intended do before the end of this year and third to remind you study one or two we'll have the last 12 months visit in December of this year and we will report the results of study one or two in the first quarter of 2021.

Depending on the external environment, and then pandemic, we anticipate speaking with the division and starting our larger study 301 in 2021. After we have data available for study one or three we also intend to design and print proposed to the division for their review and input additional studies, including importantly, it older and non ambulant patients.

I would like to thank Kodak for their responsiveness and their willingness to end formerly in 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 one or three.

Douglas S. Ingram: 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 its last 12-month visit 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 larger 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.

Now stay with the build of our gene therapy engine over the course of this quarter. We have 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 code.

Word into Shen 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 233 patient cohorts for SRP nine 001 for the treatment of limb girdle muscular dystrophy type two Wheeler LG MDT week.

Douglas S. Ingram: I would like to thank OTAC 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 an additional burden on an already overworked group of professionals at the FDA so that we may embark on Study 103. Now, starting 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 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.

Cohort one was dose at five either the 13th in cohort two was dose that to either to 14 same dose used in our studies for SRP 900 warm.

As you will recall, both cohorts were generally well tolerated with a significant dose dependent increase in expression in cohort two at world muscle. We reported the 18 month results for cohort, one showing not merely stabilization, but a substantial improvement in function above baseline and above natural history. We are.

Also reported the early six month data for cohort two where the children are already showing not near stabilization of function, but improvement in function again against both baseline against natural history.

Douglas S. Ingram: 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 two 3-patient cohorts for SRP9001 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, the same dose used in our studies for SRP 9001.

We are particularly pleased with these LG MD to results and in particular, the safety expression biomarker and functional and results of cohort two.

And then as potential read through to our remaining LG, Andy portfolio and supportive confirmatory read through to bar SRP nine 001 program VFD as the program shared at the Investor demand promoter. The same design approach and in the case of cohort two the same dose as well with respect to LG MD too we are complete.

Manufacturing and material for our next trial and will 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 developments and regulatory pathway and timing for our entire LG MD portfolio in 2021.

Douglas S. Ingram: As you will recall, both cohorts were generally well-tolerated, with a significant dose-dependent increase in expression in Cohort 2. At WorldMuscle, 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 mere stabilization of function but improvement in function, again, against both baseline and against natural history.

We continue to build our gene therapy platform and gather technologies to improve and enhance gene therapy over.

Over the course of 2020, we have completed some 22 gene therapy related transactions 20 of which were completed since this pandemic centers 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 two in 2021 at which we can update on our entire pipeline both gene therapy in our day and we will provide more details on this.

Douglas S. Ingram: We are particularly pleased with these LGMD-2E results, and in particular the safety, expression, biomarker, and functional results of Cohort 2, as they have potential read-through to our remaining LGMD portfolio and supported confirmatory read-through to our SRP 9001 program from DMD, as the programs share the same vector, the same promoter, the same design approach, and, in the case of Cohort 2, the same dose as well. With respect to LGMD-2E, we are completing the manufacturing of material for our next trial and will 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.

Early next year.

Moving on now to our R&D platform, let me now discuss our commercial performance in the quarter.

As you will recall in light of that dynamic and unpredictable nature of the COVID-19 pandemic, we withdrew our guidance for 2020. Nevertheless, due to the collaborative work of our multi multi disciplinary team I am pleased to once again report that we have been able to serve the duchenne community with our approved therapies with.

With only modest impact from the current pandemic.

For our PMO franchise currently axon this and by August our net credit 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 monitor performance closely 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 ensuring 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.

Douglas S. Ingram: We continue to build our gene therapy platform and gather technologies to improve and enhance gene therapy. During 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.

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 showed flexibility and authorizations and reauthorizations for this vulnerable DMD patient community.

Now moving to our PMO pipeline.

The FDA has accepted our filing through our third Duchenne therapy, Tazeen Ericsson, a PMO say the intended to treat those 8% of Duchenne patients who are amenable to skipping exon 45.

Douglas S. Ingram: 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 have been able to serve the Duchenne community with our approved therapies, with only a modest impact from the current pandemic. For our PMO franchise, currently Exondus and Biondus, our net product revenue for the quarter was $121.4 million, and that represents a nearly 23% increase over the same quarter last year.

The brand name for CASM Pearson will be along this 45, our PDUFA date is February 25, 25, 2021, and the review is going well, if we obtain approval for CASM theirs, and we will have three approved therapies capable together of treating nearly 30% of the DMD community.

And as we have mentioned before our army technology has the potential to breed therapy 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 and the PMO, which if successful may profoundly improve the efficacy and convenience of our R&D technology. We are in our multi ascending dose study called the momentum study for our peptide conjugated PM, our PMO and Thats candidate SRP kit.

You get the want to remind you we are using our proprietary positively charged satisfied to increase penetration.

In animal models, we have shown that if we can safely achieve appropriate dose levels. The.

Douglas S. Ingram: 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 to this pande Now moving to our PMO pipeline. The FDA has accepted our filing for our third Duchenne therapy, Casimir, a PMO therapy intended to treat those 8% of Duchenne patients who are amenable to skipping Exxon 45. The brand name for Kazimiercin will be Amondis 45.

The PMO greatly increases tissue exposure into.

Entering greatly increasing exon skipping and dangerous and thus dystrophin production.

Before the end of this year, we will provide an update on the state's cases systemic exposure and exon skipping for our PMO asked our peak if he could be one candidate at 20 makes for Qig.

And for US the most important measure of all of these and I've said this many times in the past we'll be safety considering the following our PML as are safe and their precise their ultimate limitation. However, they are also neutrally charged and penetrate muscle cells passively and they clear the body in about four hours. This will limit the amount of therapeutic and get to the.

The right place and simply increasing the dose.

We will not reverse this limitation.

Our PMO 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 ppm modes 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 to shed muscular dystrophy.

Douglas S. Ingram: Our PDUFA date is February 25, 2021, and the review is going well. If we obtain approval for Kazimiercin, we will have three approved therapies capable together of treating nearly 30% of the DMV community. And as we have mentioned before, our RNA technology has the potential to bring treatments to as many as about 85% of patients living with DMV. So we do have much left to do.

Our most significant questioning the momentum study has always been safety upon repeat dosing and maximum dose we will present, the 20 Meg per keurig results. This year, but we have already moved to 30 makes for keurig and intend of safety signals will permit to continue to dose even up to 40 Megs per keurig 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 model until we observed 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.

Douglas S. Ingram: As you will know, we are also making progress on our next generation of the PMO, which, if successful, 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 SRP5051. 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, hence greatly increasing exon skipping, and then thus less dystrophin production.

Is the PBM hours 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 in 2020 perfectly exemplified our culture of performance consistent with our meshes message our mission apologies, we kept the patient front.

Center in everything we did which means we focused on the science, we continued to execute with a sense of urgency that our mission requires and when faced with inevitable obstacles and low blocks, we did not simply accept them or regress to the mean, but we moved with rapidity and creativity to address them to remove them in.

Douglas S. Ingram: Before the end of this year, we will provide an update on the safety, systemic exposure, and exon skipping for our PPMLS RP5051 candidate at 20 mg 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 neutrally

To keep progressing towards our ultimate goal of intervening and saving the lives of as many children living with and dying from the Shen.

Griddle muscular dystrophy, and other rare diseases as science will make possible and.

And with that let me turn the call to DNS, the Pam who will provide an update on the financials.

And.

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 on a GAAP basis. The press release is available on threat because web site.

Douglas S. Ingram: They penetrate muscle cells passively, and they clear the body in about four hours. This will limit the amount of therapy they 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 for patients living with Duchenne muscular dystrophy. Our most significant question in the MOMENTUM study has always been safety upon repeat dosing and maximum dose.

Please refer to our press release for a full reconciliation of GAAP to non-GAAP financial results.

Douglas S. Ingram: We will present the 20 mg per kg result this year, but we have already moved to 30 mg per kg and intend, if safety signals will permit, to continue to dose even up to 40 mg 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, you know, purely based on animal studies.

Douglas S. Ingram: 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 a high enough dose, 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 the maximum tolerated dose. In conclusion, notwithstanding the unusual external environment, the team continues to execute with an unrelenting purpose.

Increase is primarily related to $42.5 million increase in manufacturing expenses, primarily due to the continuing ramp up of our gene therapy programs.

Ian M. Estepan: And the third quarter of 2020 perfectly exemplified our culture of performance, consistent with our message, our mission, and apologies. We kept the patient front and center in everything we did, which means we focused on the science, we continued to execute with the sense of urgency that our mission requires, and when faced with inevitable obstacles and roadblocks, we did not simply accept them or regress to the mean, but we moved with rapidity and creativity to address them, remove them, and keep progressing towards our ultimate goal of intervening and saving the lives of as many children living with and dying from Duch Limb Griddle Muscular Dystrophy, and other rare diseases as science will make possible. And with that, I will turn the call over to Ian Estepan, who will provide an update on the financials. Ian?

On a non-GAAP basis, R&D expenses were honored $59.9 million for the third quarter of 2020 compared to $110.5 million for the same period of 2019 and increase of $49 for a million dollars a year over year growth and non-GAAP R&D expenses was driven primary.

Early due to a continuing ramp up of our gene therapy.

This we recorded approximately 75 $4 million of expenses for both of the third quarter of 2020 and 2019.

Ian M. Estepan: Thanks, Doug. Good afternoon, everyone. This afternoon's press release provided details for the third quarter of 2020 on a non-GAP basis as well as on a GAP 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 Exondus 51 and Vyondus 53 was $121.4 million compared to $99 million for Exondus 51 alone for the same period of 2019. The increase primarily reflects higher demand for our product. Additionally, 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 total $16.9 million for the third quarter and are included as a reduction in our operating expenses.

Ian M. Estepan: On a gap 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.

Local gene project expression and durable physiological benefits in skeletal muscle.

Dr. Rodino, Capex lab demonstration durable soccer Dri can expression histological benefit and significantly increase resistance to contraction induced injury in the TV Amos anterior muscles in agent Alpha and beta start the guy can knock out mice that being treated respectively with alpha socket.

Hi, Ken or basis occupy can transgene containing already 74 constructs.

Moving to technical data, we announced positive two year functional results in support of our lead to gene therapy candidate SRP nine years or a one in duchenne patients.

Ian M. Estepan: The increase is primarily due to increasing demand for our product. On a gap 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 program. 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 We recorded approximately $75.4 million of expenses for both of the third quarters of 2020 and 2019. On a non-GAAP basis, 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.

Ian M. Estepan: On a gap 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. This 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 investment 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?

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Timothy Francis Lugo: Thank you, Ian, and good afternoon, everyone. Doug has already shared the highlights from our most advanced gene therapy program. I will, therefore, focus my remarks on Sarepta's presentations at this year's World Muscle Society Congress and the progress we've made in advancing our RNA portfolio. Let me start with a World Muscle Highlight.

Timothy Francis Lugo: 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 product expression and durable physiological benefits in skeletal muscles. Dr. Rodino Claypak's lab demonstrated durable sarcoglycan expression, histological benefit, and significantly increased resistance to contraction-induced injury in the tibialis anterior muscles in aged alpha and beta sarcoglycan knockout mice that had been treated respectively with alpha sarcoglycan or beta sarcoglycan transgene-containing RH74 constructs.

He was a gerbil benefits following it seemed to the administration of the gene therapy.

As you know we are developing six additional therapies are six different therapies for the treatment of six subtypes of limb girdle muster district.

We also presented non clinical data at W. M S supporting the transition of our next limb girdle construct Lyndon garden empty to see into the clinic.

Search also present the data generated from its army platform Ethan.

These included long term safety <unk> from the 40 53 101 clinical studies supporting its safety profile.

K P D data four cuss immersing from the 40 45, 101 clinical trials demonstrating dose portion of exposure and an interim analysis has immersing treated patients in the essence pivotal studies showing a statistically significant increase in skeletal muscle description expression from baseline for 48 weeks.

Timothy Francis Lugo: Moving to clinical data, we announced positive two-year functional results in support of our lead gene therapy candidate, SRP9001, in Duchenne patients. The results demonstrated that two years after a one-time infusion of SRP9001, 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 Thus, these functional data reflect a mean 1.5 point NSA improvement between years 1 and 2 post-SRP-9001 infusion. These data were generated from four ambulatory participants, aged four to seven, in Sarepta's Open Label Trial Study 101 and showed continued safety and tolerability of a one-time infusion of SRP9001 at a dose of two to 14 viral genomes per kilogram. We also announced positive clinical data for SRP9003, our gene therapy candidate for Lin-Gerdal muscular dystrophy type 2E.

All in all we were happy to be able to share so much data across our comprehensive portfolio with the academic prescribing and patients communities.

Beyond that taken we sure do you have anything that that'd be numerous develop them to cross or on a platform.

The F D. A review of our NDA for our lead PMO candidate Amanda's 45 is ongoing and from all accounts going well.

To do for date stamped that February 25th 2021 and.

And the <unk> has indicated does not currently planned hold an advisory committee meeting to discuss the application.

Moving to our post marketing commitment study for example, 51 also known as the mission study.

We are pleased that we have enrolled part one of the dose escalation on and we are in discussions with the agency about the timeline for the rehab to study.

Before I turn to R. P. P. One platform and the P. P O S or P 50, 51 program for DMD specifically.

Give you an update on the U S. Ambridge collaboration in late April we announcer early research collaboration with you with hammered that would exploit R. P. P. One technology as a potential therapeutic for COVID-19.

Timothy Francis Lugo: 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 SRP9001, that is, 2 to the 14th viral genome per kidney. We demonstrated in cohort 1 that the three participants continued to show improvements from baseline across all functional measures, including the North Star Assessment for Dysphalnopathy, otherwise known as the NSAD, in addition to Time to Rise, 4-Stair Climb, 100-Meter Walk Test, and 10-Meter Walk Run Test at 18 months. The mean NSAID improvement from baseline in cohort 1 was 5.7 points at 18 months.

More recently and based on an in vitro results. We are planning to anesthesia proof of concept Indigo study in collaboration with you a sandwich.

Now turning to our P. Thiemo developing programs for Duchenne muscular dystrophy, a key element disrupted R&D strategy is to enhance tissue are Muslim penetration of our PMO chemistry, and duck and has efficacy by increasing distraught friend expression.

We have a number of research programs that support the strategy to remind you.

P P more platform chooses a sale penetrating peptide or C. P P.

PMO, who enhanced cellular and nuclear penetration.

Our most advanced ppm, a program is SRP 50 51.

Are ongoing SRP 50, 51, 201 Mafia, sending those trials names momentum in the basket.

Timothy Francis Lugo: In Cohort 2, at 6 months post-infusion, all three participants demonstrated improvements from baseline across all functional measures. The mean NSAD improvement from baseline and core to was 3.7 points. This compares to a 3.0 point change in cohort 1 attendance.

We are pleased to say that we continue to escalate doses to level higher than it was originally planned at the initiation of this program.

This is the cause two days, we have not seen cynical in that perspective, sorry, we have not seen clinical network toxicity in our P. P O clinical trials and know you safety cigarettes have been observed across all studies dust, enabling us to keep escalating doses in the momentum trial.

Timothy Francis Lugo: Based on the safety, expression, and clinical results, we are moving the high-dose forward for future clinical development of FRP9003. 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 Microdystrophin SRP9001-101 study and the Limb-Girdle Muscular Dystrophy 2E SRP9003-101 study support durable functional outcomes at the 2-year and 18-month time points, respectively.

We have now commence dosing SRP 50, 51 in the 30 milligrams per kilogram cohort.

This year will be reviewing 12 week data from our 20 make critique cohorts and duchenne patients treated with R. P. P. Mo candidate SRP 50, 51, we will be examining systemic PK tissue penetration safety and Exxon skipping efficiency data.

I remind you that our preclinical in vitro Andy in vivo models have demonstrated a robust correlation between the amount of that sounds skipping efficiency in the amount of destruction production.

Timothy Francis Lugo: This further supports our hypothesis that because muscle is a terminally differentiated tissue, it thus enables a durable benefit following a single administration of the gene pair. As you know, we are developing six additional therapies, or six different treatments, for the treatment of six subtypes of Lin-Gerdal muscle 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 generation from its RNA platform. These included long-term safety data for GALADERSEN from the 4053-101 clinical study supporting its safety profile, PKPD data for Kazimersan from the 40-45-101 clinical trials demonstrating dose-proportional exposure, and an interim analysis of Kazimersan-treated patients in the essence, pivotal studies showing a statistically significant increase in skeletal muscle dystrophin expression from baseline to 48-wing. All in all, we were happy to be able to share so much data across our comprehensive portfolio with the academic, prescribing, and patient community. Beyond the data we shared at WMS, there have been numerous developments across our RNA pathway. The FDA review of our NDA for our lead PMO candidate Amandus45 is ongoing and, from all accounts, going well.

Net whereas we are examining 12 week time point in the dose escalation, partially mentioned study we will be using legacy 24 week data from PMO for so comparison.

I will remind you that the scope and accumulates over time and so based on observations entire PMO study, we would expect to see higher level just broken at leisure time point given the therapy is successful in.

Timothy Francis Lugo: Our PDUFA date stands at February 25th, 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 Commitment Study for Exondus 51, also known as the MISSION Study, we are pleased that we have enrolled Part 1 of the Dose Escalation Study, and we are in discussions with the Agency about the timeline for the readout of the study. Before I turn to our PPOL platform and the PPOL SRP 5051 program with DMD specifically, let me give you an update on the U.S. AMRID collaboration. In late April, we announced an early research collaboration with U.S. AMRID that would exploit our PPMO technology as a potential therapeutic for COVID-19.

Timothy Francis Lugo: More recently, and based on in vitro results, we are planning to initiate a proof of concept in vivo study in collaboration with USM. Now, turning to our PMO development programs for Duchenne muscular dystrophy, a 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 selects a cell-penetrating peptide, or CPP, to a PMO to enhance cellular and nuclear penetration.

Thank you.

Yeah. Thanks, a lot for that Jack's first let me answer the latter part of the question first that it is the temptation is.

Timothy Francis Lugo: Our most advanced PPMO program is SRP 5051. Our ongoing SRP 5051-201 multi-ascending dose trial named Momentum is about to begin. 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 nephrotoxicity in our PPMO clinical trials and no new safety signals have been observed across all studies, thus enabling us to keep escalating doses in the momentum trial. We have now commenced dosing SRP5051 in the 30 mg per kg cohort.

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 most they'll do that at.

Timothy Francis Lugo: This year, we will be reviewing 12-week data from our 20-mg per kg cohort in Duchenne patients treated with our PPMO candidate SRP5051. 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 disc growth in production. We presented SRP5051 preclinical data at the OTS meeting in late September, in which the PKPD of SRP5051 was evaluated in non-dysprophic, non-human primates. A single dose of SRP5051 resulted in sustained exon 51 skipping that was maintained for at least 28 days.

Timothy Francis Lugo: This sustained exon skipping supports the Q4 week dosing regime currently being studied in the clinic. We also observed repeat Q4 week dosing of SRP5051 for 12 weeks, demonstrating a cumulative exon skipping effect that increased after each infusion. For SRP5051, we will measure exon skipping efficiency by digital drop PCR or ddPCR, allowing us to directly compare the efficacy of our PMO and PP

Timothy Francis Lugo: 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 would not be representative of steady-state efficacy for SOP 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 mental study, we will be using legacy 24-week data from PMO for comparison. I will remind you that dystrophin accumulates over time, and so based on our observations in prior PMO studies, we would expect to see higher levels of dystrophin at later time points if the therapy is successful.

Timothy Francis Lugo: Indeed, muscle biopsies at later time points are planned in the latter part of the LEMENTIEN 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 would hand it back to Doug for Q&A.

Douglas S. Ingram: Thank you very much, Dr. Ronino. Catherine, let's open the lines for Q&A. Thank you. As a reminder, to ask a question, you need to press star 1 on your telephone. To withdraw your question, press the pound... Please limit yourself to one question.

Operator: And our first question comes from Brian Skorney with Baird. Your line is open. Hi, thank you. This is Jack Donninghan for Prime.

Operator: 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 a consistent effect compared to the data that you have from Study 102? We know there's significant variability within the first four patients of data looking at the Phase I trials with the DMD product, and we're just wondering what the lower and upper bounds of confidence are with respect to the distribution measurements that you're looking at for this new planned clinical trial? Thank you. Yeah, thanks a lot for that, Jack.

Douglas S. Ingram: So first, let me answer the latter part of the question first. It is – 10 patients is – I'm very sufficiently powered to obtain the data that we're interested in obtaining. Now, let me explain what this is about.

The line is open.

Hi, Good afternoon day. Thanks for taking my question, that's just to stay on topic with with 31 O. Three so I just wanted to make sure I understand that you you were not doing a specific potency assay, but you are using 31 O three and Lou of a specific potency essay just want to confirm.

Douglas S. Ingram: 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 were a number of reasons for that study, which is called Study 301, of course. One was for global purposes. The other is additional confirmatory data. Remember, we're going to have Study 102 that's going to be 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, this larger study, and acutely the thing that we're most interested in getting as quickly as possible, is validation of that commercial material.

That and then secondly, do you still have to do study three O. One is it still part of your assumption that you will need to submit 32, plus now 31 O three and some data from three O. One or is it your plan to go talk to F. D. A to see if you can apply.

To me that that study two and one O three show what you want those to show and not necessarily have to do three O. One.

Douglas S. Ingram: This is the same construct, but generated using a different process and a different manufacturing process, as you know, and our SALUS 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 as 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 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, watched the external environment, 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 to the pandemic, as well as just the risk to the program and the execution of the program. It dawned on us that there was a far more efficient way in the midst So there is no reason to do a placebo-controlled trial for the expression that we're looking for and for the safety that we're looking for.

The most salient information in the near term when we get one or two red out which is you know that that in patients and in biopsies. We should show that as we would predict from our all of our C. N C work the material and study one O three well from a from a commercial material perspective will perform in a similar way north from Microgestin.

Douglas S. Ingram: 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, a large, multi-centered, multi-country study, we should also propose a leaner approach, which is Study 103. And that's exactly what we did.

Douglas S. Ingram: 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 I think we all know was all on the written record, was that the agency had questions and ultimately had issues with the approach that we were taking to the policy release assay for Study 103. That could have taken us a long time to resolve, frankly.

Douglas S. Ingram: It could have taken us somewhere between two, three, maybe four, six months just to get an answer from them. I'm really pleased to say that the division was willing to meet with us informally. They met with us in September, so we're very clear about that. We came to an agreement in September. They agreed to our updated approach to the potency assay. We've 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 data for our alternative approach to the potency assay. And as we sit here today, the data's all done, the minutes are done, and we should be able to start 103 by the end of this year.

Douglas S. Ingram: 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 and the functional benefits in a well-controlled placebo-controlled trial, blinded trial from Study 102 with respect to SRP 9001. We'll have safety readouts from that study as well, and we'll have the commercial validation results from Study 103, which means we'll have microdistributed expression results. We'll have safety results from that study at the 12-week time point as well, which, of course, is a crucial time point from a safety perspective. Unfortunately, every week and every month, some percentage of those kids die.

Douglas S. Ingram: 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 to, science has to cooperate, studies have to come out the right way, but we should be able to sit down with them armed with information that shows, if we're successful, that SRP 9001 is So, thank you for your questions. Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.

Operator: Hi. Good afternoon, guys. Thanks for taking my question. Deb, just to stay on topic with Study 103. So I just want to make sure I understand this.

Operator: You are not doing a specific potency assay, but you are using Study 103 in lieu of a specific potency assay. I 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 Study 301? Or is it your plan to go talk to FDA to see if you can apply, assuming that Studies 2 and 103 show what you want them to show and not necessarily have to do 301? Yeah, thank you for the question.

Douglas S. Ingram: Let me clarify something that I might have created some confusion about. No, study what we did; we have come to an understanding with the age. 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.

Douglas S. Ingram: We didn't have clarity on precisely what those issues were, and if we had gone through a formal process, it could literally have taken two to six 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 Study 103 will give us exactly what we wanted out of an interim analysis for Study 301.

Did you sign off the potency Etsy and do you still need to do the release essay in order to get approval and in the case you have two wrong study Sweet one do you need to run another potency etsy for studies so the old one.

Douglas S. Ingram: So really, it's 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 can show that, as we would predict from all of our CMC work, the material in Study 103 will perform in a similar way, both from a microdistribution expression perspective and also With respect to Study 301, there are still lots of reasons to conduct it.

<unk> <unk> <unk>.

If you're signed off on our approach to they're really Joseph.

Douglas S. Ingram: First and foremost, this 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 that would be valuable as we bring this therapy out to patients. The third, of course, is I want to be very clear about something that I think I have 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. We have been very clear about this. I remain resolute that this is the right approach. We explicitly said we were not going to discuss this with them in advance of the Type C meeting and after the Type C meeting.

Could you use the same patterns you released 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 that we weren't confident on the timing at the time of when we would be able to get this issue resolved who the agency. We were always confident that we would get it resolved and one of the reasons for that is that we have.

And number put asking if it could be potency assay and so you know we'll use the most optimized won at the time that we start additional studies, but certainly one of the possibilities as to use the potency assay that we were using for studying one O three because.

Operator: We will get into next year. We will get the results of 102. If it is successful, we will have shown in a well-controlled trial that our therapy creates functional benefits and is doing a lot of good for these kids and that it is safe. We will have the commercial validation material out of Study 103, hopefully, not too soon after that. And then, 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, is the most appropriate and fastest way to get this therapy that is safe and efficacious to kids that are waiting for it in the U.S. That is a conversation we will have after we get the data in hand. Thank you. And our next question comes from Alicia Young with Cantor Fitzgerald. Your line is open. Hi, this is Emma on behalf of Olivia.

[noise] obtained the concurrence from the agency on that one right now.

Thank you. Our next question comes from just a sports with S. V. B lyric your line is open.

Thank you very much I was wondering have the site that you were going to use for three O. One.

Let you did did they lead you to believe that it was gonna be challenging to execute the trial.

And how do you how do you feel about their ability to collect and evaluate data from one or two in this environment.

So interestingly enough the short answer to that question would be no science, we're not coming back to us and saying you know that they should be challenging, but you know to be honest. There is an extraordinarily high motivation for insights to participate in our studies, whereas R. P nine zero.

Zero one it is certainly you know I think people are very excited about the potential for what that's convenient for children or would be shot marshals distribute show you know I can think of situations, where even in even in the raging portions of the pandemic sites, where even when fights were currently shut down they were suggesting they could start to me.

Operator: So given the agreement here with FDA on study 103 is kind of a leaner approach for getting the most important information for 9001 in the midst of COVID, do you expect kind of similar flexibility for 003 and LGMD to support a streamlined 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've said is that we need to do a couple of things with respect to—this is for Lindbergh and Weissstein, 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 process development runs, but we have a lot of analytical work to do as well.

So you know the truth is we had to make an independent assessment of this issue and it really was the vicious that's where it really comes down to it is.

Operator: 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 that, 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 better framed out.

Douglas S. Ingram: Obviously, as we've seen, given the pandemic and how busy 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. Thank you. The next question comes from Anupam Rama with J.P. Morgan. Your line is open.

Operator: Hey guys, thanks so much for taking the question. 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 to the study where you'll be looking at more functional types of measures? And has the FDA indicated any sort of, you know, interest in seeing that before you have some of the regulatory discussions, right? Yeah, that's a great question.

For the second Wag, we're very confident as relates to study one I'd see that will that last patient last visit in December and we will have a readout in the first quarter of next year and I'm very confident about that and I.

Douglas S. Ingram: No, look, this is an open-label study. The goal of SRP, the goal of study 103 is to get essentially exactly what we would have gotten out of an interim analysis from 301. It is essentially precisely the same thing.

And it also relates to the fact that it's it is while its a larger study than our study one or three it is only two sites and it certainly comes down significantly to the passion hard work and commitment that dr. mendell and his entire team.

Douglas S. Ingram: The reason I mentioned that as part one is, of course, in these studies, you have, you'll have, you know, longer-term safety follow-up. And so, in a sense, the study continues even after you get the primary readout from it. That's the same with all of our studies. It's the same with, frankly, study 102.

Thank you and our next question comes from Colin Bristow with U.B.S. Your line is open.

Yeah. Thanks for taking my question.

The first one I understand the agency hasn't fully blessed across the market, but in terms of the willingness to accept this eight to 10 patients a sufficient ever.

Douglas S. Ingram: We'll have study 102, we'll have the readout from a primary analysis, a 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 will see a statistically significant and meaningful improvement in NSA versus placebo. And then, of course, that study will continue, and those kids will continue to be monitored from a safety perspective.

Evidence of compatibility between the commercial clinical product and they signed off on that and then just quickly on on the timing of phase three initiation 301 it.

It seems like 103 is going to ring fence, the commercial to clinical product question and just I guess why not initiate the creo one either in parallel as soon as you can get the results of potency assays issue lined out thanks.

Douglas S. Ingram: So that's what we mean when we say part one, part two. 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 hoping to get out of an interim analysis of study 301, which was the previously proposed placebo-controlled trial. Thank you. Our next question comes from Gena Wang with Barclays. Your line is open.

Yeah couple of things one I want to be very clear about this we have not had discussion with the agency about the sufficiency of the evidence to support the BLM. We you know we extend that she was on purpose and I think I said long in advance they type C meeting that we explicitly don't want to have those discussions until we have data available don't want it with us.

With very busy agency I don't want to have those kinds of discussion that it be erratic level I wanted a habit with data in hand.

Operator: Thank you for taking my questions. So maybe, Doug, I was just wondering, what is the criteria for approval? Will study 102 plus study 103 be sufficient? And also, did the FDA already sign off on the potency assay? And do you still need to do the release assay in order to get approval? And in the case that you have to run study 301, do you need to run another potency assay for study 301? So the FDA has signed off on our approach to the release assay for Study 103. I can't tell you what the requirements will be precisely for approval because, as I think we've said a number of times in the past, we've all 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.

With respect to one of three would want you know one of the three was was designed originally because of the pandemic to get us the information, we really need and the leanest way without risks to the program and more importantly, without placing that risk on children, including placebo kids, who would be you know having to go ahead Dr.

His offices, where the potential of being on a placebo. So there's a number of reasons why we we talked to the agency informally we talked about the commencement of study one of three.

The reason we are we have proposed to the agency actually that we would consider.

Consider a commencement of study 301, once we had one of the three in hand, and they concurred in that that content. 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 allows us to focus on the information that we won most acutely which is the validation of the commercial material, which will will marry up with.

Douglas S. Ingram: As you can imagine, we feel a great sense of duty and obligation to move as fast as possible, so you would imagine that we are going to certainly propose the leanest approach forward, but that discussion will happen once we have the data available to us. 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 tests. 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 approval from the agency. Thank you. Our next question comes from Joseph Schwartz with SVB Lyrinc.

Results of study one or two and then have discussions with the agency.

Two is that right.

Reduces the risk to that program into the patient's along the way and then three of course, we might learn stuff from one of those three that could inform the way we designed rio or.

And so it made sense to EPS to really focus on any one or three that's what we focused on in our informal discussions with the agency and Thats, where we got the blessing the camels.

Douglas S. Ingram: Your line is open. Thank you very much. I was wondering, did the sites that you were going to use for 301 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 environment? So, interestingly enough, the short answer to that question would be, no, science is not coming back to us and saying, you know, that this would 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, you know, I think people are very excited about the potential for what this could mean for children with Duchenne Muscular Dystrophy. So, you know, I can think of situations where even in the raging portions of the pandemic, sites were, even when sites were currently shut down, suggesting they could start immediately. So, you know, the truth is we had to make an independent assessment of this issue. And it really was; this assessment really comes down to this.

Douglas S. Ingram: You know, we want to start 301. We certainly do. We have global ambitions. It'll be very important globally, and it will be good for the U.S. as well. I don't want to make it just global, but the thing that we really acutely need is, right after we have study 102 results, we need to have results from a commercial material validation study that shows that in patients, you know, that we're getting the same kinds of microdisturbing expressions and we have the same safety. We have a lot of CMC work done that tells us that should, you know, be the case, And as we thought about that and we thought about this in the summertime, frankly, we realized that, you know, we could do this as an interim look at a larger study, or we could simply, you know, adapt ourselves to the environment we're in and really create a lean study that gets us the 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 that's how we kind of landed where we were.

What assurance or I.

General messaging you have from that.

It's going to be large enough to capture the potential variance.

Of the commercial part our product and the safety of the commercial product just given what we've seen with the five year compounded and complement in some patients and others.

What what do you have in writing from the meeting on the end of 10.

But also.

Now that you have it sounds like you have the potency assay they settled what you're going to use having it validated do you have all the clinical product you'd need to potentially run three on one I just want to make sure that you are not going from 70 to 10 because of.

A lack of validated products.

Yes really good question. Thanks for asking that we got we do not have a material.

Shortage problem. So that's it thank you hadn't even considering that someone might have imagined that would be the capex. We have you know we've done many GMP ranch, we have sufficient material to start those anyway, three three or washed out or not and it will be yeah.

Douglas S. Ingram: With respect to study 102, we're 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 was, certainly, at the beginning, enormous challenges associated with this pandemic and how to adapt to it. I want also to give an enormous amount of kudos and congratulations and thanks to our clinical investigators, both at UCLA and then at Nationwide Children's Hospital. And I want to just, you know, I can't begin to describe how much I'm thankful to Dr. Jerry Mendel, our principal investigator, who, you know, attacked this issue with enormous passion to make sure that this study stayed on track and these kids were able to still come So I stand here today, notwithstanding the pandemic and notwithstanding even the potential for the second wave, we're very confident as relates to study 102 that we'll have the last patient and the last visit in December and we will have a readout in the first quarter of next year. I'm very confident about that.

Ambulatory studies as well so none of this relates to the.

The unavailability of materials.

You actually for giving me an opportunity this year to go ahead and consider that someone might have worried about that the issues that the decision about the size of the study adults. It really isn't the FDA. The division does it essentially blasted are confirmed they agree with the analysis that we're doing and they haven't given that 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 this is essentially the same thing we were going to do.

With the studies degree or wine in the form of an interim analysis on a subset of patients we were kind of looking at the eight to 12 range and next we'll go right. Now. These 10 patients in this study and that was that relies on our own evaluation and we are confident about the size of the study and were confident about.

The fact that we'll get inside and and validation around commercial material, both expression and safety I'm out of it.

Douglas S. Ingram: 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. Mendel. Thank you. And our next question comes from Colin Bristow with UBS. Your line is open.

You did touch on something I, just you know who you are well aware of this but I'll say it yet again just said we're absolutely clear we have you know I know that other programs have seen very troubling issues, though for instance comp when they complement mediated they who's in the like we've never seen those issues and there's no reason to believe.

Operator: Thanks for taking the questions. So, the first one: I understand the agency hasn't fully blessed the pasta market, but in terms of their willingness to accept these 8 to 10 patients as 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 3-0-1, it seems like 1-0-3 is going to ring fence this commercial to clinical products question, and just, I guess, why not initiate the 3-0-1 either in parallel, as soon as you can get the results of the potency assay issue ironed out? Yeah, 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.

That we would see anything like that and I'm out of our commercial process material either and so we're very confident about that but that's that's never been in a e. That's appeared with any of our or a 74 driven programs. So just wondering if that's a cool.

Thank you for your question.

Our next question comes from Vincent Chen with Bernstein. Your line is open.

Thank you very much for taking the questions.

Largely falling off and just clarifying some things feel puts us before Bruce it really just to clarify is there specific data you're waiting for from study one of the three the gifts. The start of study real one or in a non covered or you. Just go ahead and start study 301. If you wanted to see if you had sort of a line on the potency assay.

And then Oh, we didnt.

Yeah. Thank you I mean, we proposed study one of those three because of the German issues and frankly, you know to be honest.

Douglas S. Ingram: We, you know, and that's on purpose. And I think I said long in advance at the Type C meeting that we explicitly don't want to have those discussions until we have data available. I don't want to, with a very busy agency, I don't want to have those kinds of discussions at a theoretical level. I want to have them with data in hand.

The only people thought we propose this in the summer it's only become more compelling recently you know what it does appear unfortunately, certainly the United States and then probably around the world right now that you know the second wave is upon us so not only becomes more compelling.

To EPS, where we met with the agency in our formal discussions at the end of September we proposed and they concurred in the concept of US starting in one of three and we actually put those that we just started three or went after we have data from one or three and they concurred in that so.

Douglas S. Ingram: With respect to 103, you know, 103 was designed originally because of the pandemic to get us the information we really need in the meanest way without risk to the program and, more importantly, without placing risk on children, including placebo kids who would be, you know, having to go into doctor's offices with the potential of being on a placebo. So there's a number of reasons why. We talked to the agency informally. We talked about the commencement of study 103. The reason we are, we had proposed to the agency, actually, that we would consider a commencement of study 301 once we had study 103 in hand, and they concurred in that concept. There are 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 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, you know; we might learn stuff from 103 that could inform the way we design 301.

So that's the decision that we made in light of where we are and we think it makes that understands that there might be something that we were not one of three that could actually inform three awards, but we're very focused on getting the information that we're most interested in right now which is validating that commercial material, both an expression and safety.

And children with Duchenne muscular dystrophy, and having that information and share and after that.

Douglas S. Ingram: And so it made sense for 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 for. Our next question comes from Brian Abraham with RBC Capital Markets. Your line is open.

Operator: Hey guys, thanks for taking my questions. Can you clarify, is FDA sign-off on the actual potency data that you've generated using the agreed-upon approach gating 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 for seeking approval using open label rather than placebo-controlled safety and expression data from commercial-scale material? Thanks. Well, there are a couple of things.

Skipping that is higher with the Pip PMO product at early time points or are you, hoping to see several magnitudes higher of skipping could you put a finer point on that.

Douglas S. Ingram: You know, we have the data in hand. So we feel very confident that we're going to commence the study. We don't believe that we should have any gating items other than just getting it executed to commence study 103.

And are you dose escalating because maybe the skipping is not where you would like to see it yet and you think by getting the 30 or 40, you'll be able to achieve the ultimate goal, even though it appears that you are seeing great safety.

Yes, So I would say first of all don't read much into don't read anything into my comments about what we're seeing because we havent. The reason we Havent released the 20 makes PK data, we don't have that right now so.

Douglas S. Ingram: You know, 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 a placebo effect on expression.

I'm going to turn this over to Dr. O'neill too to provide some color on what we're going to look at between the two I think couple of things you know it would be nice to see some additional exon skipping even though it's at a different time points between the PMO and the PMO and 20 minutes for Chegg, but the reason that were dose escalating.

Douglas S. Ingram: 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 approval. We'll have those discussions at the appropriate time with the agency and with data. Our next question comes from Ritu Baral with Cowan. Your line is open.

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 toxicities that we know that we are creating the most exon skipping a district impossible. When we've seen any animal models that that that if you push the dose high enough and you can do some safe.

Operator: Thanks for taking the question, Doug. I hope I helped you understand this. What assurance or, I guess, general messaging do you have from FDA that the 10 patients that you're thinking about for 103 are going to be large enough to capture the potential variants of the commercial product and the safety of the commercial product? Just, you know, given what we've seen with the Pfizer compound and complement in some patients and not others? You know, what do you have in writing from the type of meeting at the end of 10? And also,

Really.

Yeah at least at the animal models bear out you will see a very substantial eventually very substantially increased wear it out exactly edge.

No its correlating between humans and animals is always difficult to to help Patrick dosing is weight based dosing that's a hybrid between the two so we don't know yet, but we're very confident in the mechanism of action.

Well I will say, one more thing and I'll turn it over to Dr. O'neill to give more data driven color on this this is all about safety for US were really well. We're curious listening is one other safety signals were 20 makes per gig what's the change. We go to 30 makes for Qig Im going to 30 makes appreciate what's the chance are you going to $40 per gig to make sure that we.

Douglas S. Ingram: 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 products you need to potentially run 3L1? I just want to make sure that you're not going from 70 to 10 because of a lack of validated products. Yeah, that's a really good question.

We get to the optimal dose for these kids with that said, Dr. Aneel and additional color on this.

Yes. Thank you very much so I think the key thing to say is that the momentum study had two objectives. The first is to test our hypothesis that the 700 peptide fuse to the PMO significantly enhance it.

Douglas S. Ingram: Thank you for asking that. We got, we do not have a material shortage problem. So that's a good thing. Yeah, thank you. I hadn't even considered that someone might have imagined that would be the case.

Thank you Sal and ultimately nuclear penetration to enable higher levels of skipping anj dystrophin expression as we have seen in our non clinical data and the second objective is whats really driving your question.

Douglas S. Ingram: We have, you know, we've done many GMP runs; we have, you know, sufficient material to start studies 103 and 301, etc., non-ambulatory studies as well. So none of this relates to the unavailability of material. Thank you, actually, for giving me an opportunity to say that, because I hadn't considered that someone might be worried about that. The issue is, you know, the decision about the size of the study is ours. It really isn't the FDA. The division doesn't essentially approve 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, that is our decision. I mean, the risk around the size of the study is ours. That's never been an A-E that's appeared with any of our R874-driven programs.

Is that we want to maximize the benefit risk and so if we can can continue notwithstanding a proof of principle.

The human up 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 maximized the benefit.

So I.

So that is the key reason for dose escalation I would reinforce yet I would reemphasize there, but we will be examining is systemic PK very importantly to the proof of principle tissue penetration. In addition to ongoing safety as well as exon skipping a.

Operator: Ciao. That's one. Thank you. Our next question comes from Vincent Chen with Bernstein. Your line is open.

Operator: Hey, thank you very much for taking the questions. A couple for me, largely following up on just clarifying some things people asked before. The 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 just 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 question. Yeah, thank you.

Data.

Thank you.

Thank you. Our next question comes from Daniel Brown with Raymond James Your line is open.

Hi, This is the Neal on for Danielle Brill. Thank you for taking my question.

Staying on the topic of Pip him Oh I'm.

Good question in terms of dystrophin expression.

Sure dose escalating are you collecting the dystrophin expression data and do you have anything.

Then you might be able to share that.

Thank you.

We're going to have an up we'll have an update on the 20 makes for Qig.

Douglas S. Ingram: I mean, we proposed study 103 because of the COVID issues. And frankly, you know, to be honest, it's only we who proposed we propose this in the summer, it's only become more compelling. Recently, you know, it does appear, unfortunately, certainly in the United States and probably around the world right now that, you know, the second wave is upon us. It only became more compelling to us when we met with the agency in our informal discussion. At the end of September, we proposed, and they concurred in the concept of us starting 103, and we actually proposed that we would start 301 after we had data from 103, and they concurred in that. So that's the decision that we made in light of where we are, and we think it makes tons of sense.

12 weeks.

Dr., Neil you're Gonna correct me, if I missed anything or if it's a 12 weeks with the ppm or were 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 were not looking for discipline right now for the simple reason that it is very early days you can get some lead of exon skipping at an early stage.

One of the things we know with certainty is that dystrophin builds over time in 12 weeks is very early to start looking for district that we've seen and with our PMO as an axon just as an example, we've seen a significant difference in the amount of disturbing 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 the strip when that Dr. O'neil do you want to add any additional color on that.

Douglas S. Ingram: 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 that 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 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 we believe we're for right statistically, significantly and clinically, meaningfully and that 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 or seeing the same safety signs out of the commercial material that we want to see in children with Duchenne Muscular Dystrophy and hopefully as close in time as possible so that we have together essentially three things.

I can confirm first that but 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 out, but as as Doug has said.

12 weeks data is very early after dystrophin expression and as we have learned a lot in the past with our PMO distro from AD.

Does accumulate over time and so that is the reason that from a proof of concept and a.

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.

Thank you and our next question comes from Salveen.

Terry with Goldman Sachs. Your line is open.

Hi, This is tonya on for Salveen.

Douglas S. Ingram: We'll see out of 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. Thank you. And as a reminder, please limit yourself to one question. Our next question comes from Tyler Van Buren with Piper Sandler. Your line is open.

And wait longer term strategy on DMD with next generation approaches using genomic medicine.

I'm not sure, but first I'll say that we are you know of course in addition to our gene therapies. In addition to our both our PML is right now and our next generation Pbms are which we just touched upon and.

And in addition to gene editing and I should tell you where the gene editing innovation Center in Durham, North Carolina under Dr., Charlie Griesbach. Thanks, looking at a number of different things, including the potential for gene editing and Duchenne up I think that's a bit that out that off in the distance. There are a number of other ideas that we're looking at as well.

Operator: Hey there, thank you. Good evening. I had a question on the momentum trial readout by your end and was just hoping you could refine expectations there. I think you mentioned specifically that 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?

But I don't think weve come to fruition, yet, but if you have any additional thoughts on our daughter or they'll let me know.

No 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 you know certainly when I think about gene delivery pending gene editing.

Douglas S. Ingram: And are you dose escalating because maybe 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 Migs per Keg data is we don't have the data in hand right now, so I'm going to turn this over to Dr. O'Neill to provide some color on what we're going to look at between the two. I say a couple of things, you know; it would be nice to see some additional exon skipping, even though it's at a different time point between the PMO and the PPMO at 20 Migs per Keg, but the reason that we're dose escalating is that it has always been our goal.

Douglas S. Ingram: 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 in districts possible, and we've seen in the animal models that that's, that if you push the dose high enough and you can do so safely, if the animal models bear out, you will see a very substantial, eventually, very substantial increase. Where that exactly is, you know, it's, you know, correlating between humans and animals is always difficult.

I did one O two data helped inform the design and scale of study one O three in any way.

I'd say studying one O. One really is informed that was one I'd see when one O three am again.

Just lingering for a moment as I want to make sure I'm very clear about the fact that we haven't had no discussions with the agency to solicit their views on what the data that would be necessary for for instance would be L. A family. So I don't want him to sleep I mean, I do agree with you that we are we are in the same position.

Douglas S. Ingram: Is it helimetric dosing? Is it weight-based dosing? Is it some hybrid between the two?

Douglas S. Ingram: So we don't know yet, but we're very confident in the mechanism of action. And so, I'll say one more thing, and then I'm going to turn it over to Dr. O'Neill to give more data-driven color on this. This is all about safety for us.

With our approach today as we would've been as we were thinking about studies, where one which with an interim analysis, probably the one difference cause started to differences one if you roll the clock back of course, you know we were under the impression that the potency assay approach that we had when he tracked into the September meeting, what's appropriate and you know that has.

Douglas S. Ingram: We're really curious to see what the safety signals are for 20 mgs per gig. What's the chance we can go to 30 mgs per gig, and if we can go to 30 mgs per gig, what's the chance we can go to 40 mgs per gig to make sure that we get to the optimal dose for these kids? With that said, Dr. O'Neill, you have the machine of color on.

That's a couple of months delay as we sorted that out and got new data. That's it a difference, but I must say in fairness and I really Wanna give tons of cheetah and stuff to the team and the willingness of Oh attached to talk to US we were able to resolve those issues in advance of one O. Three you know as fast as I think it is.

Timothy Francis Lugo: 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-penetrating peptide fused to 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 non-clinical data. So that is the key reason for dose escalation.

Possible to do I think you know and white and how busy that agency is in in light of the pandemic I think the ability to actually get in and get a formal meeting with the division. So soon after our type C meeting I do come to a resolution literally by the end of September I think and so it says a lot about.

Timothy Francis Lugo: I will reemphasize that what we will be examining is systemic PK, very importantly, to the proof-of-principle tissue penetration in addition to ongoing safety as well as exon skipping data. Thank you. Thank you. Our next question comes from Danielle Brill with Raymond James. Your line is open.

The team and it's willing to X willingness to execute in its execution ability and it also said something about the divisions 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 down I think one O. Three is has one O three is.

Operator: Hi, this is Daniel on behalf of Danielle Brill. Thank you for taking that question. Staying on the topic of PPMO, good question in terms of dystrophin expression. As your dose is coming in, are you collecting the dystrophin expression data, and do you have any idea of when you might be able to share that? Thank you. We're going to have an update on the 20 Migs per K at 12 weeks. Dr. O'Neill, you're going to correct me if I misstate anything. It's 12 weeks with the PPMO. We're actually going to compare it, ironically, to the PMO at 24 weeks.

There's a much higher we get us data much quicker I think then even though with an interim analysis of three O. One so I think in many regards we will get the information that will give us insight on the commercial material with a higher T O S. In the middle of a pandemic and faster.

And we would have done with a larger studies so other than that I think the the approaches 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 one O two that show the functional benefits of this.

Douglas S. Ingram: 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 read of exon skipping at an early stage, but one of the things we know with certainty is that dystrophin builds over time, and 12 weeks is a very early time to start looking for dystrophin. We've seen with our PMOs, and exogenous is an example, we've seen a significant difference in the amount of dystrophin that was produced literally at four years versus one year. So I'm not saying it will be that long, but 12 weeks is a bit early.

Therapy, and safety and safety signals and Tolerability and we should also have the results of this commercial validation study. The same information we would have hoped to get out of the interim analysis or study three O. One on both microtus with an expression as well and safely. So I think you know with it when the one.

Caveat that would probably you know 60 days, though it delayed versus where we were when we thought we would have been let's say in July of this year. We're basically in the same same position with the same kind of data by early next year.

Thank you. Our next question comes from her touch thing with Oppenheimer Your line or something.

Douglas S. Ingram: With that, Dr. O'Neill, do you want to add any additional color? I can confirm first 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 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 First and foremost, tissue distribution or tissue concentration, as well as exon skipping, at 12.

Hi, This is definitely have our cars sex close in maybe it's just a complication question. Since you know your earlier prepared remarks that you're gonna pursue additional studies older and now I'm doing voice cause he was just clarify whether those would be separate from studies three O. One.

Or cohorts added two that study thank you.

Yeah, It would be a separate study on non ambulatory patients at least that's the way we envision not too bad.

Thank you. Our next question comes from defy Yang with Michelle How security is your line is open.

Mm. Good afternoon. Thanks for taking my question. So just asking yeah clarifying historical classes. So back in the days before Audi discussion on potency past.

Douglas S. Ingram: Thank you. And our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

When I'm there.

Original plan was to go to the F D a.

Operator: Hi, this is Sonia on behalf of Salveen. Where do you stand with the longer term strategy on DMV with the next generation approaches unit using genomic medicine? Dr. O'Neill, first I'll say this, we are, you know, 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 There are a number of other ideas that we're looking at as well, that I don't think have come to fruition yet, but if you have any additional thoughts on that, Dr. O'Neill, please let me know. Well, I think you said it nicely. The key things are that we actually have a nice portfolio of platform approaches for gene delivery, gene editing, and our antisense. And I think that choice, you know, certainly when I think about gene delivery, pending gene editing, further evolution, and our antisense enables patients to make optimal choices, we hope, in the future. And obviously, they complement one another.

With results from loud teal.

Into rooms.

[noise] readout on three O. One at the agency did the F D a ever confirmed that won't be enough.

Ah form the basis for P. L. A the Michelle with it at the 0.2.

Off to start the conversation about potential submission.

No. It's always been our strategy I think we've communicated this often that we will have those discussions with the dimension. Once we have that in hand and that until we have that in hand, we won't have discussions about the the.

Level of evidence necessary for a BLA for the simple reason that I think it's asking a lot of the agency of the metalwork all of how busy or the pandemic Emma liked to have theoretical discussions will will get one or two executed we get the results of one or two will get the material from our.

Hershal validation study and then we'll talk to the agent and see about the past four or with with initial studies or a b L a or the like.

Anyone knows my uncle so.

But we've been very consistent another thing that first time.

Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open.

Hi. Thank you. This is Mac score on for Matthew Nurse and just a quick question is studied eating at all for initiating discussions with you did see regarding the limb girdle to eat trial with commercial material more specifically is there any read through from one of them see actually come back.

Thank you I don't think there's any gaming there's no gaming iron between studying one or three in the discussions with the agency about limb girdle to me no I think that there is no doubt that the discussions we've had with the agency about the potency assay.

Douglas S. Ingram: And I think, as we said before, you remember, we are even looking at the possibility of combinations of these treatments in the context of optimizing treatments for patients with Duchenne. And I will actually also highlight what Doug said earlier, which is that, obviously, the other thing we want to do with our portfolio for Duchenne patients is ensure that we develop data for patients at various stages of their disease, just to ensure we can maximize benefits for as many people as possible. Thank you. Thank you. Our next question comes from Joel Beattie with Citi. Your line is open. Good evening. This is Sean Egan calling in on behalf of Joel.

[noise] approach will inform the approach we take with live journal Jewish So we're in much better shape as a result of those discussions we can apply those that learning to the liberal too we wish without a doubt or the real gating item to have discussions with the agency or.

Living room, though too he's getting the G. M P material released in.

That requires us to continue to do analytical work and.

Douglas S. Ingram: 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 being a positive 102 study and, you know, positive bridging results. But maybe can you confirm that there's been 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 data from study 102 helped inform the design and scale of study 103 in any way? I'd say study 101 really has informed both 102 and 103. Again, just lingering for a moment, I want to make sure I'm very clear about the fact that we have had no discussions with the agency to solicit their views on what the data that would be necessary for, for instance, the BLA filing. If I don't want to mislead, I mean, 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, Probably the one difference; there's sort of two differences.

Well on the way, but not completely.

[laughter].

Thank you. Our next question comes from Martin Auster with Credit Suisse. Your line is open.

Hi, this is not tear up on for Mardi. Thanks for taking the question I just wanted to confirm this study one of three is a single center study. Thanks a lot.

I I believe it is but I'm gonna, let him Doctor O'neill confirm that for us.

The the phone number of sites will actually be determined as we execute studied we have actually built in redundancy because there's duck has said one of the things we did in the region region reason that we actually conceived of the one O. Three study was.

It's actually handle the or deal with the consequences of the ongoing pandemic and so we have actually built in flexibility. So.

So that we are able to enroll and execute this study as quick as possible.

Thank you is 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 time then like both of the performance of our approved therapies as well as our development programs as relates specifically to ask for too long 001. This.

Douglas S. Ingram: One, if you roll the clock back, of course, you know, we were under the impression that the potency assay approach that we had as we tracked it in the September meeting was appropriate. So I think in many respects, we will get information that will give us insight into the commercial material with a higher POS in the middle of a pandemic and faster than we would have done with a larger study. And so, other than that, I think the approach is the same.

Of course, the top of mind for so wrapped it because it is such an important program for two shed muscular dystrophy boys that are waiting we did have a shed back in September as one what can expect to have it when you're ambitious.

Douglas S. Ingram: If it 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, safety signals, and tolerability. We should also have the results of this commercial validation study, the same information we would have hoped to get out of an interim analysis from study 301 on both micro-initiative and expression as well as safety. So I think, you know, 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. But we're basically in the same position with the same kind of data by early next year. Thank you. Our next question comes from Hartaj Singh on Oppenheimer. Your line is open. Hi, this is Jackie and Hartaj. Maybe just a clarification question.

We had hoped in September that we would have a blessing them to come out and studied one or three in September but I am very pleased to say that we executed consistent.

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 studying one O three and the potency release assay associated with studying went on three we could not have I think envisioned a faster Reds.

Solution 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 update people across the course of the years, we execute but I wanted to give a lot of thanks, both too Joe chat certainly for their willingness to engage with us.

Douglas S. Ingram: 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 would 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 anticipate it.

And help us find a pathway forward I want to thank the shreffler team for their willingness to continue to execute fiercely across the organization and serve these patients and of course, one of the things locations are both those who participate in our trials as well as those patients across all of our heart disease.

Douglas S. Ingram: Thank you. Our next question comes from Defy Yang with Mazzoho Securities. Your line is open.

Both you shan't muscular dystrophy, and currently limb girdle muscular dystrophy.

Operator: Good afternoon. Thanks for taking my question. I'm just asking a clarifying historical question.

Or that's where they are commitment to the programs, but also for I'm staying with us as we continue to actually these programs. We haven't a single minded goal as an organization or success will come from our ability to intervene in the lives of patients who are suffering from these rare diseases and far far too often.

Douglas S. Ingram: So back in the days before all these discussions on potency tests started, when the original plan was to go to the FDA with results from 102 plus interim readout on 301, did the agency, did the FDA ever confirm that would be enough to form the basis for a BLA submission? Or was it at the point just enough to start the conversation about potential submission? Now, it's always been our strategy, and 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 data in hand, we won't have discussions about the level of evidence necessary for a BLA, for the simple reason that it's asking a lot of the agency in the middle of all this, of how busy they are in the pandemic, and the like I think everyone knows what our goals are in that regard, but we've been very consistent in that regard.

I understand could you share muscular dystrophy in England girdles being stolen from their families by a short life because of these diseases and we will work like mad to move as fast as possible and I do believe that studied one O three that which we proposed and was accepted by the agency is going to be the enormously important.

Step forward and our ability to accelerate therapy. The patients that are waiting sitting in 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.

[music].

Douglas S. Ingram: Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open.

Operator: Hi, thank you. This is Max Skoron from Matthew Harrison. Just a quick question: is Study 103 dating at all for initiating discussions with the agency regarding the Lim-Girdle IIe trial with commercial material? More specifically, is there any read-through from one potency assay?

Okay.

[music].

Douglas S. Ingram: Thank you. I don't think there's any gating, there's no gating item between study 103 and then discussions with the agency about Lin-Gerdal 2E. No, I think that there is no doubt that the discussions we've had with the agency about the potency assay approach will inform the approach we take with Lin-Gerdal 2E, so we're in much better shape as a result of those We can apply that learning to the Lin-Gerdal 2E without a doubt.

Douglas S. Ingram: The real gating item for having discussions with the agency on Lin-Gerdal 2E is getting the GMP material released, and that requires us to continue to do analytical work and assay work that is well on the way but not complete yet. Thank you. Our next question comes from Martin Oster with Credit Suisse. Your line is open.

Operator: Hi, this is Matt Terrell-Bond for MARDI. Thanks for taking the question. I just wanted to confirm if Study 103 is a single-center study. Thanks a lot.

Douglas S. Ingram: I believe it is, but I'm going to let Dr. O'Neill confirm that for us. The final number of sites will actually be determined as we conduct the study. We have actually built in redundancy because, as Doug has said, one of the things we did, and the original reason that we conceived of the 103 study was to actually handle 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.

Douglas S. Ingram: 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 in our development programs. As relates specifically to SRP 9001, this is, of course, top of mind for SREPTA because it is such an important program for Duchenne muscular dystrophy boys that are waiting. We did have a setback in September, as one can expect to have when you're ambitious. We had hoped that in September 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 quickly.

Douglas S. Ingram: We were able to arrange 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 could commence with little delay the next commercial validation study in an extraordinarily important program. I'll continue to update people across the course of the year as we go, but I want to give a lot of thanks both to OTAT and to the government for their willingness to engage with us and help us find a pathway forward. I want to thank the SREPTA 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.

[music].

Douglas S. Ingram: Our success will come from our ability to intervene in the lives of patients who are suffering from these rare diseases and far, far too often with respect to Duchenne muscular dystrophy and these limb girdles being stolen from their families by a shortened life because of these diseases, and 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 enormous With that, have a lovely evening, and we will continue to update you across the course of the year and into next year. Thank you.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.

Unknown Executive: .................... Copyright Australian Broadcasting Corporation. Copyright 2019 Mooji Media Ltd. All Rights Reserved.

Unknown Executive: No part of this recording may be reproduced without Mooji Media Ltd.'s express consent, www. University at Buffalo.edu www. University at Buffalo.edu www.

Unknown Executive: University at Buffalo.edu, Copyright 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. [inaudible] Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics third quarter 2020 earnings call. At this time, all lines are in a listen only mode.

Mary Jenkins: After the speaker's presentation, there'll be a question and answer session. To ask a question during this session, you'll need to press star one on your telephone. 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.

Douglas S. Ingram: Thank you, Catherine. And thank you all for joining today's call. Earlier today, we released our financial results for the third quarter of 2020. The press release is available on our website at Sarepta.com, and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon.

Douglas S. Ingram: Joining us on the call today are Doug Ingram, Ian Estepan, Dr. Gilmore O'Neill, and Dr. Louise Rodino-Klapack. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we'll be making a number of forward-looking statements. Please take a moment to review our slide 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 and 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, I will turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress. Thank you, Mary.

Douglas S. Ingram: Good afternoon, everyone, and thank you for joining Sarepta Therapeutics' 3rd Quarter 2020 Investor Conference Call. Tonight, I'm very proud to share with you the progress we have made this quarter, including our performance in serving the Duchenne community with Exondys 51 and Biondys 53, our progress with respect to our RNA platform, and the strides we have made in building out our enduring gene therapy engine. But I'm going to take things a bit out of order this evening.

Douglas S. Ingram: I'm going to commence 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 starting a trial with commercial process material this year. Let me provide some background and context.

[music].

Douglas S. Ingram: As you will know, SRP9001 is our gene therapy, and the goal of it is to treat Duchenne muscular dystrophy by safely delivering to the skeletal diaphragm and cardiac muscle, a gene that robustly codes for a truncated but functional form of the structural protein dystrophin that we call microdystrophy. 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 Drs. Jerry Mandela and Louise Rodino-Klipak, 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 on all functional measures. The children continue to improve in ways that cannot be explained by natural history.

Douglas S. Ingram: Based on this proof-of-concept study, we commence the randomized, blinded, placebo-controlled trial. You'll recall that it's study 102. Study 102 is intended to show in a well-controlled trial that 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 studies 101 and 102 was manufactured by our partner, Nationwide Children's Hospital, pursuant to a process that will not scale for large commercial purposes. However, over the last two years or so, we have developed a commercial process, and we've built significant manufacturing capacity.

Douglas S. Ingram: Assuming SRP 9001 proves effective, these efforts are expected to provide us with the capability to produce and launch a commercial product that fully serves 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 hand to conduct additional studies, we requested a meeting with OTAT.

Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics third quarter 2020 earnings call.

Douglas S. Ingram: OTAT is the division of the FDA responsible for cell and gene therapy, and we did that to obtain their blessing 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 risk 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 placebo-controlled trial. The goal of study 103 is to gain insight and validate the performance Our Type C meeting with the division, which was conducted entirely in writing, occurred in September of this year.

This time, all participants lines are in a listen only mode. After the speakers presentation. There will be a question and answer session to ask a question during the session you'll need to press star one on your telephone as a reminder, today's program is being recorded at this time I'll turn the call over to Mary Jacobs Senior manager Investor Relations. Please go ahead.

Thank you Catherine and thank you all for joining todays call earlier today, we released our financial results for the third quarter 20, <unk>. The press release is available on our website at <unk> Dot Com and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon.

Joining us on the call today are Doug Graham you had at the time Dr. Gilmore O'neal, a doctor or the lease with you know quite back after our formal remarks, well open the call for acuity.

I'd like to note that during this call, we'll be making a number of forward looking statements.

Please take a moment to review our slide on the webcast, which can be as excellent looking statements. These forward looking statements involve risks and uncertainties many of which are beyond throughout this control actual results could materially differ from these forward looking statements any such risks can material and it materially and adversely affected.

Douglas S. Ingram: In its written response, the division raised concerns with the potency release assay approach that we had proposed. As I stated at the time that this 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, 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 have 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 for 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.

The results of operations and treating crisis disruptive common stock for a detailed description of a couple of 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 FTC 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.

With that let me turn the call over to our CEO, Doug Graham who will provide an overview of our recent progress Doug.

Doug.

Thank you Mary.

Good afternoon, everyone and thank you for joining Sarepta Therapeutics third quarter, you 2020, Investor Conference call and I'm very proud to share with you. The progress we've made this quarter, including our performance in serving the Duchenne community with EXONDYS 51, and my honest 53.

Progress with respect to our already platform and the strike you have made in building out our enduring gene therapy engine.

Two things a bit on the border. This evening I'm gonna commences its call by discussing an important milestone for sarepta and for the Duchenne patient community as.

As you will have read in our press release today I'll be working with the FDA, we now anticipate dosing a trial.

Commercial process material.

Douglas S. Ingram: 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 its last 12-month visit 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 larger 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.

This year.

Let me provide some background and context.

Well no. That's 49 001 is our gene therapy and the goal is.

Used to treat duchenne muscular dystrophy, my safely delivering the scope of the F. Ram cardiac muscle a gene that robustly codes were truncated, but functional form of the structural protein district that we call micro district.

The M.D. make essentially no dystrophin, which results in rapid degeneration and inevitable das in the goal was to a restless the generation by giving them back a properly localized functional form of that structural protein.

After many years of design in preclinical testing by doctors Jerry Mendell. The beach, we don't quit back we commenced and completed a small or patient Bob.

A proof of concept study study one and one that was positive and very encouraging the therapy was well tolerated. The gene was indeed robust we delivered to the target muscles about 3.3 genome copies for nucleus. The expression of the protein approach nearly normal levels in all functional measures.

Douglas S. Ingram: I would like to thank OTAC 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 an additional burden on an already overworked group of professionals at the FDA so that we may embark on Study 103. Now, starting 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 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 excess.

The children continue 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.

You'll recall that it studied one out to study one of the true is intended to show that it.

Well controlled trials SRP nine zero, Joe one is safe and effective in children with DMD. The last one year visit will occur in December and we plan to these results from study why don't you in the first quarter of 2021 now.

Now the material for study one a one in one out she was manufactured by our partner nationwide Children's Hospital.

Douglas S. Ingram: 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 two 3-patient cohorts for SRP9001 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, the same dose used in our studies for SRP 9001.

They went through 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 built significant manufacturing capacity.

Assuming SRP nine 001 proves effective these efforts are expected to provide this capability to produce air launch commercial products to fully serve that community.

By early 2020, we completed our process development and analytical development and we commenced our GMP right correct.

Recipe nine 001 commercial process material to use in future clinical studies.

In the summer of this year with GMP material, then hand, it to conduct additional studies, we requested a meeting with okay. Okay.

Douglas S. Ingram: As you will recall, both cohorts were generally well-tolerated, with a significant dose-dependent increase in expression in Cohort 2. At WorldMuscle, 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 six-month data for Cohort 2, where the children are already showing not mere stabilization of function but improvement in function, again, against both baseline and against natural history.

Well that is the division of the EPS gave responsible for cell and gene therapy, and we did that to obtain their blessing 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 travel.

19, which dalbeattie coming to fruition and the risk that poses to clinical trial participation and execution.

Anticipation of our September type C meeting, we proposed a leaner open label commercial material validation study study one of three in the same patient population as study one of the two our ongoing let's see about controlled trial.

The goal of study one of three is to gain insight and validate the performance of our commercial process material, both micro dystrophin expression and safety and after 10 patients with the primary analysis or part one of the study conducted at 12 weeks post an infusion in all treated patients our type C meeting with the division, which was conducted in <unk>.

Douglas S. Ingram: We are particularly pleased with these LGMD2E results, and in particular, the safety, expression, biomarker, and functional results of Cohort 2, as they have potential read-through to our remaining LGMD portfolio and supportive confirmatory read-through to our SRP9001 program from DMD, as the programs share the same vector, the same promoter, the same design approach, and, in the case of Cohort 2, the same dose as well. With respect to LGMD2E, we are completing manufacturing materials for our next trial and will 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.

Hi, early in writing occurred in September of this year.

And it's written response the division raised concerns with the potency release acetate approach that we had to propose.

As I stated at the private that'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 it could have extended into next year.

However, I am pleased to report that the division was willing to work with us expeditiously and it formally 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 have spent the time since then the gathering.

Douglas S. Ingram: We continue to build our gene therapy platform and develop 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 you on our entire pipeline of gene therapy and RNA, and we will provide more details on this. Early next year,

The data necessary for our updated potency assay approach for study one of three and finalizing the meeting minutes based on those discussions the status of the next steps for our program are the.

First after discussion in obtaining division guidance, we proposed in the division accepted a potency assay approach for study one of three we have already completed the work and generated the data from the new potency assay approach for study one or three second the division will permit us to commence study 103, which we intend to do.

Before the end of this year.

Douglas S. Ingram: 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 have been able to serve the Duchenne community with our approved therapies, with only a modest impact from the current pandemic. For our PMO franchise, currently Exondus and Biondus, our net product revenue for the quarter was $121.4 million, and that represents a nearly 23% increase over the same quarter last year.

I want to remind you study one out you will have the last 12 month business in December of this year and we will report the results of study one of the two in the first quarter of 2021.

Depending on the external environment and pandemic, we anticipate speaking with the division and starting our larger study real one in 2021. After we have data available from study one of three.

We also intend to design and proposed to the division for their review and what additional studies, including importantly get older and non ambulant patients.

I would like to thank out after their responsiveness and their willingness to end, formerly and rapidly meet with US on this extremely important program even in the midst of a pad that has placed additional burden on an already overworked group of professionals at the FDA. So that we may embark on study one or three.

Douglas S. Ingram: 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 to this pan Now moving to our PMO Pipeline. The FDA has accepted our filing for our third Duchenne Therapy, Cazimere, a PMO therapy intended to treat those 8% of Duchenne patients who are amenable to skipping Exxon 45. The brand name for Kazimierzyn will be Amondis 45.

Now starting 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 one on one were published in Jama neurology reporting robust expression, good tolerability and safety and functional improvements across all measures in the cohort.

Just send away didn't catch that.

At the World Muscle Society conference in the third quarter, we provided an update on study one on one reporting not only continued safety and Tolerability, but also durability of effect with all boys continued to show functional benefits of the gene therapy at two years.

At World muscle as well, we also provided updates on our Q3 three patient cohorts.

SRP nine 001 for the treatment of living girdle muscular dystrophy type two we or L.D. MD two week.

Cohort one was dosed at five years, a 13 to go or two was dosed it to either the 14 same dose used in our studies or SRP 900 work.

As you will recall, both cohorts were generally well tolerated with a significant dose dependent increase in expression in cohort two at world muscle. We reported the 18 month results for cohort, one showing not merely stabilization, but a substantial improvement in function above baseline and above natural history. We also.

Douglas S. Ingram: Our PDUPA date is February 25, 2021, and the review is going well. If we obtain approval for casimirsin, we will have three approved therapies capable together of treating nearly 30% of the DMV community. And as we have mentioned before, our RNA technology has the potential to bring treatments to as many as about 85% of patients living with BMD. So we do have much left to do.

We reported the early 60 month data for cohort two where the children are already showing not near stabilization of function, but improvement in function again against the baseline and against natural history. We.

Douglas S. Ingram: As you will know, we are also making progress on our next generation of the PMO, which, if successful, 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 SRP5051. 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, hence greatly increasing exon skipping, and then, thus, less dystrophin production. Before the end of this year, we will provide an update on safety, systemic exposure, and exon skipping for our PPML-SRP-5051 candidate at 20 mg 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.

We are particularly pleased with these LG MD Julie results and in particular, the safety expression biomarker and functional and results and go or two.

Did that potentially new to our remaining LTAC portfolio and supportive confirmatory read through to our SRP nine 001 program.

As the pro rata share the same Baxter the fan promoter the same design approach in the case of go or to the same dose as well with respect to LG M.D. too we are completing manufacturing and material for our next trial and will engage with the agency on the design for what we hope will be the pivotal study will provide an update on both of these mad.

And our perspective on the development and regulatory pathway and timing for our entire LG M.D. portfolio in 2021.

We continue to build our gene therapy platform and gathered 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 this bad debt expenses all to a largely work from home environment. We also.

You have what is likely the largest pipeline of high potential gene therapy candidates.

Biopharma today, we are considering an R&D day in June in 2021 at which we can update on our entire pipeline both gene therapy in our day and we will provide more details on this.

Douglas S. Ingram: Consider the following. Our PMOs are safe, and they're precise. Their ultimate limitation, however, is that they are also neutrally charged. They penetrate muscle cells passively, and they clear the body in about four hours. This will limit the amount of therapy they 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 for patients living with Duchenne muscular dystrophy.

Early next year.

Moving on now to our ornate platform, let me now discuss our commercial performance in the quarter.

As you will recall in light of that dynamic and unpredictable nature of the job at 19 pandemic.

We're through our guidance for 2020, Nevertheless, due to the collaborative work of our multiyear multi disciplinary team I am pleased to once again report that we have been able to serve the duchenne community with our approved therapies with only modest impact from the current pandemic.

Our our PMO franchise currently acts on this and by August our net product revenue for the quarter.

It was $121.4 million and that represents a nearly 23% increase over.

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.

Douglas S. Ingram: 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 result this year, but we have already moved to 30 mg per kg and intend, if safety signals will permit, to continue to dose even up to 40 mg 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, you know, purely based on animal studies.

We continue to monitor monitor performance closely and 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 ensuring 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.

All of our patients received 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 bad debt and have shown flexibility and authorizations and reauthorizations for this vulnerable DMD patient community.

Douglas S. Ingram: 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 a high enough dose, 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 the maximum tolerated dose. In conclusion, notwithstanding the unusual external environment, the team continues to execute with an unrelenting purpose.

Now moving to our PMO pipeline.

The FDA has accepted our filing through our third you shed therapy Cajon IRSA.

PM out there the intended to treat that 8% of duchenne patients.

Who are amenable to skipping exon 45.

The brand name for Cat the missing would be along this 45. Our Paducah date is February 25, 25, 2021, and the review is going well if we obtain approval for guys. In there. So we will have reiterated therapies capable together with treating nearly 30% of the DMD community.

And as we have mentioned before our R&D technology has the potential to bring therapy to as many as about 85% of patients living with DMD. So we do have much left to do.

Douglas S. Ingram: And the third quarter of 2020 perfectly exemplified our culture of performance, consistent with our message, our mission, and apologies. We kept the patient front and center in everything we did, which means we focused on the science, we continued to execute with the sense of urgency that our mission requires, and when faced with inevitable obstacles and roadblocks, we did not simply accept them or regress to the mean, but we moved with rapidity and creativity to address them, remove them, and keep progressing towards our ultimate goal of intervening and saving the lives of as many children living with and dying from Duch And with that, I will turn the call over to Ian Estepan, who will provide an update on the financials. Ian?

As you will know we are also making progress on our next generation of the PMO, which if successful may it profoundly improve the efficacy inconvenience of our R&D technology. We are in our multi ascending dose study called the momentum study for our peptide conjugated PMO or PDP about that's candidate SRP if you get.

I want to remind you we are using our proprietary positively charged peptide to increase penetration.

In animal models, we have shown that if we can safely achieve appropriate dose levels. The.

The PPL greatly increases tissue exposure into.

Entering greatly increasing exon skipping and.

And then das Das dystrophin production.

Before the end of this year, we will provide an update on the state can assist systemic exposure and exon skipping for our PBM outlast RP if he could be one candidate at 20 makes for kids.

And for US the most important measure of all of these and I've said this many times in the past we'll be safety consider the following our pmls are safe and their precise their ultimate limitation. However, they are also neutrally charged you penetrate muscle cells passively and they cleared the body in about four hours. This will limit the amount of therapy, they can get to the.

Ian M. Estepan: 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 on 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.

The right place and simply increasing the dose will.

I will not reverse this limitation.

Ian M. Estepan: Now starting with our net product revenue for the third quarter of 2020 from our products Exondus 51 and Vyondus 53 was $121.4 million compared to $99 million for Exondus 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. Co-development costs under the Roche Agreement total $16.9 million for the third quarter and are included as a reduction to our operating expenses. On a gap 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.

Our PPSA technology on the other hand potentially addresses this limitation in a dose dependent wed indeed, our preclinical models have consistently show that if one can safely dose the P.P. demos to a sufficiently high level, we should hit a point, where we get a significant increase in cell exposure and a great increase it.

Exon skipping a dystrophin production and that should translate into a great increase benefit to patients living with to shed muscular dystrophy.

Our most significant questioning the momentum study has always been safety upon repeat dosing and maximum dose we will present, the 20 make up for Qig results. This year, but we have already moved to 30 makes the keurig and intend of safety signals will permit to continue to dose even up to 40 megs per gig early next year.

Ultimately potentially even higher than that.

Able to do so while we can make some educated guesses from animal model until we observed 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 it the PBM hours mechanism of action.

Ian M. Estepan: 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.

Which means we are very confident that if we can safely achieve high enough doses and 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.

The third quarter and 2020 perfectly example of by our culture.

Performance consistent with our meshes message our mission apologies, we kept the patient front and center and everything we did which means we focused on the science, we continued to execute with a sense of urgency that our mission requires and when faced with inevitable obstacles and road blocks, we did not simply accept them or regress to the mean.

Ian M. Estepan: The increase is primarily due to increasing demand for our product. On a gap 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 program. 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 We recorded approximately $75.4 million of expenses for both of the third quarters of 2020 and 2019. On a non-GAAP basis, 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.

I 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 you Shen.

My girdle muscular dystrophy, and other rare diseases as science will make possible.

And with that let me turn the call Yeah, that's the Pat who'll provide an update on the financials.

The n.

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 the gap basis.

The press release is available on throughout this website. Please.

Please refer to our press release for a full reconciliation of GAAP to non-GAAP financial result.

Starting with our net product revenue for the third quarter of 2020 from our products EXONDYS 51, and find is 53 was $121.4 million compared to $99 million for EXONDYS 51 alone for the same period of 2019 the.

The increase primarily reflects higher demand for our products.

In the quarter ended September Thirtyth 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 at the reduction into 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 cents 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 cents per basic and diluted share in the third quarter 2020, compared to a non-GAAP net loss of $84.4 million or $1.14 cents per basic and diluted share in the third quarter 2019.

Ian M. Estepan: On a gap 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. This 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 investment 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?

In the third quarter of 2020, we recorded approximately $15 million.

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 a $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.

Timothy Francis Lugo: Thank you, Ian, and good afternoon, everyone. Doug has already shared the highlights from our most advanced gene therapy program. I will, therefore, focus my remarks on Sarepta's presentations at this year's World Muscle Society Congress and the progress we've made in advancing our RNA portfolio. Let me start with a World Muscle Highlight.

And 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 and increase of $49.4 million the year over year growth and non-GAAP R&D expenses was driven primarily.

Timothy Francis Lugo: 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 product expression and durable physiological benefits in skeletal muscles. Dr. Rodino Claypak's lab demonstrated durable sarcoglycan expression, histological benefit, and significantly increased resistance to contraction-induced injury in the tibialis anterior muscles in aegis, alpha, and beta sarcoglycan knockout mice that were treated respectively with alpha sarcoglycan or beta sarcoglycan transgene-containing RH74 constructs.

Due to a continuing ramp up of our gene therapy.

Yes, we recorded approximately $75.4 million of expenses for both the third quarters of 2020 and 2019.

On a non-GAAP basis bass, DNA expenses were $50 million to $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 a year over year decrease was driven by a decrease in professional services primarily due to it.

Decrease in reliance on third party contractors as a result of an increase in hiring and head count.

On a GAAP basis, we recorded $14.3 million in other expenses net for the third quarter, a 2020 compared to $2.5 million in other expenses net for the same period of 2019.

Unfavorable change primarily reflects the interest expense on our debt facility, we entered into in December 2019.

Timothy Francis Lugo: Moving to clinical data, we announced positive two-year functional results in support of our lead gene therapy candidate, SRP9001, in Duchenne patients. The results demonstrated that two years after a one-time infusion of SRP9001, 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 Thus, these functional data reflect a mean 1.5 point NSA improvement between years 1 and 2 post-SRP-9001 infusion. These data were generated from four ambulatory participants aged 4-7 in Sarepta's Open Label Trial Study 101 and showed continued safety and tolerability of a one-time infusion of SRP9001 at a dose of 2-14 viral genomes per kilogram. We also announced positive clinical data for SRP9003, our gene therapy candidate for limb-girdle muscular dystrophy type 2E.

And finally, we had approximately $1.8 billion in cash cash equivalents and investments as of September Thirtyth 2020.

With that I'll turn the call over to Gilmore for an update on our research and development activity Gilmore.

Thank you Ian and good afternoon, everyone.

Doug has already shared highlights from our most advanced gene therapy programs.

I will therefore focus my remarks on Sarepta as presentations that this year's World Muscle Society Congress and the progress you've made in advancing our R&D portfolio.

Let me start with the world muscle highlight.

This year's meeting USAID virtual format because of the ongoing COVID-19 pandemic.

Nevertheless, we were able to present 16 posters that described data across Raptors, R&D and gene therapy platforms.

From our gene therapy platform, the Nonclinical data clinical data that we presented support the hypothesis that the RF 74, and makes Teekay seven constructs, we use generate durable gene posit expression and durable physiological benefits in Sydney for muscle.

Dr. Rodino, Capex flat demonstration durable dr. glassman expression histological benefit and significantly increase resistance to contraction in juice injury in the TV Amos anterior muscles in agent Alpha and beta sockets like a knockout mouse.

Timothy Francis Lugo: 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 SRP9001, that is 2 to the 14th viral genome per kid. We demonstrated in cohort 1 that the three participants continued to show improvements from baseline across all functional measures, including the North Star Assessment for Dysphalnopathy, otherwise known as the NSAD, in addition to time to rise, forced air climb, 100-meter walk test, and 10-meter walk run test at 18 months. The mean NSAID improvement from baseline in cohort 1 was 5.7 points at 18 months.

Trichet, respectively without the talk is like that or patient sockets icon transgene containing or 74 constructs.

Moving to technical data, we announced positive to your functional result in support of our lead gene therapy candidate SRP nine years or one in your Shen patients.

The results demonstrated that two years after a onetime infusion SRP nine years or a one.

Participants exhibited the mean 7.0 point improvement in the North Star ambulatory assessment or an essay as compared to baseline.

Please note that remember that one year post treatment. The mean increase was 5.5 points from baseline does this.

This functional data reflect a mean 1.5 point NSC eight improvement between years, one and two hosts SRP nine 001 infusion.

Timothy Francis Lugo: In Cohort 2, at 6 months post-infusion, all three participants demonstrated improvements from baseline across all functional measures. The mean NSAD improvement from baseline and core 2 was 3.7 points. This compares to a 3.0 point change in cohort 1 of... Based on the safety, expression, and clinical results, we are moving the high-dose forward for future clinical development of SRP9003. 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 Microdystrophin SRP9001-101 study and the Limb-Girdle Muscular Dystrophy 2E SRP9003-101 study support durable functional outcomes at the 2-year and 18-month time points, respectively.

These data were generated from four ambulatory participants aged four to seven in Sarepta Open label trial study 101.

And showed continued safety and tolerability of a onetime infusion.

P. nine years or 100 dose up to to the 14 viagene homes per kilogram.

We also announced positive clinical data or SRP nine user or three our gene therapy candidate for limb girdle muscular dystrophy type to eat.

These results include an 18 month functional data from three clinical trial participants in cohort one the low dose cohort and six month function data from three participants in cohort two the high dose cohort, which was dosed at the same dose that we are using for EPS or P. nines user one that is two to the <unk>.

Timothy Francis Lugo: This further supports our hypothesis that because muscle is a terminally differentiated tissue, it thus enables a durable benefit following a single administration of the gene pair. 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 generation from its RNA platform.

14, RMG knows purchase.

We demonstration cohort one the three participants continues to show improvements from baseline across all functional measures, including the Northstar assessment for just started not pathie otherwise the tenants a D condition to time to rise four stair climb hundred meter walk test and 10 meter walk run test at eight.

Teen mom.

The mean NSC 80 improvement from baseline in cohort one was 5.7 points at 18 months.

In cohort two at six months post infusion all three participants demonstrated improvement from baseline across all functional measures the mean and the AG improvement from baseline in quarter, two was 3.7 points.

Timothy Francis Lugo: These included long-term safety data for Gauda Durson from the 4053-101 clinical study supporting his safety profile, PKPD data for Kazimersan from the 40-45-101 clinical trials demonstrating dose-proportional exposure, and an interim analysis of Kazimersan-treated patients in the essence pivotal studies showing a statistically significant increase in skeletal muscle dystrophin expression from baseline to 48-28. All in all, we were happy to share so much data across our comprehensive portfolio with the academic, prescribing, and patient community. Beyond the data we shared at WMS, there have been numerous developments across our RNA pathway. The FDA review of our NDA for our lead PMO candidate Amandus45 is ongoing and, from all accounts, going well.

This compares to a 3.0 point change in cohort one at six months.

Based on the safety expression and clinical results, we are moving the height of support for future clinical development of SRP nine juries are true.

To sum up these presentations, we are very pleased oh therapy seem to be well tolerated. They submit the data presented at world muscle from the Micronet scope and SRP Nines user one 101 study and the limb girdle mustard, a suite to eat SRP nines years, or three 101 study support Europe.

Those functional outcome at the two year, an 18 month time points respectively.

This further supports higher hypothesis that because muscle is a terms differences you tissue. It does enable 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 subtype of limb girdle muscular dystrophy.

Timothy Francis Lugo: Our PDUFA date stands at February 25th, 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 Commitment Study for Example 51, also known as the Mission Study, we are pleased that we have enrolled Part 1 of the Dose Escalation, and we are in discussions with the Agency about the timeline for the Re-Advisory Study. Before I turn to our PPOL platform and the PPOL SRP 5051 program for DMD specifically, let me give you an update on the U.S. AMRID collaboration. In late April, we announced an early research collaboration with US AMRID that would exploit our PPM1 technology as a potential therapeutic for COVID-19.

We also presented non clinical data at WMS supporting the transition of our next limb girdle construct limb girdle mg to see into the clinic.

[noise] Sarepta also presented data generated from an R&D platform.

These include a long term safety data regarding Terreson from the 40 53 101 clinical studies supporting its safety profile.

PK PD data for cousins Larson from the 40 45 loans are a lot of clinical trial, demonstrating dose portion exposure as an interim analysis has immersed in treating patients in the essence pivotal studies showing a statistically significant increase in skeletal muscle to spoken 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.

Timothy Francis Lugo: More recently, and based on in vitro results, we are planning to initiate a proof of concept in-vehicle study in collaboration with USM. Now, turning to our PMO development programs for Duchenne muscular dystrophy, a 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 selects a cell-penetrating peptide, or CPP, to a PMO to enhance cellular and nuclear penetration.

Beyond the data we shared a gentlemen.

Having numerous developments across our R&D platform.

Sta review of our Anda for our lead PMO candidate a modest 45 is ongoing and from all accounts going well.

Opt to do today stands at February 25th 2021.

The FDA has indicated it does not currently plans 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 heart one at the dose escalation arm and we're in discussions with the agency, but timeline for the react study.

Before I turn to our people our platform and SRP 50, 51 program with DMD specifically.

Let me give you an update on the U.S. Amarin collaboration in late April We announced early research collaboration with you at average that would explain our PPSA technology has the potential therapeutic for COVID-19 more.

Timothy Francis Lugo: Our most advanced PPMO program is SRP 5051. Our ongoing SRP 5051-201 monthly ascending dose trial named Momentum is about to begin. 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 nephrotoxicity in our PPMO clinical trials, and no new safety signals have been observed across all studies, thus enabling us to keep escalating doses in the momentum trials. We have now commenced dosing SRP5051 in the 30 mg per kg cohort.

More recently and based on in vitro results. We are planning to anesthesia proof concept indigo study in collaboration with us.

Now turning to our PMO development programs for Duchenne muscular dystrophy.

A key element of stretches R&D strategy is to enhance tissue or must with penetration of our PMO chemistry, and up and has efficacy by increasing dystrophin expression.

We have a number of research programs that support the strategy to remind you our ppm or platform chooses a cell penetrating peptide or CPP sort of PMO, so enhanced cellular and nuclear penetration.

Timothy Francis Lugo: This year, we'll be reviewing 12-week data from our 20-mg per kg cohort in Duchenne patients treated with our PPMO candidate SRP5051. 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 SRP5051 preclinical data at the OTS meeting in late September, in which the PKPD of SRP5051 was evaluated in non-dystrophic, non-human primates. A single dose of SRP5051 resulted in sustained exon 51 skipping that was maintained for at least 28 days.

Most advanced ppm, a program is SRP 50 51.

Our ongoing SRP 50, 51 to zero, one multi ascending dose trial names momentum is investing [noise].

We are pleased to say that we continue to escalate doses to lever higher than it was originally planned at the initiation of this program.

This is because to date, we have not seen tinsley that press such it sorry, we have not seen clinical netflow toxicity in our PMO clinical trials and no new safety signals have been observed across all studies, thus, enabling us to keep escalating doses in the momentum trial.

We have now commenced dosing SRP 50, 51 in the 30 milligram per kilogram cohort.

This year, we will be reviewing 12 week data from our trenching maker cake cohorts in duchenne patients treated with our PMO candidate SRP 50 51.

We will be examining systemic PK tissue penetration safety and exon skipping efficiency data.

Timothy Francis Lugo: This sustained exon skipping supports the Q4 week dosing regime currently being studied in the clinic. We also observed repeat. Q4 week dosing of SRP5051 for 12 weeks demonstrated a cumulative exon skipping effect that increased after each infusion. For SRP5051, 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. 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.

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 a mentor to spoken production.

We presented SRP 50, plus 51 preclinical data at the meeting in late September and wish the PK PD events or P. 50, 51 was evaluated in non discotheque nonhuman primates.

A single dose of SRP 50, 51 resulted in sustained exon 51 skipping that was maintained for at least 28 states.

Sustained exon skipping supports the Q4 week dosing regime currently being studied in the clinic.

We also observed repeat.

Q4 week dosing of EPS or P 50, 51 for 12 weeks.

Demonstrating a cumulative exon skipping effect that increased after each infusion.

Timothy Francis Lugo: So although the data we generate will not be representative of steady-state efficacy for SOP 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 mental study, we will be using legacy 24-week data from PMO for some comparison. I will remind you that dystrophin accumulates over time, and so based on our observations in prior PMO studies, we would expect to see higher levels of dystrophin at later time points if the therapy is successful.

For SRP 50, 51, we will measure exon skipping efficiency by digital drop Pcr or DD, PCR, allowing us to directly compare the efficacy of our PMO and Timo testing now.

Now it is important to note that tried quite a 12 week is an early time points were assessed exon skipping. We are confident that this is an appropriate time point to demonstrate proof of concepts that the CPP or sell penetrant peptide enhances muscle tissue exposures.

US enhances downstream exon skipping efficiency.

So although the data we generate will not be represents but steady state efficacy Prestopino 50, 51. It will determine if we should move this technology for with the urgency necessary to meet the needs of patients with Duchenne no.

Timothy Francis Lugo: Indeed, muscle biopsies at later time points are planned in the latter part of the Mementum study once we have selected our final dose for SRP5051. 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 would hand it back to Doug for a Q&A. Doug?

No that whereas we are examining trophy type points in the dose escalation part of the mentioned study we will be using legacy 24 week data from PMO for so comparison.

I would remind you that just broken accumulates overtime and so based on observations in prior chemo study, we would expect to see higher level just broken at leisure time point different therapy is successful.

Indeed muscle biopsies at leisure time point, our plan in the latter part of the mentioned study once we have selected our final dose for EPS or P 50 51.

Finally, I want to thank all 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.

Douglas S. Ingram: Thank you very much, Dr. Rodino. Catherine, let's open the lines for Q&A. Thank you. As a reminder, to ask a question, you need to press star 1 on your telephone. To withdraw your question, press the pound. Please limit yourself to one question.

COVID-19 pandemic.

Now I would hand back to Doug for acuity Doug.

Operator: And our first question comes from Brian Skorney with Baird. Your line is open. Hi, thank you. This is Jack Donagan for Prime.

Thank you very much Doctor on you know Kathryn let's open the lines for queuing it.

Thank you as a reminder to ask a question you need to press star one on your telephone to withdraw your question press the pound key.

Operator: 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 a consistent effect compared to the data that you have from Study 102? We know there was significant variability within the first four patients of data looking at the Phase I trials with the DMD product. We're just wondering what the lower and upper bounds of confidence are with respect to the district and measurements that you're looking at for this new planned clinical trial. Thank you. Yeah, thanks a lot for that, Jack.

Please limit yourself to one question.

And our first question comes from Brian Skorney with Baird. Your line is open.

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 patient clinical trial, you're expecting initiate and will the data be strong enough to show this in effect compared to the data that you have.

Study one of two we know there's significant variability within the first four patients.

Data looking at the phase one trials of 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.

Douglas S. Ingram: So first, let me answer the latter part of the question first: very sufficiently powered to obtain the data that we're interested in obtaining. Now, let me explain what this is about.

Yeah. Thanks, a lot for that Jack So first let me answer the latter part of the question or is that it is the temptation is.

Douglas S. Ingram: 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 are a number of reasons for that study, which is called Study 301, of course. One is for global purposes.

Very sufficiently powered to obtain the data that we're interested in that and 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 Magellan will still do that at some point as well there was a number of reasons for that study which is called.

Three or four and of course, one issue is global purposes. The other is additional confirmatory.

Douglas S. Ingram: The other is additional confirmatory data. Remember, we're going to have Study 102 that's going to be read out at the beginning of next year, so we'll already 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, this larger study, and acutely the thing that we're most interested in getting 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 our Salus 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 as 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 most interested in right now, which is the validation of our commercial material, both on expression and on And then, of course, in the summer, as we thought this through, we watched the external environment.

Data remember, we're going to study one or two that is going to read out with beginning of next year. So we're already going to have.

Results from study, one or two both on safety and function as the cost structure, but the other thing that we would get out of study one much larger study in it and it's usually the thing that we're we're most interested in <unk> to get as quickly as possible is validation of that commercial material. This is the same construct but.

Generated using a different process in a different manufacturing process as you know and I salads units and so what we had planned with respect to three a one is to get what we really are most interested in right now we would do an interim analysis a subset of those patients around the same subset is Russia.

It was one of the three early next year. So we would start that study, but we would actually get the real data that mature. We're most interested in right now which is the validation of our commercial material both on expression.

And aren't safety early next year, and then of course in the summer as we thought this through we watched the external environment, we thought about the risks associated with a larger study the potential risk to patients for another well Chivo controlled study as one example in the midst of a pandemic exposure from the pandemic.

Douglas S. Ingram: 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 to the pandemic, as well as just the risk to the program and the execution of the program. It dawned on us that there was a far more efficient way, in the midst of this pandemic, to get exactly the same information, and that's where we devised the concept of study 103. So there is no reason to do a placebo-controlled trial for the expression that we're looking for and 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, a large, multi-centered, multi-country study, we should also propose a leaner approach, which is Study 103. And that's exactly what we did.

As well as just the rest of the program and the execution of the program. It dawned on us that there is a far more efficient way in the midst of this pandemic to get exactly the same information and batch where we devised the concept of study one of three so well there is no reason to.

Do a placebo controlled trial for the expression that were looking for and for the safety that were looking for and we've always known we only needed about 10 patients or so eight to 10 patients to get that information and so rather than getting that information out of a larger study I guess multi large multi centered multi.

Our country study, we should also propose a leaner approach, which is study one of three and that's exactly what we did and as you know we went to the agency in writing in September with this proposal we the the big issue that occurred of course in the September meeting, which is where I think we all know was all on the radar rack or.

Douglas S. Ingram: 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 I think we all know was all on the written record, was that the agency had questions and ultimately had issues with the approach that we were taking to the Policy Release Assay for Study 103. That could have taken us a long time to resolve, frankly.

It wasn't yet the agency had questions and ultimately.

Had issues with the approach that we were taking to the post your release asset for study one out of three.

That could have taken us a long time to resolve frankly could have taken us somewhere between you know two three and 84 six months just to get an answer from it I'm really pleased to say that the division was willing to meet with US importantly, they met with US in September so were very clear about that we came due.

Douglas S. Ingram: It could have taken us somewhere between, you know, two, three, maybe four, six months just to get an answer from them. I'm really pleased to say that the division was willing to meet with us informally. They met with us in September, so we're very clear about that. blinded trial from 102 with respect to SRP 9001. We'll have safety readouts from that study as well, and we'll have the commercial validation results from Study 103, which means we'll have microdistributed expression results. We'll have safety results from 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 CNC-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. But one thing we all know, of course, all of us are well aware, that in the United States and around the world, every single day, thousands and thousands of children wake up in the morning with Duchenne muscular dystrophy, and throughout that day Unfortunately, every week and every month, some percentage of those kids die.

An alignment in September they agreed to and to our updated approach on the 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 from our alternative approach to the potency assay and as we sit here today that data is all done the minutes are done and we shouldn't be able to start one of three by the end of this year, which means sometime.

In 2021 really on the earlier side of 2021, I'm hopefully fairly close to one another we should have both a readout of study one or two which will well show us both the efficacy the functional benefits in a well controlled placebo controlled trial blinded trial from one or two with.

I respect the SRP nine 001, little FCC read out from that study as well and we'll have the commercial.

Commercial validation results from study, one or three which means we'll have much more well had a 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, but from a safety perspective. We also will have a wealth of additional CMC related information budget.

Which we've already gathered and about point of course, we will sit down with the agency and talk about the steps for one thing. We all know of course all of US are well aware that in the United States and around the World every single day, thousands and thousands of children wake up in the morning would you shed muscular dystrophy and throughout.

Douglas S. Ingram: 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. Hopefully, at the time we have that, and, of course, science has to cooperate, the studies have to come out the right way, but we should be able to sit down with them, armed with information that shows, if we're successful, that SRP 9001 is safe and effective, and that the commercial material has been validated, along with the clinical performance that we'll see in the studies. So thank you for your questions. Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.

That day, they did generate and unfortunately every week and every month some percentage of those kids die. So with all of that information available to US we will 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 to the science has to cooperate that you'd have to come out the right way, we should be able to sit down with them armed with information that shows if were successful, but SRP Nigerians here, one is the safe and effective and the commercial material has been validated it along with the clinical performance that we'll see out of 71 or so.

Thank you for your question.

Thank you. Our next question comes from disease.

Odd with Bank of America. Your line is open.

Douglas S. Ingram: Hi. Good afternoon, guys. Thanks for taking my question. Deb, just to stay on topic with Study 103. So I just want to make sure I understand this. You are not doing a specific potency assay, but you are using Study 103 in lieu of a specific potency assay. I just want to confirm that.

Hi, Good afternoon, guys. Thanks for taking my question that just to stay on topic with with that anyone of those three so I I just want to make sure I understand that you you were not doing a specific is the asset but you are using 31 out of three in lieu of Asia Pacific CFA, just want to kind of.

From 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 that a two plus now that you want to three and some data from three I want to or is it your plan to go talk to FDIC to see if he can apply it.

Douglas S. Ingram: 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 Study 301? Or is it your plan to go talk to FDA to see if you can apply, assuming that Studies 2 and 103 show what you want them to show and not necessarily have to do 301? Yeah, thank you for the question.

Assuming that that study tail and went to three so what you want those to show and not necessarily have to do the Korean won.

Yeah. Thank you for the questions and let me clarify something that that.

Douglas S. Ingram: Let me clarify something that I might have created some confusion about. So, study what we did; we have come to an understanding with the age. 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.

Might have created some confusion about that study what we did we have come to an understanding with the agency on the assay approach to study one of the three 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 one out.

The division had questions in disagreed with the approach that we were taken taking we didnt have clarity on precisely what that those issues were and if we had gone through a formal process could literally have taken two to six months to ultimately have enough clarity to nowhere to go by the end of September.

Douglas S. Ingram: We didn't have clarity on precisely what those issues were, and if we had gone through a formal process, it could literally have taken two to six 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 Study 103 will give us exactly what we wanted out of an interim analysis for Study 301.

Remember, 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 gather the data for that that's already done and completed and so we have the potency approach now for study one of the three and that allows us of course, the startup study one or three with respect to study 301, So and study one of those three will get its exactly what we wanted out of an interim analysis for study 301. So.

Really it is a very it's an it's a very thoughtful approach to a pandemic gathering information Reis study 103 and get the most salient information in the near term when we get one or two read out which is you know that that in patients and in biopsies, we could show that as we would predict from.

Douglas S. Ingram: 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 can show that, as we would predict from all of our CNC work, the material in Study 103, from a commercial material perspective, will perform in a similar way, both from a microdis With respect to Study 301, there are still lots of reasons to conduct it. First and foremost, this is a global study. We have global ambitions.

All of our CMC work the material in study 1003, well from a from a commercial material perspective will perform in a similar way both for Microdisplays 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 as a global study.

We have a global ambitions. It is our goal to get approvals around the world and of course study 301, well 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.

Douglas S. Ingram: 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 that would be valuable as we bring this therapy out to patients. The third, of course, is I don't 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. We've been very clear about this. I remain resolute that this is the right approach.

The additional information it would be valuable as we were bringing this therapy 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 you know we're 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 one or two and now the readout from from this commercial material.

Validation study one out of three 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 and I'm in advance of the type C meeting after the type C meeting. So we'll we'll get into next year, we'll get the result of one or two if it's successful we'll have shown in the world.

Douglas S. Ingram: We explicitly said we weren't going to discuss this with them in advance of the Type C meeting and after the Type C meeting, so we'll get into that next year. We'll get the results of 102. If it's successful, we'll have shown in a well-controlled trial that our therapy creates functional benefits and is 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 too soon after that. And then, 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, is the most appropriate and fastest way to get this therapy if it's safe and efficacious for kids that are waiting for it in the U.S. That's a conversation, obviously, we'll have after we get the data in hand. Thank you. And our next question comes from Alicia Young with Cantor Fitzgerald. Your line is open. Hi, this is Emma on behalf of Alethea.

Controlled trial, but our therapy is.

His creates functional benefits and he's doing a lot of good for these kids in that it's safe we will have the commercial validation material out of study one of three hopefully not far after that and then with all of that armed with that we will sit down with the the U.S. and the division and talk about what in light of the quality of the data in it.

I think we have what is the most appropriate and the fastest way to get this therapy is safe and efficacious. The kids that are waiting for it. That's a conversation obviously will have after we get the data.

Thank you and our next question comes from Alicia Young with Cantor Fitzgerald. Your line is open.

Hi. This is on for me so given the agreement Harris Afghans anyone asked me is kind of a leaner approach for getting an extra pricing information for nine years or one and then it's just kind of end is there do you expect kind of similar effect study for a year three and I'll give you a streamlined program.

Operator: 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, do you expect kind of similar flexibility for 003 and LGMD to support a streamlined 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've said is that we need to do a couple of things with respect to—this is for Lindbergh and Weissberg, 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 process development runs, but we have a lot of analytical work to do as well.

Well, we won't know that until we have conversations with them. Obviously, so I don't want to make any presumption is one of the things that we said is that we need to do a couple of things with respect to this is the limb girdle I assume you're saying 93.

We have to do it to get to 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 presence and on the right. 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 nine 003, and then with data in hand, we want to sit down with the agency.

Operator: 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 that, 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 better framed out.

Talk about that and talking about the next trial and hopefully what we would like to believe will be our pivotal trial for nine 003, but we'll give an update on that early next year. Once we have that that better framed out obviously as we've seen given the pandemic to how busy the agency is the opportunities to.

Operator: Obviously, as we've seen, given the pandemic and how busy 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. Thank you. The next question comes from Anupam Rama with J.P. Morgan. Your line is open.

Have discussions with the agency our formal and we've got to be very thoughtful about that so I want to make sure. We have the right type of information in hand, when we have those discussions and then we can give a better view on.

What the pathway forward is for nine years your free.

Thank you. Our next question comes from a new Palm Rama with JP Morgan Your line is open.

Douglas S. Ingram: Hey guys, thanks so much for taking the question. 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 to the study where you'll be looking at more functional types of measures, and has the FDA indicated any sort of, you know, interest in seeing that before you have some of the regulatory discussions, right? Yeah, that's a great question. No, look, this is an open-label study. The goal of SRP, the goal of Study 103, is to get essentially exactly what we would have gotten out of an interval analysis from 301. It is essentially precisely the same thing.

Hi, guys. Thanks, so much for taking the question I'm I'm, sorry, I'm, just a little bit confused so for study one of three.

You looking at safety and some of the assay comparability work right and I think that that 12 week and you called that part one so are there additional parts the study where you'll be looking at more functional type of measures and FDA.

You indicated any sort of interest in seeing that before you have some of the regulatory.

Regulatory discussions like that.

Yeah. It's a great question no no look this is an open label study the goal of SRP Gold study 103 is to get essentially exactly what we would have gotten out of an interim analysis for the three out what it is it is essentially precisely the same day. The reason I mentioned that as.