Q2 2020 Sarepta Therapeutics Inc Earnings Call

Ladies and gentlemen, please stand by your conference call will begin momentarily. Thank you for your patience and please standby.

Unknown Executive: Ladies and gentlemen, please stand by. Your conference call will begin momentarily. Thank you for your patience, and please stand by. Copyright 2020 Mooji Media Ltd. All Rights Reserved.

Unknown Executive: No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. BF-WATCH TV 2021, Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Second Quarter 2020 Earnings Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, we will conduct a question and answer session. To ask a question during the session, you will need to press the star and then one on your cell phone.

[music].

Unknown Executive: As a reminder, today's program is being recorded. At this time, I'll turn the call over to Mary Jenkins, Manager of Investor Relations. Please go ahead.

Mary Jenkins: Thank you, Operator, and thank you all for joining today's call. Earlier today, we released our financial results for the second quarter of 2020. The press release is available on our website at Sarepta.com, and our 10-Q was filed with the SEC earlier this afternoon.

Douglas S. Ingram: Joining us on the call today are Doug Ingram, Beau Cumbo, Ian Estepan, Dr. Gilmore O'Neill, and Dr. Louise Rodino-Quaypak. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements. Please take a moment to review our 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 annual report on Form 10-K and most recent quarterly report on Form 10-Q filed with the Securities and Exchange Commission, as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. With that, let me turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress.

So what the therapeutics second quarter 2020 earnings call.

At this time, all participants are in listen only mode.

After the speakers presentation, we will conduct a question and answer session.

The asked the question during the session I need to press Star then one on your telephone.

As a reminder, today's program is being recorded.

At this time of the call over to marry Jenkins manager Investor Relations. Please go ahead.

Thank you operator, thank you all for joining todays call earlier today, we released our financial results for the second quarter 2020. The press releases are available on our website at <unk> Dot Com and our 10-Q filed with the FCC earlier back again joining.

On the call today are duck Ingram so comes out.

Dr. Gilmore Aneel, Dr. I believe or do you know play back after our formal remarks, well open the call for acuity.

No that during this call we will be making a number of forward looking statements. Please take a molecular if you are side on the webcast, which contains forward looking statements.

These forward looking statements involve risks and uncertainties, which are beyond its control.

Actual results could materially differ from these forward looking statement.

Douglas S. Ingram: Thank you, Mary. Good afternoon, and thank you all for joining us for Sarepta Therapeutics' second quarter 2020 investor conference. As I have mentioned in the past, on March 13th of this year, all but a small contingent of our workforce transitioned to a virtual work environment. Notwithstanding this unusual approach, we are not merely remaining productive but have arguably become even more efficient and effective as we advance our multi-program, multi-platform genetic medicine ambition. As you will hear this afternoon, we have continued to serve the patient community with our approved therapies, have already achieved or remain on And as we have generated additional evidence in 2020, and continued to build confidence that our unique approach to gene therapy is proving successful and highly differentiated. With that, let us review our performance. As we continue to serve our patient community while endeavoring to keep them safe in this pandemic, I am pleased to report that our second quarter net sales stand at $111 million. $0.3 million, an 18% increase over the same quarter last year.

Petrobras can materially and adversely affect the business the results of operations and trading crisis disrupt a common stock for a detailed description of up 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 Securities Exchange Commission as well.

The company's other.

The company does not undertake any obligation to publicly update its forward looking statements, including any financial projections provided today based on subsequent events or circumstances.

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

Thank you Mary.

Afternoon, and thank you all for joining us for Sarepta Therapeutics second quarter 2020, Investor Conference call.

As I've mentioned in the past on March 13, two of this year.

But the small contingent of our workforce transition to a virtual work environment.

Notwithstanding this unusual approach we are not merely remaining productive.

But arguably become even more efficient and effective as we advance our multi program multi platform genetic medicine ambitions.

As you will hear this afternoon.

We have continued to serve the patient community with L. approved therapies.

I've already achieved remained on track for her many players wanting 20 miles Stephens.

Douglas S. Ingram: As I mentioned in our last quarterly conference call, we withdrew our 2020 guidance in light of the potential impact of COVID-19 on clinic vision. As you can see, that impact has thus far been modest. Given the uncertainties of the external environment, we are not ready yet to set full-year guidance.

Expanded our three pronged approach to building our enduring gene therapy engine.

And that's we have generated additional evidence your 2020.

Continued to build confidence you could argue with unique approach the gene therapy.

He is proving successful in highly differentiated.

Douglas S. Ingram: However, consistent with what we have seen thus far in 2020, we anticipate that any continuing impact from COVID-19 will remain relevant. Moving to our development programs, let me begin by commenting on our RNA franchise. In the second quarter, we completed our NDA submission for Casimir, our RNA therapy built on our PMO platform and designed to treat the 8% of the Gishen community who are exon 45 amenable. The PDUFA date for Kazimierz should be in the first quarter of 2021.

With that let US review our performance.

As we continue to serve our patient community, while endeavoring to keep gotta safe in this band and the Guy I'm pleased to report that our second quarter net shales stand at 111.

$3 million, an 18% increase.

Over the same quarter last year.

As I mentioned in our last quarterly conference call, we withdrew or 2020 guidance in light of the potential impact.

Cobot 19 on clinic visit.

As you can see that impact has thus far been modest.

Given the uncertainties of your external environment, you're not ready yet just for your guidance. However, consistent with what we have seen thus far in 2020, we anticipate that any continue when you're back from go up at night team.

Douglas S. Ingram: If we are successful in obtaining this approval, Kazimersan will be our third FDA-approved therapy, bringing the percentage of the Duchenne community with available PMO therapies to nearly 30%. With a successful Kazimiercin approval, we will have more than doubled the size of the treatable patient population since Teplerson was first approved. However, as successful as our PMO platform has been, we are not satisfied with the status quo.

The were made modest.

Moving toward development programs, let me begin by commenting on our ordinary franchise.

The second quarter, we completed our N D. A submission from CASM your should our army therapy built on our PMO platform and designed to treat the 8% a big shouldn't community.

Sure Exon 45 amenable.

But do for date for Casimir city should be in the first quarter of 2021.

Douglas S. Ingram: We have been working on our next generation of the PMO, which, if successful, may profoundly improve the efficacy and convenience of RNA technology. We are in our multi-ascending dose study called the momentum study for our peptide conjugated PMO or PPMO, and that is candidate 5051. Here 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, PPMO greatly increases tissue exposure, in turn greatly increasing exon skipping and thus, distribution and production.

If we're successful what opinion this approval cousin Mercent will be our third FDIC approved therapy, bringing the percentage of Duchenne community would available PMO therapies to nearly 30%.

Well the successful CASM your should approval, we will have more than doubled the size of the treatable patient population since a couple person was first approved.

That's successful was our PMO platform has bad we're not satisfied with the status quo.

We're working on our next generation of the PMO, which if successful they profoundly improve the efficacy and convenience.

About ornate technology.

We are in our multi ascending dose study called the momentum study for peptide conjugated PM hour P.M.L. and that is candidate 50 51.

Douglas S. Ingram: Treating Duchenne is all about increasing the production of the structural shock absorber. So if the PPMO candidates are able to increase exon skipping and dystrophin production, we could see a profoundly more efficacious RNA platform, and that monthly dosing versus the PMO weekly dosing. We would have a far more convenient therapy, as well.

Sure we are using a proprietary positively charged peptide to increase penetration.

In animal models, we have show, but if we can shacey achieve appropriate dose levels. The p. PMO greatly increases tissue exposure in turn greatly increasing exon skipping and us dystrophin production.

Douglas S. Ingram: In the second half of this year, we will have completed and will release our Safety, Tissue Exposure, PKPD, and Comparative Exxon Skipping studies for our PPMO 5051 candidate at 20 mg per kg. This will be an important proof of concept for the therapy, not only within DMD but more broadly as a potential RNA platform to treat diseases where our steric blocking RNA technology could provide therapeutic benefits. Let's move now to our gene therapy engine. There are three pillars upon which we are building our gene therapy engine. First, our pipeline. Second, manufacturing capacity and manufacturing expertise.

Turning to shed, it's all about increasing the production of the structural shock absorber dystrophin jump. The P. PMO candidates are able to increase exon skipping and dystrophin production, we could see a profoundly more efficacious arent a platform.

That monthly dosing versus the P M a weekly dosing.

I would have a far more convenient therapy as well.

And the second half of this year, we will have completed and we'll release, our safety tissue exposure PK PD and comparative exon skipping for our P. PMO 50 51 candidate.

20 makes put cig.

This would be an important proof of concept for the therapy, not only within DMD, but more broadly as a potential arent a platform to treat diseases, where our spirits blocking ordinary technology could provide therapeutic benefit.

Douglas S. Ingram: And third, advancing and improving the science and effectiveness of gene therapy. Over the course of 2020, we have not only stayed on track, but having successfully dosed a significant number of DMD and LGMD patients, and with the additional data we have generated already this year, we continue to build confidence that our unique approach to gene therapy research and development is first-in-class and replicable. Consider the additional confirmatory data on our gene therapy platform that have been generated already this year. One of the most significant challenges with full-body neuromuscular gene therapy is safely delivering the proper number of genome copies.

Let's move now to our gene therapy engine.

There are three pillars upon which we are building our gene therapy engine first our pipeline second manufacturing capacity and manufacturing expertise.

Answered advancing as improving to shy its effectiveness of gene therapy itself.

Over the course of 2020, we have not only stayed on track, but having successfully dosed three significant number of D. N D and LG M b patients and with the additional data we have generated already this year, we continue to build confidence that our unique approach to gene therapy research and development.

Douglas S. Ingram: In this regard, Sarepta's programs have shown good tolerability and exceptional expression at reasonable doses. You will recall that in 2018, we announced the results of Study 101, our first four DMV patients on SRP9001, reporting a mean of 3.3 genome copies per nucleus, protein expression approaching normal as measured by Western blot, IF positive fibers, and IF intensity, and that all patients improved significantly on each and every functional endpoint measure On that basis, we commenced a placebo-controlled trial for SRP 9001 in the fourth quarter of 2018, using clinical materials. Then, in 2019, we announced the results from our three-patient low-dose cohort for SRP9003 to treat LGMD2E. This is important for our platform because SRP9001 and SRP9003 share much in common, including the design approach under the guidance of Dr. Louise Rodino-Klapak, the same viral vector, R874, and the same promoter, the heavy chain, MHCK7. We were pleased to report that even at a quarter of our SRP-900 dose, we had exceptional expression. As an example, over 50% of beta-circle glycine-positive fibers were achieved.

His first in class and replicable consider the additional confirmatory data on our gene therapy platform that has been generated already this year one of the most significant challenges with full body neurovascular gene therapy is safely delivering the proper number egina copies to sell nuclear in this regard syrup.

This programs have shown good tolerability and exceptional expression at reasonable doses you will recall that in 2018, we announced the results of study what I won our first for DMD patients on SRP 90 wells, you're one reporting a need of 3.3 genome copies for nucleus protein.

An expression approaching normal as measured by western blot.

I have positive fibers and I ask intensity I've got all patients improved significantly on each and every functional endpoints measured.

On that basis, we commenced equal cubo controlled trial rest RP 90 years. Your one in the fourth quarter of 2018 using clinical material.

Then in 2019, we announced the results from our three patient low dose cohort for SRP nine 003 to treat LG M.D. too.

This is important for our platform because SRP nods years, your one and SRP Nigerians your own three share much in common putting their design approach under the guidance of Dr., Luis where do you know quite back the same viral vector or each 74 at the same promoter heavy Jane MHC catch up.

Douglas S. Ingram: Every child improved significantly on every functional measure at NIAID. In 2020, we will have generated additional consistent data and gained more experience with our concept. In the second quarter, the one-year results for Study 101 in Duchenne were published in JAMA Neurology, showing that every boy in the study improved significantly on each and every function line at one year. In the same month, we announced the results of our second three-patient cohort treated with SRP9003 for LPMD2E, using the same dose that we have used for SRP 9001 for the channel. We were very pleased to announce that with the increased dose, we yet again confirmed the ability of our construct to safely deliver robust gene therapy. The children in the study had 4.2 genome copies per nucleus on average.

We were pleased to report, but even on a quarter up our SRP 900 dose we had exceptional expression as an example over 50% beta circle.

I see that fibers.

Were achieved.

Every child improved significantly on every functional measures at nine months.

In 2020, we have generated additional consistent data engage more experience without constructs in the second quarter. The one year results for study what I wanted to Shannon were published in Jama neurology showing that everybody in the study improved significantly on each and every functional endpoints.

One here.

In the same bonds, you announced the results of our second three patient cohort treated with SRP denies your free LTM Beach we.

Douglas S. Ingram: There was a significant dose-dependent increase in expression, with children achieving 62% of normal on Western blot, 72% of protein-positive fibers, and 73% on in. Additionally, in our 41-patient placebo-controlled study 102, using SRP9001 for DMD, we have dosed all children for the main analysis and are dosing children on crossover as well. By now, between our two studies for SRP 9001 and our study for SRP 9003, we have dosed over 35 patients with active therapy, far more than any similar clinical program in the studies preceding. The second pillar of our gene therapy engine is our manufacturing. And we have built impressively over the last two years.

Using the same dose that we have used for SRP nines years your one.

For Duchenne.

We were very pleased to announce that would the increase dose we yet again confirmed the ability of our construct to safely deliver gene therapy robustly.

Children in the study had 4.2 genome copies per nucleus on average there was a significant dose dependent increases an expression with children, achieving 62% of normal on western blot, 72% of protein positive fibers.

And 73% on intensity.

Additionally, in our 41 patient what she bought controlled study one or two using SRP nine 001 for DMD.

Does all children for the main analysis and our dosing children on crossover as well my now between our two studies for SRT nine 001, and our study for SRP nine 003, we have just over 35 patients with active therapy far more than any similar clinical programs and studies are proceeding that's pace.

Douglas S. Ingram: We have among the greatest capacity available for gene therapy and biotech in just two years between our dedicated suites at Catalan and our dedicated site in Lexington, with Thurmond Fisher. At the same time, we have built out our centralized gene therapy manufacturing expertise within Sarepta. It is this group that drives the analytical and process development approaches across our programs, and with our partners across Burlington, Andover, Cambridge, and our Gene Therapy Center of Excellence in Columbus, we now have some 270 professionals dedicated to technical operations, manufacturing, and quality. For SRP 9001, we have completed process development and analytical development, and we have completed GMP runs for the material we plan to use, both for our next clinical trial and commercial. For SRP 9003, we're in GMP runs now.

The second pillar of our gene therapy engine is our manufacturing expertise and there we have built impressively over the last two years, we have among the greatest capacity available for gene therapy in biotech in just two years between our dedicated suite, you're traveling and our dedicated site in Lexington.

Thermo Fisher.

At the same time, we have built out our centralized gene therapy manufacturing expertise within Sarepta. It is this group that drives the analytical and process development approaches across our programs with our partners across Burlington adds over Cambridge, and our gene therapy Center of excellence in Columbus, We now.

I'll have some 270 professionals dedicated the technical operations manufacturing.

And quality.

Recipe nine 001 do you have completed process development and analytical development I have completed GMP runs for the material went to use both for our next clinical trial and commercially for SRP nine 003, we're in GMP runs now.

Douglas S. Ingram: The third pillar of our gene therapy engine is bringing together the technology and tools necessary to improve and advance the science and effectiveness of gene therapy. We are a science-driven company, and I am pleased to note that COVID-19 has done nothing to slow our progress in this endeavor. Having built out one of the deepest and most valuable gene therapy pipelines, commencing in 2017, and then spending an enormous effort in the last two plus years on building out our manufacturing prowess, commencing in 2019, we began to aggressively look for opportunities to advance the science of gene therapy, to complement our internal program development. In this quarter alone, we have added four new approaches to our armament. In May, we announced our partnership with Dino Therapeutics for the use of their AI and machine learning approach to develop and prove CAP.

The third pillar of our gene therapy engine is bringing together the technology tools necessary to improve in advanced science and effectiveness of gene therapy.

We are a science driven company and I'm pleased to note that troubled 19 has done nothing to slow our progress in this endeavor.

Being built out one of the detested most valuable gene therapy pipelines commencing in 2017, and then spending an enormous effort in the last two plus years on building out our manufacturing progress commencing in 2019, we began to aggressively look for opportunities to advance the science a gene therapy.

To complement our internal programs about.

In this quarter alone we have added four new approaches to our argument carrier.

In May we announced our partnership with Dido therapeutics for the use of their AI and machine learning approach.

Douglas S. Ingram: From there, we entered into a partnership with Selecta Biosciences to use their mTOR technology in an effort to empower re-dosing, and then we entered into a partnership with Hans at Biopharma to access Enlifidase with the goal of using it to ablate pre-existing neutralizing antibodies and to open gene therapy to patients that would otherwise be left behind. And then from there, we entered into a relationship with Kodiak Biosciences to explore the use of exosomes. Across Gene Therapy, Gene Editing, and RNA

Who develop improved Katz.

From there we entered into a partnership with select a bio sciences to use their important technology in an effort to empower we don't see and then we entered into a partnership with Honda Bio pharma to access and live today is with the goal of using it to a Blake preexisting neutralizing antibodies and you open.

In gene therapy to patients that would otherwise be left behind.

And then from there we entered into a relationship with Kodiak biased sciences to explore the use of Exosomes.

Across gene therapy gene editing.

Douglas S. Ingram: Now, looking forward, we have important gene therapy engine milestones across the remainder of 2020. First, with respect to SRP 9001, we have two major efforts ongoing. We must complete Study 102, our blinded placebo-controlled trial using clinical materials. That trial is on track to have its last patient and last visit by the end of this year and to read out in the first quarter of 2021. Secondly, with GMP commercial material now in hand, our goal is to start our next trial in the second half of this year. Our remaining gating items there are the following. First, engaging sites and obtaining IRB approvals. The pandemic has certainly created some challenges, but the team is working through them, and things are going quite well. And second, gaining alignment with the FDA on initiating the use of the GMP material, which will occur this quarter. With respect to SRP 9003, our goal is to start our pivotal trial in 2021. Our two gating items here are these.

And on it.

Now looking forward, we have important gene therapy engine milestones across the remainder of 2021st with respect to SRP nine 001, we have two major efforts ongoing.

We must complete study one or two are blinded placebo controlled trial using clinical material.

That trial is on track to have last patient last visit by the end of this year into read out in the first quarter of 2021.

Secondly, with G.M.P. the commercial material now in hand, our goal is to start on much trial in the second half of this year, our remaining gating items, there or the fall first engaging sites in obtaining IR be approvals. The pandemic has certainly created some challenges here, but the team is working through them.

Things are going quite well and second gaining alignment with yesterday on the initiation using the GMP material, which will occur this quarter.

We expect Sharkey nine 003, our goal is to start a pivotal trial 2021.

Our two gating items here are these first completing assay development and obtaining the release of our GMP Ron's seconds, completing a dialogue with the agency on the appropriate regulatory development pathway.

Douglas S. Ingram: First, completing assay development and obtaining the release of our GMP runs, and second, completing a dialogue with the agency on the appropriate regulatory and development pathway for SRP 9003, will provide insight into the development pathway for our other five LGMD candidates. We will provide an update on the LGMD discussions and our GNP materials for SRP 9003 in early 2021. And, if you will indulge me, on a personal note, the second quarter marked my three-year anniversary at Sarepta.

For SRP nine 003. This is an important dialogue as it will not only inform the development.

For SRP Niger zero, three but we believe.

Well provide insight into the development pathway.

Our other five LG I'd be candidates, we will provide an update on the LG M.D. discussions and our GMP material rest RP nine 003 in the early 2021.

About if you'll indulge me on a personal note the second quarter marked my three year anniversary at Sarepta.

Douglas S. Ingram: In three years, we have made an enormous amount of progress toward our goal of bringing a better, longer life to those living with..., too often dying from rare diseases. And we have done so by building and articulating an ambitious vision to become the leader in rare disease genetic medicine with a robust and productive RNA platform and an enduring gene therapy engine. By gathering the resources and talent to make that a reality, and then ruthlessly executing with the rapidity that, to the extent possible, matches the urgency of the very patients that we serve, patients who have their movement and their lives stolen from them bit by bit, daily. In the last 3 years, we have built a pipeline with over 40 programs, are now in 10 clinical trials advancing multiple therapies, have made enormous progress in building our 3-pillar gene therapy engine from ideation to reality, and are seeing consistent and confirming results. As I reflect on our progress, the credit should go to... The sophisticated, dedicated, and hard-working professionals that make up our over 1,000-strong workforce.

In three years, we have made an enormous amount of progress toward our goal of bringing a better longer life.

Did those living with into often dying from their disease and we have done so by building. It articulating an ambitious vision to become the leader in rare disease genetic medicine with robust and productive on a platform and then enduring gene therapy younger my gathering the resources and talent to make data.

We already.

And then ruthlessly executing with them a pity that to the extent possible.

Matches, the urgency of the very patients that we serve patients.

After movement in their lives stolen from them bit by bit daily.

An hourly in the last three years, we have built a pipeline with over 40 programs are now in 10 clinical trials advancing multiple therapies have made enormous progress in building some ideation to reality, our threed pillar gene therapy engine and are seeing consistent and confirming results thus far.

As I reflect on our progress the credit should go to three groups the sophisticated dedicated and hardworking professionals that make up our over 1000 strong workforce at Sarepta.

Douglas S. Ingram: Our external partners, the best and brightest in genetic medicine around the world, and, of course, our patient community, a community that not only relies on but also informs us and guides us often. So we are clear, now is not yet the time for a victory lap or premature celebration. We are encouraged by our success so far, but we have much to do over the course of the next 15 months and still much more to prove. You can count on this team.

Our external partners in my opinion, the best and brightest in genetic medicine around the world.

And of course, our patient community a community that not only relies upon us, but also informs us and guides us and often pushes us.

So we are clear now is not yet the time for victory lap or premature celebration. We are encouraged by our success so far.

Bo: Stay on mission, to address and remove obstacles that appear in front of us, and to execute four patients. Waiting for our therapist. And with that, I'll now turn the call over to Bo for a commercial update. Thank you, Doug. Good afternoon, everyone.

We have much to do over the course of the next 15 months I still much more to prove but you can count on this team stay on mission.

To address and remove obstacles that appear here in front of us.

I too would execute for patients.

Waiting for our therapies.

With that I'll now turn the call over tableau.

Herschel uptick Oh.

Bo: All our experienced teams at Sarepta are continuing to work through the headwinds of the COVID-19 pandemic. I'm pleased to report that our product revenue for the second quarter of 2020 totaled $111.3 million. We've overcome some unique obstacles created by the pandemic and are extremely proud of the teams and their accomplishments in the face of these challenges. While we're still navigating and responding to the strain the pandemic has placed on the health care systems, the modifications we've made to our commercial execution strategy have allowed eligible patients to start and stay on therapy in this unprecedented time. Our strong relationships with external partners have played a key role in the ability to start new patients and keep others on their path. This is a testament to our team's expertise and commitment to our mission to serve the Duchenne community.

Thank you Doug good afternoon, everyone.

All are experienced teams that sarepta are continuing to work through the headwinds of to cope with my team and then.

I'm pleased to report that our product revenue for the second quarter 2020 totaled 111.3 million.

We've overcome some unique obstacles created by the pandemic are extremely proud of the teams and their accomplishments in the face of these challenges.

While we're still navigating in responding to the strain pandemic has placed on the health care systems. The modifications, we made to our commercial execution strategy have allowed eligible patients to start and stay on therapy in this unprecedented time.

Our strong relationships with external partners have played a key role in the ability to start you patients keep others on their therapy.

This is a testament to our teams expertise and commitment to our mission to serve the Duchenne community.

We continue to provide an uninterrupted supply of therapies for patients and mitigate nature treatment disruptions through a unified effort with our manufacturers distributors specialty pharmacies health care providers and payers money.

Bo: We continue to provide an uninterrupted supply of therapies to our patients and mitigate major treatment disruptions through a unified effort with our manufacturers, distributors, specialty pharmacies, health care providers, and payers. Many of our patients are choosing not to delay or stop therapy, and we believe this is partly due to the fact that the majority of patients on Exondys 51 and Biondys 53 are receiving weekly infusions in their homes. We are currently working closely with health care providers and specialty pharmacies to transition additional patients to weekly home infusions, since many clinics and hospitals still have restrictions in place. We have thoughtfully deployed measures to minimize the risk of transmitting COVID-19, which includes making personal protective equipment available to all our patients who have requested supplies. This will help ensure that patients have access to protective equipment when nurses administer their weekly infusions at their homes.

Many are many of our patients are choosing not to delay or stop therapy and we believe this is partly due to the fact that the majority of patients on EXONDYS 51, if I understood 53 are receiving weekly infusions in their homes.

We're currently working closely with health care providers and specialty pharmacies to transition additional patients to weekly home infusions since many clinics and hospitals still have restrictions that plays.

We have thoughtfully deployed measures to minimize the risk of transmitting cobot 19, which includes making personal protective equipment available to all our patients who have requested supplies.

This will help ensure that patients have access to protective equipment when nurses administer their weekly infusions after homes.

Bo: Patient safety remains our top priority, and we will continue assessing any and all efforts that will help patients feel safe during this unusual time. We continue to monitor the pandemic and are ready to react quickly with additional modifications to our commercial strategy, especially in places seeing surges in infection. As noted last quarter, the dynamics of initiating treatment with Exondys 51 and Biondys 53 remain effective. However, since many clinics are not seeing patients for normal in-person appointments, this has resulted in fewer patients initiating treatment.

Patient safety remains our top priority and we will continue assessing any and all efforts that will help patients feel safe during this unusual time.

We continue to monitor the pandemic and are ready to react quickly with additional modifications to our commercial strategy, especially in place places seeing searches and infections.

As noted last quarter, the dynamics of initiating treatment with EXONDYS 51 in my honest 53 remain effect.

Since mini clinics are not seeing patients for normal in person appointments. This has resulted in fewer patients initiating treatment.

Physicians typically want to monitor patients in the clinic for the first couple of confusion and we've worked with key opinion leaders to find options for patients to safely initiate treatment with final just 53 or EXONDYS 51 in their home or an alternate site rather than the clinic.

Bo: Physicians typically want to monitor patients in the clinic for the first couple of infusions, and we've worked with key opinion leaders to find options for patients to safely initiate treatment with Biondis-53 or Exondis-51 in their home or an alternative site rather than. This has provided physicians and patients with a path to initiate care. However, hospitals in each state are operating under different rules and regulations. We anticipate the intake of Starforms will slowly increase as states ease restrictions and clinics resume normal operations. From a reimbursement standpoint, our health care providers have become experts regarding the authorization and reauthorization process for our products. And due to the ongoing education of managed care organizations, reimbursement efforts have been productive. We are confident that, over time, eligible patients will ultimately receive access to reimbursements for Biontis 53 and Exontis 51 and start therapy in a timely manner.

This is provided physicians and patients a path to initiate care.

Hospitals in each state or operating under different rules and regulations, we anticipate the intake of stock warrants will slowly increase the states east restrictions and clinics resumed normal operations.

From a reimbursement standpoint, our health care providers have become experts regarding the authorization in reauthorization process for our products.

And due to the ongoing education to managed care organizations reimbursement efforts have been productive.

We are confident that overtime eligible patients will ultimately receive access reimbursements for by almost 53 in EXONDYS 51, and start therapy in the timely manner.

We have successfully adapted our weekly engagements with key opinion leaders and payers to virtual interactions are discussions with key opinion leaders and other health care providers are focused on identifying patients amenable to exon 51 at 53, skipping and driving prescriptions.

Bo: We have successfully adapted our weekly engagements with key opinion leaders and payers to virtual interactions. Our discussions with key opinion leaders and other health care providers are focused on identifying patients amenable to Exxon 51 and 53 skipping and driving prescriptions. We also continue to educate payers about the importance of patients starting and staying on therapy regardless of ambulation status, age, or gender.

We also continue to educate payers about the importance of patient starting staying on therapy, regardless of emulation status age or gender.

We're encouraged by these efforts, which has resulted in new start forms and new patients initiating treatment starts during the quarter.

Bo: We're encouraged by these efforts, which resulted in new start forms and new patients initiating treatment during the quarter. Moving on to Exxon 45. In June, we announced the completion of our NDA submission for Casimirsin, or SRP 4045. As we await FDA's response, our commercial and medical affairs teams are preparing for another successful launch. The foundation of our plan will be tailored to reaching patients who are amenable to Exxon 45 Skippy, who represent another 8% of the Duchenne community. We will leverage our knowledge and experience from the Exondus 51 and Biondus 53 launches to facilitate patient access to Casamerson as quickly as possible. While we're very proud of the accomplishments the team has made to date, we still have an immense amount of work ahead of us.

Moving onto exon 45 in June we announced the completion over in India submission for CASM person or SRP 40, 45, as we await ft. A's response, our commercial and medical affairs teams parent for another successful launch.

The foundation of our plan will be tailored to reaching patients amenable to exon 45, skipping who represent another 8% of the check community.

We will leverage our knowledge and expertise experience for me the EXONDYS 51, and biologist 53 launches to facilitate patient access to CASM person as quickly as possible.

Well, we're very proud of the accomplish accomplishments. The team has made to date, we still have an immense amount of work ahead of us with each new therapy does developed in advancing our pipeline we have the responsibility to pave the way for patients to access. These treatments. This is an incredible responsibility and one that we do not take lightly the depth of our experience.

Bo: With each new therapy that is developed and advanced in our pipeline, we have the responsibility to pave the way for patients to access them. This is an incredible responsibility and one that we do not take lightly. The depth of our experience on our teams has helped us navigate through complex launches in these unprecedented times. With each new launch and lesson learned, we become a stronger company. One that's better able to serve our patients and deliver on our mission as the global leader in precision genetic medicine. And with that, I will now turn the call over to Ian for an update on our finances. Thanks, Bo. Good afternoon, everyone.

On our teams has helped us navigate through complex launches in these unprecedented times with each new launch in lessons learned we become a stronger company one that's better able to serve our patients and deliver on our mission as the global leader precision genetic medicine and with that I will now turn the call over to Ian for an update on our financials Ian.

Thanks.

Good afternoon, everyone. This afternoon's press release provided details for the second quarter of 2020 on a non-GAAP basis as well the GAAP basis.

Ian: This afternoon's press release provided details for the second 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 press release is available on <unk> website.

We refer to our press release for a full reconciliation gap.

Financial results.

Net product revenue for the second quarter 2020 from our products EXONDYS 51, and BYOD. This 53 was $111.3 million compared to $94.7 million for EXONDYS 51, along for the same period in 2019.

Ian: Net product revenue for the second quarter of 2020 from our products Exondys 51 and Vyondys 53 was $111.3 million compared to $94.7 million for Exondys 51 alone for the same period of 2019. The increase primarily reflects higher demand for our products. In the quarter ended June 30, 2020, we recognized $26 million of collaboration revenue, which primarily relates to our collaboration arrangement with Roche. Co-development costs under the Roche agreement totaled $8.9 million for the second quarter and are included as a reduction to our R&D expenses. On a gap basis, we reported a net loss of $150.8 million and $276.4 million, or $193.374 per basic and diluted share for the second quarter of 2020 and 2019, respectively. We reported a non-GAAP net loss of $117.9 million, or $1.51 per basic and diluted share, in the second quarter of 2020 compared to a non-GAAP net loss of $61.2 million, or $0.83 per basic and In the second quarter of 2020, we recorded approximately $13.3 million in cost of sales compared to $15.9 million in the same period of 2019.

The increase primarily reflects higher demand for our products.

In the quarter ended June Thirtyth 2020, we recognized $26 million collaboration revenue, which primarily relates to our collaboration arrangement with Roche the co development costs under the Roche agreement totaled $8.9 million for the second quarter and are included as a reduction to our R&D expenses.

On a GAAP basis, we reported a net loss of $150.8 million and $276.4 million or 193, and 374 per basic and diluted share for the second quarter of 2020 2019, respectively.

We reported a non-GAAP net loss of $117.9 million or $1.51 per basic and diluted share in the second quarter 2020, compared with non-GAAP net loss of $61.2 million or 83 cents per basic and diluted share in the second quarter of 2019.

In the second quarter 2020, we recorded approximately $13.3 million in cost of sales compared to $15.9 million.

Same period of 2019 did decrease is primarily due to write offs of certain batches of EXONDYS 51, not meeting our quality specifications for the three month ended June Thirtyth 2019, with no similar activity for the three month ended June 30 20, Tony.

Ian: The decrease is primarily due to write-offs of certain batches of Exondys 51 not meeting our quality specifications for the three months ended June 30, 2019, with no similar activity for the three months ended June 30, 2020. On a gap basis, we've recorded $188.5 million and $113.3 million in R&D expenses for the second quarter of 2020 and 2019, respectively, which is a year over year increase of $75.2 million. This increase is primarily related to an $81.6 million increase in manufacturing expenses, primarily due to the continuing ramp-up of our microdistricting program. On a non-GAAP basis, R&D expenses were $160.4 million for the second quarter of 2020 compared to $87.5 million for the same period of 2019, an increase of $72.9 million. The year-over-year growth in non-GAAP R&D expenses was driven primarily due to a continuing ramp-up of our microdistricts in program. Now, turning to SG&A, on a GAAP basis, we recorded $73.7 million and $67.4 million of expenses for the second quarter of 2020 and 2019, respectively, a year-over-year increase of $6.3 million. On a non-GAAP basis, SG&A expenses were $55.1 million for the second quarter of 2020, compared to $52.3 million for the same period of 2019.

On a GAAP basis, we recorded $188.5 million and $113.3 million in R&D expenses for the second quarter, 2020, and 2019, respectively, which is a year over year, increasing 70 point $75.2 million increase is primarily related to.

81.6 million dollar increase in manufacturing expenses, primarily due to the they continuing ramp up on my could dystrophin program.

On a non-GAAP basis, R&D expenses were $160.4 million for the second quarter of 2020 compared to $87.5 million for the same period of Twain maintain an increase of $72.9 million.

The year over year growth and non-GAAP R&D expenses was driven primarily due to a continuing ramp up of our micro dystrophin program.

Now turning to ask DNA on a GAAP basis, we recorded $73.7 million and $67.4 million of expenses for the second quarter, 2020, 2019, respectively, a year over year increase of $6.3 billion.

On a non-GAAP basis to ask DNA expenses were $55.1 million for the second quarter 2020, compared to 52.3 million for the same period of 20, maintaining an increase of 2.8 million.

Ian: An increase of $2.8 million. The year-over-year increase was driven by significant organizational growth and expansion that supported our commercial launch, as well as our over 40 therapies in various stages of development across several therapeutic modalities. On an exact basis, we recorded $12.4 million in other expenses net for the second quarter of 2020 compared to $0.9 million in other expenses net for the same period of 2019. The unfavorable change primarily reflects interest expense on our death facilities entered into in December 2019. We had approximately $2.1 billion in cash, cash equivalents, and investments as of June 30, 2020. And with that, I'll turn the call over to Gilmore for an update on our research and development activities. Gilmore?

The year over year increase was driven by significant organizational growth and expansion that's supported our commercial launch as well as our over 40 therapies in various stages of development across several therapeutic modality.

I think that basis, we've recorded $12.4 million in other expenses net for the second quarter 2020, compared to point $9 million and other expenses that are the same period of 29 team.

On favorable change primarily reflects interest expense on our debt facilities answered in December 29.

We had approximately 2.1 billion in cash cash equivalents and investments as of June Thirtyth, 2020, and with that I'll turn the call over to Gilmore for an update on our research and development activities Gilmore.

Thank you and good afternoon, everyone.

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 thus focus my remarks on the progress of our RNA portfolio, which comprises one of the three platforms Sarepta uses to drive its precision genetic medicine therapeutic strategy. I will begin with the PMO portfolio.

Doug has already shared highlights from our most advanced gene therapy programs I will focus my remarks on the progress of our R&D portfolio, which comprises one of the three platform Sarepta uses to drive its precision genetic medicine therapeutic strategy.

I will begin with the PMO portfolio.

As Doug mentioned in June as planned we completed the India Rolling submission to the asking for CASM question.

Timothy Francis Lugo: As Doug mentioned in June, as planned, we completed the NDA rolling submission to the FDA for casualty. If accepted and subsequently approved, we would have more than doubled the size of the treatable patient population since Teplerson was first approved. Importantly, our post-marketing requirements, or PMR studies, are progressing despite the challenges arising from the COVID-19 pandemic. In summary, the mission, the 402 PMR study for a Tet person is dosing, and we have enrolled the first cohort of patients. The essence study of gonadirsen and casimirsen is progressive.

If accepted and subsequently approved we went up more than doubles the size of the treatable patient population since a tetrasun was first approved.

Importantly, our post marketing requirements or pay more studies are progressing despite the challenges arising from the cobot 19th pandemic in summary, the mission follow to pay more studies for a tough person is dosing and we have seen rose the first cohort of patients.

The essence study have gone interest and that hasn't person is progressing.

Timothy Francis Lugo: Thanks to the immense efforts of investigators, patients, and their families, and our clinical operations team, we have managed to minimize the disruptive impact of COVID-19 on the trial. Prior to the onset of the pandemic, we had already been moving many patient visits, including for dosing, to their homes. In recent months, we have significantly increased the number of patients who benefit from home visits. As we were accelerating plans for at-home visits, we did initially see some patients miss dosing. Nevertheless, now, I am pleased to say that the new mitigation has significantly improved the situation, and most patients are on track. All of our mitigation strategies comply with guidance from regulatory agencies around the world on the conduct of trials during the COVID-19 pandemic. Indeed, the pandemic has served not only as a disruptor but a catalyst to permanently change our approach to clinical trial execution.

Thanks to the immense effort of investigators patients and their families as our clinical operations teams. We have managed to minimize the disruptive impact cobi nine teams on the trial.

Prior to the onset of the pandemic, we had already been moving any patient visits including for dosing to their hopes in recent months, we have significantly increased the number of patients using home visits.

As we were et cetera racing plans for national visits we did to initiate some patients missed doses of business.

Nevertheless, now I am pleased to see you mitigation has significantly improves the situation and most patients are on track.

All of our mitigation strategies complied with Guidances from regulatory agencies around the world on the conduct trials joining to cope with 19 penta.

[noise] Indeed, the pandemic has served nobility as a disruptor, but a catalyst to policy change our approach to kill it could try to execution.

Timothy Francis Lugo: Thus, while not being complacent, we are confident that we can deal with and minimize the impact on all of our future trials in the face of surges in COVID-19 infection. Before I turn to the PPMO platform and the PPMO 5051 program for DMD specifically, let me give you an update on the U.S. AMRIT collaboration. In late April, we announced an early research collaboration with US AmRibs that would exploit our PPMO technology as a potential therapeutic for COVID-19. The work is ongoing with UF Amherst, and we have expanded the collaboration to work with the leading research group in Early results support performing additional confirmatory experiments.

Why not being complacent, we are confident we can deal with and minimize the impact on all of our future trials in the face of searches included 19 infections.

Before I turn to be P. PMO platform and people 50, 51 program for DMD, specifically that May give you an update on the U.S. Ambridge collaboration.

They April we announced an early research collaboration with U.S. Ambridge that would exploit our p. PMO technology as a potential therapeutic for covert 19.

The work is ongoing with U.S. language.

An expanded the collaboration to work with a leading research group in Sweden.

Early results support performing additional confirmatory startups.

Now turning to PMO develop comes a key element of stretches R&D strategy is to enhance tissue or muscle penetration of our PMO chemistry, and thus enhanced efficacy by increasing dystrophin, especially.

Timothy Francis Lugo: Now turning to PPMO development, 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 uses a cell-penetrating peptide, 2-PMO, to enhance cellular and nuclear activities. Our most advanced PPMO program is SLP 5051. Our ongoing SRP 5051-201 multi-ascending dose trial, named Momentum, is progressing, and all patients in the 20mpk cohort have been dosed. COVID-19-related shutdowns caused one patient to miss a dose, but since then, with new mitigations in place, we are executing well. Just to remind you.

We haven't done sort of research programs that support the strategy.

To remind you are p. PMO platform fuses a sell pension peptides PMO. So it has failure as nuclear penetration.

Our most advanced Timo program is Esso P 50, 50, well.

Our ongoing SRP 50, 51 to a one multi ascending dose trial named momentum is advancing at all patients in the 20 being for key cohort have being dosed.

Copas 19 relationship towns caused one patients I missed the dose, but since then with new Mitigations in place we are executing well.

Just to remind you we started the momentum study at Formnext, Okay, I'd have escalators already to 20 Bucks bucket.

Timothy Francis Lugo: We started the momentum study at 4 Migs per Kg and have escalated already to 20 Migs per Kg. This represents dosing beyond that which we originally intended. We plan to continue to dose-escalate based on our views of safety, and so far, we have not seen any safety issues. This year, we will be reviewing 12-week data from our 20-week per-kid cohort of Duchenne patients treated with pfimo 5051. We will be examining systemic PK, tissue penetration, safety, and exome skipping data. We will measure exon skipping by digital drop PCR or ddPCR, allowing us to directly compare the efficacy of our PMO and PPMO candidates. Our pre-clinical in vitro and in vivo models have demonstrated a robust correlation between the amount of exon skipping and the amount of dystrophin production. We will be publishing these days.

This represents dosing beyond that which we originally anticipated.

We plan to continue to dose escalate based on reviews of safety has so far we have not seen any safety signals.

This year, we will be reviewing 12 week data from our 20 big quirky cohorts of Duchenne patients treated with P. people are 50 51.

We will be examining systemic teekay.

Your penetration safety and exon skipping data.

We will measure exon skipping by digital drop PCR part D PCR, allowing us to directly compare the efficacy of our PMO PMO candidates.

Our preclinical in vitro and in vivo models have demonstrated a robust correlation between the amount of exon skipping tenant magic to spoken production.

We would publishing these stages.

Duff exon skipping is a good marker for the kinds of to spoken production, we expect to see over time.

Timothy Francis Lugo: Thus, Ekpon Skipping is a good marker for the kinds of disproven production we expect to see over time. 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 cell-penetrating peptide or CPP will enhance muscle tissue exposures and thus enhance downstream exon skipping. This allows us the potential to move this technology forward with the urgency necessary to meet the needs of patients with Duchenne. It is also important to remember that dystrophin accumulates over time, as we have observed in our PMO, and so we expect to see higher levels of dystrophin at later time points if therapy is successful.

It's important to note. That's a lot of 12 weeks isn't early time point to assess exon skipping. We are confident that this is an appropriate time point to demonstrate proof of concepts that the sell penetration peptide for CTP would enhance muscle tissue exposures, and thus and hands downstream exon skipping.

This allows us the potential to move this technology forward with the urgency necessary to meet the needs of patients with to shed.

It is also important to remember that just profaned accumulates over time as we have observed in our Kimball said.

So we expect to see hired it looks to spokesman nature time close if therapy a successful.

Timothy Francis Lugo: Muscle biopsies at later time points are planned in the latter part of the momentum study once we have selected our final dose. The readout for Momentum would be important for the 50-51 program, but additionally, it would potentially expand to other PPMO Duchenne programs. We have already designed and selected five additional PPMO candidates that could treat 50% of Duchenne patients who carry skip amenable mutations in their dystrophy gene. I do want to highlight that rare deletions susceptible to exon skipping impact an additional 35% of patients with Duchenne, and we are creating a development strategy that will attempt to accelerate the approval of PPMO compounds if successful for these patients using a novel platform or extrapolation strategy. Non-DFD and non-muscle therapeutic area targeting is a key pillar of Sarepta's R&D strategy.

The biopsies that later time points, our plans in the latter part of the momentum study once we have so that's our finances.

To read outs for momentum would be important for the 50 51 program dose selection, but additionally would potentially extend to other people move Duchenne programs. We've already designed in selected five additional chemo candidates in fact that could treat 50% up duchenne patients who carry skip a medical mutations in their spoken cheap.

I do want to highlight the rare deletions.

That's supposed to exon skipping impact an additional 35% patients with Russia, and we are creating a development strategy that would attempt to accelerate the approval.

He chemo compounds if successful for these patients using a novel platform Oren extrapolation strategy.

Proof of concept for P. people in DMD Duchenne, what also read through to the selection of that chemistry to target new non muscle therapeutic areas.

No the empty and non losses have use Gary talked that he is a key pillar of syringes R&D strategy.

In summary, I'm very pleased with our response to the incredible challenges created by the covert 19 pandemic at the progress you've made during this time.

Timothy Francis Lugo: In summary, I am very pleased with our response to the incredible challenges created by the COVID-19 pandemic and the progress we've made during this time. 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 gastrointestinal problems. Now I would hand it back to Doug for Q&A. Doug?

Finally, I want to take all the patients their families study sites in coordinators, My R&D colleagues and our partners who have done so much work under incredibly difficult circumstances coming into our urgent mission to deliver you highly effective therapies to people's with desperate diseases.

Now I hand back to Doug for acuity Doug.

Douglas S. Ingram: Thank you very much, Dr. O'Neill, and Crystal, with that, let's open the call for questions. Thank you. Ladies and gentlemen, if you have a question at this time, please press the star followed by the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key.

Thank you very much Dr. O'neil and crystal with that let's open the call for questions.

Thank you ladies and gentlemen, if you have a question at this time. Please press the star followed by the number one key when you're Touchtone telephone. If your question have been answered or you wish to remove yourself from the Q. Please press the pound too and then the interest of time, we do ask that you. Please limit yourself to one question per caller.

Tazeen Ahmad: And in the interest of time, we do ask that you please limit yourself to one question per caller. And our first question comes from Tazeen Ahmad from Bank of America. Your line is open.

And our first question comes from to the Nahmad en Banc of America. Your line is open.

Douglas S. Ingram: Good afternoon. Thanks so much for taking my question. Deb, I just wanted to get a little bit more color as it relates to the FDA discussion this quarter. Can you talk about some of the more important items that you'll need to get alignment on from the agency? And also, do you plan on asking them about the plans to test in non-ambulatory or older patients as well? Thank you. So thanks a lot for that, Tazeen.

Good afternoon. Thank so much for taking my question, Bobby once again, a little bit more color I wasn't really appreciate it's got some to order.

Talk about some of them more important items that you'll need to get alignment on from the agency and also do you plan on asking them about the plant pots and non ambulatory or older patients as well. Thanks.

So thanks, a lot for that to the Insulet, Let's review one of the things. We had said earlier this year that we would have GMP material on hand by July of this year and the good news is that we do so we've got two things to do as as you know we've got a get our next study using commercial process material.

Douglas S. Ingram: So let's review. One of the things we said earlier this year was that we would have GMP material on hand by July of this year. And the good news is that we have.

Ill up and running and getting patients dosed and we're going to do that in the second half of this year and the team notwithstanding covert 19, and and the distractions that occur and some of the challenge is occur with German 19 have done really remarkable job keeping on pace and moving to get that study started but before we can do that.

Douglas S. Ingram: So we've got two things to do. As you know, we've got to get our next study using commercial process material up and running and getting patients dosed. And we're going to do that in the second half of this year.

We have to have our meeting with the agency as I said.

In my my prepared remarks, we will be meeting with the agency this quarter and there really are just two things that you know there there are significant things, but there are two things that we need to get alignment and concurrence on with the agency. The first of course is our C.M.C. approach itself for the commercial material to use the commercial material in the next study we're very pleased.

Douglas S. Ingram: The first, of course, is our CMC approach to using commercial material in the next study. We're very pleased at how these GMP runs have come out. You know, we're very, very confident in the approach that we're taking. From our perspective, there are no significant quality attributes that are different from the clinical material in a manner that would be predicted to affect the therapy in any way, functionally or efficacy-wise or safety-wise.

How these GMP runs that come out I'm very very confident in the approach that we're taking from our perspective there are no.

Significant quality attributes that are different from that the clinical material in a manner that would wouldn't be predicted the effect the therapy in any way functionally or efficacy wise or safety wise. So that's one significant concur as we need and of course. The second one is to gain concurrence on this the next study.

Douglas S. Ingram: So that's one significant concurrence we need. And, of course, the second one is to gain agreement on the next study. Certainly, in connection with that, we will have conversations with the agency about our nonambulatory study as well. You know, it is one of our goals to commence the nonambulatory study as soon thereafter as possible, perhaps even close to being concurrently with the next study, the main study that we'll be using if we're successful in the approval of the therapy in the United States. Thank you. Our next question comes from Salveen Richter of Goldman Sachs. Your line is open. Good afternoon.

Certainly in connection with that will we will have conversations with the agency about our non ambulatory study as well you know it is one of our goals to commence the non ambulatory study as soon thereafter as is possible, perhaps even close to being concurrently with the next study the main study that will.

Be using if we're successful for the approval of the therapeutic United States.

Thank you.

Our next question comes from Salveen Richter from Goldman Sachs. Your line is open.

Good afternoon. Thanks for taking my question. It's successful how do you CPP PMO platform fitting into that the treatment paradigm versus Pmone gene therapy in DMD and what are your plans for non DMD your purchase on the Ford.

Salveen Jaswal Richter: Thanks for taking my question. It's successful. How do you see the PPMO platform fitting into the treatment paradigm versus PMO and gene therapy in DMD? And what are your plans for non-DMD approaches on the board? Yeah, that's a great question.

Yeah, that's a great question I'm going to Oh, I'll answer that briefly and then I'll turn this over to Dr. a meal they'd be talk about some of the areas. We could take this R&D and technology. So.

Douglas S. Ingram: I'm going to, I'll answer that briefly, and then I'll turn this over to Dr. O'Neill to maybe talk about some of the areas we could take this RNA technology. So first and foremost, the excitement of the PPMO, if it is successful, is for an even more profound impact from an RNA perspective with respect to Duchenne muscular dystrophy. Now, of course, the question will immediately arise thereafter. What is the, you know, how will gene therapy and RNA coexist? And the short answer to that is we don't yet know.

First and foremost the excitement of the P. PMO. If it is successful is for a and even more profound impact from an M&A perspective with respect to Duchenne muscular dystrophy now of course. The question will immediately arise thereafter of what is the you know how well the gene therapy and barring a co exist.

In the short answer to that as we don't yet know there will certainly be even that even with a transformative gene therapy there will be.

Douglas S. Ingram: There will certainly be, even with transformative gene therapy, a place for a profound RNA for Duchenne muscular dystrophy in children who, for instance, are screened out for gene therapy in places where gene therapy is not available or is not yet available. So there will already be a significant place for it. And if one considers just the pre-existing neutralizing antibodies alone, that is with respect to our Capsid right now, about 15% or so, and that population that would be screened out until we've been able to address that issue scientifically, that is larger than the Ateplersen population. But of course, with a significantly more impactful RNA platform, it may very well be the case that there is a role for a combination, both of gene therapy and of RNA.

A place for a profound or a day for duchenne muscular dystrophy and children, who for instance, our screened out for gene therapy in places where gene therapy is not available or not yet available. So there will already be a significant place for items. One considers just the pre existing neutrally at neutralizing antibodies alone that is with respect to.

Our capsid right now about 15% or so and that population that would be screened out until we've we've been able to address that issue scientifically that is larger than the tupperware said population, but of course with a significantly more impactful arent a platform. It is very well be the case.

There is a role for combination both live gene therapy, and a bar a day. So first we need to see what the P. PMO will look like and then we're doing work even as we speak right now from a non clinical perspective to test the hypothesis about whether a profound gene therapy, followed either in the near term or in the longer term.

Douglas S. Ingram: So first we need to see what the PPMO will look like. And then we are doing work even as we speak right now from a non-clinical perspective to test the hypothesis about whether a profound gene therapy followed either in the near term or in the longer term with a profound RNA would be synergistically beneficial to patients. But beyond that, of course, if one of the things about our PMO is that the PMO is a neutrally charged, it is, it is creating phenotypic change in these children, giving them longer time out of a wheelchair, et cetera. But to move beyond DMD, we need a more penetrative, penetrative RNA technology like the PPMO for work. But if it does.

With a profound or a day would be synergistically beneficial to patients, but beyond that of course, if one of the things about our PMO is that the pure most neutrally charge.

As it is creating phenotypic change in these children, giving them longer time out of a wheelchair et cetera, but moved beyond the M.D., we need up a more penetrated penetrate true or are they technology like the ppm over works, but if it does.

The theory is that we can take this far beyond the M.D. and the research group has already working on the kinds of areas, we would take that but perhaps would that I can turn this over to dr. I'd be able and can touch on that issue.

Douglas S. Ingram: The theory is that we can take this far beyond DMD, and the research group is already working on the kinds of areas we would take this. But perhaps with that, I can turn this over to Dr. O'Neill, who can touch on that. Thanks very much, Doug. I think you actually articulated that very nicely. The beauty of the RNA technology and the PMO chemistry specifically is that we have proof of biology. We have demonstrated that we can deliver the PMO to muscle and actually see downstream skipping and dystrophin upregulation, or rather skipping and dystrophin isoform expression by returning it to in-frame. Through PPMO experimentation with 5051 and the study readouts, we hope to test the hypothesis that increased exposure driven by the cell-pentrum-peptide fusion to the PMO will enhance tissue exposure in muscle.

Thanks, very much Doug I think you actually articulated very nicely the beauty out the R&D technology and the PMO chemistry, specifically is that we have proof of biology, we have demonstrated that we can deliver the PMO to muscle and actually see downstream skipping and dystrophin.

Up regulation or rather skipping and discos isoforms expression by returning it to can frame.

[music].

With the P. PMO experimentation with 50 51.

Study read as we hope to test the hypothesis that increased exposure driven by the I sell penetrant peptides fusion to the PMO winning has tissue exposure and bustle, but we actually also though is that will extrapolate beyond just that muscle tissue other tissues and.

Timothy Francis Lugo: What we actually also know is that this will extrapolate beyond just that muscle tissue to other tissues, and as you're aware, many tissues are amenable, and certainly the PPMO and PMO have demonstrated tropism for other tissues, including liver, kidney, heart, etc., and we are actually doing a comprehensive genome-driven review of those tissues and the associated diseases to identify those that are amenable to exome skipping. So, and with And of course, later this year, we'll have some of the PK PD tissue dosing safety and Exxon skipping, importantly Exxon skipping for 50-51 as our proof of concept we have already built.

You are aware many tissues are amenable on certainly Ah the t. PMO and people have demonstration focus and for other tissues, including liver and kidney Hearts et cetera, and we are actually doing a comprehensive at GE, though at driven at review of those tissues and the association.

Seasons.

To identify those that are amenable to exon skipping I'm. So that is worth it is ongoing and I'm very excited about it.

And with that one final thing I will say moving back to DMT, just and I think people notice, but I'll remind you you know we're currently using 50 51, exon 51, P. PMO as our proof of concept and of course later this year, we'll have the some of the PK PD tissue dosing safety.

Ed Exon skipping importantly, exon skipping for 50 51 as our proof of concept we have already built beyond 50, 51 constructs with that peptide conjugated to them.

Timothy Francis Lugo: Beyond 50-51, constructs with the peptide conjugated to them for exons that could treat already about 50% of the Duchenne community with a path, as Dr. O'Neill mentioned in his opening remarks, with a path to get to a significant percentage beyond that, perhaps another 35% beyond that with a slightly more exotic platform approach. We will start moving as rapidly as we can, assuming, of course, that the results support that when we look at them later this year. Thank you. Our next question comes from Anupam Rama of J.P. Morgan. Your line is open.

Or exxon's that could treat already about 50% of didn't Chen community with a path as Dr. O'neil mentioned in his opening remarks, when they passed to get to a significant percentage beyond that perhaps another 35% beyond that with a.

Slightly more exotic platform approach and so and we will we will start moving as rapidly as we can assuming of course that the results are support that when we look at a later this year.

Thank you.

Our next question comes from I know Palm run off from JP Morgan Your line is open.

Hey, guys. Thanks, so much for taking the question we got it.

Anupam Rama: Hey guys, thanks so much for taking the questions. We've got a quick one here on 9001 safety recently, and I think some of it may revolve around some comments from Dr. Meng Zhao, maybe at ASGCT, that 9001 may be associated with some sort of mild complement. Any context you can provide here and just maybe remind us of how frequently the DSMB meets for study two. Thanks so much.

Quick one here on on we've gotten a lot of inbound on nine girls or a one thing you recently and I think some of it may revolve around comment from document. So maybe it can't ppt that nine 001 will be associated with some sort of mild complement activation and contact you can provide here and just like we were my.

And.

How frequently did the SMB meets for first study to thanks, so much.

Douglas S. Ingram: Sure, I'm going to turn this question over to Louise, who can answer this, but I will say up front, just so we're absolutely clear, that was a misunderstanding. There is absolutely no signal that we've seen of complement associated with 9001 at all, but I think Dr. Rodino-Kleipac can provide the context around that misunderstanding. Dr. Mandel was speaking about his broad experience in gene therapy and that included other vectors like AV9. As Doug mentioned, we presented our data at different medical meetings as well as investor calls on LGMD2E as well as our JAMA Neurology paper. I think people were reading through comments he was making about other programs. You know, this has been seen in a number of other programs primarily associated with AAV-9. He wasn't speaking to R-874.

Sure I'm in answering this question over to Luis you can answer this but I will say up right. Just so we're absolutely clear there would that wasn't misunderstanding, there's absolutely no signal that we've seen a compliment associated with nine 001 at all but I think dr. video playback can provide the context around that misunderstanding.

Sure yet Dr and Bell I was speaking about his broad experience and gene therapy and not include a other factors like a benign as Doug mentioned, we presented our data in both different at medical meetings as well as an investor calls on it.

He is well known examiner algae.

I just to reiterate we've not seen any evidence.

On the activation in our study out anyone quickly.

As long as planned.

Interruption.

I think we're reading through comments he was making about other programs. You know that this has been seen in a number of other programs primarily associated with a benign he wasn't speaking to our at 74, we've seen nothing were related to complement there and just to remind you and of course, you know I know dr., Neil as a proper sciences.

Douglas S. Ingram: We've seen nothing relating to complement there. And just to remind you, and of course, you know, I know Dr. O'Neill is a proper scientist. You know, we have to measure ourselves by the evidence on hand. But the good news for us is that, with respect to R-874, across both Duchenne Muscle District and Lynn Girdle, we have now dosed, as you heard in my opening remarks, over 35 children. And study 102 continues to move apace. So, you know, I think the evidence on our broad safety profile is only getting bolstered over the course of the last 24 months and really significantly this year. Thank you. Our next question comes from Brian Skorney from Baird. Your line is open. Pardon me, sir, we're not able to hear you.

We have to we have to.

It's a measure ourselves by the evidence on here, but the good news for US is that with respect to Rx seven four across the two shun must move district in limb girdle, we have now dose as you heard in my opening remarks over 35.

Children in the study one or two continues to move to pay so I.

And I think the evidence on our broad safety profile I think is only getting bolstered over the course of blast 24 months and really significantly this year.

Thank you. Our next question comes from Brian Skorney from Baird. Your line is open.

Okay.

Uh huh.

Well.

Pardon me, so we're not able to hear you.

[laughter].

And we'll move on to our next caller, Matthew Harrison with Morgan Stanley.

Brian Peter Skorney: And we'll move on to our next caller, Matthew Harrison of Morgan Stanley. Hi, this is Max Skor on behalf of Matthew Harrison. Just a quick question, based on the recent agreements you signed, how are you thinking about integrating these new technologies into your pipeline? Thank you. We are. Thanks a lot for that question, Max. So just to remind everybody, as I said in my opening remarks, we've done a number of really interesting transactions over the last quarter to evolve the science of gene therapy. You know, as there is Dino, which is artificial intelligence and machine learning for making better capsules; we have Kodiak, which is an entirely different approach, using exosomes for a delivery device that you can use in RNA gene therapy and gene editing.

Hi, This is Mac score on for Matthew Harrison Art, just a quick question based on recent agreements you signed how are you thinking about integrating these new technologies into your pipeline. Thank you.

We are thanks, a lot that question Max.

Just to remind everybody I think you heard of my opening remarks, we've done a number of really interesting transactions over the last quarter two.

To to a mall the science and gene therapy, you know.

There's a bomb we've got Dido, which is artificial intelligence and machine learning for making better caps is we've got.

Kodiak, which is an entirely different approach using exosomes for delivery device that you could use in Arnie gene therapy gene editing and then I think.

Brian Peter Skorney: And then I think sort of more near term, perhaps, but really impactful is both HANSA with M. lipidase and Selecta with mTOR. HANSA's technology would ablate pre-existing neutralizing antibodies so that you could essentially empower, at a minimum, empower the people that would otherwise have pre-existing neutralizing antibodies that they would have gotten environmentally, have them in the frame for the ability to get gene therapy

It is more near term, perhaps but really impact was but honda within with and live for days and select that would into our Ponzis technology would up weight.

Preexisting neutralizing antibodies, so that you you could.

Essentially in power at a minimum and power the people that would otherwise have pre existing neutralizing antibodies that they would have got environmentally having been in frames for the ability to get gene therapy. The of course select as there's this concept of co administering their inventory technology with a gene therapy.

Matthew Harrison: And, of course, Selecta is this concept of co-administering their mTOR technology with the gene therapy so that you could essentially trick the body into believing that the gene therapy that it's receiving and the catheter it's receiving is self and not Florence, and you don't build up neutralizing antibodies, which could empower redosing and even multiple doses over time. The short answer to your question, however, is we've just entered into these agreements. These tools have gone into the arsenal that Dr. Rodino-Klapack and her team have to advance this, and we're looking carefully at the timelines and how we can move these as fast as possible forward. As you can imagine, as a mission-driven organization, it is our goal to move these technologies as fast as possible and improve gene therapy as much as possible, and, more importantly, bring the largest number of patients into the frame for gene therapy. So we don't have timelines right now, but we're moving as fast as we can on that, and I suspect we'll have updates early next year.

So that you could essentially trick the body into believing that the gene therapy that it's that its receiving and the cap and its receiving itself and not for US. If you don't build up you know buildup neutralizing antibodies, which could in power, reducing the multiple doses over time. The short answer on your question. However is we just entered into these agreement.

These tools have gone into the armamentarium that Dr. Reddy, you know quite back and her team have to advance this and we're looking carefully at the timelines and how we can move these as fast as possible forward as you can imagine you know as a mission driven organization. It is our goal to move these technologies as fast as possible and improve.

Gene therapy as much as possible, but more importantly, bring the largest number of patients into frame for gene therapy. So we don't have timelines right now, but we're moving as fast as we cannot that I suspect will have updates early next year.

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

Martin Oster: Thank you. Our next question comes from Martin Oster from Credit Suisse. Your line is open. Hi everyone, this is Mark An from Mardi.

Hi, everyone. This is mark on for Marty. Thanks for taking my question. So so my question relates to the upcoming read out for SRP five tariff pipeline I know that you framed the program relative tags onto us in terms of dystrophin expression.

Martin Oster: Thanks for taking my question. So my question relates to the upcoming readout for SRP5051. I know that you framed the program relative to exondus in terms of dystrophin expression. I'm curious, what is the level of exon skipping that exondus achieves in humans?

I'm curious what is the level of exon skipping that exone thats the chiefs in humans and could you speak to the magnitude of improvement in exon skipping, you're hoping to see but that's our the fiber pipeline as part of this initial clinical trial up they think it sure dr. meal. He might want to take this talk a little bit about what will be looking for in the.

Martin Oster: And could you speak to the magnitude of improvement in exon skipping you're hoping to see with SRP5051 as part of this initial clinical trial update? Thank you.

Timothy Francis Lugo: Dr. O'Neill, you might want to take this and talk a little bit about what we'll be looking for in the second half, and perhaps the way we would look to compare it to what we might be seeing with Teplersen, Goldersen, and Kazimierz. Yeah, so I think the key thing is that we will be looking, first of all, it's very important to understand that we are using digital drop PCR. And we will actually be looking at that for PMO and PPO. It's important to actually distinguish that from the older quantitative RT-PCR that was used in the past.

Second half and perhaps the way we would look to compare it to what we might be sitting with the type person Gunderson Canton, Michigan.

Yes, So I think the key thing is that we would it be looking first of all its very important understand that we are using different dropped PCR ER and we will actually go he basle, Tim will people, it's important to actually distinguish that from the.

The older quantitative Archie piece or the C news in the past, we will actually be looking at data from both PMO start to samples and then looking at our GDP. So our in our 50 51 program.

Timothy Francis Lugo: And we will actually be looking at data from both PMOs. Thank you all for joining us for today's webinar. We're going to start with samples and then look at our DDPCR in our 5051 program. I think the other point I want to make is that, or restate, we have actually, with our non-clinical data, both in vitro, in cell lines, as well as in animal models, seen a robust correlation between DD, digital drop PCR, and dystrophin levels. What we've actually seen there is a ratio of between 2 to 3.

I think the other point I want to make it that's or restage is that we have actually with our nonclinical data both in vitro and cell lines as well as in animal models at seen a robust correlation between DT different dropped PCR adds to stroke from levels and.

What we've actually seen there is the ratio of between two to three obviously, we have to validate that in children, but what we've seen in our experimentation todays has been I should say gives us confidence with regards to both the robustness of the combination the ratios and what we hope to see.

Timothy Francis Lugo: Obviously, we have to validate that in humans, but what we've seen in our experimentation to date has been, how should I say, gives us confidence with regard to both the robustness of the correlation, the ratios, and what we hope to see in our human studies. Thank you. Our next question comes from Alethea Young from Cancer Fit Cheryl. The line is open.

In our human studies.

Unknown Executive: Hey guys, thanks for taking my question and congrats on the quarter. You know, I just wanted to talk a little bit about kind of hitting the GMP material and the comparability. It seems like that's a big deal for you guys, and I wanted to talk about what that means going forward for this and other platforms of yours. And then just on Celecta and that mTOR, I was just interested in Dr. Klepak's perspective on how to think about redosing and how the technology, hypothetically, might be important in that. Okay, before I turn it over to Louise to talk about Selecta et al. So thank you, Alithi. I agree with you. It's a big deal. I mean, and it's not a one-quarter effort.

Thank you.

Our next question comes from elite the a young from Cantor Fitzgerald. Your line is open.

Hey, guys. Thanks for taking my question and congrats on the quarter you know I just wanted to talk a little bit about I'm kind of hitting the GMT p. material and the comparable they seemed like that the big deal for you guys and want to talk about what that means going forward for that and other platforms of yours and then just on select and that inventory I'm always just interested dr. clay that's perspective on like how to think about.

The other thing and how to technology and I can statically might be important in that thank you.

Okay before I turn it over to two Luis to talk about.

Select at all so I think you leave the I agree with you the big deal I mean, it and it's not a one quarter effort. The fact that we have GMP material on hand, right. Now is the result of an enormous amount of work by a significant number of professionals over a long period of time you know we started this.

Douglas S. Ingram: The fact that we have GMP material on hand right now is the result of an enormous amount of work by a significant number of professionals over a long period of time. You know, we started this really at the ideation stage a couple of years ago and said we were going to build out this gene therapy engine. And we knew at that time that we needed to build out manufacturing, not simply for capacity but also expertise, process development, analytical development, etc. And we, you know, you've sort of lived with us as we've worked through that process, optimized or, or in the process of optimizing process development, getting all of our analytical development done. There are 24 assays involved here, all are complete, either qualified or validated, as required for each of those. And then, of course, we've done numerous runs, and having GMP material on hand right now is enormously important. And, and I will now also say, of course, we also have to meet with the agency, we're going to do that this quarter, we have to get them to, you know, concur in our view of the material, etc.

Really at ideation stage, a couple of years ago that we were going to build out this gene therapy engine and we knew at that time that we need to build out manufacturing not simply for capacity, but also expertise process development analytical development et cetera, and we you know you you've sort of lived with us as we work through that process optimized or right.

You know the process of optimizing process development getting all of our analytical the moment done there's 24 hour assays that bulkier all or can we.

Slide or validated in the case is required for each of those and then of course, we've done numerous runs and having GMP material on hand, right now is enormously important and and it. It will now I will also say of course, we also have to meet with the agency we're going to do that this quarter, we have to get them. There you know concur and our view.

I'm going to trail et cetera, but we feel very good about where we are the results that we've seen and here very good question, it's going to.

Douglas S. Ingram: But we feel very good about where we are and the results that we've seen. And to your very good question, it's going to pay significant dividends on our platform more broadly. You know, as I said, and I think in my prepared remarks, this concept of a gene therapy engine isn't simply a narrative. It is a platform that is built on three significant pillars, all of which are required to build an enduring gene therapy platform. The first, of course, is that pipeline. And we have a significant pipeline between research and things in the development stage. And even in the later development stage, we have approaching 30 programs right now, at least, depending on how you count them. And then, of course, the latter part I've talked about, that Louise will talk to you about, is advancing the science, making gene therapy even more effective, and bringing more patients in so they can get treated. Of course, that middle concept of manufacturing is crucial.

It's going to pay significant dividends on our platform more broadly you know as I've said and I think in my prepared remarks.

This concept of a gene therapy engine is it simply a narrative. It is it is a platform that is built on three significant pillars.

All of which are required to build an enduring gene therapy platform. The first of course is that pipeline and we have a significant pipeline between research and things in the development stage and even in the later development stage, we have approaching 30 programs right now at least depending on how you count them then of course that the latter part I talked about is.

Luis will talk to you about is the advancing the science makings gene therapy, even more effective and bringing more patients and so they can get treated in of course that middle concept. The manufacturing is crucial and I'm very proud of this team for having decided early all at the very ideation of this concept of building.

Douglas S. Ingram: And I'm very proud of this team for having decided early on at the very ideation of this concept of building a gene therapy platform to begin to invest significantly both in the talent and beyond the talent in building manufacturing. So the fact that we have GMP material on hand right now speaks volumes to 9001, but also 9003, also the rest of our limb girdles, and I believe beyond that into the other gene therapy programs that are sitting behind those programs. So I said at the end of my opening remarks that it is so easy to become hubristic when you have a little bit of success. And we don't want to do that.

Gene therapy.

Platform to begin to invest significantly both in the talent and beyond the talent on in building manufacturing. So the fact that we have GMP material on had right now speaks dreams to nine 001, but also nine 003 also the rest of our limb girdle and I believe beyond that into the other gene therapy program.

Arms that are sitting behind US program. So we're we're I don't want to get I said in live into my opening remarks, it's so easy to become.

To to get Hubris, when you have a little bit of success and we don't want to do that we have a lot yet to do I think meeting with the agency as it is a significant next step for us, but we're very excited about the progress to date and we're very excited frankly about the results that we received to date. So we have more results to come in we have to.

Douglas S. Ingram: We have a lot yet to do, but I think meeting with the agency is a significant next step for us. But we're very, Then the one year on 101, and now, of course, the high dose on 9003, and the exceptional expression we're getting there, and the good safety profile that we're seeing across all of the programs. Here's some confidence that we're on the right track to be able to do what we're trying to do. And what we're trying to do is simply something that will be commercially successful, but far more profoundly than that. We want to bring a much better life to these patients when they are girdle and send patients, and then beyond that, who are living with and degenerating from, you know, as I said before, far too often, succumbing to these rare genetic disorders. Thank you for that. And with that, I apologize.

No two at the beginning of next year, but certainly we as you triangulate the results were getting booked one or one vendor nine months on one or one then the start of one or two and the fact that we've been able to dose all of the kids for the main study and then a low dose on Nigeria's your three in the nine much there and then the low dose a nine 003 in the successful one year.

There than the one year on one or one to now of course, the high dose on nine 003 and exceptional expression, we're getting there and.

The good safety profile that we're seeing across all the programs gives us some confidence that were on the right track to be able to do what we're trying to do what we're trying to do is simply something that will be commercially successful, but far more profoundly than that we want to bring a much better lives to these patients when hurdle in duchenne patients and then beyond that.

We are living with degenerating from you know as I said before far too often.

Succumbing to.

These rare genetic diseases. So thank you for that question and would that I apologize I ramp up for a second so I should turn this over to Dr. Reddy on way back again, if you can talk to select table.

Douglas S. Ingram: I rambled for a second, so I should turn this over to Dr. Rudian Kuwait again, and we can talk about selecting them all. Thank you for that question. We're excited about both HANZA and Selecta.

Yeah, Yeah. Thank you for that question. So we're excited about both on a bolt ons on Wassa Hans gives us opportunity too.

Douglas S. Ingram: HANZA gives us an opportunity to ablate antibodies in patients that are positive for AAV antibodies, so that helps us potentially get to those 15% or so patients that have pre-existing antibodies and also gives us the opportunity potentially for re-dosing down the road. Selecta is something we're particularly excited about because it has the potential to prevent those antibodies from forming in the first place. So with the first dose of gene therapy, patients could potentially be co-administered this drug and then prevent those antibodies from forming with the potential to re-dose down the road. So we just entered into these agreements, and there are additional non-clinical studies to be able to prove that these will be effective and safe, but we're definitely excited about the potential there. We want to make sure that we have every tool to reach all patients, and that's our goal. You know, we may never need it, but it's better to be looking at it proactively, and that's what we're doing. So, thank you. Thank you. Our next question comes from Tyler Van Buren on Piper Sandler. Your line is open.

Blake antibodies.

Patients that are positive for eight now body, so that helps sequentially I get it done.

Her center, so patients that have preexisting antibodies and also because this appetite potentially all everything down the road black that we're particularly excited about because that has with the council to prevent those antibodies from farming and not in the first place so Alan.

The first doesn't gene therapy Cookie cutter networks are the dropped sequentially not prevent those antibodies warming with the potential simply does that in the route.

We just think of it but these agreements and I think the sun non clinical studies to be able to accrue a that they won't be effective pain.

But where we're definitely excited about the potential there we want to make sure that we have every every call to reach all patients and that's our goal that were Jeff.

Now, we may never need it, but it's not a clean.

Got it.

Yeah.

Thank you.

Thank you.

Our next question comes from Tyler Van Buren from Piper Sandler Your line is open.

Hey, good afternoon.

Tyler Van Buren: Hey, good afternoon. Just a quick follow-up question on the momentum trial. So you mentioned that you started at four mixes per keg and are up now to 20 mixes per keg. But if I'm not mistaken, you mentioned you could also potentially go higher than that. So based upon the animal model data, can you just define a ceiling or dose ceiling that you observed? And what that was based on?

A quick follow up question.

The momentum trials so.

You mentioned that you started that forward mix for kids and or up now the 20 mix for kick, but if I'm not mistaken you mentioned you could also potentially go higher than that so based upon the animal models.

Just.

Define potentially feeling.

It goes ceiling you observe.

And what that was based on I'm, assuming it was some sort of safety or toxicity.

Douglas S. Ingram: I'm assuming it was some sort of safety or toxicology issue, Yeah, thank you for that question. So the short answer is that we're going to continue to, so first understand the following: we're already above what we would have considered success, at least from our preclinical models. Now, please don't overread that we've got to get the data, we've got to see the biopsies, and we've got to do the work. And so I don't want to oversell it. But I will say, if you look from a preclinical prediction perspective, we're already beyond that point where we would have said we, you know, we're very excited. This is great.

Yeah. Thank you for that question. So the short answer is that we're going to continue.

So first I understand the following we're already above what we had we would have considered success.

At least from our preclinical models now please don't don't over read that we've got to get the data we've got to see the biopsies and we've got to do the work and so I don't want to oversell. This but I will say if you look from a preclinical prediction perspective, we're already beyond that point, where we would have said we were very excited and this is Greg we're going to continue to push that.

Douglas S. Ingram: We are going to continue to push that dose. We know what we're looking for. And what it is is a real, that in preclinical models, that will be the dose-limiting signal that will help us choose the dose. Our goal, of course, is to achieve, you know, reasonably achieve the highest dose that is safe for these kids. And so we're going to continue to dose up until we get to a place where we think we've seen a signal that tells us that we're at the right margin between, you know, safety and efficacy. And certainly, we're going to go to 30 mg per kg this year. So you won't have any doubts about 30 mg per kg.

Yes, we know what we're looking for and what it is isn't you'll see that in preclinical models that will be the dose limiting signaled that will help us choose the dose our goal of course is to achieve.

You know reasonably achieved the highest dose.

That is safe for these kids and so we're going to continue to to dose up.

Until we get to a place where we think we've seen a signal that that tells us that were at the right margin between safety and efficacy and then certainly we're going to go to 30 makes for kick. This year. So you will you will have a data I'm pretty mixed for keurig it.

Douglas S. Ingram: It won't come in time, but we'll have the 20 mg per kg, which will certainly be in sight. Is there anything there that I missed, Dr. Argyris? No, you nailed it.

I don't come in time, but we'll have the 20 makes for keurig, which will be be certainly insightful for us.

Is there anything there that I missed Dr. O'neil.

No you're nails US you weigh the target, Oregon is the Kitty and that's what we're monitoring closely and has been good so far.

Brian Corey Abrahams: The target organ is the kidney, and that's what we're monitoring closely, and it's been going well so far. Thank you. Our next question comes from Brian Abrahams from RBC Capital Markets. Your line is open.

<unk>.

Thank you. Our next question comes from Brian Abrams from RBC capital markets. Your line is open.

Douglas S. Ingram: Hey guys, thanks for taking my question and congrats on all the progress. With the full one-year data for 9001 now published, I'm curious how this longer-term data will guide you with respect to conduct, patient selection, and end-point selection for your next studies. Just when we look across some of the positive results, but maybe a little bit of variability, measure-to-measure and CK and function across the NSAA components, as well as the learnings maybe there from the cardiac MRIs. Thanks.

Hey, guys. Thanks for taking my question and congrats and all the progress.

With the full one year data for nine 001, now published I'm curious how this longer term data guides you with respect to conduct.

Patient selection endpoints selection for your next studies, just when we look across some of the the positive results, but maybe a little bit of variability measured a measure and he can function.

Across the Hana say components I suppose the learnings maybe there from the cardiac memorize. Thanks.

Gena Wang: Yeah, I would say broadly one of the values of study 101 is that it allows us real-time insight as we build out study 102 and then as we look forward to our commercial process trial as well. So we already had a significant amount of experience with 101 by the time we commenced study 102, so it had already informed our thinking, and it had informed the design of that study, as well as the selection of the primary functional endpoint being NSAA. We've had an opportunity to continue to monitor these children, as you saw, of course, and then we have the one-year data. Reported in JAMA Neurology.

Yeah, I would say broadly one of the values.

Why is that it it allows us real time insight as we build out as we built out study one or two and then as we look forward to our commercial process trial as well. So we already had a significant amount of experience with one or one by the time we commenced study.

In one or two so it already informed our thinking I informed the powering up that study as well as the selection of the primary functional endpoints being an essay we've had an opportunity to continue to monitor. These children. As you saw of course and maybe of the one year data that reported out in Jama neurology.

And I will tell you that it good.

Douglas S. Ingram: And I will tell you that it is confirming the approach that we took with respect to study 102, the way we chose NSA, and frankly, the way we have powered that study. So we feel very good about where we are. And I think 101 has been very helpful in helping us, you know, power that study and give us confidence that we're on the right track. Thank you. Our next question comes from Gena Wang from Barclays. Your line is open.

It is confirming of the approach that we took with respect to study one or two the way, we've chosen and I say and frankly the way we have powered that studies. So we feel very good about where we are I think what a one has been very helpful.

And then helping us power that study and give us confidence that were on the right track.

Thank you.

Next question comes from Gena Wang from Barclays. Your line is open.

Thank you for taking my questions. That's one question regarding chemo has sleep.

Douglas S. Ingram: Thank you for taking my questions. I have one question regarding PPMO that has three parts. So the first is just a follow up to the earlier question. Could you remind us the percentage of exon skipping for exon D51 in early animal data?

The first thing said just follow up with <unk> earlier question could you remind us the percentage of exon skipping <unk> ex Xtandi 51, Andy and animal data in the second question is put the no MISO known yet program what peptide you have.

Douglas S. Ingram: And the second question is for the non-muscle, non-DMV program; what peptides do you have in mind for the PPMO program? And lastly, do you see antibody-based therapy as a threat to your PPMO franchise? Yeah, right.

In line for the ppm, Oakland and lastly, do you see antibody Aluko based therapy threat to your PMO franchise.

Yeah. Okay. So first of all the last question I answered, though I mean, we're excited that other folks are looking at researching ways to bring better lashed duchenne muscular dystrophy, but we certainly feel that you know in that we're our programs all of them. The most advanced.

Douglas S. Ingram: Okay, so first of all, to the last question, I'll answer no, and we're excited that other folks are looking for ways to bring better lives to Shamusker District, but we certainly feel that, you know, in that we are, our programs are the most advanced and the most hopeful. So we're really focused on our own programs. Going back to your other two questions, I will turn this over to Dr. O'Neill, who can give you some perspective. But broadly speaking, and I'll let Dr. O'Neill touch on this with more expertise than I. So first of all, know that the percentage of exon skipping you might look at historically with respect to Teplerson won't be meaningful here because the approach to looking at exon skipping is different.

And the most helpful. So we're really focused on our own programs going back to your other two questions I will turn this over to Dr. O'neill to can give you some perspective, but broadly speaking and I'll, let dr. O'neil touch on this with more expertise to me. So first of all know that the percentage of exon skipping you might look to in the historically with respect to tell person it won't be meaningful here because.

As the the approach to looking at exon skipping as different we're using digital dropped PCR now in the past we used a difference a different form I think it was our.

Douglas S. Ingram: We're using digital drop PCR now. In the past, we used a different form. I think it was RPCR, but Dr. O'Neill will remind us of that. And so it's a bit like apples to oranges.

Our PCR, but dr. aneel I will remind us of that and so it's a bit apples to oranges. The good news just so we know is that when we when we announced the results of the 20 bags on the P. PMO, we will have data using the same exon skipping technology for a tablet.

Douglas S. Ingram: The good news, just so we know, is that when we announce the results of the 20 megs on the PPMO, we will have data using the same exon skipping technology for Teplerson. So there will be an ability to see what we might have seen with the Teplerson versus what we will see with 5051. And then I believe I'll let Dr. O'Neill confirm it, that we would be using the same proprietary peptide that we're currently using, that we've put a lot of work into. But Dr. O'Neill, you can correct me if I've said anything incorrect. No, that's incorrect.

So there will be an ability to see what we might have seen with the tougher said versus what we will see with 50 51, and then I believe all let Dr. O'neill confirmed that we would be using the same proprietary peptide that we're currently using that we put a lot of work into the doctor on the L. you could you can correct me if I have said anything correct.

Yes.

No that's correct Egina you asked.

Timothy Francis Lugo: And I think, Gena, you asked two questions about peptides and the PMO skipping. I think I could do one better with regard to the D2P0 than the animal, in that we did actually look at it at 24 weeks, actually over several weeks periods, but at 24 weeks in the PROMOVY in humans, in patients, we saw about 0.6% skipping that exoskeleton. But it's very important to emphasize that this is digital drop PCR. It's not the quantitative PCR that was used in prior descriptions. And that, I think, is disclosed in our MDA poster. So the beauty of the DDPCR is that it's very tight and actually allows you then to compare across patients and, very importantly, and more importantly, Thank you very much for that collaboration that we announced. It's also part of an overall approach to both improve tissue penetration and, frankly, specific or target or tissue specific targets. Thank you. Our next question comes from Joel Beattie from Citi. Your line is open.

Yeah, just big restate dressed two questions about peptide and the people to skipping I think I could do what beshore with regard to the GDP soared than the animal in that we did actually.

Okay passage at 24 weeks actually over several week periods, but a 24 weeks into PROMOVI insurance in patients.

So about 0.6% skipping exon skipping, but it's very important emphasized that digital drop PCR, it's not the quantitative.

PCR.

That was used in prior descriptions that I think is disclosed in our empty a poster. So do you have to de PCR is it's very tight actually allows you've been to compare.

A cross patients and very importantly, and more importantly, two protein expression downstream and then you asked the question about peptides.

We've not disclosed the nature of this pension peptide.

But I think Doug and I have already highlighted this earnings call and others that we continue to we're never complacent, we're never satisfied with the status quo and we continue to invest in exploring and optimizing our possibly better peptides and obviously our code yet.

Timothy Francis Lugo: Hi, this is Sean Egan calling in for Joel. Thanks for the updates today and for taking my questions. Maybe could you talk a little bit about the package you plan to go to the FDA with in regards to the path forward for limb and girdle muscular dystrophies in general? I guess aside from the fact that these are mostly monogenic conditions, what other factors help make the case for an accelerated path to approval, and what else should we be considering? Yeah, thank you for that. Great question.

Collaboration that we announced is also part of an overall approach to both improve tissue penetration and frankly, a specific or target or tissue specific targeted.

Thank you.

Next question comes from Joel Beatty from Citi. Your line is open.

Hi, This is Sean Egan, calling in for Joel Thanks for the updates today and for taking my question.

Maybe could you talk a little bit about the pack that you plan to go to the FDA with in regards to the path forward for linker It'll go let's go to squeeze in general.

Douglas S. Ingram: So I think, as I said in my opening remarks, we have two significant things to do over the course of this year. One is to complete the GMP runs, which is a combination of two things, just so we're clear. It's not simply the runs themselves, but it's, of course, all the assay work. We can leverage a lot of what we've done. I mean, an enormous amount of what we've done with 9001, but there are bespoke assays for each particular program, so we've got to complete that work. As well, and the second thing to your good question is that we need to engage in a dialogue with the agency about the appropriate regulatory and development pathway forward. And one of the things we said is that we've already started initiating that dialogue there, and we intend to have a meeting before the end of this year on that issue as well.

I guess aside from the fact that these are mostly monogenic conditions what are their factor of help make the case for an accelerated path to approval and what else should we be kind of consider.

Yeah. Thank you for that Great question, So I think as they said in my.

Opening remarks, we have two significant things to do over the course of this year. One is to complete GMP right, which is a combination of two things. This that were clear it's not simply the runs themselves, but its of course, all the assay work.

We can we can leverage a lot of what we've done I mean, an enormous amount of what we've done with 900.

One, but there are the spoke at assays for each particular program. So we've got to complete that work as well in the second thing to your good. Good question is we've got we need to.

Engaging a dialogue with the agency about the appropriate regulatory and development pathway forward. When things. We said is that will we will we've already started.

Yeah commencing a dialogue there tend to have a meeting before the end of this year on that issue as well into your why would we we are I know I think were unabashed about our view at least and we'll see where we end up that that it would be in the best interests of patients and also appropriate from a development and regulatory perspective, you have a rapid.

And accelerated approach to the development of not only that girdle to me, but also.

A minimum the other sarver black Hansen, perhaps beyond that there really are a number of.

Douglas S. Ingram: There really are a number of characteristics of this disease and this therapy that we at least believe justify that. To your point, these are well-characterized monogenic diseases. We know what is causing these diseases. It's the lack of a structural protein that is the sole and exclusive reason that these children are degenerating and are living shortened lives. Second of all, these are ultra-rare diseases, so they are as rare as Duchenne muscular dystrophy is. These are, in aggregate, you know Linverdal is significant. Individually, these are small disease states.

Characteristics of this disease and this therapy that Ria police believe.

Justify that to your point these are well characterized monogenic diseases. We know what is causing these diseases and it's the lack of a structural protein that is we sold one exclusive reason that these children are generating and our living shortened lives.

Second of all these are ultra rare disease. So these are as various duchenne muscular dystrophy is these are.

In aggregate Olin girdle is significant individually. These are small disease stage, so that creates a.

Douglas S. Ingram: So that creates a compelling reason to find a creative approach to this. The third reason, of course, is that this is the therapy at hand because of the particular genes and proteins at issue here. We are able to comfortably package in our Rh74 capsid a gene that codes for the native protein.

Compelling reason to find the accretive.

Approached this the third reason of course is that this is that the therapy at hand, because of the particularly jeans proteins that issue here, we were able to comfortably package in our already 70 forecasted then the a gene that coach for.

The native protein. So we can replace he precise native protein that these children are lacking in the absence of which is causing their demands and so the only remaining question that is can we can we produce a significant amount of it and the short answer is that we've seen in the.

Douglas S. Ingram: So we can replace the precise native protein that these children are lacking and the absence of which is causing their demise, and so the only remaining question then is can we can we produce a significant amount of it and the short answer is that we've seen in the both the low dose and the high dose that indeed we can in the low dose we were already producing a significant percentage and i might be off by a percentage or two but on western blot um i believe we were um in the 30 percent and in in on um protein positive fibers we were over 50 percent and then of course as you've seen in the higher dose it was well tolerated and even as it's well tolerated we're able to to we get 4.2 genome copies per nucleus the expression is over 70 percent um on both protein positive fibers and on intensity and nearly that on western blot um and so you know from our perspective this is you know you look at the guidance and you look at the statements that the agency's made you know publicly about opportunities in gene therapy this seems on its face at least to be the kind of gene therapy that would justify an accelerated approach to bringing these therapies to these kids, With that said, we have work to do over the course of this year, both in GMP and in dialogue with the agency to align on that. I won't make promises in advance about where we'll end up with those, but we certainly will come back at the beginning of next year and give you an update on those discussions with the agency. And at that time, hopefully we can plan out exactly what the path is, not just for QE, but for all of the other limb kernels. Thank you. Our next question comes from Vincent Chen from Bernstein. Your line is open.

Hi, boasts a low dose and the high dose that indeed, we can low dose we were already producing a significant percentage I might be off by percentage or two but on western blot I believe we were in the 30% send in on approaching positive fibers, we were over 50% and then of course as you saw.

Scene in the higher dose it was well tolerated and even it as it is well tolerated we're able to.

We get 4.2 genome copies for nucleus. The expression is over 70% on both posting positive fibers and on intensity and merely bad on western blot and so you know it from our perspective. This is you look at the guidance and you look at the statements that the agencies made.

Publicly about.

Opportunities and gene therapy. This seems on its face at least to be the kind of gene therapy that would.

Justify or an accelerated approach to bringing these therapies to these kids.

With that said, we're up work to do over the course of this year, both in GMP and a dialogue with the agency tail light on that I won't make promises in advance about where where we'll end up with those but we certainly will come back.

The beginning of next year and give you an update on this discussions with the agency.

And at that time, we hopefully we can plan out exactly what the path is not just for two we but for all of the other girls as well.

Thank you.

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

Douglas S. Ingram: Thanks for taking the question and congrats on the progress. Over the last few months, in addition to, I guess, your updated one-year data for your DMV gene therapy program, I guess we've also seen some updates from your competitor or peer, Pfizer's microdistributed gene therapy program, and clearly they're different programs, but I was wondering whether you have a sense whether their findings could provide some insight into the likely effect size with microdistributed gene therapy, and if so, Well, let me say that I'll say I'm going to do my best to talk about our programs and not about others.

Thanks for taking the question congrats on progress.

The last few months in addition to I guess your updated one your data for your gene therapy program I guess, we've also seen some updates from.

Your competitor or pure Pfizer's, Microdisplay and gene therapy program.

Clearly there are different programs, but I was wondering whether you have us.

Do you think that their findings could provide some insight into the likely effect size with microfrance with micro just a gene therapy and if so how is this affected how you think about what is the likely effect size with a microphone gene therapy, and you're thinking around the the powering of Oh study too.

Well, let me say, but I'll say I'm Gonna do my best to talk about our programs and not about others I will say that to the extent that that that others.

Douglas S. Ingram: I will say that to the extent that others see some functional, [inaudible] We're seeing on every functional endpoint, with respect to those kids, and then you go over to limb girdle, very similar, there's an enormous amount of read-through. And of course, you see the same thing, you get great expression, it appears to be tolerable and safe, and we're getting, you know, even at a low dose, in one year, with a low dose of LGM, the QE construct, SRP 9003, you've seen significant benefit on every functional endpoint there, and then we've got great expression with respect to the higher dose, the 2E to the 14th, What I would say, you know, this is... What I'm going to try to avoid talking about other programs, because, as I was discussing with someone earlier today, for those of you on the call that may play chess, there's a famous strategy in chess that says you're supposed to play the board, don't play the opponent, and that's what we're going to do.

See some functional.

Signals, even with very modest expression that of course only.

Gives us additional confidence in what we have seen both pre clinically and given the robust expression that we're able to two achieved with our current constructs the functional results that we odyssey and that frankly.

Although they are small numbers, what we appear to be seeing already as you know we've talked about with study one on one of the first more kids every child, he's not they're not stabilized they're improving on every functional endpoints on with respect to the those kids and then you go over to live girdle very similar.

Northern suburb read through and of course, you see the same thing you get great expression.

It appears to be tolerable and say and we're getting.

Even the low dose in one year with the low dose abeles, yet the you too we construct SRP Niger as your three you've seen significant benefit on every functional endpoints. There and then we've got great expression with respect to the higher doses to either the 14th.

Using super coil PCR. So so we're excited there what I would say you know this is what I'm going to try to do is a void.

Talking about other programs because as I was discussing with someone earlier today.

For those of you on the call that May play chess, there's a famous strategy and chestnut says you're supposed to play the board don't play the opponent and that's what we're going to do and frankly, you know we're excited about the way the board's wideout laying out right now you know our gene therapy engine and the approach that we take with these constructs isn't unique to us and it is differentiated from others. It starts you first.

Douglas S. Ingram: And frankly, we're excited about the way the board's laying out right now. Our gene therapy engine and the approach that we take with these constructs is unique to us, and it is differentiated from others. It starts first, frankly, and I say this with the potential of embarrassing Dr. Louise Rodino-Klepack and her team, but it does start with that team. Under Louise's guidance, the design, empirical testing, and optimization of these constructs are unique to our approach, and I think it's yielding benefits. Our capsid is different from others. We alone use RH-74. Our promoter is unique to us; it's MHCK-7. Frankly, just focusing on our programs and not on others, the evidence continues to build that our approach is the best. Hopefully, it's not only differentiated, but it's paying off to the benefit of patients. And I've talked about this already, but I'll remind you, you know, Study 101. We're very excited about the results that we've seen, both from expression, tolerability, and safety, but also function. We've seen that out to one year, as we've seen in JAMA Neurology this last quarter. And then, of course, we had the start of 102.

Frankly, and I say this you know, but the potential of embarrassing dr. Luis or do you know clay packet achieved but it does start with that team under Luis is guidance. The design empirical testing and optimization of these cars trucks is unique to our approach and it's.

I think its yielding benefits.

There are capsid is different than than others. We alone use our age 74, our promoter is unique to us its MHC K seven we allow and use them I mean, she K seven and the transgene that we use is unique to ours and I think that's why.

Frankly, just focusing on our programs and not on others. The evidence continues to build that our approach hopefully is not only differentiated but it's paying off to the benefit of patients and I've talked about this already but I'll remind you know study 101, we're very excited about the results that we've seen both from expression tolerability.

And safety.

But also function, we've seen that out to one year.

As we've seen in Jama neurology this quarter. This last quarter and then of course, we had the started in one or two we've now dose all of the kids to the main.

Douglas S. Ingram: We've now dosed all of the kids for the main study, and we're dosing kids on crossover. And that study continues apace. And I think that says a lot about the construct, but I think it also says a lot about the team that was able to overcome obstacles in the middle of this pandemic, both at Nationwide and at SREPTA. And then, of course, we have 9003, both low dose and high

Study and were dosing kids on crossover in that study continues.

Pace and that's I think that says a lot about the construct but I think it also says a lot about the team it was able to overcome obstacles in the middle of discount them, both at nationwide and that syrups and then of course, we have nine 003, boes low dose and high dose.

Douglas S. Ingram: And what we're seeing both from an expression perspective, but also, at least currently, with respect to the low dose from a functional perspective, and what we've seen from a safety and tolerability perspective. So we really want to focus on our programs, but we're very excited about the results we've received so far. And from our perspective, our goal is to move as fast as possible. This only creates an obligation for us to get going for the future. Thank you. The next question comes from Joseph Schwartz from SBB Levering. Your line is open.

And what we're seeing both from an expression perspective, but also at least currently with respect to the low does from a functional perspective.

But we've seen from a safety and Tolerability perspective, So just we really want to focus on our programs. We're very excited about.

The results. We've we've received so far and from our perspective, our goal is to move as fast as possible. This only creates for US an obligation we could go in for instance.

Thank you.

Our next question comes from Joseph Schwartz from SVB, leaving your line is open.

Douglas S. Ingram: Thanks very much. Given the NSAA is comprised of 17 domains and they're scored from 0, 1, and 2, I was wondering if there are certain patterns in the patients that have been treated with 9001 that make you confident that the results will be replicated in phase 3 or, you know, different time course observations. Any sorts of characterizations you can share that, you know, make you particularly optimistic? Yeah, I can turn this over to Louise.

Thanks, very much so given the NSS is comprised of 17 domains and their scored from tier one and two I was wondering if there are.

Certain patterns in the patients that have been treated with 9001 that.

Makes you confident that the results will be.

Replicated in the.

Phase three or you know different time course observations any any any sorts of characterizations you can share that.

Thank you, particularly optimistic.

Douglas S. Ingram: I'll make an introductory statement about it. I mean, what excites me, like, first of all, of course, there is always a risk in over-analyzing small data sets. This is four children with respect to 9001, and so far, three children with respect to 9003 that we've seen functional results regarding. But, with that said, you ask a very good question, which is, so you're seeing these significant improvements across this composite score of NSA, which is built on lots of individual tests. It could be the case.

Yes, I can turn this over to Luis I'll make it.

And introductory statement about it I mean, what excites look first of all course.

There there is always risk and over analyzing small data sets business for children with respect to 900 warranted. So far three children with respect to nine 003 that we've seen functional results regarding but with that said you. Rick you you ask a very good question, which is so you you.

You are seeing these significant improvements across this composite score of NFC, which is built on lots of individual pass.

It could be the case.

Douglas S. Ingram: That what we're seeing in aggregate is one function that is significantly improving versus all of the other functions. And then you can worry about what that might mean. The thing that excites us a lot and gives us confidence, both in DMD with 101 as well as currently with the low dose of Lin-Gerdal, because that's where we've seen the functional results so far, is that every kid is benefiting on every functional end. And if you look at the composite, they're benefiting across all of the functions in that composite. It is really, they are generally improving functionally, both on time But with that, Dr. Rodino, you might have some more nuanced views than I've just given. I think you captured it well.

That was that what we're seeing in aggregate is one function that is significantly improving versus all of the other functions and then you can worry about what that might mean, the thing that gives us a lot of that excites us it gives us confidence both in DMD with one or one as well as with currently with the load.

Most of let girdle, because that's where we've seen the functional results. So far is that every kid is benefiting on every functional endpoints and if you look at the composite there Ben they're benefiting across all of the functions in that composite. It is really they are generally improving functionally both on prime test on NSS.

Okay and on the individual components of that I, say, which which is certainly confirmatory, but with that but you will be CE mark.

I'd now.

You might have some more nuance views than than our skin.

I think you captured it well I think whats important is that.

Douglas S. Ingram: I think what's important is that, as well as the other supportive measures like Time to Rise, as well as all of the time tests, we see supportive data coming out of our 101 study that led to the powering of our study 102. And so we feel confident, based on those results across those measures, as well as other studies, like our Lumb-Girls study, which we will support. Thank you. Our next question comes from Desai Yang from Missoula Security. Your line is open.

Across the components of and I say as well on the other support of measures like from time to ride.

As well as all the time kept me the importance of data coming out of our one on one study that led to the the powering up our our study when our Q I mean, we feel confident.

Based on those results across both measures as well as our other studies like our local study that that well.

Well.

[music].

Thank you.

Our next question comes from the Difei Yang from Mizuho Securities. Your line is open.

Douglas S. Ingram: Hi, good afternoon. And thanks for taking my question. I have a quick one with regard to the 9001 program registration pathway. So to what extent do you expect the interim analysis of study 301 to be part of that package? It is certainly our goal that if we are successful... in the, with 102 and with an interim analysis of study 301, that the interim analysis of study 301 would play a significant role in the registration of the trial. And one of the things I said was, if all goes well, and we start this study in the second half of this year, then we should have, in the first quarter, a significant data set on the functional aspects, as well as the safety and tolerability aspects of 9001 for treating Duchenne muscular dystrophy.

I could that can you and thanks for taking my question I have a quick one with regard to be on 9001 program record station no pathway.

Let me. Thank you you get back on the interim analysis effort that these three or one will be part of that Patrick.

It is certainly our our goal that it's very accessible.

In the.

With one or two and with an interim analysis sub.

Study three one and that the interim analysis of three or what would play a significant role.

The registration other trialing and what are the things I said is in the first if all goes well and we start this study in the second of up this year than we should have in the first quarter is significant data stat on this the functional aspects as well as the safety and Tolerability aspects were nine 001 to treat duchenne muscular dystrophy Clos.

Both study one or two and an interim analysis of REO. One we would have functional results showing and the placebo controlled manner that the therapy provides functional benefits.

Douglas S. Ingram: And across both study 102 and an interim analysis of 301, we would have functional results showing in a placebo-controlled manner that the therapy provides functional benefits to these children, that it's working, that it's benefiting them, that we would have a very significant data set on safety and tolerability across the two studies. Zolgensma, and in that program, there are no biopsies, but here we have the opportunity to get

To these children that it's the benefits that is working as it's benefiting them, but that we would have a very significant data set on safety and tolerability across the two.

Studies, and then of course with with biopsies and Thats one of the things that we get here that some programs you don't get like for instance.

So jensen.

And that program that there aren't a biopsy, but here we have the opportunity to get biopsy. So that means in the first quarter of next year, we could have it via an interim analysis not only all of the CMC work that we've already done showing that in all of the material ways. It ought to operate in the same way is the clinical material, but also we would have actual pure.

Douglas S. Ingram: So that means in the first quarter of next year, we could have it be an interim analysis. Not only all of the CMC work that we've already done, showing that in all of the material ways it ought to operate in the same way as the clinical material, but we would also have actual empirical, you know, in vivo biopsy data showing the expression levels as well as safety and tolerability. And on that basis, we would certainly intend to approach and discuss with the agents the opportunity to submit a BLA.

Nicole you know in vivo biopsy data showing the expression levels as well safety and Tolerability and on that basis, we would certainly intend to approach and discussed with the agent to the opportunity to submit for.

For MPLX.

Douglas S. Ingram: But that will be a discussion that we'll have with data in hand in the first quarter of 2020. Thank you. And I am showing no further questions from our phone lines at this time.

But that will be a discussion that we will have with data in hand in the first quarter of 2020 now.

Thank you.

And I am showing no further questions from on the phone lines at this time, let's turn the conference back over where did that the ingram from or for any closing remarks.

Unknown Executive: I would now like to turn the conference back over to Doug Ingram for any closing remarks. Thank you very much. Thank you all for participating this evening. And thanks for the questions. We really appreciate the opportunity to answer them. I'll repeat my apologies.

Thank you very much. Thank you all for participating this evening and thanks for the the questions.

We really appreciate the opportunity to answered them I'll repeat apologies I will keep what I said that the in my opening remarks, which is simply we'd have a lot to do as an organization. We've had a lot of success. We're very excited about the progress we've made to date on our gene therapy engine. We're very excited about the opportunity to continue to sit this to serve our duchenne muscular dystrophy.

Douglas S. Ingram: I will repeat what I said in my opening remarks, which is simply that we have a lot to do as an organization. We've had a lot of success. We're very excited about the progress we've made to date on our gene therapy engine, and we're very excited about the opportunity to continue to serve our Duchenne muscular dystrophy community with our two approved therapies. And hopefully, if approved, three therapies by the first quarter of next year. And we're very excited about the potential for our next generation RNA technology, PPMO, to deliver an even more profound impact, both in Duchenne muscular dystrophy and beyond Duchenne muscular dystrophy to other areas where steric blocking technology could bring therapeutic benefit to patients.

Community with our two approved therapies and hopefully.

If approved three therapies by the first quarter of next year and we're very excited about the potential for our next generation already technology PMO to deliver even more profound impact both in duchenne muscular dystrophy and beyond Duchenne muscular dystrophy to other areas, where scaring blocking technology could bring therapeutic benefit.

Patients we have a lot to do so as much as we are excited about the progress we've made to date it would it be mistake for us to develop hubris or complacency and hope you would agree with me that the team at Sarepta does not intend to do that this is a team that's very focused I'm really proud of our team I'm very proud of our partners I'm very proud of our.

Douglas S. Ingram: We have a lot to do. So as much as we are excited about the progress we've made to date, it would be a mistake for us to develop hubris or complacency. And I hope you would agree with me that the team at Sarepta does not intend to do that.

Douglas S. Ingram: This is a team that's very focused. I'm really proud of our team. I'm very proud of our partners. I'm very proud of our clinical investigators who have continued to serve these patients during what has been, for everyone, a trying time over the course of 2020. We'll stay on mission, and I look forward to providing additional updates as we progress across 2020. And with that, have a wonderful evening and the rest of the program. Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect. Everyone, have a wonderful day.

Clinical investigators who have continued to serve these stations during what has been for everyone.

Trying time over the course of 20 to 20 will stay on mission and I look forward to providing additional updates as we progress across 2020 would that have a.

Wonderful evening and best of the week.

Ladies and gentlemen, thank you and participating in today's conference. This does conclude the programming you may all disconnect everyone have a wonderful day.

[music].