Q1 2022 Sarepta Therapeutics Inc Earnings Call

Yeah.

Based on our performance to date, we can confirm our prior guidance of net product revenue of over $800 million.

For full year 2022, translating into product revenue growth of over 30%.

Over 2021.

Our chief customer officer gallon Marie will provide additional color on our performance in a moment and our CFO E&S, Japan will provide an update on our financials.

In the first quarter, we continued to advance our large pipeline of potentially life enhancing therapies.

Just on the rare genetic diseases across our three platforms.

As you know Thats, RNA gene therapy, and gene editing as well.

As you know we are now in pivotal trials for our lead programs in both of our gene therapy <unk>.

And our RNA platform.

With respect to our gene therapy platform, we continue to initiate sites globally.

And to dose embark on 120 patient pivotal trial for SRP nine here or there on <unk>.

<unk> gene therapy, largely agnostic to mutation to <unk>.

Duchenne by delivering a truncated by functional version of dystrophin.

Embark is well powered and informed by the wealth of positive expression.

<unk> and functional evidence that has come from previously dosing.

Over 80 patients across three studies.

And as I've said, often you should assume that the success in embark a well powered phase III pivotal study.

We'll be our path to a successful launch of SRP 901 in the United States and around the world.

As I have also confirmed in the past.

We're exploring with the FDA the possibility of a more expedited BLA filing for SRP 901.

Anticipating your questions.

We will provide an update once those discussions are completed and will not provide additional color until that time.

But again for now at least one should assume that embarked which will read out next year.

Is our pathway to approval.

As we continue enrollment of embark we're also leveraging our world leading gene therapy platform.

To advance our sticks LG MD candidates, all of which share the same or a 74 vector and many of the same promoter.

<unk>.

On the R&M side, we're enrolling and dosing and momentum heartbeat.

Our pivotal trial for SRP $50 51.

Our next generation RNA based key PMO or the treatment of Duchenne patients amenable to skipping exon 51.

We are particularly excited to move momentum forward given the results of part a and momentum part a we were encouraged to see 18 times greater exon skipping and eight times greater districts, then over a temporary thing and we saw it in half the time.

And at one fifth the drug exposure if confirmed it momentum part D. S. Okay, 50, 51 could be a profound improvement over the current standard of care at the same time, we are progressing the preclinical work for additional ppm.

To treat a much greater percentage of the Duchenne population than we currently treat.

Our head of R&D, and Chief Scientific Officer, Dr. Louise Rodino playback will provide additional color on the performance of our R&D pipeline and Readouts in the first quarter in a moment.

Now I recognize that for many biotechs and for those that invest in them. The last 15 months or so have been challenging.

And some biotechs have particularly struggled.

In response to external environment, we feel no shame for it for that but swept the remains.

On the other hand in a very strong position despite the external environment.

We continue to enjoy strong revenue growth.

Well on our way to eventually achieving advantage $1 billion in yearly revenue milestone.

We entered 2022 with over $2 $1 billion on our balance sheet.

And even as we have aggressively invested in our pipeline, we exited the first quarter with over $2 billion in cash our pipeline continues to perform and we are in pivotal trials with potentially transformative therapies in both RNA and gene therapy platforms.

And we have one of the strongest and most operationally excellent teams and.

And all of the genetic medicine and with our success, we're not standing still but we are growing.

In addition to the expansion of our genetic therapy center of excellence in Eastern Ohio, We.

We are building out a new 288000 square foot facility in Bedford, Massachusetts.

Where we will centralize our efforts, including RNA research and process development function.

<unk> biology gene therapy process development and quality control and we're building early phase GMP gene therapy manufacturing capacity that will help accelerate our future programs and.

And we continue to grow and add best in class talent as well in 2022, we will add another 40% to our employee base.

Bulk of whom will be in research development.

Regulatory affairs.

Clinical development and technical operations.

And with that let me turn the call over to our head of R&D and our Chief Scientific officer, Dr. Luis really not quite back for an update on our research and development activities Luis.

Thanks Todd.

We are pleased with the continued progress and momentum Islander, R&D program I'll begin today with a late stage clinical programs.

For SRP 9001, our gene therapy in development for the treatment of Duchenne.

The data presented to date continues to give us confidence in therapy.

After the detected.

With an emphasis on improving function quality of life, and preventing premature and I like that.

Driving this transformative effort is the underlying strength of our contract combined with our deep understanding of Duchenne.

I'm not going to be and our site.

We have demonstrated consistently.

Three trials.

One that you want us to do you want us to me having against 85 patient study.

Eddie.

Based on these results we would expect to see benefits have continued to increase over time.

The progressive nature of Duchenne.

<unk> study.

Sustained functional improvement as compared to natural history.

Now in here for a follow up.

And notably the safety profile has remained consistent across different.

Different patient Asia athlete.

We continue to generate data from studies 100, 112, and three including data from part one of that do you want us to and one year data from study one out of three.

As we have mentioned on our fourth quarter call. We plan to perform an integrated analysis of the one year data from study 101, one O two and while not a free for all patients who received the targets there.

Our plan is to shed totality of these data with regulators and prevent all of these results at a medical meeting later this year.

In parallel enrollment embark for study 301 are 120 patient global multicenter double blind placebo controlled phase III trial evaluating commercially representing a 39 years there wasn't material in patients with Duchenne.

You mean, the ages afforded by then remains on track we would expect to have the trial fully enrolled in the middle of the year.

Now continuing with a gene therapy franchise.

For SRP nine further free and our other programs, we continue to make good progress with respect to building our manufacturing process.

Leading assay development and validation.

Already the test commercially representing a material in a clinical trial, we will discuss the study design without that.

Moving now to our RNA platform for.

For our next generation <unk> program SRP 5051 in development to treat individuals with Duchenne amenable to exon 51, skipping enrollment continues on pace for part B of the momentum study.

Remind you momentum part D is a multi arm global ascending dose study of SRP 5051, which is monthly.

Assessing dystrophin protein level and skeletal muscle following FRP 50 51 treatment.

As we've guided previously we anticipate part D to be fully enrolled in the second half of 2022.

If the trial is successful.

Part D will serve as a pivotal study for SRP 5051.

Plan to seek an accelerated approval.

Now turning to some updates on the 2022 muscular Dystrophy Association annual clinical insights conference that took place in March.

Sure data from across our pilot plant at the conference.

<unk> three podium and 10 poster presentation, notably for the FRP lines. There is there are three programs our lead gene therapy in development for the treatment of limb girdle muscular dystrophy type CE or LNG and recently, we reported new data from the two dose cohorts and study SRP 900 free one on one.

We also share the full results from explorer DMD study to assess the rate of preexisting antibodies to the <unk>.

74 vector and individuals with Duchenne.

For study SRP 9001 on what we presented three year functional and senior biopsy data from cohort one the low dose.

Cohort two year functional and biopsy data from cohort two the high dose cohort.

Safety standpoint, since gene therapies, only one time.

Is that sort of typically observed during the first few months after dosing.

Therefore as expected we can not observed any new safety.

Significant drug safety events at year. Three these results continue to reinforce the favorable safety profile therapy, using a V or a 74 factor <unk>.

Which often leads to other gene therapies administered with this sector.

In terms of the durability of the therapy. The results show that the persistence of the SRP nine zero their feedback during transit muscle continues to drive meaningful levels of data sets look like at protein expression over time.

Turning to sustained improvements in functional outcomes.

We are very pleased with these results because of the potential recruits or a port.

Portfolio of five other LGD program.

It's also the same AAV <unk> form factor.

These data are also important for the reasons for ongoing SRP 9001 probe acquisition, because the SRP nine builds out the program uses the same AAV <unk> 74 in vector and they CK seven promoter and design and approach.

Nine zero or what.

As we add to the growing body of clinical evidence for these programs supported consistent safety and durability data for one program has returned to the platform.

Also presented at MDA for data from explorer DMT.

Ah study assessing the rate of pre existing antibodies to the AAV are 74 vector and individuals with Duchenne.

The final results demonstrate that the majority of patients screened 86, 1% or zero negative, meaning they have a titer of less than one to 400 for anti AAV <unk> 74 total binding antibodies.

This low prevalence of antibodies against AAV Ars 74.

<unk> supports the broad applicability of <unk> 74, based gene therapy for patients with Duchenne.

The findings of this study are important for several reasons.

Because pre existing antibodies against AAV vector to hamper the therapeutic efficacy and potentially some of the safety concerns we.

It's imperative that we have a reliable way to prescreen individuals before they rethinking therapy <unk>.

Additionally, our goal treat all individuals with duchenne and ability to better understand the population with pre existing antibodies allows us to target our research and development efforts by novel ways to knockdown preexisting antibody.

These individuals' could be eligible to receive therapy in the future.

Further our comprehensive approach of measuring total binding antibodies.

<unk> improved the safety and efficacy of AAV based gene transfer therapies.

The result.

One study have also been observed.

Yeah.

Including for the embark study for SRP 9001.

We believe our observed low screen out rate will allow more patients to be eligible to receive SRP 901 compared to other gene therapy.

As I conclude today I would like to thank my direct to colleagues who remain grounded in our mission to translate very best buy into the very best treatments for patients in the shortest time possible.

Thanks, as well to our partners and science clinical trial investigator and the patient community for their dedication.

I will now turn the call.

On our commercial activity gallon.

Alan.

Thank you Luis and good afternoon, everyone.

Driven by continued demand for three RNA base PMO therapies I'm pleased to report that the team delivered approximately $190 million net product revenue for the first quarter of 2022.

This performance represents more than 50% growth or greater than $60 million and net revenue growth over the approximately $125 billion of net revenue for the first quarter of 2021.

For the first quarter of 2022 compared to the first quarter of last year we.

We delivered nearly 10% growth for exon 51.

And more than 50% growth for bio under 53.

While maintaining our market leadership position in the exon 53 medical population.

The performance of a modest 45 continued unabated in the first quarter of 2022.

With 22 quarters.

With consecutive quarter over quarter growth, it's tempting to gloss over the day to day challenges. The team has overcome to deliver on our objectives I'll take a moment to elaborate.

Firstly as we come to expect through our deep experience in serving the Duchenne community and consistent with our historical experience insurance changes at the beginning of each year.

Pat did our revenue across all three therapies.

Second we saw competition for newly diagnosed patients in the four to seven year old bridge from our own embark trial for SRP 9201.

We planned for this issue and factored in to our 2022 guidance.

This competition disproportionately impacts exon 51, and <unk> 53.

Due to our penetration in these populations and subsequent reliance on these patients from new starts.

Lastly, in addition to facing competition from the embark trial. We are also actively enrolling exon 51, our medical patients and our mission study and part B of the momentum study to support the approval of our PMO candidate SRP $50 51.

Our performance for the first quarter is even more impressive in light of the fact that all of this competition from our own R&D group.

We expect the pressures from clinical trial enrollment will persist for the remainder of the year.

But we remain comfortable with our 2022 net product revenue guidance of over $800 million.

I will now outline.

Individual net product revenue for the first quarter for each of our three approved RNA based PMO therapy.

Beginning with exon 51, which totaled roughly $117 million.

Resenting approximately 9% growth over the first quarter of 2021.

You'll notice the revenue dip slightly compared to the fourth quarter of 2021.

This was expected and primarily driven by the insurance changes at the beginning of each year.

By the end of the first quarter of 2022.

<unk> had worked through this challenge and we are now exactly where we forecasted we would be at this point in the year.

Expectations for the remainder of the year to return to modest growth trajectory. For example is 51.

For by August 53 revenue totaled approximately $28 million, representing roughly 60% growth versus the first quarter of 2021.

As we have noted previously with smaller revenue per bottle.

53, when compared to a modest 45.

It's primarily driven by a larger than expected exon 45 amenable population compared to the exon 53 population.

This is also consistent with what we've seen in clinical trials.

In General we're pleased with the performance of bond was 53 and <unk>.

Similarly, our continued leadership position within the exon 53 amenable population.

For a modest 45 revenue totaled nearly $44 million, representing greater than 25% and sequential growth over the fourth quarter of 2021.

The team continued to execute at the launch cadence of 145, driving both patient identification and also working hard to gain access for the patients who have already submitted start forms.

We expect the growth of a modest 45 to continue in the coming quarters.

I'm proud of the successful start to 2022 and of our dedicated and highly motivated team who work every day to execute on our mission and support for nearly 30% of patients.

Who are amenable to one of our three approved RNA based PMO therapies.

With the fully integrated biotechnology company focused on Duchenne and other unmet needs of precision medicine, we look forward to working closely with our R&D colleagues as they discover and develop therapies such as SRP 9301.

An even larger proportion of the duchenne population as well as advancing our deep portfolio of therapies and gene therapy.

RNA and gene editing.

And now I'll call I'll turn the call over to Japan for an update on our financial Ian.

Thanks, Alan and good afternoon, everyone. This afternoon financial results press release provided details for the first quarter of 2022 on a non-GAAP basis as well as the GAAP basis. Please refer to the press release available on <unk> website for a full reconciliation of GAAP to non-GAAP financial results.

For the three months ended March 31, 2022, the company recorded revenue of $210 8 million, which consists of net product revenue and collaboration revenues compared to revenue of $146 9 million for.

For the same period of 2021, an increase of $53 $9 million.

Net product revenue for the first quarter of 2022 from our PMO exon skipping franchise was $188 8 million.

Compared to a $124 9 million for the same period of 2021.

For the first quarter of 2022 individual net product sales were $117 $1 million for exon 50, $143 6 million for a modest 45 and $28 $1 million for <unk> 53, the increase in net product revenue, primarily reflects higher demand for our products and a full <unk>.

Order of a modest 45 sales during the three months ended March 31, 2022, given its commercial launch in February of 2021, and as noted earlier in the call. We are reiterating our 2022 total revenue guidance of greater than $880 million for a net product revenue guidance for our RNA free.

<unk> of greater than $800 million.

And each of the quarters ended March 31, 2022, and 2021, we recognized $22 million of collaboration revenue, which relates to our collaboration arrangement with Roche and.

And reimbursed are all co development costs under the Roche agreement totaled $17 7 million for the first quarter of 2022 compared to $13 4 million for the same period of 2021.

On a GAAP basis, we reported a net loss of $105 $1 million and $167 $3 million or $1, <unk> and $2.10 per basic and diluted share for the first quarter of 2022 and 2021, respectively.

We reported a non-GAAP net loss of $48 6 million or <unk> 56 per basic and diluted share in the first quarter of 2022 compared to a non-GAAP net loss of $114 5 million or $1 44 per basic and diluted share in the first quarter of 2021.

In the first quarter of 2022, we recorded approximately 31 $4 million and cost of sales compared to $22 3 million in the same period of 2021 the.

The increase in cost of sales is primarily due to increasing demand for our products, partially offset by write off of certain batches of a product not meeting the quality specifications for the three months ended March 31, 2021 with no similar activity for the three months ended March 31 2022.

On a GAAP basis, we recorded $194 3 million and $195 $1 million and R&D expenses for the first quarter of 2022, and 2021, respectively, a year over year decrease of $800000.

This decrease is primarily due to decreases in market research with academic institutions and decreases in upfront and milestone expenses during the first quarter of 2022 compared to the first quarter of 2021.

On a non-GAAP basis, R&D expenses were $173 2 million for the first quarter of 2022 compared to $177 5 million.

For the same period of 2021, a decrease of $4 $3 million.

Turning to SG&A on a GAAP basis, we recorded approximately $71 8 million and $71 $1 million.

<unk> expenses for the first quarters of 2022, and 2021, respectively, an increase of $700000.

The increase was primarily driven by an increase in professional service expenses.

On a non-GAAP basis, the SG&A expenses were $53 2 million for the first quarter of 2022 compared to $51 5 million for the same period of 2021, an increase of $1 $7 million.

On a GAAP basis, we recorded $17 $3.

$17 $3 million in other expenses net for the first quarter of 2022 compared to $15 $5 million and other expenses net for the same period of 2021 and the increase primarily reflects an increase in our mark to market adjustments on our strategic investments during the three months ended March 31, 2022 compared to the same.

Period of 2021.

We had approximately $2 billion in cash cash equivalents and restricted cash and investments as of March 31 2022.

On our current assumptions, we believe our balance sheet provides us runway beyond the read out of study 301 and into 2024 and with that I'll turn the call back to Doug to start the Q&A.

Thank you very much and let you open the line for questions.

Absolutely at this time, if you would like to ask a question. Please press star one on your Touchtone phone.

You may withdraw your question at any time by pressing the pound key.

And once again for your questions today, but its star one.

And we'll take our first question from Colin with UBS.

Please go ahead.

Hey, good afternoon, and congrats on all the progress.

Doug maybe you could just give us a quick update on.

When you expect to meet with FDA regarding the path forward and filing strategy Tonight. There is there one.

Assuming that Hasnt happened, yet and then.

Just quickly on your competitive fight about to initiate trials in the U S. So just wanted to update you on how you view them as a competitor there from a timing and.

Guess clinical profile perspective thanks.

Yes, Colin Thank you very much for both of your questions and actually particularly appreciate the first one because it gives me the opportunity to answer this for everyone.

The short answer is that as I've said before I said in the prepared remarks, and I'm going to be consistent about this we have said that we are going to talk to the FDA.

Aye.

And we will provide an update once we have concluded those discussions.

And.

I would.

Prefer not to provide additional color until we have all of those discussions completed and we are in a position to provide an update and then I promise you all we will provide an update.

In the interim as I've said many times.

The embark is very well powered placebo controlled study, we're very excited about it its recruiting and dosing and we are getting additional sites up and running.

Literally on a weekly basis and that will.

Enroll around the middle of this year and then we will have a readout next year and that ought to be the assumption of our pathway to approval both in the United States and around the world unless and until we hear something different.

As it relates to Pfizer, Yes, we did see that Pfizer announced date.

Recommence.

Study that had been placed on clinical hold.

For safety reasons.

Previously.

It doesn't affect US is the short answer we're focused on our program. We're focused on enrolling embark we're very very excited about it mark.

Embarks protocol.

Is it enjoys a very straightforward.

The entrance criteria and the like.

It is almost everywhere in the world in outpatient protocol.

Which will benefit not only the enrolment of the Embarq, but we will certainly benefit the label for embark as well.

Also im very happy to say enjoys a relatively very low <unk>.

Screen out rate, which as you know the screen out rate for SRP 9001 at <unk> 74.

Is less than 15%.

That does not appear to be the case with other cost drops.

So we're very focused on our program very focused on.

Continuing embark and I think that.

We see as our primary competitor Duchenne muscular dystrophy, and we take that very seriously and we're going to get embarked fully enrolled.

And then we're going to get that read out.

High conviction on the success of that therapy, and that we're going to get out there with the kids.

States and around the world with the success of the dark so thank you very much for that comment.

As a reminder.

Our one.

Also to ask that you limit yourself to one question.

Thanks.

Ryan with RBC capital markets. Please go ahead.

Hi, good afternoon, and thanks for taking my questions.

I think there's maybe a little bit of confusion around phase III timelines I was hoping you could clarify it sounds like nine shows here one enrollment is on track for mid this year. So when one considers screening and data analysis should we be expecting top line data release around mid 2023 or closer to year end and then maybe on a similar.

<unk>.

The Registrational path for <unk> I recognize you werent in a position to comment on the specifics of ongoing FDA dialogue, but just taking a step back should we be thinking about this.

Elevated approval or full approval or are there any middle ground expedited scenarios, we should contemplate such as maybe a rolling BLA with existing data and integrated one year analysis that you could update at the end of the submission the embarq data when that becomes available.

Yes, so embark is a 52 week study.

So we're fully enrolled around the middle of this year that means we will have data by around the middle of next year and of course, then we will have to ensure that we get a total weighted then and quality controls and all of the data, including the secondary endpoints of Biomarkers time, So I'm sure it'll be.

It'll be in the second half of <unk>.

Up next year and then our goal is to.

File as soon thereafter as possible and our goal is to file in 2023.

With respect to again I'm going to be careful I'm not going to provide updates until we have something to update on.

Embark is the goal of embark has a full approval just so we're very clear about that switching to embark for instance was an accelerated approval.

We intend to have dialogue with the division.

At the FDA about the potential for a <unk>.

Faster.

Approach the most obvious faster approach would be the use of the accelerated approval pathway to bring this therapy to patients with.

We certainly think the data justifies that dialogue, we have three studies of data we have exceptional expression, we have a very good and very superior safety profile, we have very consistent functional benefits across.

All of the studies, so I think that dialogue makes a ton of sense for us, but we will provide an update.

The outcome of those discussions when they are completed.

Okay. Thanks.

<unk> Cuda with credit Suisse.

Please go ahead hi.

Thanks for taking the question.

Just wanted to kind of timelines for study 103 data readout I think you've said that.

You would get that one year data before kind of it should publicly so should we expect that we will get one year one O three data with.

The FDA conversation update or could that be reported.

For that potentially.

We will.

At a medical meeting this year.

Luis and team are sort of mapping out right now we will provide an update on SRP 9001.

It will include some data from 103. It will include two year data for one or two part to some additional very inch.

Testing information, including an integrated analysis across our studies and that'll be that'll occur. This year, we don't have the time to share yet with it but working on that.

Well move next to Ciena with Barclays. Please go ahead.

Hi, This is Sean on for Gena. Thanks for taking all my questions. Maybe just two quick one.

When I saw the.

Approval pathway for all lines there was a one outside of the US frequently in Europe do you have any feedback from EMEA on the approval requirements is it only halfway for full approval or any other possibility for expedited process.

And another question is on the related revenue.

Train a sales milestone that.

You can receive from Roche I remember the total amount is one 7 billion could you give us some color on the breakdown of Nikola Tre versus commercial milestones there.

Sure I'm going to I'm going to leave the second question.

And so consistent with what we've said historically in the past.

Sticking to Europe , I just want to be.

Respectful of our very good partner Roche notched up in front of them I will note.

Just simply noting the theoretical level that there of course is the opportunity for getting into the sort of traditional approval in Europe and there is a more expedited pathway, it's different than the United States, but there is a.

Conditional approval pathway that exist in Europe , and I'm sure, we'll be thinking creatively together about which of those pathways makes the most sense for the patients that we serve.

With that you might want to touch briefly on milestones.

Yeah as it relates to the milestones we haven't broken out the exact details between the split between commercial or regulatory but the question. We often get is in terms of timing and when that is going to be.

<unk>.

Very late and regulatory.

Framework or obviously post launch that will be very back end loaded.

Milestone payments.

We'll take our next question.

Brian <unk> with Baird.

Go ahead.

Hey, good afternoon.

Okay.

Thank you for taking my question.

So I'm just going to answer the Pfizer a recent announcement I know that they're moving back into the clinic in the U S.

Moving into the phone it sounds like there are some restrictions on believe someday hospitalization period post dosing was just wondering can you remind us of any sort of protocol requirements. Nine years. There. One has proposed dosing is there an overnight observation period or or any sort of mandatory post dosing observation period. Thanks.

Other than in Japan, everything is outpatient positions obviously have.

Discretion, if they want to keep.

Keep a child over night, if they won but outpatient dosing and everywhere bunch of debt, so very different than the Pfizer protocols.

Okay.

Sure it's when it's informed by.

Experience that we both had with these therapies and the safety profile of Cabela's.

Okay.

Our next question comes from <unk> Gill with Needham <unk> Company. Your line is open.

Yeah.

Hey, good afternoon, everyone and congrats on progress in this quarter.

Just a quick one from us so assuming as Pfizer is going to be opening sites and me less.

It doesn't exacerbate.

Exacerbate that the competition for patients that usually go on our service.

If you have any commentary around that thank you.

I think the greatest.

Competition for Exxon to.

As director.

Dallas is noted for you earlier.

Based on this in the United States competes with embark.

It competes with <unk>.

Emission.

And I'm trying to remember Theres, a third one down you'll have to help me with it.

The momentum.

And the momentum of course and momentum.

For <unk> 50, it could be one but.

But notwithstanding all of that and that existed of course dragging into this year Exxon does.

<unk> grew fairly substantially versus the first quarter.

Last year versus the first quarter of this year and our guidance for the year has that in it. So we're not particularly concerned about it and then on the competition for patients for our relative gene therapies with.

Without being excessively snarky, we are not at all concerned about the demand that we have for SRP 9001 and embark.

Yeah, Thanks to retool with Cowen. Please go.

Go ahead.

Hi, guys. This is Sean Mcmullen affirmative two quick questions from US what updates are you presenting at the <unk> of this month and maybe PP&E also in June and then when should we expect topline data from the momentum study. Thank you.

Luis to undertake that.

At <unk>, we are presenting.

Preclinical data.

On cardiac outcomes for our 9001.

And then we'll be doing follow up presentations for our clinical programs consistent with Wayne.

Previously we.

We don't have any.

Sure.

Our power.

Glenn outlined PP&E.

Okay. Thanks.

Our ties with.

Oppenheimer <unk> company. Please go ahead.

Great. Thank you thanks for the question.

Just continuing on <unk> part.

And if you study actually had boys most of them over the age of eight during.

During 11, 13 10 years.

I think you just mentioned that Youre seeing about.

80, 85% of patients without that are still negative <unk> 74.

You can talk about your <unk> opportunity.

Yeah.

The context of quarter Boy also ex U.

And then maybe boys that might not get gene therapy I'm Tricia. Thank you.

Hi, Josh Thanks for that question I mean, one of the answers to that question right now.

Is that we don't know with certainty what the.

The impact will be on the PMO and PMO from the launch of gene therapy, and I think one of the things I've said.

Prior.

Earnings call was that we're making what I think is a relatively conservative assumption that there's going to be a pretty significant amount of cannibalization.

RNA technology, PMO, and maybe to a lesser extent PMO term gene therapy, but to your very good point.

Think there's reason to believe that's excessively conservative.

First things first let's start with the fact that there will be about 15% hopefully a little bit less than that release slightly under 14% of our sterile prevalent study tells us that will screen out and so we have solved the issue of <unk>.

Knocking down trees that neutralizing antibodies will screen out for gene therapy. There may be older children that have an opportunity to get on.

On RNA technology before they're able to get on a gene therapy, and so that opportunity will exist as well.

And I think.

There will be geographic area.

Having I have.

I've worked in countries outside the United States have launched products outside of the United States the vagaries of the various.

Systems outside of the United States are different region to region and sometimes not.

Perfectly aligned with what you might think it's perfect economic sense, but you have to do with budgetary issues and yearly budgets versus longer budgets and I think there is a real opportunity geographically as well to offer.

Some patients.

P PMO or PMO.

As well so I think there is a real potential.

Even if theres not co dosing.

For a significant amount of.

Of the use of the PMO and when the <unk> approved the PMO.

That's why we're going so strenuously.

Forward with the <unk>. It was just the way you know we will.

Just about double the number of patients that have a PM PMO available to them with the <unk> that we're working on pre clinically right now and all of that is booked for another.

Which is the concept that we might be able to to provide even greater longer term benefits to patients through the use of a one time therapy SRP 9001, and then a chronic therapy thereafter, there are issues associated with that first we need the science to support that conclusion.

And then we've got to do the final go economic work to justify that concept, but I think there is a lot of potential promise with our <unk> and that's why we're so excited about it.

And with that said I'll turn it over to <unk> a piece of this answer as well if I'm not mistaken.

I was actually I missed the second half of the previous questions about the readouts for momentum.

When that study part D is expected.

Complete enrollment at the end of the year and into.

<unk> 2008 week endpoint.

I expect to present the top line data in 2023, sorry for missing that.

Yeah.

Thanks.

Joseph with <unk> Securities. Please go ahead.

Hi, Thanks very much.

I was wondering if.

You can speak to the steroid treatment regimens being used and embark and how balanced they are between the treatment and placebo arms are there any key differences and.

Are you doing anything to.

Enhance the interpret ability of the data and the contribution from 9001.

In these patients when you report the data.

Thanks, Joe.

The board start to answer and the reason for getting new ones that I mentioned, we tell me, but the answer is they are identical.

Across both arms placebo controlled trial, all kids are on stable steroids before they entered the trial.

And then they both get the same regimen of stair mortgage, including the same regimen of pre dosing steroids as well as Luisa beginning new onset SMA.

That's accurate.

And the same.

Okay.

Okay.

Yeah.

With William Blair. Please go ahead.

Thanks for the question and I promise I won't ask a SBA question, but maybe one on the base business you mentioned that the exon 45 amenable population is larger than maybe originally expected can you dig into that a bit maybe how many patients do you expect a few years ago, what's your current thinking and is it.

Something that also kind of an ex U S phenomenon or just U S.

Well, it's definitely.

Whatever this phenomenon that we're seeing.

And then Darren you can take it from where I am.

And the project whatever we're seeing is definitely not a U S specific issue because we've seen it in the U S. You've seen it in Europe , as well and how it how is that the case, it's because why would we have seen it in Europe , because we have actions in Europe and one of the things we noted fairly early on and it caught us.

<unk>.

We caught us off.

Surprised us was that enrollment for for exon 45 went very fat realm.

Relative to what we would've expected from our experience with by August .

<unk> began to give us the view that there is perhaps a difference in the update versus what.

What we thought and that of course, we've launched the commercial therapy.

<unk>.

Uptake has been tremendous I do want to say.

I do really when I say significantly into our field base force our commercial colleagues in our medical affairs colleagues. There are a lot of that has to do with execution, we have gotten better and better and better.

And then they linger on that for a second to make the point, we have now had cumulative to $2 billion in sales, we've already achieved that as an organization.

We achieved the second $2 billion.

Significantly less than half the time of the first $1 billion.

And I think a lot of that has to do some of that push us to get approvals. Some of it has significantly to do with.

With execution the team really knows how to serve these patients communities none of them by the way has to do with price increases because we don't do price increases, we certainly have not yet since the inception.

As we look across that we don't know with certainty yet.

The prevalence rate is the <unk> between these two but I think there are some studies there was a study if I'm not mistaken.

Canada that would've put.

It was inconsistent with what the sort of the common.

Belief is but input.

Put the exon 45, maybe even above 10%, but we are standing behind that yet we don't know, but valid perhaps you have more insight into their CRM provider.

No just exactly what Doug has said and thank you for the question by the way I think historically all of the epidemiology that we were looking to share.

Showed the two populations the exon 53 amenable population in the 45 medical population, where the exact same size and its Doug.

As Doug.

And the first time that we got that this wasn't the case, where it was in our clinical development program and what we saw in the clinical development program is exactly what we see playing out right now in the commercial market.

And so that our assumptions are based on the alternate initial epidemiology and as Doug said there are some new publications that are more in line with what we saw in the clinical development.

Space and what we're seeing in the commercial market. So we're continuing to look at this as we go.

No.

Nothing obvious in terms of differences regionally as Doug said in the clinical development program.

Enrollment was with a global global trial, where we saw the same phenomenon. That's what we're seeing in this U S market.

Again, thanks for the question.

Once more for your question.

Yeah Juan.

Okay.

Kristen <unk> with Cantor Fitzgerald. Please go ahead.

Hi, good afternoon, everybody. Thanks for taking the question wanted to ask one around longer term plans of the company. So if you see this cannibalization around gene therapy and are able to solve the problem for the 15% or so of patients with preexisting neutralizing antibodies given the success you've seen would you.

Consider utilizing the PMO platform for other potential indications are areas beyond DMD.

Absolutely what were exploring that pre clinically right now, but perhaps luis is going to provide a bit more color on that.

Thanks for the question, we're extremely excited about the opportunities for keeping them on both ends.

One of my presentation, but then also other indications.

My phone, but also include other targets.

Target based on the PMO stability.

Penetrate CFO .

To come on that but we're certainly very excited about the opportunity for multiple indications.

Okay.

Well take our next question.

With <unk>.

Sure Henry.

Hi, Thanks very much for taking my question. So my question is on the LTE M. D program and sorry, if I missed if you had provided an update.

What about the mix up and also the timeline are you still working on the CMC issues and so do you have a plan to move the <unk> program forward or do you think given the prevalence the basket study will make more sense than youre trying to align.

On that point please.

Yeah. So first of all we are definitely exploring the concept of a basket study.

Which can be very interesting for us or at least a basket approach for all of the start of <unk>, but that isn't that is not delaying our activity with respect to <unk> and SRP nine years' year, three with respect to SRP 9003, the rate limiting step is is CMC I wanted to be very clear about.

What kind of CMC, it's not really the process development at all in fact, we've we've manufactured.

Therapy, so it's not about that and we've really benefited from all of the work we've done with SRP nine Joe Joe one.

Its the analytical work in getting all of the assays together one would assume that you could have sort of a generic assays across multiple programs such as not the case. There are a number of different assays that require them to be bespoke for each.

Particular therapy, but the good news is we know exactly how to do it we've done it with 9001 to great effect, we don't have to guess about that the process. It takes some time, it's a combination of design, but it's also testing in Paris to Jim and then testing. So it's it's moving along nicely not ever has.

Fast as I would want but I don't think there's anybody who thinks that I am.

Patient about anything.

But it's going to take a little bit of time, but we're on track, which would help get the assays can please louisa by if I misstated that.

Yeah.

Accurate.

I just will add that we are actively enrolling or our natural history study.

Jeremy or L. J M D and so that will certainly support it then.

<unk> had for our next phase of the trials in terms of patient identification.

And also understanding the natural history much long form are defined.

And that's enrolling well.

Yes.

Well take our next question.

Hey, Kim with <unk> capital. Please go ahead.

Yeah.

Hum.

Okay.

Denis.

I just wanted to ask a quick question can you just provide a bit more color about your statement that you made about the cost of sales very sad.

Uh huh.

Our write offs of certain batches of the company's products are not meeting a quality specification.

Sure I'll turn that to Ian here, Yes that was just related to this.

To be clear related to our PMO franchise that there there were a few batches.

Last year that.

Didn't meet our standards and therefore, we got them off but nothing too.

Nothing significant at all and didn't have any major impact.

We saw none of that.

This happens in some runs don't meet your qualification.

So from time to time it happens, we obviously didn't have any this quarter.

Yes.

For your question Star one.

Next to Catherine with Evercore ISI. Please go ahead.

Hey, Thanks for taking my question I'm, just wondering what the status of the essence confirmatory trial enrollment was if I look at the clinical trustees that enrollment should be done soon thanks.

And we should be fully enrolled by the end of this year.

Yeah.

Yeah.

Mark This morning Star one.

Next to Matthew <unk> with Morgan Stanley . Please.

Please go ahead.

Hi, Thanks for taking our questions. This is when John line from Matthew So wondering whether you already have any regulatory discussion with FDA about the LTE M D program.

Oh, the answer can be program I'm.

I'm sorry go ahead I apologize so if so then.

What the minimum requirement you are expecting from the recreation.

So apologies for having interrupted you, yes, so we haven't had.

Actual meetings with them we've had.

Written responses from the promote at.

It was about not mistaken last year, we haven't updated it we're going to have one comprehensive discussion with them. Once the CMC issues are in a position where we can we can have a discussion with them both about the clinical design as well as.

The and show them, the CMC and get their blessing on the manufacturing we had a general discussion with them.

Writing last year, and which day and independently interestingly enough Europe as well.

Firms the potential or.

For the use of beta <unk> Gan as a surrogate endpoint.

We obviously have additional.

Discussions that we need to have in a more concrete discussion about the actual development program, but certainly conceptually that there was an acknowledgment of that possibility.

And of course it makes.

Brilliant.

To remind everyone with respect to SRP 9003 that is a gene therapy that treats a very rare disease.

It's a disease that is characterized well characterized by the fact that it is.

Patients that are degenerating and dying as a result of the lack of a structural protein bar <unk> given the size of that gene SRP 9003 is able to deliver a construct that codes for the full length wild type data cyclical I can properly.

Localized.

And we're seeing very very good expression.

The kinds of expression that we see with 9001, we're seeing the kinds of safety.

That we see with 9001 clearly are 74 is performing very well and so the idea of using a more expedited pathway and using surrogate endpoints makes a ton of sense now we just have to get our CMC done and then we have to have some dialogue.

The division.

And get their concurrence on the design of that next trial that will get going on it hopefully get going on that and the other cycles like as well.

Got it appears there are no further questions at this time I would now like to turn it back to Doug for any closing remarks.

Well. Thank you all very much for joining us this evening and for your questions. We appreciate all of them were very excited about the progress that we've made we're very excited about our ability to serve the community that we serve and to continue to advance our research pipeline.

As we advance our development programs, including.

Including completing our pivotal trial enrollment for embark and including <unk>.

Completing our pivotal trial for <unk>.

We're a momentum as well and I look forward on behalf of <unk>.

All of the team at <unk> to provide additional updates as we gain additional progress over the course of 2022. Thank you all have a lovely evening.

Okay.

This does conclude today's program. Thank you for your participation you may disconnect at any time and have a wonderful evening.

[music].

Yeah.