Q2 2022 Sarepta Therapeutics Inc Earnings Call
Yeah.
The one one.
[music].
Ladies and gentlemen, thank you for standing by and welcome to Sarepta Therapeutics' second quarter 2020 Journeys Conference Call.
However, because of the growth of our revenue, from a net cash burn perspective, I actually expect it to be relatively flat for 2022 and 2023.
And from my perspective, it was the right decision to have approved Exondus in the first place.
Yeah.
Dear ladies and gentlemen, thank you for standing by.
Second quarter's Twenty-twenty Joinings conference call.
At this time, all participants are in a listen-only mode.
At this time all participants are in a listen only mode. After the Speakers' prepared remarks, there'll be a question and answer session. Just a question. During this session you will need to press star one one please.
After the speaker's prepared remarks, there will be a question and answer session.
To ask a question during this session, you will need to press star 1 1.
Please be advised that today's conference may be recorded.
Please be advised that today's conference maybe recorded I would now like to turn the conference over to you speak of Haas today, Mary Jenkins senior manager of Investor Relations.
I would now like to turn the conference over to our speaker host today, Mary Jenkins, Senior, Manager of Investor Relations.
I'll turn the PPMO question over to Luis, and then I'll comment on the interaction with the PPMO.
And I certainly think Lyondis and Amondis as well deserve the benefit.
Thank you, Livia, and thank you all for joining today's call.
Yeah, on the PPMO, we've submitted information to FDA and are waiting for their feedback, so we'll update as soon as we have the results from that.
They are benefiting patients significantly.
Earlier today, we released our financial results for the second quarter 2022. The press release is available on our website at sarepta.com, and our 10-Q was filed with, the Securities and Exchange Commission earlier this afternoon.
One moment for our next question.
With that said, there are going to be a lot of differences between this accelerated approval and the prior approval. The first of which, of course, is the amount of data that supports this. The data has really built from Exondus. The Exondus approval is a lot of data. It's a lot of data.
Thank you Olivia and thank you all for joining today's call.
Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, and Dr. Louise, Rodino-Klaypak.
And our next question, coming from Jelena of Salve Invicta with Goldman Sachs.
Your line is open.
Thank you.
Hi, thanks for taking our question, and congratulations on the feedback.
We were wondering, is there a way for us to make sure that we're getting the right information?
Earlier today, we released our financial results for the second quarter 2022 press release is available on our website that surround it outcome and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon.
On the call today are Doug Ingram and at the time boundary and Dr. Louise Rodino quite that after our formal remarks, we'll open the call for Q&A.
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.
Note that during this call we were making a number of forward looking statements. Please take a moment here.
Please take a moment to review our webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond, Sarepta's control.
Webcast, which contains our forward looking statements. These forward looking statements involve risks and uncertainties many of which are beyond <unk> control actual results could materially differ.
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.
From these forward looking statements and any such risks can materially and adversely affect the business the results of operations and trading prices for <unk> common stock for.
For a detailed description of applicable risks and uncertainties. We encourage you to review the company's most recent quarterly report on Form 10-Q filed with the SEC as well as the company's other SEC filings.
For a detailed description of applicable risks and uncertainties, we encourage you to review, the company's most recent quarterly report on Form 10-Q, filed with the SEC, as well as the company's other SEC filings.
The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances.
<unk> does not undertake any obligation to publicly update its forward looking statements, including any financial projections provided today based on subsequent events or circumstances.
And now I'll turn the call over to our President and CEO, Doug Ingram, who will provide an, overview of our recent progress.
We're going to fail, we're going to fail, we're going to fail.
And now I'll turn the call over to our President and CEO , Doug Ingram, who will provide an overview of our recent progress.
Doug?
Thank you, Mary.
Thank you Mary good afternoon, everyone and thank you all for joining US Therapeutics second quarter 2023 financial results Conference call.
Good afternoon, everyone, and thank you all for joining Sarepta Therapeutics' second quarter, 2022 financial results conference call.
And how the discussions in Europe are progressing for a potential faster path to approval?
The Exondus was approved on 12 patients.
Thank you.
We're not talking 12 patients.
I will discuss our outstanding quarterly performance in a moment, but given its importance to the, patients that we serve, to Sarepta, and in my view, to the entire field of gene therapy, I will begin by focusing on our progress this quarter with the largest near-term gene therapy, As you will recall, we previously disclosed that we were engaging with the U.S. FDA about the possibility of submitting a Biologics License Application, or BLA, for the accelerated approval of SRP 9001 to treat Duchenne muscular dystrophy.
Luis, do you want to take that call, that question?
But 90 paties for multiple studies.
I will discuss our automobile quarterly performance in a moment.
It is important to the patients that we serve.
The first part of the question, could you- I think the question is just-I think it's a split, and I'd say it's a-I think it's a good split.
The entire field of gene therapy, I will begin by focusing on our progress this quarter with the largest near term gene therapy opportunity in Biopharma.
Approximately 60-40 ambulatory to non-ambulatory VIP on that, so we'll model that if you think about the accelerated approval versus the full approval.
The functional results are concordant. They're significant.
<unk> <unk>, our gene therapy for the treatment of Duchenne muscular dystrophy.
That's correct.
The key values on them are .0001.
And then the European discussions are going well in our three countries.
As you will recall, we previously disclosed that we were engaging with the us FDA.
About the possibility of submitting a biologics license application or BLA.
The global trial with European patients included.
For the accelerated approval of <unk> to treat duchenne muscular dystrophy.
Certainly, our partners, Roche, are driving the next U.S. development and conversations and discussions with health authorities are proceeding well.
We also caution numerous times that we would not change our base case assumption on the timing of approval.
We also cautioned numerous times that we would not change our base case assumption on the, timing of approval unless we had strong conviction on the receptivity to an accelerated approval, BLA by the FDA. As we announced last week, our discussions are now complete and our base case assumption, has indeed changed.
Unless we have strong conviction on the receptivity to an accelerated approval BLA.
Yeah.
And obviously, our developments in the U.S. are going well.
As we announced last week, our discussions are now complete.
Base case assumption has indeed changed over the course of the second quarter.
Thank you.
Over the course of the second quarter, we engaged with FDA in an in-depth review with, the agency of the wealth of evidence that supports the safety and efficacy of SRP 9001 and the functional benefits associated with the robust expression of shortened functional dystrophy when treated with SRP 9001. This included the safety and tolerability data unique to SRP 9001, the preclinical of, animal models supporting its benefits, the various function-related biomarkers associated with the nearly 90 patients dosed with SRP 9001 across studies 101, 102, and 103, and the impressive and consistent functional results, which is, of course, NSAA and multiple time tests across those studies.
And our next question coming from the line of Colin Bristow with UBS.
Dave's with FCA.
In depth review with the agency of the wealth of evidence that supports the safety and efficacy of <unk> one.
Functional benefits associated with the robust expression of shortened a bit dysfunctional district, and when treated with SRP 9201. This.
This included the safety and Tolerability data unique to <unk>.
001, the preclinical animal models supporting it benefits the various function related biomarkers associated with the nearly 90 patients dosed with SRP 900 water glass studies, one O one one or two.
103.
The impressive and consistent functional reserve.
Results, which is of course NSA, a multiple time pest across both studies.
I would like to thank the FDA for its time its commitment and its input.
I would like to thank the FDA for its time, its commitment, and its input as the review, spanned multiple meetings and included input and guidance across the FDA, including CBER leadership, the Office of Tissues and Advanced Therapies, as well as the Center for Drug, Evaluation and Research, including its Office of Neuroscience and Office of New Drugs.
Your line, is open.
Hey, good afternoon and a big congrats on the progress.
Abuse spanned multiple meetings that included input and guidance across the FDA include.
Including Zebra leadership, the opposite tissues, and advanced therapies as well as the center for drug evaluation and research, including its office of neuroscience and office of new drugs.
So a few from my side, regarding, the discussions around the accelerated pathway.
Based on that review and the written guidance provided to SIREP the last week, we announced, that we intend to submit a BLA for accelerated approval of SRP 9001 to treat ambulatory patients that have Duchenne muscular dystrophy.
Can you give us any color on what was discussed regarding the sort of titering or product consistency issues in part one and sort of what FDA comfortable with this?
Based on that review and the written guidance provided to screw up the last week, we announced that we intend to submit a BLA for accelerated approval.
On the expression versus function data, this is something you've been teasing us with for a while.
SRP 9001.
To treat ambulatory patients that have Michelle muscular dystrophy, we intend to compile and submit our BLA. This fall we will hear whether an advisory committee has requested by the FDA after our BLA as filed with one as requested by the FDA, we would anticipated.
We intend to compile and submit our BLA this fall.
We will hear whether an advisory committee is requested by the FDA after our BLA is filed.
If one is requested by the FDA, we would anticipate it in the spring of 2023.
Spring of 2023, and we are planning and preparing for just that.
We are planning and preparing for just that.
Assuming a successful review, we anticipate approval and launch in mid 2023.
Assuming a successful review, we anticipate approval and launch in mid-2023.
To that end, in addition to completing and submitting our BLA, we are immediately readying, ourselves for what will be the largest gene therapy launch in the United States. That will include augmenting our commercial and medical affairs organizations, site readiness, and importantly, building sufficient inventory to serve the community at launch without delay.
This should be completing and submitting our BLA.
Immediately.
Ourselves for what will be the largest gene therapy launch in the United States that will include augmenting, our commercial and medical affairs organizations.
<unk> readiness, and importantly building sufficient inventory to serve the community at large without delay.
Okay.
As we prosecute our BLA, we continue to execute EMBARQ.
As we prosecute our BLA, we continue to execute embark that's all 120 patient pivotal trial for SRP 9001.
That's our 120-patient pivotal trial for SRP 9001.
The demand has been intense for EMBARQ and site initiation and enrollment ramped enormously, in the second quarter. Based on our current screen rate, we should be fully screened and enrolled in the next, few weeks.
Demand has been intense for embark in site initiation and enrollment ramped enormous weird in the second quarter.
Based on our current screen rates, we should be fully screened and enrolled in the next few weeks one of the concepts that have been discussed both within the FDA AD within Congress is encouraging companies to have their confirmatory trial confirmatory trial.
One of the concepts that has been discussed both within the FDA and within Congress is, encouraging companies to have their confirmatory trial underway at the time of an accelerated approval. We anticipate Embark to act as our confirmatory trial for an accelerated approval and Embark will be fully enrolled by the time our DLA is filed.
Underway at the time of an accelerated approval, we anticipate embarked to act as our confirmatory trial.
For an accelerated approval and embark will be fully enrolled by the time, our DLA as filed.
Furthermore, we anticipate dosing an additional cohort in study 103 to study what our research, informs us are what low-risk mutations in the currently excluded 1-17 range with the goal to narrow the exclusions to a low single-digit percentage by the accelerated approval time.
Furthermore, we anticipate dosing an additional cohort in study one or three to study what are researching forward with us.
Low risk mutations currently excluded one to 17 range with the goal to narrow the exclusions to a low single digit percentage by the accelerated approval time, we also intend to initiate a separate placebo controlled non ocwen non ambulatory studies later this year that study has designated study.
We also intend to initiate a separate placebo-controlled non-ambulatory study, later this year. That study is designated study 303 or Envision.
Area three or envision.
On the RNA platform, encouraged by seeing 18 times greater exon skipping and eight times, greater distribution production in half the time and one-fifth the dose of current standard of care, we initiated Momentum Part B, a pivotal trial for exon 5051, our next-generation RNA-based PPMO for the treatment of Duchenne patients amenable to skipping exon 51.
On the RNA platform encouraged by seeing 18 times greater exon skipping eight times greater dystrophin production in half the time at one step to go is a current standard of care.
We initiated momentum part D. A pivotal trial for us because one our next generation RNA based P. BMO for the treatment of Duchenne patients amenable to skipping exon 51.
While dosing continues globally, we announced in the quarter that FDA has placed a hold on, dosing in the United States while we provide additional information and context around cases of hypomagnesemia.
While they seem continues globally, we announced in the quarter that FDA has placed a hold on dosing in the United States, while we provide additional information and context around cases of Hypomagnesaemia. We've provided the requested information and we continue to guide to completion of enrollment for momentum part D. In the second half of <unk>.
We have provided the requested information, and we continue to guide to completion of enrollment for Momentum Part B in the second half of 2022.
'twenty two.
We've confirmed in momentum part D. S. O P 50, 51 could be a profound improvement over current standard of care. So at the same time, we are progressing with the preclinical work for additional <unk> to treat a greater percentage of the Duchenne population, our head of R&D and Chief Scientific officer, Dr. Louise Rodino quite back.
We've confirmed in, Momentum Part B, SLP 5051 could be a profound improvement over current standard of care.
So, at the same time, we are progressing the preclinical work for additional PPMOs to treat, a greater percentage of the Duchenne population.
Our head of R&D and chief scientific officer, Dr. Luis Rubino-Klepack, will provide further color on the performance of our R&D pipeline.
We will provide further color on the performance of our R&D pipeline now.
Now to quarterly performance.
Now, FDA has seen it.
And that hunts on everyone of them.
Now to quarterly performance.
The underlying biological activity is unequivocal, from my perspective, all of the benefits is unequivocal.
This afternoon, we announced another exceptional quarter of execution and performance as we continue to serve the duchenne patient community.
This afternoon, we announced another exceptional quarter, of execution and performance as we continue to serve the Duchenne patient community with our three approved therapies, exon is 51, myon is 53, and amon is 45. Total revenue for the quarter was approximately $233.5 million. Net product revenue was $211.2 million, exceeding consensus and growing almost 50% versus the same quarter last year. Given our overperformance, we are now raising our full-year net product revenue guidance, to between $825 million and $840 million.
Our approved three approved therapies, it's August one by honestly a degree.
And demand is 45.
Total revenue for the quarter was approximately $233 5 million.
Net product revenue was $211 $2 million.
Leading consensus and growing almost 50% versus the same quarter last year.
Given our over performance, we are now raising our full year net product revenue guidance.
Summarizing, I could hardly be prouder of the Sarepta team for their tenacious execution this quarter.
Between 825 million and.
At $840 million.
Summarizing.
Could hardly be prouder of the <unk> team for their tenacious execution this quarter.
Even as we serve the community with our currently approved therapies.
Even as we serve the community with our currently approved therapies, we made what could be a monumental leap in the advancement of SRP 9001 to the broader patient community.
What made what could be a monumental leap in the advancement of SRP 90012, the broader patient community.
My colleagues and I are confident that this work will translate into a better life for individuals and families living with Duchenne in the United States and around the world.
Colleagues and I are confident that this work will translate into a better life for individuals and families living with Duchenne in the United States and around the world.
I want to thank my Sarepta team.
I don't think Mike director team I want to thank our committed investigators and the patients who participated in our studies.
I want to thank our committed, investigators and the patients who are participating in our studies.
And I wanted to give a special thanks to the FDA for its prime and guidance as we progress all of these cohorts are necessary.
The success of SRP 9001.
And I want to give a special thanks to the FDA for its time and guidance as we progress.
When should we expect to see it?
And the safety is laudable as well.
And with that let me turn the call over to our head of R&D and Chief Scientific Officer.
All of these cohorts are necessary for the success of SRP 9001.
And then just finally, the letter that you got from FDA, who was the signatory on the letter?
Thank you.
Third release would be not quite that.
And with that, let me turn the call over to our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Kleinfeld.
Yeah, so I'll answer each of them in turn.
Louise?
So first of all, with respect to consistency, remember, the issue that occurred with respect to the clinical material previously that related to part one, didn't relate to part two of study 102, but it related to part one, had everything to do with the titering method that was being used by our partner Nationwide Children of Hospital. They had this supercoiled titering method that resulted in when we looked, at them with a more accurate and tighter titering method that we saw that 60% of the batches were less than the target dose.
We're not making a small amount of this functional protein, we're making robust amounts of it.
Luis.
Thanks, Doug.
The significant achievements, we've made recently with respect to FRP signs are there one our gene therapy candidate to treat Duchenne muscular dystrophy represents not just an important moment for us wrap that but more importantly for the patient community.
Thanks, Doug.
The significant achievements we've made recently with respect to FRP 9001, our gene therapy, candidate to treat Duchenne muscular dystrophy, represents not just an important moment for, Sarepta, but more importantly for the patient community. Notably, we announced this past Friday, July 29th, our intent to submit a BLA seeking accelerated, approval for FRP 9001. We're thrilled with this development as it speaks to the strength of the underlying science, and the data we've generated to date. I want to thank the team for all their work supporting this positive outcome and engaging, with the FDA, while also working on the BLA submission in parallel.
That doesn't exist anymore.
We're making upwards of 50% or more on blot.
So just to be very clear, even before we moved to our commercial manufacturing process itself, we had already developed a linear titering method that was far more precise.
Notably we announced this past Friday July 29, I intend to submit a BLA seeking accelerated approval for SRP 9001.
And then generally speaking, our commercial process is, you know, in really all regards, much tighter.
So we feel very good about the consistency of the process.
Generally speaking, we did, we showed everything at the agency, including all of the biomarker data, preclinical data, expression data, functional data, expression, CK, and function data together.
We're making over 70% on positive fibers.
Well look it's about <unk> of it.
Thanks to the strength of the underlying science and the data we've generated to date.
We're not going to provide additional updates nor do I really want to provide any sort of blow by blows in the agency.
And the intensity level is off the charts.
I want to thank the team for all their work supporting with positive outcome and engaging with the FBI. While also working on the BLA submission in parallel.
Due to this major effort, we are well positioned to submit our BLA this fall. The data we announced in early July, including important functional clinical results from, studies 101, 102, and 103, and our integrated analysis, will support this BLA submission. To remind you, studies 101 and 102 use clinical material, and study 103 uses commercially, representative material. I'll now briefly recap these results for you.
I think the obvious next step for us with respect to this therapy in the patient community is to get this BLA filed, get this BLA reviewed, and if successful, get this therapy to as many patients who would benefit as possible.
Think of this major effort, we are well positioned.
By this fall.
And then finally, as relates to the signatory on the letter, the letter that we received came from the head of CBER, Dr. Peter Marks.
If you've ever seen one of our immunofluorescent images, you should know they're not enhanced. And they light up enormously.
The data we announced in early July including important functional clinical results from studies 101, one O two and three and our integrated analysis.
We're not making a small amount of this functional protein.
Thank you.
It's unequivocal.
And the other thing that's going to be different is that our goal here is to win on the science with the division as a whole.
This BLA submission.
One moment for our next question.
To remind you that these one on one and two clinical material and study 103 is a commercially representative material.
Our next question coming from the line of, Richard Burrell with Collin Yelena Salfin.
Good afternoon, guys.
And that is exactly what we're going to do.
I'll now briefly recap. These result for you starting with anyone else III our endeavor.
Starting with study 103 for Endeavor, we showed that patients in cohort one with an N of 20, improved four points from baseline on NSAA.
Thanks for taking the question.
And I'm very confident about the approach that this team is going to make.
I think we've done extraordinarily good work over the last five-plus years in forging a very positive, science-based, respectful relationship with the agency.
Sounds like patients in cohort one at the end of 'twenty improved four points from baseline.
Yeah.
Pretreatment had a mean baseline NSAA of 22, and at week 52, improved to a mean of 26, approaching the top end of the NSAA scale. For example, these patients can now perform two activities unassisted that they were not, able to perform prior to therapy, or four activities that they needed assistance with that they now can do on their own.
I want to move to gene therapy inventory for a second.
And that will persist through the accelerated improvement.
Pre treatment had a mean baseline F 'twenty two.
And finally, I would note that with respect to the advice that we've received and the input that we've received in advance of our decision and conviction to submit this BLA, we have not been able to meet the expectations of the agency.
We have had broad-cross FDA discussions on this topic.
We had CBER leadership.
We had OCAT.
We could do to improve for me in 'twenty.
We had CDER. Inside of CDER, we had the Office of New Drugs.
We had the neurodivision.
So we've had a lot of discussions.
Approaching the top end of that.
None of that is to suggest that we're not going to have a full, robust review.
They don't pre-approve a BLA.
Yeah.
They approve a BLA for filing, and then we'll have a full review.
Example, these patients cannot perform two activities I system, but they were not able to perform privacy therapy.
For activities that go live at the system.
They now can give on that.
Equally impressive, SRP 9001 treated patients improved 3.8 points on unadjusted means, and, 3.2 points using least squared means at 52 weeks on NSAA, compared to the propensity matched external control group, with a P value of less than .0001. These results are impressive, as they demonstrate that commercially representative SRP 9001, increases motor function, and further confirms our confidence in the treatment effects of our therapy, increasing the probability of success for Embark for study 301.
Can you comment on the inventory that you have on hand, how long it's good for, and how much you intend to generate by the time of potential approval?
And then we may have an outcome.
Equally impressive SRP nine Jonesboro untreated patients improved three eight points on unadjusted and.
And the flip side of that is, how much progress have you made on centers that are qualified to administer the therapy?
And then hopefully, if all goes well, I certainly believe it would or we wouldn't be filing a BLA.
Three two clients you can lease square footage of 52 weeks an MSA.
<unk> to the propensity last external control group with a P value of less than 0.001.
These results are impressive as they demonstrate the commercially representative ethnarchy ideal zero, one improved motor function and further confirms our confidence in the treatment effect of our therapy.
Based on the probability of success or embark study 301.
Also, these data increase our level of conviction for Embark, because the same commercially, representative SRP 9001 material is being used in both Endeavor and Embark.
Also these day to increase our level of conviction from box because the same commercially representative FRP line here or there wasn't material is being used in endeavour and embark.
Speaking of Embark, our clinical operations team has also executed flawlessly, and as, a result, enrollment in this study is nearly complete.
I know that's something you guys have been working on like every single world muscle I've attended.
We'll have our approval.
And speaking of embark our clinical operations team has also executed flawlessly and as a result enrollment in the studies complete.
Can you talk to the number of centers and what the administration capacity is?
In summary, 31 O three demonstrated improvements across all key secondary functional endpoints such as time July 10 meter walk run time to account for steps and 100 meter walk right.
In summary, study 103 demonstrated improvements across all key secondary functional endpoints, such as time to rise, 10-meter walk-run, time to ascend four steps, and 100-meter walk-run. Based on these data, patients receiving SRP 9001 improved significantly on every functional, measure.
Yeah, so I'm going to turn this question over, the question on the center is to our head of customer interaction, Dallan Murray.
Just on these data patients receiving SRP 9001 improved significantly on every functional measure.
I'll now recap our long-term results.
But before I do that, on gene therapy inventory generally, we'll be in a very good place to launch the therapy.
But in that regard, this approach is going to be different than Teflon Checked.
Ill now recap on long term results.
We intend to be in a place where we can have sufficient capacity to launch this therapy without delaying and assuming that we are alone in launching our therapy to fully serve the community without delay. And we'll have by then, our anticipation is a couple of years of shelf life on therapy so we can build a robust amount of inventory to ensure that we can do that.
But I do want to say, with all of that said, we still have, The good news in the end of the day, with respect to the Teplisin, is that yes, we did the right thing.
These data are particularly important, because they answer two of our most common questions.
These data are particularly important because they answered two of our most common question are these data are clinically meaningful and must be a factor.
Are these data clinically meaningful, and is the effect durable?
First, we will look at our original four patients after four years of treatment on SRP 9001, from study 101. As a reminder, we conducted two analyses, NFAA change from baseline over 4 years in the 4 treated boys, and then in comparison to an external control group using propensity score weighting.
With that said, Dallan, perhaps you want to touch on the question about our centers of excellence.
And as a result of doing the right thing, a lot of patients have benefited.
First we will look at our behalf for patients after four years of treatment on SRP nine drills are one from study 101.
Yeah, thanks for the question, Ritu.
And a lot of patients have benefited in advance of what would be, if all goes well, a very transformative therapy.
As Doug previously mentioned, externally, the target is to do that is higher than, you know, a little bit north of 50 sites in total.
Yeah, maybe I'll just add, and Doug already said it, but I'll just kind of reiterate it.
And as you have noticed and seen at the prior WorldMuscles, we've identified this as a critical success factor and literally been working on it for years.
And 50 centers, because these are highly specialized neuromuscular centers, will treat more than 80% or up to 80% of the eligible population.
You know, we had just announced today that essentially Embark is practically fully enrolled.
We have seen this as a rate loader for prior gene therapy launches in terms of having sites ready to go and trained on day one.
As a reminder, we conducted two analysis and I say a change from baseline over four years for treated boys and then in comparison to an external control group using propensity score rating.
So essentially, we would have to wait about a year.
And so our aim for day one will be to allow, you know, to have enough sites ready to go to allow all eligible patients to be treated in a timely manner.
So there's really no incentive for us, other than Doug's good point about the patients, for us to move forward if we didn't feel that we were going to get a fair review and that there wasn't broad support across the agency.
And I certainly wouldn't, you know, obviously the market still remains challenging.
And we're not going to commit dollars unless we thought, you know, we were going to be successful in getting this patient to therapy. Obviously, to Doug's good point, you know, we have to go through the review, but we're not going to commit dollars in this market unless we thought that there was a good chance for an ultimate approval.
These data showed that patients in Study 101 demonstrated a mean increase of 7 points in total NFAA score from baseline in year 4.
Thank you.
These data showed that patients with study 101 demonstrated a mean increase of seven point in total NSA score from baseline and therefore.
Importantly, as these are older patients, around 9 years old at year 4, and because Duchenne is a disease that gets progressively worse, these patients would, according to the natural history of Duchenne, be in the steep decline phase of their disease.
And our next question coming from the line up.
Importantly, these are older patients around nine years all of that for them. Because this is a disease that got progressively worse. These patients one according to the natural history of Duchenne in steep decline came from their disease.
However, instead of declining, they have increased their function and maintained that increase, thereby demonstrating a distinct treatment effect that increases over time, supporting the durability of FRP 9001.
However, instead of declining and increase their function and maintain that increase, thereby demonstrating a distinct treatment effects that increases over time supporting durability SRP 9001.
Based on the individual patient-level data we showed, it's clear that all of these patients have remained stable and well above their baseline for this time period. No single patient drove the mean of the group.
Based on the individual patient level data. We showed it is clear that all of these patients have remained stable and well above their baseline for this country no single patient drove the name of the group.
Further, when we compared the treated patients to the propensity-matched external control, we observed nearly a 10-point difference on unadjusted means and a 9.4-point difference using least-squared means, with a p-value of 0.01 at 4 years.
Further when we compare the treated patients propensity matched external control.
Nearly a 10 point difference on unadjusted Mi nine four point difference evenly scrutiny with a P value of 0.01 at four years.
As an example, the FRP 9001 treated patients can now do 5 activities that those in the external control group were not able to accomplish. We are pleased to see that the treatment effect has continued to increase over time.
Example.
<unk> 001 treated patients can now be five activity, but those external control group, we're not able to accomplish.
Please proceed with the treatment effect has continued to increase over time.
It's also important to note that precipitous decline in years 3 and 4 of the external control group.
It's also important to note that precipitous decline in your three and four of the external control group. These boys are now in the steep part of the decline.
These boys are now in the steep part of the decline phase of their disease, whereas the treated patients remain stable.
Whereas the treated patients remain stable.
Moving now to our 2-year functional results from 20 patients who received FRP 9001 in Part 1 of Study 102. At 1 year, we saw a 3-point median difference between the FRP 9001 group and the external control group. At Week 96, this grew to a 5-point median NSAID difference with a p-value of 0.0001.
So that works for us.
Yun Sung with VTIG.
Moving now to our two year functional results from 20 patients visit the SRP 9001 part one study why don't you.
We can target some key centers of excellence, many of whom are already dosing with flugelsma.
One year, we saw a three point median difference between the SRP 9001 group and the external consultant at week 96. This grew to five point meeting NSA a difference for the P value of zero point, you know Theres a lot.
The fact that only approximately half the patients in the treated group received a target dose makes these results even more impressive.
The fact that only approximately half the patients initiated group receives a target dose makes these results even more impressive.
I will now review the integrated efficacy analysis for all patients in Studies 101, 102, and 103 who received a target dose of 1.33x1014 protected genomes per kilogram compared to an external control. In this integrated analysis of 1-year functional data from patients who received a target dose of FRP 9001, 52 in all, we showed that the treated patients improved 2.4 points in MSAA total scores from baseline. When compared to a propensity-weighted external control group, MSAA changed from baseline 1 year after treatment for the treated patients, with 3.1 points higher on unadjusted means and 2.4 points higher using least-squared means, with a p-value of less than 0.0001.
So, as you said, we're making progress and the plan is to have them ready to go on day one.
Your line is open.
I will now review the integrated efficacy analysis for all patients and studies on a one one or two or three who received the target, though 133 times kind of the 14th vector genomes per kilogram and parents of an external control.
I will say also two things.
Great.
And this integrated analysis of one year functional data for patients to receive the target dose of SRP 9001, 52, and all we showed that the treated patients improved two four points and MSA total scores from baseline when comparison propensity weighted external control group.
Certainly, we have a lot of work to do given that we're looking to an accelerated approval, which is a very tight timeline.
Thank you very much for taking the question.
With that said, and then that means we have real work to do and we want to approach it with an enormous amount of energy and humility.
It's a change from baseline one year after treatment for the treated patients were three one points higher on unadjusted mean, and two four points higher or you won't be scrubbing with a P value of less than zero.
But I would hope that over the last six years, we have shown the community what we can do to serve the Duchenne community with our therapies. The most recent results that we've seen with a quarter over a prior quarter growth of just about 50% hopefully gives people additional confidence that when SRP 9001 is approved, we'll be able to fully serve the community and robustly get that therapy to centers and also support centers in the appropriate use of the therapy so we get optimal results with patients, which of course is our goal.
So a follow-up question on the non-ambulatory patient.
As you can appreciate, these data now reinforce the consistency of MSAA improvement across three independent studies, and show mean improvements across key secondary functional endpoints, such as time-to-rise and 10-meter walk-front.
Our next question coming from the line of Matthew Harrison with Morgan Stanley.
Was that a study, the new study, required by the FDA during your discussion with the agency?
Or what.
As you can appreciate these data have reinforced the consistency of NSA improvement cop three independent studies.
So mean improvement across key secondary functional endpoints.
It is time to rise and 10 meter walk run.
We were also pleased to share expression data from all of the studies, which demonstrated consistency for both our clinical and commercial manufacturing processes.
We were also pleased to share our expression data from all of the studies with demonstrated consistency from both our clinical and commercial manufacturing.
Further, the safety profile of SRP9001 remains consistent and manageable with no evidence, of clinically relevant complement activation.
Further the safety profiles of <unk>.
Those are ones that are most consistent and manageable with no evidence of clinically relevant complement activation.
In summary, these new data and our integrated efficacy analysis have demonstrated that SRP9001, performs well above what natural history would predict and supports potential as a disease modifying agent.
Hi, thank you for taking our questions.
And based on your answers to the previous question, I guess it's not going to be part of the confirmatory study required, again, by the FDA.
In summary, with new data and our integrated efficacy analysis has demonstrated a husky Nashville marijuana performance well above what natural history would predict.
And secondly, just wanted to confirm the timeline.
Of course, the capsule is a disease modifying agent.
Now turning to limb girdle muscular dystrophy, or LGMD, programs in our gene therapy franchise.
This is Max Gore on for Matthew Harrison.
I believe you talked about potential accelerated approval around mid-year 2023.
Now turning to limb girdle, muscular dystrophy, where else AMD program and our gene therapy franchise.
For SRP9003 and our other LGMD programs, we continue to make progress with respect to, building the necessary steps of our manufacturing process, including LGMD-specific assay development and validation.
I guess this question can extend to Envision, but how are you managing variability in the Phase III in BARC trial?
So that should be before you get top-line data from the EMBARQ Phase 3 study.
It's actually an ideal for free and our other al Jumpy program, we continue to make progress with respect to building the necessary steps of our manufacturing process.
But what happens if the EMBARQ Phase 3 study misses the primary endpoint?
<unk> specific assay development and validation.
In addition, our natural history study, Jeremy, also continues to enroll and represents a, key component of our LGMD development pathway.
And do you think you can lower the standard deviation below, let's say, the four to five points we've seen in most of the natural history studies?
In addition, arent natural history studies, Germany also continues general.
Thank you very much.
That's a key component of our <unk> development pathway.
Our commitment to advance the best science and then translate that science into therapies, for rare disease patients around the world remains strong. The progress we've made to date based on the clinical evidence, as well as the dedicated, and tireless team of scientists and professionals positions us favorably to deliver on this commitment.
Louise, do you want to touch on the control that we have at Embark?
Our commitment to advance the best science and translate that science into therapies for rare disease patients around the world remains strong.
Sure, thanks for that question.
For one, I would say we have a great deal of learnings from 102 which we applied to study 301 or Embark.
The progress we've made to date based on our clinical evidence as well as dedicated and tireless team of scientists and professional.
It sounds a favorably to deliver on its commitments.
Thank you to the patients, families, and investigators for their role in bringing forth these important, therapies.
And so some of those included our inclusion exclusion criteria.
Thank you to the patients families and investigators for their role in bringing these important therapies.
I will now turn the call over to Dallin for an important update on our commercial activities.
One of the things we did was the rise time less than five seconds, for example, to ensure a population, Mahomet Juniors population.
Has that possibility come up at all during your discussion with the FDA?
I will now turn the call over to John for an important update on our commercial activity talent.
Dallin?
Thank you, Louise.
Having said that, our study is extremely well powered.
Would that be any room of flexibility, depending on how the data look like?
Thank you Luis.
In the second quarter of 2022, the team delivered double-digit growth across all three approved, RNA-based PMO therapies.
And given the recent study 103 results, it gives us even more confidence in 301 in terms of the outcome of that trial.
So the first question, the Envision North 3303, obviously, is our decision.
In the second quarter of 2022, the team delivered double digit growth across all three approved RNA based PMO therapies.
So we certainly have applied our learnings.
And we've been planning that for quite some time.
We eclipsed $200 million in net quarterly product revenue for the first time, generating, over $126 million for Exondys 51, $54 million for Armandys 45, and $30 million for Biondys, 53. This represents roughly 12% growth over the prior quarter and almost 50% compared to the, second quarter of 2021.
In addition, as Doug spoke to earlier, the consistency of our titering in addition to the learnings that we put into the inclusion exclusion criteria.
So that did not come up with the agency.
We eclipsed $200 million and net quarterly product revenue for the first time generating over $126 million for exon 50, 154 billion for a modest 45 and <unk>.
Thank you.
$30 million 453.
One moment for our next question.
This represents roughly 12% growth over the prior quarter and almost 50% compared to the second quarter of 2021.
We are thrilled with this performance, and in order to properly contextualize, it's important, to note that we experienced ordering volatility due to the July 4th holiday, which fell on a Monday this year. We believe that approximately $5 million may have been pulled forward from Q3 into Q2 as, a result.
Now, next question coming from the line up.
That was our decision.
We are thrilled with this performance and in order to properly contextualized. It's important to note that we experienced ordinary volatility due to the July 4th holiday, which fell on a Monday this year.
With respect to the timing, yeah, if all goes well, the accelerated approval would be in advance of a readout at EMBARQ.
Hey, good afternoon.
Thank you for taking my question.
We believe that approximately $5 million may have been pulled forward from Q3 into Q2 as a result.
I urge the analysts to incorporate this pull forward into their models for Q3.
I urge the analysts to incorporate this pull forward into their models for Q3.
As a result of our performance in the first half of the year, as you've already heard, I'm happy to say that we're increasing our full-year net product revenue guidance from over $800 million to a range of between $825 and $840 million.
And we haven't had detailed discussions about EMBARQ and its results.
As a result of our performance in the first half of the year as you've already heard from Doug I'm happy to say that we're increasing our full year net product revenue guidance from over $800 million to a range of between 825.
But on the other hand, we're very confident about EMBARQ.
$140 million.
As we mentioned on our first quarter earnings call, there remain a number of important factors, which could swing our final number in either direction for the rest of the year. These include competitive enrollment into some of our own clinical trials.
As we mentioned on our first quarter earnings call. There remain a number of important factors, which could sway our final number in either direction for the rest of the year. These include competitive enrollment into some of our own clinical trials.
They are somewhat hard to predict when it comes to the 30% of the Duchenne population, that we serve.
They're somewhat hard to predict when it comes to the 30% of the Duchenne population that we serve.
As such, we've provided this $15 million range, which we intend to narrow as we get closer, to the end of the year.
As such we provided $15 million range.
Which we intend to narrow as we get closer to the end of the year.
It goes without saying that I'm very proud of the execution and commitment across all, our teams at Sarepta, which enables this kind of success and growth.
Has there been a fundamental shift in how the FDA views gene therapy to proceed with a BLS submission with what feels like a priority review for a very broad population?
We're very well-powered.
It goes without saying that I'm very proud of the execution and commitment across all of our teams extra raptor, which enables this kind of success and growth.
And would you need to provide any biomarker data at month three from the Embark study to complement the BLA?
We're over 90% powered.
So we feel very good about it.
We were over 90% powered before we saw the readout on Study 102, Part 2.
Moving on to the performance of each of our three PMO therapies, Exondus 51 has continued, to generate strong double-digit growth as we approach the six-year mark post-launch, representing more than 23 quarters of growth and generating nearly $2 billion in cumulative revenue since the 2016 launch.
Thank you.
Moving on to the performance of each of our three P&L therapies.
Exxon is 51 has continued to generate strong double digit growth as we approach the six year Mark post launch.
Thank you very much for the question.
Representing more than 23 quarters of growth and generating nearly $2 billion of cumulative revenue since the 2016 launch.
The growth of nearly 8% over the first quarter of 2022 represents another successful effort, by the team in overcoming and managing the predictable headwinds caused by insurance changes at the beginning of each year.
The growth of nearly 8% of the first quarter of 2022 represents another successful effort by the team overcoming and managing the predictable headwinds caused by insurance changes at the beginning of each year.
The team continues their efforts to find new patients and overall, we expect very modest growth for <unk> 51 for the remainder of the year.
The team continues their efforts to find new patients and overall we expect very modest, growth for Exondus 51 for the remainder of the year.
By 153 grew more than 35% over the second quarter of 2021 and over 7% compared to the prior quarter.
Lyondis 53 grew more than 35% over the second quarter of 2021 and over 7% compared to the, prior quarter. We have continued our market leadership position in the Exon 53 amenable population and our, team is continuing their efforts to get new patients on therapy and maintain existing patients.
Continued our market leadership position in the exon 53 amenable population.
And our team is continuing their efforts to get new patients on therapy and maintain existing patients.
We don't expect any substantial changes with Lyondis in the coming quarters.
We don't expect any substantial changes with final onto us in the coming quarters.
A modest 45.
Amondus 45 continued its very successful launch with a second straight quarter of more than, 25% growth over the prior quarter.
It's very successful launch for the second straight quarter of more than 25% growth over the prior quarter. As we've previously mentioned the pace of both start forms and conversion on the therapy has been faster than our launches for <unk> and by August .
As we've previously mentioned, the pace of both start forms and conversion onto therapy, has been faster than our launches for Exondus and Lyondis.
As such, we expect the growth rate to start to slow in the coming quarters as we continue, to get more of the eligible population on therapy.
We expect the growth rate to start to slow in the coming quarters as we continue to get more of the eligible population on therapy.
The amount is 45 wash has been selective most successful to date and it's worth mentioning that the team used this launch as a dry run to sharpen our skills in execution.
The Amondus 45 launch has been Sarepta's most successful to date and it's worth mentioning, that the team used this launch as a dry run to sharpen our skills in execution as we prepare the team for a potential SRP 9001 launch.
As we prepare the team from <unk>.
Potential SRP nine years here one March.
Assuming a positive outcome from a regulatory perspective, this will not just be the most, important launch in Sarepta's history, but very likely the most important launch in the history of precision genetic medicine.
Assuming a positive outcome from a regulatory perspective. This will not just be the most important launch interruptus history, but very likely the most important launch in the history of precision genetic medicine.
I cannot emphasize enough how proud we are of our highly motivated team and the mission driven work. They do every day to support the nearly 30% of patients who are amenable to one of our three approved RNA based PMO.
I cannot emphasize enough how proud we are of our highly motivated team and the mission-driven, work they do every day to support the nearly 30% of patients who are amenable to one of our three ProDarna-based PMOs.
Look, I think that I think the agency's always been committed to gene therapy.
I am pleased with our current momentum and success in the first half of 2022.
I'm pleased with our current momentum and success in the first half of 2022 and for, our team's enduring commitment and unwavering execution.
And I think that justification for this accelerated approval BLA, which will be the first accelerated approval BLA in gene therapy.
And for Hurricanes enduring commitment and unwavering execution.
We'll continue to serve the Duchenne community with our PMOs while we evolve and prepare, ourselves to launch SRP 9001 for an even larger segment of the Duchenne population.
We will continue to serve the Duchenne community with our PMO, while we evolve and prepare ourselves for launch SRP. Neither zero one for an even larger segment of the Duchenne population.
Our work won't stop until we have effective therapies for all patients living with Duchenne, muscular dystrophy.
Work won't stop until we have effective therapies for all patients living with Duchenne muscular dystrophy.
And with that, I'll turn the call over to Ian Estepan for an update on our financials.
And, you know, in in vivo gene therapy, I think is a result of the data that we have.
And we now have even more conviction on the strength of the power.
And with that I'll turn the call over to E&S, Japan for an update on our financials.
Ian.
Thanks, Dallin, and good afternoon, everyone.
You know, I would remind you, this is not a scant data set that justifies this filing.
And it's only increased if you apply that.
Thanks, Alan and good afternoon, everyone.
This afternoon's financial results press release provided details for the second quarter, of 2022 on a non-GAAP basis as well as a GAAP basis. Please refer to our press release available on our website for a full reconciliation of, GAAP to non-GAAP financial results.
So we feel very good about where we are with that.
This afternoon financial results press release provided details for the second quarter of 2022 on a non-GAAP basis as well as the GAAP basis. Please.
Please refer to our press release available on our website for a full reconciliation of GAAP to non-GAAP financial results.
For the three months ended June 30, 2022, the company recorded total revenues of $233.5 million, which consists of net product revenues and collaboration revenues, compared to revenues of $164.1 million for the same period of 2021, an increase of $69.4 million. As a result, we are raising our 2022 total revenue guidance to a range of $905 to $920 million, and our net product revenue guidance for our R&A franchise to a range of $825 to $840 million.
Oh, by the way, I want to update.
I think I said 60-40 ambulatory non-ambulatory, the epi is more, I think.
For the three months ended June 32022, the company recorded total revenues of $233 5 million, which consists of net product revenue and collaboration revenue compares to revenues of $164 1 million for the same period of 2021, an increase of $69 $4 million.
Net product revenue for the second quarter of 2022 from our PMO exon skipping franchise with $211 2 million compared to 141 $8 million.
Same period of 2021.
Second quarter 2022 individual net product sales were $126 $4 million. For example, 50 $154 7 million for a modest 45 and $30 $2 million for <unk> 53.
The increase in net credit revenue primarily reflects.
Increasing demand for our product.
As a result, we are raising our 2022 total revenue guidance to a range of $905 million to $920 million and our net product revenue guidance for our RNA franchise to a range of $825 million to $840 million.
In each of the quarters ended June 30, 2022 and 2021, we recognized $22.3 million of collaboration revenue, which relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $26.4 million for the second quarter of 2022, compared to $18 million for the same period of 2021.
And each of the quarters ended June 32022, and 2021, we recognized $22 $3 million of collaboration revenue, which relates to our collaboration arrangement with Roche the Reimbursable co development costs under the Roche agreement.
$96 4 million for the second quarter of 2022 compared to $18 million for the same period of 2021.
On a GAAP basis, we reported a net loss of $231 $5 million or $2 65 and.
And 81.
$1 million or $1 <unk> per basic and diluted share for the second quarter of 2022 and 2021, respectively. We.
We reported a non-gap net loss of $103 million, or $1.18 per basic and diluted share, in the second quarter of 2022, compared to a non-gap net loss of $130.6 million, or $1.64 per basic and diluted share, in the second quarter of 2021. In the second quarter of 2022, we recorded approximately $37.8 million in cost of sales, compared to $19.5 million in the same period of 2021. The increase in cost of sales is primarily due to increasing demand for our products, and right off of certain batches of our products not meeting quality specifications for the three months ended June 30, 2022, with no similar activity for the three months ended June 30, 2021.
We reported a non-GAAP net loss of $103 million or $1 18 per basic and diluted share in the second quarter of 2022 compared to a non-GAAP net loss of $136 million or $1 64 per basic and diluted share in the second quarter of 2021.
In the second quarter of 2022, we recorded approximately $37 $8 million and cost of sales compared to $19 $5 million in the same period of 2021.
The increase in cost of sales is primarily due to increasing demand for our product and write off of certain batches of our product not meeting quality specifications for the three months ended June 32022 with no similar activity for the three months ended June 32021.
On a gap basis, we recorded $252.3 million and $239.6 million in R&D expenses for the second quarter of 2022 and 2021, respectively, a year-over-year increase of $12.7 million. The increase is primarily due to increasing in manufacturing expenses due to shortfall payment accrual related to our manufacturing supply agreement with Thermo Fisher, partially offset by decrease in upfront and milestone expenses during the second quarter of 2022, as compared to the same period of 2021.
On a GAAP basis, we recorded $252 $3 million and $239 $6 million in R&D expenses for the second quarter of 2022, and 2021, respectively. A year over year increase of $12 $7 million. The increase is primarily due to increasing in manufacturing expenses due to a shortfall.
Payment accrual related to our manufacturing and supply agreement with Thermo Fisher, partially offset by decrease in upfront and milestone expenses during the second quarter of 2022 as compared to the same period of 2021 on a non-GAAP basis R&D expenses were $234 million.
On a non-gap basis, R&D expenses were $230.4 million for the second quarter of 2022, compared to $220.7 million for the same period of 2021, an increase of $9.7 million.
For the second quarter of 2022 compared to $227 million for the same period of 2021, an increase of $9 $7 million.
Now, turning to SG&A, on a GAAP basis, we recorded approximately $154.3 million and $72.3, million of expenses for the second quarter of 2022 and 2021, respectively, an increase of $82 million. The increase was driven primarily by an increase in stock-based compensation expense due to, the CEO grant modification agreement executed during this quarter. It's important to highlight, though, that this is a non-cash expense.
Now turning to SG&A on a GAAP basis, we recorded approximately $154 3 million and $72 $3 million of expenses for the second quarter of 2022, and 2021, respectively, an increase of $82 million.
The increase was driven primarily by an increase in stock based compensation expense due to the CEO Grant modification agreement executed during this quarter. It is important to highlight though that this is a noncash expense.
On a non-GAAP basis, the SG&A expenses were $63.7 million, and for the second quarter, of 2022, compared to $54 million for the same period of 21, an increase of $9.7 million.
On a non-GAAP basis, the SG&A expenses were $63 7 million and for the second quarter of 2022 compared to $54 million for the same period, a 21, an increase of $9 7 million.
On a GAAP basis, we recorded $17 million in other expenses net for the second quarter, of 2022, compared to $16.2 million in other expenses net for the same period of 2021. The increase is primarily due to losses on disposal of assets during the three-month, end of June 30, 2022.
On a GAAP basis, we recorded $17 million in other expenses net for the second quarter of 2022 compared to $16 2 million.
In other expenses net for the same period of 2021.
The increase is primarily due to losses on disposal of assets. During the three months ended June 32022.
At the end of June 30 of 2022, we had approximately one nine to $1 $95 billion in cash cash equivalents and restricted cash and investments.
At the end of June 30, 2022, we had approximately $1.95 billion in cash, cash equivalents, and, restricted cash in investments.
So, for once, it's finally nice to be last in the lineup, because I actually get to conclude, by saying that we're absolutely thrilled with the feedback we received from the FDA for, 9-0-0-1.
We have nearly 90 patients worth of data. We have years of preclinical and animal data that shows how the surrogate endpoint, which is the 9001 protein, will perform. And then, you know, we translate it into patients and we've seen great results.
And, Dallin, you correct me, 50-50.
No.
I wanted to finally, Matt, but nice to be lapsing, the lineup because I actually get to conclude by saying that we're absolutely thrilled with the feedback we received from the FDA for <unk> and I think as everyone knows we previously gave our spend and managed our expenses and obviously very challenging market. However, based on the recent news you'll now be ramping up.
I just want to make sure I didn't mistake.
Is that correct, Dallan?
I think, as everyone knows, we've previously gated our spend and managed our expenses, and this is obviously a very challenging market. However, based on the recent news, we'll now be ramping up our manufacturing capacity and, further building out our commercial infrastructure so that we're prepared to serve the maximum number of patients with SRP 9-0-0-1, if approved by the middle of the year.
Yes, sir.
We've even seen great results over the longer term where you see what we would have anticipated and predicted, which is essentially a disease modifying therapy where you get a very significant benefit in the first year. And then as we would expect from a disease modifying therapy in a degenerative disease, you see that benefit grow significantly over time.
Our manufacturing capacity and further building out our commercial infrastructure. So that we're prepared to serve the maximum number of patients with SRP nine during their one if approved by the middle of the year I thought. It was also actually important to highlight though that due to the timing of these activities actually don't anticipate a material change in our spend for the remainder of the.
You saw at the two year mark in 102, we had a five point delta.
And then you look at these kids, small, I will admit, a very small cohort, but still pretty impressive.
I thought it was also actually important to highlight, though, that due to the timing, of these activities, I actually don't anticipate a material change in our spend for the remainder of the year, and I still expect our cash runway to extend into 2024.
A year and I still expect our cash runway to extend into 2024. So finally I just wanted to echo Doug's comments and thank the FDA for taking the time to evaluate our data and we look forward to the review of our BLA submission so with that I'll turn the call back over to Doug to start the Q&A.
So, finally, I just want to echo Doug's comments and thank the FDA for taking the time to evaluate, our data, and we look forward to the review of our BLA submission.
You see the, you know, nearly a 10 point delta versus natural history.
Closer to 50-50 in the estimated tribal populations.
And then finally on Embark, there has been no suggestion from the agency as we stand right now that that they would need to see additional information from Embark.
Apologies for that misstatement.
So, with that, I'll turn the call back over to Doug to start the Q&A.
Our next question coming from the line up, Brian Skorney with Verity, the line is open.
Doug?
Very good afternoon everyone, thanks for taking my question.
Thank you very much, Ian.
Thank you.
Livia, let's open the line for Q&A.
Just to add to the questions around the FDA discussion, I just wanted to see if you had discussed with the FDA at all the thought about expanding the placebo controlled portion of MBARC.
And our next question coming from the line-up.
Thank you very much and let's open the line for Q&A.
Certainly.
Sixian Xu with Bernberg.
Ladies and gentlemen, as a reminder, to ask a question, you will need to press star 1-1.
I know both the size and the follow up period of the placebo controlled portion of Essence was increased after Exondus' approval in order to have definitive results from a larger two year study.
I'm just wondering, was there any discussion about doing this for MBARC if the AA pathway relieves a little bit of the pressure to get an early approval?
Yeah, there wasn't.
No discussions like that have occurred.
Your line is open.
Certainly and ladies and gentlemen, just a reminder to ask a question you will need to press star one one.
Obviously, we have not proposed that.
Great, thanks.
Please stand by while we compile the Q&A roster.
Please stand by while we compile the Q&A roster.
Now, first question coming from the line of Anupam Rama with JPMorgan.
With respect to Essence, one of the reasons that we increased the size of Essence, and it was actually, I think initially it's a suggestion of the FDA, was to ensure that we had Essence properly powered. And so we did just that.
I want to add my congrats to the progress as well.
Okay.
The issue with respect to MBARC is, as we look at it right now, we're very well powered. So we're over 90%, strongly over 90% powering based on our analysis.
In fact, I would note that as we looked at the various potential ends, the highest end that we could look to at the time was 120 patients.
Just a few clarification questions.
And our first question coming from the lineup I know if I'm wrong with Jpmorgan. Your line is open.
So we feel very good about where MBARC is.
First, based on your communication with the FDA, I guess, has FDA explicitly encouraged you to file based on next Saturday approval?
Your line is open.
And secondly, I want to ask Ian around the SG&A OPTIC expense in the second quarter.
Hey, guys.
You mentioned that was primarily driven by non-cash stock options.
Thanks for taking the question, and congrats on all the progress.
Hey, guys. Thanks for taking my question and congrats on all the progress.
Can you talk about the factors that led FDA to get comfortable with a potential anti-inflammatory, vaccine?
Can you talk about the factors that led.
To get comfortable with.
Potential approval in all ambulatory patients versus something more age restricted supported seven year olds and how does this change the addressable population based on your market research.
Thank you very much function of accounting work as well on the bottom.
First of all.
I'm not going to do a lot of detail about the back and forth with the agency I give you the broad strokes answer.
At least speaking the way the got comfortable generally of course.
As our very.
Sure.
At the head of research and lower I would say that we have a wealth of data that supports it.
But there too.
And its benefits over a broad group of patients and so we think it's appropriate now given the guide that we have right now to file a BLA for <unk>.
So, I'm going to go ahead and turn it over to Anupam Rama.
And that's where we ended up, because we wanted to make sure we prioritized success in that trial.
Should we assume the expenses in Q3 and Q4 should come down substantially?
For the ambulatory population, there's no reason to believe that as a therapy as a benefit.
Anupam?
Great.
Thank you.
Yeah.
Thanks, Doug.
Yes, thanks.
So, as a reminder, to ask a question, you will need to press star 1-1.
Thank you.
Please stand by while we compile the Q&A roster.
One moment for our next question.
For the seven year old.
And that has shown repeatedly that it is multiple studies that would it be ineffective child wasn't younger or older.
It ultimately will not affect the addressable patient population I wonder you're very clear it is not our goal.
Tree simply be ambulant population as large as that population is as a percentage of entire duchenne. Our goal is to have the broadest possible label and the regulations will provide for that given the fact that the mechanism of action.
Now, first question coming from the line of Anupam Rama with JPMorgan.
Our next question, coming from Delana of HeartSus, thank you.
Our therapy is.
Really applicable.
Your line is open.
Your line is open.
Hey, guys.
Equally applicable across all age groups to the extent that patients have.
Skeletal muscle diaphragm muscle and cardiac muscle weather benefit from this shortened a functional dystrophin protein.
Approaching corporately localized so we've got to do additional work to get that label expanded.
Number of days, we will be doing we will start our non ambulatory study as I mentioned, it's called envision our study three as we were going to get that started this year.
Data from that even before it reads out there'll be a placebo controlled trial that will have data from that even before then we will have expression and safety experience that we can add to the expression of safety experience, we already have with non ambulatory patients as you may know in some of the cohort.
In study 103, we had with dose non ambulatory patients, including very much heavier patients over 80 kilograms and significantly older patients not ambulatory nearly 20 years old and that a few times. So this will add to that and then we would seek to supplement to expand the label beyond ambulatory. So.
The ultimate addressable population.
<unk> is our goal to make it all patients.
Great.
Thank you and just a follow up.
Obviously, the ambulant population is approximately 50% of the population. So if you were just modeling four to seven year olds.
You would at a minimum have to double the available patient population based on now in ambulant patient population at a minimum.
Thank you.
Yeah.
Thank you and our next question coming from the line of genome language Barclays. Your line is open.
I just got two questions.
And again, really nice update.
Thanks for taking the question, and congrats on all the progress.
Thank you for taking my questions also congrats on the accelerated approval path. So I have three parts of question.
On the FDA communication, what I would say is that based on our communication, and the written advice from the agency, we have enormous, we have significant conviction on the concept of submitting for an accelerated approval PLA.
Can you talk about the factors that led FDA to get comfortable with a potential anti-inflammatory, vaccine?
One is, I was just wondering, as you mentioned, you've had a lot of conversations with the FDA over the last few months.
Good morning.
Accelerated approval with the FDA feedback so what would the main endpoints that serve the basis of the submission of an accelerant approval and did the FTE validate the propensity way to control and lastly, do you expect FTE to request the embark data before accelerated approval.
So, as a reminder, to ask a question, you will need to press star 1-1.
Yes. Thank you very much so first of all I mean.
And now let's see, the first question coming from the line of Anupam Rama with JPMorgan.
If there was to be an adcom, can you just maybe speculate on what aspects could FDA focus on?
And we feel very good about the approach that we're taking.
They move to justify the accelerated approval of course is the totality of all of the evidence, including all of the employees and that includes even preclinical work.
Ultimate.
And the point that would it be the surrogate endpoint would be the lines of zero one.
Shortened the functional.
<unk> approach.
Protium.
That would justify.
Well, we certainly provided the entire data set including our propensity.
Alex I think it's a very compelling certainly played a significant role in dialogues that we've had with the agency and then as it relates to embark there was never a.
And then with that, Ian, perhaps you want to talk about the non-cash items.
Discussion or suggested by the agency that they either would require or wood away.
Barclays will be very drove or otherwise so that was a good wishes that arose at our multiple discussions with the agency.
Thank you.
I mean, would it be various efficacy databases?
Yes, thanks.
Thank you our next question.
Our next question coming from the line of Steven <unk> with RBC capital. Your line is open.
Your line is open.
Could it be the manufacturing?
So, as it relates to, yes, you're going to see the biggest this quarter.
There will be some smaller stock-based compensation expenses. Over the coming quarters, about $50 million that's spread out through probably over the next year.
Alright. Thanks. This is Steve on for Brian Congrats on the progress and thanks for taking our question could you share a bit more on what you've learned from reviewing the totality of the lenders are one data on the relationship between micro dystrophin expression and functional endpoints, including CK and what gives you comfort there that the FDA.
Hey, guys.
Could it be anything safety related?
So, much significantly less.
But remember, you know, the most important thing to think about here is that this is a, you know, this expense is non-cash charge.
So, it has no impact at all to our overall net cash flow.
And our next question coming from the line of Danielle Brill with Raymond James.
Your line is open.
This is aligned with.
With a relationship there between expression and function.
I mean, knowing full well, it's just pure speculation on the part, but I imagine you would have gotten a sense of where FDA is comfortable and where they're not.
Hi, guys.
I think what gives us comfort that we have multiple oil and gas.
Discussions and meetings.
And then just secondly, can you just remind us of the royalty or the tiering structure you have at Roche on XUS-04-SRP-9001?
Good afternoon.
But.
Lumen telephonic meetings.
The division.
Thank you.
Thanks for the questions.
Both <unk> capable leadership Cedar opposite drugs, the Euro Division, which has a particular expertise in district monopolies.
Sure.
Two quick ones.
And as a result of that we have significant.
Significant conviction based on written feedback we've received from the FDA that we ought to seek a BLA for accelerated approval. We used do you want to comment any further on.
I'll turn the royalty question over to Eden in a second.
Given the proximity of the anticipated accelerated approval to embark reading out, I'm curious to hear what you're thinking on the payers' front.
Look, thank you, Harkesh, for predicting in advance that I would be wildly speculating on the adcom.
Any of the underlying data or saturation.
I mean, I would say, look, we feel great about where we are. We've got an enormous wealth of data that justifies the approach that we're taking right now.
And certainly between our strength.
Strength of our data.
And the preclinical data on them.
Obviously, all of this is a review issue.
One for our preclinical data looking the.
Those are on dystrophin to function has.
Continue for all of our clinical studies, we see consistency across those kind of a clinical study with.
<unk> 9000, a lot just a fan on the.
The data component, but keep going back to that.
Totality of the data the expression data the biomarker data on functional data.
Hum.
Sure.
On the animal data.
<unk> exactly what we would've seen.
The studies that we've run we've run.
We will go on my watch.
Little bit I would remind everybody we have dose literally 90 patients just in study 101, one or two or country I'm not talking about Mark which as you know we will have in the next three weeks.
Fully enrolled that study and that will be another 60 patients before we cross the mobile.
We've seen very consistent results very consistent financial results.
101, one or two or three very very strong P values across it all of the underlying biological loggers.
Support the conclusion that the therapy provides significant benefit all the protein was properly localized at historical MLR acting as a shock absorber, one way or the division that is <unk>.
Suitcase, a very noisy endpoint and yet every one.
One of our studies, we see significant drops in CK that integrate into their share of the benefit.
We're also seeing in the functional results, both NFC and drive test all of which are concordance.
We've seen third party at muscle MRI that event.
<unk> quoted in the reduction of fat in fibrotic tissue.
There's just a wealth of totality of evidence that supports the conclusion from our perspective, the SRP 901 therapy and the results and shortened but functional protein, which was rationally designed over 14 or more years to both design and.
Review of natural history, and then empiricism justifies a conclusion that the that our protein is functional we have a very laudable safety profile.
We'll submit our BLA.
Is it possible that they'll drag their feet to implement coverage, or are you expecting full buy-in?
And on the basis of all of that plus the written feedback we've received from the FDA.
Certainly appropriate and we have an enormous amount of conviction about the pathway forward.
BLA for an accelerated approval for the <unk> population and then follow up with the amount of that population soon.
As soon as reasonably possible they are an important.
Part of our mission.
It'll be filed.
And then I appreciate that you've generated much more data at this point, but have you set a new precedent here, and do you anticipate that your competitors will follow suit with pursuing accelerated approval?
And our next question coming from the line of Judah Frommer with credit Suisse. Your line is open.
Thanks for taking the question, and congrats on all the progress.
Thank you.
Yeah, Hi, Thanks for taking my question and congrats as well on the progress.
We were just kind of curious given how close the timelines are between the accelerated BLA filing and the Embarq data coming out in your mind.
Is the accelerated BLA somewhat.
A low risk option.
To explore approve ability and does it in any way compromise if you didn't get the accelerated approval the ability to quickly file with the Embarq data thereafter.
To the point, where if it has not accelerated we should still be thinking about the same timelines for for a phase III violence.
Well first I'll answer the last question first which is this will actually speed up the.
Our discussion will be on a BLA would be agency, but so we're clear we would not file I want to be very clear about this we have said this.
Many times over the last many months.
Would not submit a BLA.
Or accelerated approval.
Unless we have developed.
Strong.
Evidenced based conviction.
The BLA would be well received and that we would get a very.
<unk>.
Reductive review so we don't see this as you know.
Our low risk issue would have been even easier for us to simply await the embarq readout now waiting for the Embarq readout and then compiling a BLA thereafter, and then filing a BLA after.
Timeline to get this therapy.
The children.
Ladies.
But as much as the year and given the feedback that is clearly the more appropriate and frankly ethical thing to do to submit a BLA for an accelerated approval and given the data that we have to get this therapy to Jacob as soon as possible I would remind you all that while the MTV. So estimate be very similar between those two scenarios.
So it is not the same answer for the children are waiting for this therapy every single solitary hours every single day not.
To be overly dramatic about it but it is not dramatic have objected to that.
Yes.
Horrible disease, the generating these kids and stealing from them their muscle. So we can get this therapy.
Prove on an accelerated basis, there will be thousands of children that will be we'll have had but that.
That muscle say it would have otherwise been lost as a result of that.
Can you talk about the factors that led FDA to get comfortable with a potential approval, in all ambulatory patients versus something more age-restricted to four to seven year olds?
Probably a year gap between what.
Traditional approval would be if we filed the BLA after embargoed out versus our ability to file a BLA now and get an accelerated approval for the ambulant population. So it is.
And how does this change the addressable population based on your market research?
But again I want to be very clear.
People that might say.
Almost sort of suggesting that there is a flyer now.
As a result of <unk>.
Significant.
In depth review and a significant number of meetings with the FDA what gave us the conviction.
Submit an accelerated approval BLA, which we won't be doing this call. Thank you very much for your question.
Thank you and our next question.
Thank you very much.
If all goes well, we'll have a very positive review.
Yeah.
Thanks for the kind words as well, Anupam.
Thank you very much for your question.
So, on the second question first, our ability to submit for our conviction around the BLA is unique to our therapy.
And the wealth of data that we have on our therapy, and the 90-plus patients across three therapies of data that we have, and the 14 years of clinical work that supports that, and the safety profile, which is unique. It's unique to SRP 9001.
And our next question coming from the line of Justin <unk> with.
With Bank of America. Your line is open.
So first of all, I'm not going to give you a lot of detail about the back and forth with, the agency.
I'll give you the broad stroke answer. Broadly speaking, the way the agency got comfortable generally, of course, as our very pithy head, of research and development would say, is the data.
Thank you all for joining us today and I hope you have a great rest of your day.
Hey, guys. Good afternoon, thanks for taking my questions.
You have said not to expect a meaningful uptick in expenses in <unk>, but as they ramp up commercial supply can you give us a sense of how expenses in 2023 could compare to this year and then separately can I ask on <unk> should we expect the next update either data wise are on task.
Thank you.
I totally agree with that given the fact that the mechanism of action of our therapy is equally applicable, it ought to be equally applicable across all age groups to the extent the patients have skeletal muscle, diaphragm muscle, and cardiac muscle that are benefitted from this shortened but functional distrapin protein properly localised.
So weÃve got to do additional work to get that label expanded.
Forward. Thanks.
Yes, it's a family friends with front, you'll see an uptick in opex, however, because of the growth of.
Our revenue from.
From a net cash burn perspective, I actually expect it to be relatively flat.
For 2022 and 2023.
Now I'll turn the call.
No question over to Luis I won't comment on that.
Interactions with a peak level.
Got it.
<unk>.
Submitted information to the FDA.
There are a number of things we will be doing.
We haven't been informed by the FDA that we're going to get an adcom.
And waiting for their feedback.
Davidson.
Okay.
We will start our non-ambulatory study.
We will prepare as if we're going to get an adcom.
Results from that.
Hi, gentlemen, my next question.
And our next question coming from the line of solving Mitchell with Goldman Sachs. Your line is open.
As I mentioned, itÃs called Envision or Study 303.
It wouldn't be at all surprising if we had an adcom.
WeÃre going to get that started this year.
Hi, Thanks for taking my question and congratulations on the feedback.
WeÃll have data from that even before it reads out. It will be a placebo-controlled trial, but weÃll have data from that even before then, because weÃll have expression and safety experience.
But we can add to the expression and safety experience we already have with non-ambulatory patients.
We were wondering if you would be willing to divide the population will be accepted label in younger patients as part of this accelerated approval process and how the discussions in Europe are progressing for potential faster path to approval. Thank you.
As you may know, in our cohort in Study 103, we dosed non-ambulatory patients, including much heavier patients, over 80 kilograms, and significantly older patients, non-ambulatory, nearly 20 years old.
WeÃve done that a few times, so this will add to that.
Luis do you want to take that call.
Question.
Then we would seek through a supplement to expand the label beyond ambulatory.
So the ultimate addressable population certainly is our goal to make in all patients.
The first part of your question could you.
I think the question is.
The split.
And I'd say that.
Approximately 60, 40, ambulatory and non ambulatory and VIP.
On that.
The model that if you think about the accelerated approval versus before approval.
That's correct.
The European discussions are going well.
Three outlines trials a global trial.
Our European patient concluded.
Certainly.
Partners are driving me ex U S.
It's about mountain conversations and discussions but.
Health Authority.
Are proceeding well and obviously our development.
Thank you.
If we had an adcom, we would actually invite it.
Are supportive of that as well.
Thank you and our next question coming from the line of Colin Bristow with UBS. Your line is open.
Just to follow up, obviously the ambulant population is approximately 60 percent of the population.
It would be another opportunity, frankly, for us to highlight our data about safety and efficacy and the like.
So if you were just modeling four- to seven-year-olds, you would, at a minimum, have to double the available patient population based on now an ambulant patient population at a minimum.
Hey, good afternoon.
Big Congrats on the progress.
So.
So it'd be.
Thank you.
I am sure that adcom would go into all of the issues.
It is on that basis that we're filing for accelerated approval.
Got into the discussions around the accelerated pathway can you give us any color on what was discussed with algorithms are sort of titratable product consistency issues in part one and sort of won't get FDA comfortable with this.
And our next question coming from the line of Gina Wang with Barclays.
Certainly, the CMC issues, although we feel very solid on the CMC issue.
And I don't think we're setting a new precedent.
Your line is open.
Obviously, on the ability of our SRP-9001 protein to predict clinical benefit, which I think the data is an understatement to say that it's powerful.
I think this is very consistent with the statutes and the regulations, and frankly, the precedent at the FDA about where an accelerated approval is appropriate.
On the expression versus function data. This is something you've been teasing us with us for a while now FDA has seen it when should we expect to see it and then just finally, the lessor that you got from FDA, who was the signatory on Melissa. Thank you.
Thank you for taking my questions.
We've got an enormous amount of data on that, given how many patients we've dosed, how many analysis we've done, and all of the preclinical work.
But I want to be very clear.
Of course, safety, but even on that, as we've said, of course, you have to take safety very seriously.
That decision stands on the data in front of us, which is unique to SRP 9001, and unique to the SRP 9001 protein, which is, from our perspective at least, unequivocally beneficial to patients. And we can safely deliver that therapy in great expression levels.
We have a very laudable safety profile, at least as we stand here right now.
As relates to payers, I would say as challenging as payers can be, we've forged a very positive relationship with payers over the nearly six years since the approval of Exondis.
Yes.
And so I don't want to make it seem easy.
Dallin and his team work every day and fight every day, to ensure that patients get on therapy and stay on therapy across our three approved therapies.
Can you give us in terms of first of all with respect to consistency remember the issue that occurred with respect to the clinical material previously.
But hopefully you will see in the results that we've had, which is, I used to say 20 quarters, it's 20-something quarters of positive quarter-over-quarter-over-quarter-over-quarter growth.
A calendar so far of over 40% compounded annual growth rate, and even a 50% growth over the same quarter last year, that given a therapy and having the opportunity to take that therapy to patients, we are a company that knows how to execute, knows how to work with payers, knows how to get this therapy not only delivered to the community, but get community, you know, support community, the community to support patients getting on therapy and staying on therapy with respect to chronic therapy, or in this case, getting therapy and getting it appropriately with respect to this one-time-two therapy.
So, you know, there's a lot of work to be done.
But I'm very confident that there is no better way.
That was related to part one didn't relate to part two of study one or two but it related to part one.
Had everything to do with tighter and method that was being used by our partner nationwide Childrens hospital. They had this supercoil tighter in the massive that resulted and when we looked at them with a more.
More accurate tighter and tighter and methods that we saw that.
60% of the.
Yes.
Batches were.
We're less than target does that doesn't exist anymore. So let's be very clear even before we move to our commercial manufacturing process itself, we had already.
Developed a linear tied to remarket that was far more precise and then generally speaking our commercial.
We feel good about all of it.
Process is.
Really all regards much tighter.
So we feel very good about the consistency of the process generally speaking we did we shut everything with the agency.
I'm sure if there was an adcom, we don't know that yet, if there was an adcom, we would expect them to explore all of those issues.
Including all of the biomarker data preclinical data expression data.
Functional data expression CK and function data together, we're not going to provide additional updates nor do I really want to provide any sort of blow by blow. The agency I think the obvious next step for us.
Again, I think the totality of evidence, That we have with respect to SRP 9001 and the justification for accelerated approval is very robust right now.
With respect to this therapy in the patient community.
Is to get this BLA file to get this BLA reviewed their successful get this.
<unk> had many patients who would benefit as possible and then finally as it relates to the signatory on the.
Letter.
The letter that we received came from the head of Subaru Dr. Peter marks.
Also, congrats on the accelerated approval path.
Thank you.
Thank you gentlemen, our next question.
Our next question coming from the line of Ritu <unk> with Cowen. Your line is now open.
So I have three parts of questions regarding the accelerated approval, the FDA feedback.
And our next question, coming from the line of Kristen Kluska with Cancer, Health, the line is open.
Good afternoon, guys. Thanks for taking the question I wanted to move to gene therapy inventory for a second can you can you comment on the inventory that you have on hand.
So what were the main endpoints that served the basis of a submission of an accelerated approval?
Hi, everyone.
Congrats on a very exciting quarter for the company.
How long, it's good for them and how much you intend to generate.
By the time of potential approval and the flip side of that is.
How much progress <unk> made on.
Centers that are qualified to administer the therapy I know thats something you guys have been working on every single world muscle I've attended.
Can you talk to the number of centers and what the administration capacity.
Yeah, so I'm going to.
Turn this question over.
Question on the centers to our head.
Customer interaction Gallagher.
And did the FDA validate the propensity-weighted control?
So, most of my questions have been asked, so I'll change topics a little bit here in gene therapy.
Before I do that on gene therapy inventory generally we are we'll be in a very good place to launch the therapy, we have chosen to be in a place where we can have sufficient capacity to launch of this therapy.
And lastly, do you expect FDA to request the EMBARQ data before accelerated approval?
So, based off the path you took with SRP 9001 and your discussions with the agency, has this changed how you might envision some of the trial designs for the limb girdle programs?
Without delay.
Assuming that we are alone in launching our therapy to fully serve the community without delay or will have by.
And, of course, I understand here that you'd want to see some supportive data before figuring, out the path forward, but any initial thoughts at this stage?
By then.
Presentation is a couple of years have a shelf life on therapy. So we could build a robust.
Mount of inventory to ensure that we can do that.
Yeah, thank you very much.
And Louise, do you want to touch on limb girdle?
That said, Alan perhaps you want to.
Got you on the question about Orange.
Centers of excellence.
Yes. Thanks for the question read Q&A as you have noticed and seen it.
Sure.
<unk>.
World muscles, we've identified this as a critical success factor.
Literally been working on it for three years.
Thank you for that question.
We have seen this.
Rate limiter for prior gene therapy launches.
In terms of having sites ready ready to go in and trained on day, one and so on a per day, one will allow us to.
So, there's a, ton of work going on in limb girdle at SRP.
<unk>.
Enough sites ready to go to allow piece all eligible patients to be treated.
Timely manner, so as Doug previously mentioned externally.
As you know, we have five programs, and we've been working hard on all of the CMC-related activities, including the LGMB-specific assays to support the program. Certainly, all of the data that we've collected with SRP 9001 is supportive of the limb girdle program using the same RE74 vector and the, promoter, in many cases, and delivery method.
And so, the data that we generated today is supportive.
We also have our data, which we've shared with limb girdle 2E, that has been very promising in both expression and functional results as well.
The target is to do that is higher than a little bit north of 50 sites.
In total 50 centers.
And so, we're taking all of that collected data and, obviously, learnings from our pathway with 9001 to apply where we can.
These are highly specialized neuromuscular centers.
More than 80% or up to 80% of the.
Eligible population so that works for us we can target some key centers of.
Many of whom are already dosing with skill transfer so.
These are obviously smaller populations, but there's a lot of learnings that we can apply, and we're moving swiftly to get to our next set of trials in the limb girdle.
As you said, we're making progress and the plan is to have them ready to go ready to go on day one.
So, thanks for the question.
I will say also Tuesday.
Certainly we have a lot of work to do given that we were.
Working through an accelerated approval, which is a very tight timeline with that said and then that means we have real work again, we wanted to approach it with an enormous amount of energy and humility.
But I would hope that over the last six years, we have shown.
The community what we can do to serve the Duchenne community with our therapies most.
The most recent results that we've seen with the quarter over prior quarter growth or just about 50% hopefully gets people additional confidence that when <unk> zero. One is approved we'll be able to fully.
The community and robustly get that therapy.
The centers can also support centers.
Appropriately use of the therapy. So we get optimal results for patients which of course is our goal.
Thank you.
And our next question coming from the line of Matthew Harrison with Morgan Stanley . Your line is open.
And our last question, coming from the lineup, Gavin Clark-Gartner with Ivocora SI.
Hi, Thank you for taking our questions. This is Mac score on for Matthew Harrison.
Your line is open.
I guess this question can extend to envision, but how are you managing variability in the phase III embark trial and do you think you can lower the standard deviation below lets say the 4% to five points we've seen with.
We've seen it most of the natural history studies. Thank you very much.
Sure Rich do you want to.
Touch on the.
The controls that we have in embark.
Sure. Thanks for that question.
For one I would say we have a great deal of learnings from one or two which we applied to study 301 are embarked on its own.
Including our inclusion exclusion criteria.
One of the things we get the right timeline five seconds for example.
To ensure a population.
Jamie its population, having said that our study is extremely well powered and given the recent 71 of three results against us even more confidence in me.
<unk>.
And 301 in terms of the outcome of that trial and you certainly have applied our learnings.
In addition.
Earlier.
The consistency of our catering in addition to the right.
With that we put into the inclusion exclusion criteria.
Yeah.
Thank you and we will make my next question.
And our next question coming from the lineup.
<unk> <unk> with Guggenheim. Your line is now open.
Hey, thanks for taking the question.
Hey, good afternoon. Thank you for taking my question.
Just two.
And has there been a fundamental shift in how the FDA views gene therapy to proceed with a BLA submission with what seems like a priority review for a very broad population and would you need to provide any biomarker data at month three from the inbox studied the complement of BLA. Thank you.
I just wanted to ask if you could give any more, granularity around the status of the CMC work and thoughts on the timeline for engaging with the FDA.
Thank you very much for the question look I think that.
Is it maybe a later this year thing or more like a 2023 event?
I think the agency has always been committed to gene therapy, I think the justification for this accelerated approval BLA, which will be the first accelerated approval BLA in gene therapy.
So first of all, to justify the accelerated approval, of course, it is the totality of all of the evidence, including all of the endpoints, and that includes even preclinical work.
Thanks.
On limb girdle in particular?
In in vivo gene therapy.
As a result of the data that we have to remind you. This is not a scan data set that justify those filings.
Nearly 90 patients worth of data we have.
The ultimate endpoint that would be the surrogate endpoint would be the 9001 shortened functional glycerin protein.
Here's the preclinical and animal data that shows how the surrogate endpoint, which is the 9001 approach and will perform and then we.
Translated into patients and we've seen great results, we didnt see a great results over the longer term, where you see what we would have anticipated and predicted which is essentially a disease modifying therapy, where you get that you get a very significant benefit in the first year and then as you would expect from a disease modifying therapy.
A degenerative disease, you'll see that benefit grow significantly over time and you saw the two year Mark in one or two out of five by Delta and when we look at these kids small I will admit a very small cohort but still.
Creating impressive you'll see.
The nearly a 10 point delta versus natural history, and then finally on <unk>.
Embarked there has been no suggestion from the agency as we stand right now.
That they would need to see additional information from embark.
Yeah.
Yeah.
Yeah.
Our next question coming from the line of Brian Koning with Baird. Your line is open.
Okay.
That would justify.
Yeah, for limb girdle.
Hey, good afternoon, everyone. Thanks for taking my question.
You know, we certainly provided the entire data set, including our propensity analysis, and I think it's very compelling.
Yeah.
It certainly played a significant role in the dialogue that we had with the agency.
Just.
To add some of the questions around the FDA discussion do you want to see if they're there.
You had discussed with the FDA at all the thought about expanding the placebo controlled portion of embark I know both the size and the follow up period of the placebo controlled portion of essence was increased after <unk> approval in order to have.
Afinitor results from a larger to your study I was just wondering was there any discussion about doing this for embargo, but a pathway.
Leaves a little bit of a bit of a pressure, but I got an early approval.
And then as relating EMBARQ, there was never a discussion or a suggestion by the agency that they either would require, or would await any of the EMBARQ data, either interim or otherwise.
Yes, there wasn't.
Just like that have occurred obviously read we have not proposed that.
With respect to asset was one of the reasons that we.
So that was a good issue that arose in our multiple discussions with the agency.
<unk> increased the size of vessels and it was actually I think initially at the suggestion of the FDA was to ensure that we had absolute properly powered.
Thank you.
So we did just that the issue with respect to embark is as we look at it right now we're very well powered.
Thank you.
Over 90% strongly over 90% powering based on our analysis. So we feel very good about where embark is it that I would note that.
As we've looked at the various potential at the highest end and that we could look to at the time was 120 patients that's where.
That's where we ended up because we wanted to make sure we prioritize success in that trial.
So, we're trying to get good looking.
Alright, Thanks, a lot.
Thank you.
One moment for our next question.
Our next question.
Our next question coming from the lineup, Stephen, Mellon with RBC Capital.
We are working hard on the CMC for our limb girdle, program. There's a lot of work to be done.
And our next question coming from the line of our testing your line is open.
Your line is open.
We've learned an enormous amount that we can capitalize on as a result of SIP-9001.
Great. Thank you for I, just got two questions and again really nice uptake.
We've already put the same capsid, the same promoter with respect to many of our limb girdles, but a lot of it is just takes time, and it's an empirical process to build some of these assays in particular out.
Hi.
One is I was just wondering as you mentioned you've had a lot of conversations with the FDA over the last few months.
If it wants to be an AD com can you just maybe speculate on what aspects could FDA focus on I mean would it be various efficacy database is could it be the manufacturing could it be anything safety related.
Thanks.
Knowing full well that is just pure speculation on my part, but I imagine you would've gotten a sense from where.
FDA is comfortable in where they're not and then just secondly can you just remind us of the.
The royalty or they're cheering structured Roche on ex U S for SRP nine days. Thank you.
This is Steve.
Sure I'll turn the alter the royalty question everybody said, yes look I think you guys were predicting in advance that I would be wildly speculating on the AD drop I mean, I would say.
I'm for Brian.
Congrats on the progress and thanks for taking our question.
Look we feel great about where we are we've got and then norm a wealth of data that justifies the approach that we're taking right now obviously all of this the review issue, we'll submit our BLA it'll be filed if all goes well we'll have a very positive review we haven't been.
Can you share a bit more on, what you learned from reviewing the totality of the 9001 data on the relationship between microdistrofrent expression and functional endpoints, including CK? And what gives you comfort there that the FDA is aligned with the relationship there between expression and function?
Thanks.
I mean, what gives us comfort is that we had multiple in-depth discussions and meetings live, but, you know, a room and telephonic meeting with their division, both OTAC, CBER leadership, CBER, Office of New Drugs, the neurodivision, which has a particular, expertise in dystrophinopathies.
Informed by FDA that we're going to get an AD com, we will prepare as if they're going to get an answer on that wouldn't be at all surprising if we had and that we would actually invited we're excited to be another opportunity frankly for us the highlight.
Our data both safety and efficacy and the like are there regarding and I am sure that AD Com would go into all of the issues certainly the CMC issues already feel very solid on the GNC is obviously.
On the correlate.
The ability of our SLP I hear a zero one protein too.
To predict clinical benefit which is the data.
I think it is an understatement to say that it's.
That it's.
Powerful we've got an enormous amount of data on that given how many patients. We've dosed have any analysis, we've done and all of the preclinical work and that of course safety, but even on that as we said of course.
Or would you have to take safety very seriously we have a very laudable safety profile at least as we stand here right now so we feel good about all of it I'm sure that there wasn't a drop I don't know that yet there wasn't a outcome, we would expect them to explore all of those issues, but again I think the totality of evidence.
And as a result of that, we have significant conviction based on the written feedback we've received from the FDA that we ought to seek a BLA for accelerated approval.
We feel very good about where we are and how this review would track.
That we have with respect to SRP 901, and the justification for accelerated approval.
There is.
Very robust right now we feel very good about where we are and how this review would track.
Yeah, and then as it relates to our royalty arrangement of the brooch, it's based on extra sales and surprisingly, the actual royalty rate is, you know, goes from low double digits to the high teens.
Yes.
As it relates to our royalty arrangement with Roche.
Based on ex U S sales and surprisingly.
The actual royalty rate.
Those from low double digits to the high teens, and that's actually based off of our manufacturing yield though determined the exact level.
Louise, do you want to comment any further on any of the underlying data or situation?
I'll add that certainly between the strength of our data was in the preclinical data and what we've learned from our preclinical data, linking the 9001 dystrophin to function has continued through all of our clinical studies. We see consistency across those clinical studies with 9001 dystrophin.
And Ken win win win for our next question.
And the data is compelling, so I'll just keep going back to that.
And that's actually based off of our manufacturing yield, though, determined the exact level.
So, we're working like mad.
The totality of the data, the expression data, the biomarker data and functional data is what bore us.
Our next question coming from the line of Tim Lugo with William Blair. Your line is now open.
Thank you for our next question.
Okay.
Congratulations on all the progress for our locations during the quarter.
And you.
You mentioned that the expression and safety data from the non ambulatory study would be available around the time of a potential approval.
Our next question coming from the line of Tim Lugo with William Blair, Eliana is open.
Is that something that could be available.
Supplemented in the filings is that something that could be available prior to approval prior to an outcome. I guess can you just talk a bit about.
When that could come out through 2023.
Yes. Thank you very much for the question and thank you very much for making the point that I hope, we all make in which is the.
The animal data that predicted exactly what we would have seen in the studies that we've run, we've run.
Congratulations on all the progress for patients in the quarter.
Lelise, if you want to touch on any of these issues in more detail, but I do think we're working hard to try to get a lot of this done this year.
We certainly have learned in the development of the assays that for each of the limb girdle subtypes there are still specific assays that have to be developed for each one, such as Doug alluded to, it takes time, so that's what we're working on.
The importance of this accelerated approval pathway.
It is of course important to see that that is of course important in my opinion to the entire field of gene therapy.
And, you know, you mentioned that the expression of safety data from a non ambulatory study would be available around the time of a potential approval.
But it is particularly important to these patients because that is the primary motivator for all that we can that we're successful. This accelerated approval there will be in the United States thousands of patients who would have been the generating over a period of time when at least from my perspective. They will have a therapy that will be of great benefit to the service and then Paul.
Is that something that could be available, you know, or kind of supplemented in the filing?
The short answer on your other question as we I can't speculate on that right now that's not a topic that has been discussed with the agency and it is something that we're going to have to do.
Consider it.
Candidly, whether whether there is a value to whether it would be received and whether we would be capable of providing.
Out of the envision study or studies ERP any additional safety or expression data that's never been discussed with the FDA would have to discuss it internally our primary goal with respect to the non ambulatory population right. Now is to get that study started a year working on getting that that study started as soon as possible and we certainly want to do that.
Thank you and our next question coming from the line of Gill with Needham Your line is open.
We'll just keep, you know, we'll kind of go on, we'll actually run a little bit.
Is that something that could be available prior to approval prior to an adcom?
There's only so fast one can go in.
I would remind everybody, we have dosed nearly 90 patients just in study 101, 102, and 103.
I guess.
You have to rely upon some of the preclinical studies that support these assays, but we're working like mad on that and understand that it's a high-priority plan.
Good afternoon, and thank you for taking our questions and let me add my congratulation, especially considering what this means for patients.
I'm not talking about the mark, which as you, know, we will have in the next few weeks, I think, fully enrolled in that study.
Can you just talk a bit about when that could come out to 2023?
Thank you, and I'm showing no further questions at this time.
So in 2023, who might be facing a world that has both gene therapy and CMO at the same time in similar patient populations.
What kind of sales dynamic you might see between these two populations do you think patients are going to switch or go on monotherapy and maybe go down to another.
And that'll be another 60 patients before we cross them over.
Yeah, thank you very much for the question.
Thank you.
Yeah. So there's a lot that we have to.
There's a lot of modeling we have to do with respect to the best and then some of it will just be empirical as we launch the therapy. Our current plan assumes a significant amount of cannibalization I would say with respect to the initial approval, which would be for the ambulant population, obviously, we still have the PMO.
And we've seen very consistent results, very consistent functional results in the 101, 102, and 103. Very, very strong P-values across it, all the underlying biological markers support the conclusion that this therapy, provides a significant benefit.
And CK, you know, CK is a very noisy end point.
All the protein is properly localized to the sarcolemma, acting as the shock absorber one would have envisioned it is.
And yet, in every one of our studies, we see significant drops in CK.
And, you know, thank you very much for making the point that I hope we're all making, which is the importance of this accelerated approval pathway.
It is, of course, important to us.
We are available to the non ambulant population. So it shouldn't have any impact there and beyond that we see.
Think there is potentially a very compelling argument.
Or the PMO to continue even in patients who are planning to or have received gene therapy for a host of reasons.
That is, of course, important, in my opinion, to the entire field of gene therapy. But it is particularly important to these patients.
First reason is that there is already evidence in the literature.
And that is the primary motivator for all of this. We can, if we're successful with this accelerated approval, there will be in the United States thousands of patients who would have been degenerating over a period of time when, at least from our perspective, they will have a therapy that will be of great benefit to them.
Support the proposition that there is a benefit to patients getting on a PMO in advance of gene therapy that it would in fact, not only protect them in advance of gene therapy, which is of crucial importance, but also that it might actually enhance expression and the benefits of gene therapy.
Apologies.
The short answer on your other question is, you know, I can't speculate on that right now.
That's not a topic that has been discussed with the agency.
And it is something that we're going to have to consider independently, whether there is a value to whether it would be received and whether we would be capable of providing out of the envisioned study or study three or three, any additional safety or expression data that's never been discussed with the FDA.
And we'd have to discuss it internally.
If one is on a PMO or <unk> got to prove the PG amount and then the coexistence of those two there may very well be a benefit to patients and we're doing some work on that right now from a preclinical perspective.
And then as I said before there will be certainly patients who will have available to them either in United States around the world.
Our primary goal, with respect to the non-ambulatory population right now, is to get that study started. And we're working on getting that study started as soon as possible.
<unk> technology and knowledge in therapy, or gene therapy, or not and so I think there is a particular value.
Both the patients and choose or opt out of having both of these modalities coexist. So while our current modeling is relatively conservative and assume that a significant amount of cannibalization, we're going to have to play this out and see if that is actually the case over the long run.
Therapies coexist.
And we certainly want to do that.
Thank you.
I would now like to turn the call back over to Mr. Ingram for any closing remarks.
Thank you.
Coming from the line of Joseph Schwartz with SBB Securities. Your line is open.
And our next question, coming from Delano at Gale Plum, with Neham.
All right.
Thank you and best wishes as you advance through this regulatory process I realize some of you were not at the company when it was approved but given some similarities to today at least on the surface and the fact that there were significant differences in opinion at the FDA back then.
Neham, is open.
Thank you very much, and thanks for your time this evening.
Good afternoon, and thank you for taking our questions.
I think you will all hopefully come away from this call at least understanding how excited we are, both with respect to our current performance.
And let me add my congratulations, especially considering what this means for patients.
So, in 2023, we might be facing a world that has both gene therapy and PMO at the same time in similar patient populations.
Any thoughts of what kind of sales dynamics you might see between these two populations?
I was wondering if you can provide us with any insight into the degree to which those waning of the FTE today, our unified or split it all on their opinion on the recent guidance to file for accelerated approval in other words, how broad is the buying new.
G versus when Exxon this was in the one rate and is there.
And champion pushing for SRP 9001 approval of the agency.
Now as there was for its own just 51.
Theyre not need to be for any reason that you can point to.
Do you think patients are going to switch or go on one therapy and maybe go down to another?
Well a couple thoughts on that one I wasn't here.
At the approval.
Although I did come not too long after that approval occurred in the launch occurred. So some of my comments will be based on the historical record of that not all my own personal experience I've experienced.
They are on this in a long list and I have experience with respective manager Joe one today, obviously I wasn't geared towards epilepsy Alexander.
This will this will be significantly different so we're very clear.
First of all first of all let's be very clear before I say anything else I wanted to be clear Exxon doesn't my honest in the monitors are doing an enormous amount of good for patients in the United States and to some extent overseas as well we have some real world data that is going to be coming out to be published and presented at world muscle, but ill make exactly that point across.
Thank you.
I don't want to lose sight of that.
Yeah, so there's a lot that we have to, there's a lot of modeling we have to do with respect, to this.
I wouldn't let me lose sight of the fact that we really are doing an enormously great job, in my view, of serving the current community with our approved therapies, and it shows in our performance, and it shows in our guidance, but we're very, very excited about where we are with SRP 9001, certainly with respect to our conviction around a BLA, and then, of course, with respect to the progress we've made with respect to our confirmatory trial at BARC, and now the hard work starts.
It always seems like the hard work starts for SREP, but we don't afford ourselves much of a pat on the back, but we've got a lot of work to do in front of us.
And then some of it will just be empirical as we launch the therapy.
We have to get our BLA submitted. We have to get through the review process.
Our current plan assumes a significant amount of cannibalization.
We have to get our site readiness ready to go and really tune up our ability to launch what will be an enormous therapy, and we have to build an enormous amount of inventory to support this launch that patients are not waiting because of manufacturing, and we're very confident we'll get there, but we'll give updates along the way as we do that.
I would say, you know, with respect to the initial approval, which would be for the ambulant, population, obviously we would still have the PMO available to the non-ambulant population, and so it shouldn't have any impact there. And beyond that, we think there is potentially a very compelling argument for the PMO to, continue even in patients who are planning to or have received gene therapy for a host of reasons.
Thank you.
The final thing I'd like to say, and I made a comment briefly on this same thing last time, and I'll say it again, and that is that I know this year has been a very challenging time for the biotech investor, and it seems sometimes, and I understand why, but it seems sometimes that hope and vision are lately replaced with a sort of blinkered pessimism that results from what has been a tough year, Surepta, in my view, is a leader in genetic medicine for rare disease, and we intend through our scientific execution and our tenacity to lead that return to optimism, and when optimism returns, and optimism will, of course, return, it should be for companies like Surepta that preferentially benefit. Companies like Sarepta that, at least in my opinion, know how to execute and get things done.
Thank you for your time.
The first reason is that there is already evidence in the literature to support the, proposition that there is a benefit to patients getting on a PMO in advance of gene therapy, that it would, in fact, not only protect them in advance of gene therapy, which is of crucial importance, but also that it might actually enhance expression and the benefits of gene therapy if one is on a PMO or if we get approved at a PPMO.
And with that, I would ask you all to have a lovely evening.
Ladies and gentlemen, that does conclude our conference for today.
And then the coexistence of those two therapies may very well be a benefit to patients, and, we're doing some work on that right now from a preclinical perspective.
And our next question is coming from the line of Joseph Schwartz with SVP Securities.
Thank you for your participation.
And then, as I said before, there will be certainly patients who will have available, to them, either in the United States or around the world, an RNA technology and not a gene therapy or a gene therapy and not an RNA.
So I think there is a particular value of both the patients and to Sarepta to having, both of these modalities coexist.
Your line is open.
You may now disconnect.
So while our current modeling is relatively conservative and assumes a significant amount, of cannibalization, we're going to have to play this out and see if that is actually the case over the long run or if these therapies coexist.
The conference will begin shortly.
To raise your hand during Q&A, you can dial star 11.
Thank you for your time.
Basically every ambitious of benefits. So it was a tremendous benefit to patients and from my perspective. It was the right decision to have approved the strongest in the first place and I certainly think by honest with him on his well deserved the benefit base they are benefiting patients significantly.
Thank you.
With that said there are going to be a lot of differences between this accelerated approval.
And the prior approval the first of which of course was the amount of data that supports that the data has really built from Exxon.
Scientists was approved on 12 patients were not talking 12 90 patients with multiple studies. The functional results are concordance. There is significant the P values on them.
That is a great addition of the benefits that we're also seeing in the functional results, but the NSCA and time test, all of which are concordance.
We've seen the third party at muscle MRIs that have been concordant in the reduction of fat and fibrotic tissue.
So there's just a wealth of totality of evidence that supports the conclusion from our perspective that the SRP9001 therapy and the results in shortened but functional protein, which was rationally designed over 14 or more years through both design and review of natural history and empiricism, justify the conclusion that our protein is functional.
I would 0.0001 and that kind of on every one of them the underlying biological activity.
We have a very laudable safety profile. And on the basis of all of that, plus the written feedback we've received from the FDA, we think it is certainly appropriate and we have an enormous amount of conviction about the pathway forward as we seek a BLA for an accelerated approval for the ambulant population and then follow up to the non-ambulant population as soon as reasonably possible.
Unequivocal from my perspective all.
All of the ambitious benefit is critical on the safety is laudable as well we are not making a small amount of this functional protein dystrophin language zero, one vision, we're making robust amounts right, we're making upwards of 50% or more on western blot, we're making over 70% on dystrophin positive.
Fibers and the intensity level is off the charts.
If you've ever seen one of our.
Unit fluorescence synergies you should know theyre, not enhance and they light up enormously. So there is there is unequivocally the amount of expression and then the other thing that's going to be differences, but this is that our goal here is to win on the science with the division.
It's a very important part of our mission.
Operator.
And our next question coming from the line-up, Jada Fromer with Credit Suisse.
Your line is open.
<unk> as a whole and that is exactly what we're going to do.
And I'm very confident about the approach of this team is going to make I think we've done extraordinarily good work over the last five plus years in forging a very positive science space respectful relationship with the agency and that will persist through the accelerated approval.
Approval pathway and finally I would note that with respect to the advice that we've received and the input that we received.
In advance of our decision and conviction to submit BLA we'd had.
Broad cross FBA.
FDA discussions on this topic.
We have cheaper leadership, we haven't always had we had the cedar inside at Cedar we had the opposite.
Drugs, we had the neuro division. So we've had a lot of discussions none of that is to suggest that we're not gonna have a full robust with you. They don't pre approve a BLA approval BLA for filing and then we will have a full review and then we may have an AD com and then hopefully if all goes well I certainly believe that or we wouldn't be filing a BLA.
Our approval, but.
That.
In that regard this approach is going to be different than that.
But I do want to say with all of that charge.
The good news at the end of the day with respect to establish it as of yesterday did the write down and as a result of doing the right thing a lot of patients in benefit in a lot of patients have benefited every batch of what would be if all goes well a very transformative therapies.
Yeah.
Yes, maybe I'll, just add and better rates that are just kind of reiterate it.
Just announced today that essentially embark.
Practically fully enrolled so essentially we would have to wait about a year. So there's really no incentive for us other than both good points about the patients for us to move forward. If we didn't feel that we are about to get.
<unk>.
A fair view and that there wasn't a broad support across the agency and I certainly when obviously this market still remains challenging.
And we're not going to commit dollars.
Unless we thought we are going to be.
The successful in.
Getting these patients to therapy, obviously did the <unk>.
Point.
We have to go through the review, but we're not going to commit dollars in that market.
We felt that there was a good chance for an ultimate approval.
And best wishes as you advance through this regulatory process.
Thank you and our next question coming from the line of Kim sung with <unk>. Your line is now open.
I realize some of you were not at the company when Exandus was approved, but given some, similarities to today, at least on the surface, and the fact that there were significant differences in opinion at the FDA back then, I was wondering if you can provide us with any insight into the degree to which those weighing in at the FDA today are unified or split at all in their opinion on the recent guidance to file for accelerated approval.
In other words, how broad is the buy-in now at the agency versus when Exandus was in the, limelight?
And is there as strong a champion pushing for SRP 9001 approval at the agency now as, there was for Exandus 51?
Great. Thank you very much for taking the question. So a follow up question on the non ambulatory patients was that stuff.
Thanks for taking the question and congrats as well on the progress.
Or does there not need to be for any reason that you can point to?
Well, a couple thoughts on that.
Studies, the new study are required by the FDA during your discussion with the agency and based on your answers to the previous question I guess is not going to be part of the confirmatory studies.
Robert again by the FDA and secondly, just wanted to confirm the timeline.
We were just kind of curious given how close the timelines are between the accelerated BLA filing and the EMBARQ data coming out.
One, I wasn't here at the approval of Exandus, although I did come not too long after that, approval occurred and the launch occurred.
In your mind, is the accelerated BLA somewhat of a low-risk option to explore approvability? There's probably a year gap between what a traditional approval would be if we filed the BLA after the embark readout versus our ability to file a BLA now and get an accelerated approval for the ambulant population.
So some of my comments will be based on the historical record and not on my own personal, experience.
But again, I want to be very clear, people that might say, you know, almost sort of suggesting, you know, there's a flyer.
I have experience with Avalandus and Amandus, and I have experience with respect to 9001, to date.
I believe you talked about potential et cetera approval.
Midyear 2023, so that should be before you get topline data from two part phase III study.
What happens is to embark phase III study missed is the primary endpoint is that possibility come up at all during your discussion with the FDA would there be any room of flexibility depending on how the data looks like.
Obviously, I wasn't here for a couple of years on Exandus.
This will be significant.
, and, the, United States.
So we're very clear.
So.
So on the.
The first question.
The vision of our 33 or three obviously.
It was our decision.
We've been planning that for quite some time, so that that did not.
Come up with the agency that was our decision with respect to the timing yes.
No, it was a result of a significant, in-depth review, a significant number of meetings with the FDA that gave us the conviction to submit an accelerated approval BLA, which we will be doing this fall.
If all goes well.
The approval would be in advance of a readout in the Mark.
We haven't had detailed discussions about embark.
And.
Its results, but on the other hand, we're very confident about embark we're very well powered for over 90% powered so we feel very good about it we were in over 90% powered before with other readout on.
Study one to part two and we now have even more conviction on the strength of the powering was only increase if you apply that so we feel very good about where we are.
Oh by the way I want to update I think I said 60, 40 ambulatory amount as non ambulatory to update more I think in dollar and you correct Me 50, 50, I just want to make sure I was mistaken.
Is that correct Alan yes.
The 50 50, and they play a prevalent population.
I apologize for that misstatement.
Okay.
Thank you and our next question coming from the line of fixtures shoe with Dan Burke. Your line is open.
Great. Thanks.
Okay.
And my congrats to the progress as well and just a few clarification question.
First on the based on your communication with the FDA.
Has FDA explicitly encourage you to file a.
Based on the accelerated approval.
And secondly, I wanted to ask.
And around the the SG&A uptick.
<unk> expense in the second quarter, you mentioned, the that was primarily driven by noncash stock options.
Should we assume the expenses.
Other expenses in Q3, and Q4 should come down substantially.
Thank you.
Yes, so thanks.
The FDA communication, what I would say that based on our communication on the rig.
Should the agency we have enormous yet.
We have significant conviction on the concept of submitting for an accelerated approval BLA and we feel very good about the approach that we're taking and then would that be a drop sort of talking about debt and noncash items.
Yeah. Thanks, so as it relates to yet youre going to see the big hit this quarter.
There will be some smaller.
Stock based compensation expenses.
Over the coming quarters about $50 million, that's spread out probably.
Probably over the next year, so much significantly lag, but remember the most important thing to think about here is that this is a.
This expense is noncash charge so.
No impact at all to our overall net cash burn.
And our next question coming from the line of Danielle <unk> with Raymond James Your line is open.
Hi, guys. Good afternoon. Thanks for the questions two quick ones given the proximity of the anticipated accelerated approval to embark reading out.
I'm curious to hear what you're thinking on the payers front is it possible that they'll drag their feet to implement coverage or are you expecting for buying and then I appreciate that you've generated much more data at this point, but have you set a new precedent here and do you anticipate that your competitors will follow suit with pursuing accelerated approval. Thank you.
Yes. Thank you very much for your question so on the <unk>.
Thank you very much for your question.
Thank you.
Second question first.
Our ability to submit for our conviction around the BLA is unique to our therapy and the wealth of data that we have on therapy, and the 90 plus patients across three therapies.
<unk> data that we have in the 14 years of preclinical work that supports that and the safety profile, which is.
Unique to SRP nine zero wanted it on that basis that we're filing for accelerated approval and I don't think we're setting a new pricing algorithm.
Very consistent with the.
Statutes, and the regulations and frankly, the precedent that the FDA about where an accelerated approval is appropriate but I want to be very clear that decision is.
First of all, let's be very clear before I say anything else.
Scans on the data in front of US, which is unique to F&B, Nigeria Bureau, one and unique to the SRP 9001 protein, which is from our perspective at least unequivocally.
Beneficial to the patients and we can we can safely.
Deliver that therapy and great expression levels as it relates to the payers.
I would say you know as challenging as payers can be God, we forged a very positive relationship with bayer's over the nearly six years since the approval of the Exxon This and so I don't want to I don't want to make it easy.
<unk> and his team work everyday and fight every day to ensure that patients get on therapy and stay on therapy.
Across our three approved therapies, but hopefully you will see in the results that we've had which is I used to say 20 quarters, it's 20, something quarters of positive quarter over quarter over quarter over quarter growth.
You are so far of over 40% annually.
The annual growth rate and even a 50% growth over the same quarter last year that given a therapy and have any opportunity to take that therapy to patients. We are a company that knows how to execute and knows how to work with payers knows how to get this therapy not only delivered to.
The community by community support community support patients getting on therapy and stay on therapy with respect to chronic therapies or in this case getting therapy and getting it appropriately.
With respect this onetime gene therapy, so there's a lot of work to be done.
But I'm very confident that.
There is no better team.
Certainly no better team that with respect to Duchenne muscular dystrophy than the team that you have that to raptor fighting everyday for patients and so I'm very confident about our ability to translate an approval into therapy that can benefit patients.
Thank you and our next question coming from the line of Christian. Please go with Cantor Fitzgerald. Your line is open.
Hi, everyone. Congrats on a very exciting quarter for the company. So most of my questions have been asked so I'll change topics a little bit here in gene therapy. So based off the path you took with SRP 9001 in your discussions with the agency has this changed how you might envision some of the trial design.
<unk> for the limb girdle programs and of course, I understand here that you'd want to see some supportive data before figuring out the path forward, but any initial thoughts at this stage.
And Louise I'll touch on limb girdle.
Alright, Thank you for that question.
So it was before.
Kind of work going on in <unk> and limb girdle trumps anything or we have five programs that we've been working hard on.
All of the CMC related activities, including Allergan deal specific assays to support the program certainly all of the data that we've collected.
SRP 9001 in support of the limb girdle program being understanding semi car vector in the promoter in many cases.
And delivery method.
Data that we generate data supportive we also have our data, which we've shared with you.
Hum very promising in both expression I'm, sorry thoughts as well.
We're taking all of that collective data and learnings from our pathway with 9000 marijuana plant.
Where we can do is obviously smaller populations, but theres a lot of learning that we can apply and we're now moving quickly.
Set of trials.
So thanks for the question.
Thank you and our last question coming from the line of Kevin Clark Gardner with Evercore ISI. Your line is open.
Yeah, Hey, thanks for taking the question I just wanted to ask if you could give any more granularity around the status of the CMC work.
Thats on the timelines for engaging with the FDA as it maybe.
Maybe later this year thing or more like a 2023 of them. Thanks.
On a limb girdle in particular.
Yes, yes for limb girdle Simon.
Yes, so we're trying to get the idea that we are.
We're working hard on the CMC for our limb girdle programs.
There's a lot of work can be done we've learned an enormous amount, but we can capitalize on as a result of a 39 zero what do those specific assets.
With respect to many of our lenders.
But a lot of it is just takes time and it is an empirical process to build some of these assays in particular, so we are working like Mad Luisa do you want to touch on any of these issues in more detail, but I do think we're working hard to try to get a lot of those done this year.
Yeah, I would add.
We certainly have unwinding the development of the assay for each of them.
Limb girdle subtypes that specific asset class to be at about for each one in Florida.
I think alluded to it takes time for that.
Morning.
Yes.
And then the good news the good news is that we know exactly what we need to do.
Given the SRP 901, the other good news is that there is no significant enormous inventive step in any of this this is really just work and empirical assay development.
Confirmation and bad debt because of the frustrating things sometimes is that it just takes time and that's what we're working on right now and there's only so fast.
Could go where you have to rely upon.
Some of the preclinical studies.
Support the bathroom, but were working like mad on that understand that.
It's a high priority for us.
Thank you and I'm showing no further questions at this time I would now like to turn the call back over to Mr. Ingram for any closing remarks.
Alright, Thank you very much and thanks for your time. This evening I think we'll all hopefully come away from this call at least understanding how excited we are.
Both with respect to our current performance I don't want to lose side of that I went down.
Balance here and it wouldn't let me really excited of the fact that we really are doing an enormously great job five years of serving the current community with our approved therapies and it shows in our performance and it's showing up in your guidance, but we're very very excited about where we are with SRP 9001.
Certainly with respect to our conviction around the BLA and then of course with respect to the progress we've made with respect to our confirmatory trial in March and now the hard work starts. We got you know I mean, it always seems like the hard work starts for cigarettes, we don't afford ourselves as much of a Pat on the back but we've got a lot of work to do in front of us.
Have to get our BLA submitted we have to get through the review process, we have to get our site readiness ready to go and really tuned up our ability to launch what will be an enormous therapy and we have to build an enormous amount of inventory to support this launch with that patients are not waited because of manufacturing and we're very confident we'll get there, but we will give updates along the way.
That would be that the final thing I would like to say and I made a comment briefly on this Wednesday last time and I'll say it again and that is that I know this year has been a very challenging time for the biotech investor.
And it seems sometimes I understand why but it seems sometimes that hope.
<unk> R lately replaced with a sort of blinkered pessimism that results from what has been a tough year, but I would remind us all that.
But as challenging as it may be what we all do together that's the biotechnology organization that our scientists are professionals, but importantly also those on this call today those of you who invest in buyout biotechnology.
Unbelievably important to society Eurostar optimism the science of genetic medicine in particular has made revolutionary advances over these years, we and others will translate the science with therapies that will improve the human condition and make outsized returns for those like us who have taken the risk on genetic medicine.
Terrific and my view is a leader in genetic medicine for rare disease, and we intend to our scientific execution in our capacity to lead that returned to optimize them and went optimism matures and optimism will of course return it should be for companies like <unk>.
That that potential profession.
Preferentially benefit companies like us with a strong balance sheet with strong revenue with best in class talent with a strong late stage pipeline poised to improve lives on some distant future, but literally very soon companies.
Companies like <unk> out there, but at least in my opinion know how to execute and get things done.
That I would ask you all to have a lovely evening. Thank you for your time.
Ladies and gentlemen that does conclude our conference for today. Thank you for your participation you may now disconnect.
Okay.
One moment for our next question.
I want to be clear.
Our next question, coming from the lineup, Tasneem Ahmad with Bank of America.
Exondus and Lyondis and Amondis are doing an enormous amount of good for patients in the United States and to some extent overseas as well.
Your line is open.
We have some real-world data that's going to be coming out.
Hi, guys.
It's going to be published and then presented at World Muscle.
Good afternoon.
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
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Thanks for taking my questions.
It will make exactly that point.
Ian, you had said not to expect a meaningful uptake in expenses in 4Q, but as you ramp up commercial supply, can you give us a sense of how expenses in 2023 could compare to this year?
Across basically every indicia of benefit.
And then separately, can I ask on PPMO, when should we expect the next update, either data-wise or on path forward?
So it was a tremendous benefit to patients.
Thanks.
And from my perspective, it was the right thing to do.
Yeah, so just on the expenses front, you'll see an uptick in op-ex.
And it's a great thing to do.
The conference will begin shortly to raise your hand during Q&A you can dial style Q&A you can dial star one one.
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