Ready to go? Awesome. Thanks everyone for joining us at the Sarepta Fireside Chat at the 46th annual TD Cowen Healthcare Conference. I am covering analyst Ritu Baral, with us from Sarepta today is Ian Estepan, President and COO. Thanks Ian for joining us. Let's start with ELEVIDYS and its current commercial rep. On the Q4 call, Sarepta guided to 2026 net product revenue of $1.2 billion-$1.4 billion, noting it was comfortable with the current 2026 PMO revenue consensus estimate of $900 million. This implies that 2026 ELEVIDYS revenue will be between about $300 million and $500 million, with $500 floor run rate if nothing else changes, whether that be sirolimus, whether it be label re-expansion, et cetera.
What has changed from January, to, for you guys to amend your estimates for 2026 at least?
Yeah. Well, first off, thanks for having me. It's a real pleasure. Of course, we'll be making a number of forward-looking statements. Before I get to your direct question, I think it's important to actually take a step back and think about the dynamics, because one source of confusion that we've gotten feedback on is, you know, really just understanding the dynamic of a one-time therapy versus a chronically dosed therapy. For example, if you just looked at our current quarter that we reported, you know, it had $110 million. You know, times that by four, you should be at 440, right?
Mm-hmm.
You really have to understand the dynamic with a one-time therapy where you're starting it from zero every quarter.
Yeah.
Right? There is not a built-in install base.
It's all nuclease-resistant.
Exactly.
It's a queue of nuclease-resistant.
Exactly.
Yeah.
The other dynamic that's important to realize is the long turnaround time, which is around six months. Right now, we're kind of working through start forms that were written during the summer.
Got it.
and beyond, right?
That six months, is that longer than it was previously? If so, for what reason?
It's traditionally been between four and six months.
Mm-hmm.
It's still within that range.
Okay.
Right? That's the dynamic that's really important because, you know, when you start from no patients each quarter, we're looking at the run rate from a start form perspective right now.
Mm-hmm.
Using that as a base case to set our guidance. We don't, so to your good point, where we obviously were comfortable around $500 million at JP Morgan, so we had about four to six weeks worth of data from a run rate perspective.
Mm-hmm.
From start forms, where we currently are and working through the start forms that are already in queue, that's working through.
For the next six months.
F or the next six months.
You extrapolate, like if you sort of map out the next six months, and then you flatline that's your 300?
Correct.
Okay. If you accumulate, like you take the area under the curve for the next 6 months, you get an inflection, that's the 500-.
Correct.
I nflection upward.
Exactly.
Got it.
Remember, from a calendar perspective, because there is such a long lead time, even if all the initiatives were hitting the ground running right now.
Mm-hmm.
R ight? You wouldn't see that translate to sales until six months later. You're running out of just time from a calendar perspective, but from an opportunity perspective, everything's intact of, you know, you know, from the number of eligible patients who are available and the opportunity perspective.
To that point, that $500 million assumes positive impact from the initiatives that you talked about, the ongoing Salesforce expansion? Can you walk us through the individual steps, like basically the delta on the Salesforce expansion, how long it'll take to train and deploy them, any color on where they're coming from? Is there, I guess, a unique element to expanding and detailing a, you know, $1 billion potential gene therapy that is different than, you know, $1 billion small molecules that we should keep in mind?
Yeah, I mean, the dynamic as it relates to the education that has to happen right now is, as a one-time therapy, you are somewhat precluded from using another AAV approach going forward. Now that being said, there's a wealth of safety data, and now with the three-year EMBARK data, a wealth of efficacy data, which where we see that as a drug modifying agent, we're seeing exactly what one would expect in terms of increasing separation over time. We're very-.
Okay.
P leased with the way that the data's panned out. That's an important message. These are the types of things, that the sales force have to-.
The data that your reps are going out with is only getting stronger.
Correct.
O ver time, essentially.
Exactly. Right.
Okay.
That certainly balances the efficacy conversation.
Mm-hmm.
From a safety perspective, a lot of education to put everything in the appropriate context, right? The denominator is very important as you think about what is your overall risk, from the therapy. That's critical. Obviously, just the, I know that you were asking about the sales force.
Mm-hmm.
They're just now kind of hitting the ground running. The first wave.
They're trained, they're hired up.
The first wave has been hired.
Mm-hmm.
H as been trained, but we're also doing a contract sales force.
Oh, okay.
T hat we're looking to expand to also, so about doubling from the number of reps, that we currently have, and they'll be more focused on, more of the peripheral sites and finding patients.
Got it. Okay. The 50% more, or the first wave are Sarepta employees, then they've hired a more technical detail. Is that fair to say?
Correct. Yeah, that's fair.
The doubling is actually this contract force, and you said their focus is...
Is more on the peripheral sites and patient finding.
The lower volume sites. What sort of patient finding activity?
It's just a matter of obviously we've seen claims for a lot of patients, but that does not necessarily mean that they're having the conversations with physicians.
Mm-hmm.
A round exon skip, around gene therapy or exon skipping. It's getting those patients in front of the physicians and getting them to a referral site, and making sure they have balanced information.
Got it. On your Q4 call, you guided to a slightly down Q1. What specific factors are driving that?
Yeah. From that perspective, you know, now especially relatively late into the quarter, I think you know for each prescription has to be written specifically for each child, right?
Mm-hmm. Yep.
Filled for each child because it's a weight-based therapy.
Yep.
We have good line of sight into the quarter, and the kits have to be done about two weeks in advance.
Mm-hmm.
We have good kind of line of sight, from that perspective. However, what you can't account for is just the sicknesses-.
Mm-hmm.
C ancellations and things like that. The down 15% captures that aspect.
Mm-hmm.
O f which we just, are just unknown until the patients actually get dosed.
Is that a conservative assumption of cancellations and sickness based on recent precedent?
Yeah.
flu season precedent?
We just wanted to factor in everything. We don't want to be.
Okay.
in a position where we disappoint the Street.
Got it.
we factored in everything in giving that guidance.
You're assuming cancellations that maybe haven't quite happened yet?
Correct.
Okay. Got it. That's very helpful. In January, you emphasized that over the year, Sarepta's commercial goal was to detail ELEVIDYS efficacy data sets now including the three-year EMBARK data and less time on reestablishing comfort with the safety profile. Has that been the feedback of the sales force right now, in the sense that when they go into the field that the pull on questions, the questions posed are more around the efficacy data sets, or are they still getting questions on safety?
I think there's questions around safety, but it has to be put in context with efficacy.
Mm-hmm.
Right? Risk benefit is always paramount whenever you're making any decision like this and even heightened as it relates to a one-time therapy. I think the efficacy data is important to balance out what, you know, there could be any potential concerns around safety.
Got it. What has reception been to that three year EMBARK data?
I think it's actually one of the best receptions one could hope for. What I mean by that is physicians were thrilled to see the data but also encouraged that it was very consistent with their own experience, right? They have been not surprised per se, that they're seeing continued separation...
Mm-hmm.
From what you would expect from natural history, but also to see that it was very consistent with what they've experienced. You're not seeing necessarily a ton of variability in terms of response where you know, maybe I would have just an outlier of patients doing one thing.
Mm-hmm.
It's not consistent with the larger data set. People have been very pleased to see that their experience is very consistent with the larger data set that they didn't necessarily have access to.
Got it. Are you still seeing like new prescribers, or really has everybody who's going to write ELEVIDYS at some point written at least one script?
We have seen new referrals.
Okay.
... not new prescribers.
Okay.
... sites that have not, you know, necessarily had a patient that they're now referring them to one of the bigger sites.
I see. Okay. This is post three-year EMBARK data?
This is post three year EMBARK data. Yeah. Patrick just mentioned it on the call-.
Mm-hmm.
That we're seeing two dynamics that are, you know, somewhat encouraging, not to overinterpret very small numbers. That couple of sites who haven't written in a long time have written.
Mm-hmm. Good. Love that.
Referrals from, a couple of physicians who have.
New referral sites.
Exactly.
T o existing administration sites. Got it. You previously guided to top line Cohort 8, sirolimus pretreatment data in nonambulant patients for ELEVIDYS treatment. You'd previously guided to second half, and then on the last call you noted despite high patient and investor... I'm sorry, high patient and physician interest, also investor interest. Patient and physician interest, no nonambulant patient had yet been dosed. You received the green light to start enrollment in late November. Are there gating items to that first treatment? Is it site activation? You know.
Yeah, exactly. This is logistics, right?
Mm-hmm.
There's a nuance to it. The agency agreed to the study design-
Mm-hmm
You still have to go through the contracting process and IRB approvals.
Okay.
It's just logistics to get through, even though the agency agreed in concept to actually get the sites to be in a position.
The sites open.
to be able to dose.
How many sites?
Right now there are five.
There are five sites. Okay. Are they close to dosing?
Yes.
Okay. The five are open now?
Yes.
Okay.
F ive sites that are in the stages of opening.
Mm-hmm.
I know one site is definitively open right now.
As you think about that data, what do you want top line to include? You know, is it what liver biomarkers, you know, between all the enzymes, ALT, AST, GGT, bilirubin, like what's the most meaningful of this.
Yeah. The real primary endpoint is the rate of ALI.
Yes.
Um-.
As defined by? The ALI definition is what on the other biomarkers?
It could be two times, three times normal of GGT.
Mm-hmm. Will you also be looking at, like, ALT, AST?
Yeah.
Yeah.
All, we'll be looking at all of them, yes.
It's GGT defined.
Yeah
... ALI. Okay. That's not usually how we think about drug-induced, like DILI, right? It's usually like bilirubin and ALT. Is this a unique feature of an AAV-associated liver injury that's sort of GGT focused?
Yeah, it's GGT focused especially because you often have variability as it relates to ALT and AST, that's why you don't typically look at.
Oh, in DMD patients.
Yeah, in DMD patients.
Okay. Understood. That makes sense. What about bilirubin? Is it, like, by the time bilirubin moves, it's too late?
Yeah, they. We look at it much earlier.
Okay. Before the bilirubin starts to move.
Actually having an impact.
Got it. As part of this, you will be doing a biopsy to see the impact of sarcoglycan on potential expression.
Yes.
How are you taking the biopsy? How are you assessing the expression levels? You know, what's the current standard for assessment of muscle content-based adjustments to this analysis?
Yeah, obviously from our perspective we wanna. Different companies do it different ways.
Mm-hmm.
W hich I think is actually important when you're comparing expression levels across programs. I think it's very challenging to do that. The normal control can be very different than one uses. That has an impact on the overall quantification. That being said, we will do it in the exact way that we've-.
Mm-hmm.
D one it always in terms of the EMBARK readout and the like. It's gonna be completely consistent with the way that we've always done it.
When could we get the first indications of impact on efficacy? Will it be from that first top-line data?
I don't know if we'll have the biopsies just because, as you know, it takes time.
Mm-hmm.
Actually process and get it from both the Western Blot and IF perspective. I would expect that the real key to this, to your good point, we're very interested to see if there's an impact and there's a strong mechanistic reason as to why you might see increased expression when using an.
Mm-hmm.
Regimen.
Right.
That being said, we wanna get the top-line data out from a safety perspective to see if we've had an impact on ALI in the non-ambulant patient population.
What is the probability that this top-line data is delayed into 2027?
We feel good from an enrollment perspective. Obviously, it's slated to really back end of the year.
Mm-hmm.
Could you always have some level of slippage? Yes, but I wouldn't expect any major delay.
Was the non-ambulant indication in the label formally removed in the label update? You know, once you get that Cohort 8 data, could it restore that language or restore it quickly without sort of a review process.
Yeah.
A formal review process.
We haven't defined that with the agency.
Mm-hmm.
It was, as you know, you've seen the label, so it was removed from the label.
Mm-hmm.
The pathway to restoring it is not something that's been defined. I think it may have some level of impact. The data may have some level of impact.
Mm-hmm.
If the data is sufficient and what the pathway is. We haven't had those formalized conversations. Now obviously could be an sBLA.
Mm-hmm.
We're just gonna have to see. Step one is just getting the data. Hopefully it's, has a significant impact on ALI, and then we'll engage with the agency to discuss kind of the pathway forward.
As you were setting up Cohort 8, right, did you set an expectation for ALI or other, whether it's expression, for thresholds that would restore the indication?
Not formally with the agency.
Okay. Has it been a discussion topic?
I think we wanna look to reduce the risk by at least 30%.
Got it.
You know, again, we'll see, you know, we'll see where we net out.
Moving on to the Arrowhead assets, you noted that your initial FSHD DM1 data is still on track for 1Q. Could we please start by recapping which dose cohorts and what endpoints will be included in the first interim data set?
Yeah. before I do that, maybe let me.
Sure.
T he opportunity a little bit because I actually think you can get more insight from this readout than one would normally expect just because there's been so much work in the siRNA space and with ASOs.
Mm-hmm.
That I think there's a lot more information that we can glean from that.
Specifically within DM1 and FSHD.
Within DM1.
Yeah. Mm-hmm.
and FSHD specifically.
Yep.
Right. When you take a step back and kinda look at the siRNA approach, which is currently in development, you did not see a dose response curve at all, right?
Mm-hmm.
With the mAb.
Yep.
There's could be two reasons why that could be occurring, right? It could be the transferrin receptor.
Mm-hmm.
It could be the mAb itself and the interaction with the transferrin receptor.
Mm-hmm.
When you look at the ASO approach, you actually see a very good dose response curve, from a muscle concentration perspective, right? Since that's using the transferrin receptor also.
You mean the transfer and ASO approach-.
Correct.
which is the Dyne approach, right?
Yes.
Mm-hmm.
I'm not calling people out by name.
I will.
when you see that you do.
Mm-hmm.
A very good muscle concentration perspective. However, because of the ASO approach.
Mm-hmm.
T hat you're dependent on RNase to be available for knockdown to occur.
Mm-hmm.
You actually don't see that translate to a PD perspective.
Mm-hmm.
Right?
Okay.
With the siRNA approach with the mAb, you didn't see any dose response curve from a muscle concentration perspective. of course, from a splicing perspective, you don't see.
You couldn't see it-.
You couldn't see it.
'cause enough doesn't get in anyway.
Enough get in. It doesn't alter.
Cause there aren't enough doors open or whatever...
Correct.
T he mechanism is. Yep.
You're just not getting enough into the cell.
Yep.
... You can't have more splicing. You've seen flat from that perspective also. What we really wanna see is really focusing on the muscle concentration with an siRNA approach, because if you're able to get more into the muscle, what you've seen from a preclinical perspective.
You can have a dose response.
is that you can get higher, you can get a higher dose response curve, which will drive more knockdown.
Okay.
I think that's very important because as you know, especially as it relates to DM1, the level of repeats is correlated to.
Yes.
D isease progression.
Yeah.
Right? If you have the congenital form or over greater than 1,000 repeats, obviously incredibly severe. If you have the classical form, you're between 200 to 500, obviously severe, but not as severe as the congenital form. Everyone knows that, you know, the level of repeats you have is correlated to disease severity, so therefore getting the highest knockdown will translate into, you know, the best...
Best.
O verall efficacy. Whether you can differentiate that at a year or something, who knows? Fundamentally, if you're getting the best knockdown-.
Mm-hmm.
I t will lead to the best clinical outcome. With all that being said, going back to your question, you know, what we're looking for, it's very low doses, what we're looking for is a dose response curve from a muscle concentration perspective, from a PK perspective.
Mm-hmm.
To see, because this is the big question, is with using the TRiM platform and the siRNA approach, can we get more into.
More into the muscle.
... the muscle, which will actually lead to higher knockdown.
Mechanistically, the RNA stuff is figured out.
Exactly.
... by precedent. Okay. Then the doses that will be included in the trial.
It's one and a half and three for DM1.
Mm-hmm.
For FSHD, it's onw, three, and six.
Got it. How long are you treating them for?
This is just a single dose.
Single dose.
So we're taking-.
Yep.
... biopsies at 30 and 90 days.
Got it. You have confidence that they, the expression will have happened and be sustained over 90 days or?
Well, we'll see.
Okay.
Again, this is proof of concept.
Mm-hmm.
... and we'll see what the correct dosing regimen will be, but as long as you're driving the knockdown, that's what's most critical.
Got it. What, have you seen this sort of increasing muscle concentration with preclinical assays and sort of increasing knockdown with dose escalation in an intracellular basis, with DM1 or FSHD? They don't really have good preclinical model. I mean, there are some preclinical models.
We.
not great ones.
... Brandy, I think we have good preclinical models-.
Mm-hmm.
and that is certainly what we've seen, from a preclinical perspective. The more you can get into the muscle, the more...
Mm-hmm.
... knockdown you end up getting.
Do you have, Are you gonna disclose any updated preclinical DM1 or FSHD data before this clinical data set?
No, the big focus has been.
Okay.
... the clinical data. We haven't been doing a lot of preclinical work.
When the program's mature enough for functional data, what do you see as the bar? Where has that been set for DM1 splicing and VHOT in DM1?
I mean, I think there's a danger, especially as you look at clinical data. VHOT does respond very quickly, but it's to the point that I was trying to make earlier where, because it responds quickly, at 48- weeks, I don't necessarily know if you can see differentiation.
Mm-hmm.
If you're driving the most knockdown, you're gonna see from a long-term perspective, because this is so tightly correlated to the number of repeats you have.
Mm-hmm.
You know, I think knockdown and proof of concept from a functional measure, whoever has the highest knockdown will ultimately get the most share.
Sarepta noted ongoing CASI 22 assay development delayed splicing data into second half. What work remains on that assay, and what potential is there for further delays?
Yeah, wouldn't expect any further delays.
Mm-hmm.
This is just around the validation.
Mm-hmm.
This is validation work that's going on. The team's made good progress on that, so, we'll have that data, with some of the higher dose cohorts.
Avidity, before it was acquired, indicated that it had developed a proprietary DUX4-related gene knockdown biomarker. What bar do you see... I'm sorry. We'll get to the biomarker next, just what's the bar for the DUX4 downregulation? We'll get to the biomarker.
I mean, you've seen where they've been in kind of that 20% range.
Mm-hmm.
We'll just have to see how this translates.
Mm-hmm.
I think you can ultimately. There you have to you know, really, to your point, kind of compare how the assays that are being currently reviewed and how similar and different, you know, different companies are doing. Ultimately, if you measure downstream knockdown, I think you'll, you know, if you get more into the cell, you're going to see more knockdown.
What about biomarker approach?
They have.
FSHD?
Yes.
Yeah, they have that proprietary-.
Yeah, they have...
Yeah.
the ARO-DUX4. Our team's working on that right now.
Mm-hmm.
Obviously, that's early.
Your team's working on using ARO-DUX4?
On, on-.
Like assessing ARO-DUX4.
... trying to validate it.
Got it.
Obviously we don't have, you know, all the information. The team's working on that now and looking to potentially use that as an assay. That obviously just came out recently.
Got it.
... the team's just starting to work on it.
What does it sound like timelines will be to full top-line data sets?
By full top-line data sets, you mean?
All the cohorts.
By the end-.
Sorry.
... of the year.
Okay. Besides top line phase I, II data, what else might gate a pivotal trial start in FSHD and DM1?
Oh, it's gonna be-.
Different things.
... your commercial manufacturing process.
Okay. How long do you think that will take?
Into 2027.
Into 2027.
Yeah.
Really a next trial, maybe second half of 2027 assuming success.
In 2027, you know, you know, we don't have exact visibility.
Mm-hmm..
... into, you know, there's obviously more work to do from a commercial manufacturing scale perspective, but things are on track, and so we feel.
Got it.
... good in 2027.
I do wanna touch on your PMO franchise. Recently a competitor announced what we see as kind of compelling pivotal data for a direct competitor, EXONDYS. If that drug is approved, what's Sarepta's strategy to counter their launch and maintain EXONDYS share, and will you play on price?
Just to answer your last question first, I think, this isn't a GLP-1 market, right? I don't think price is... You know, we have to make these viable, and with such a you know, small populations...
Mm-hmm.
I don't think there's as much flexibility on price, as real large indications.
Have margins improved with your PMOs?
they've been-.
Since.
relatively stable.
Okay.
As it relates to the competitive dynamic, again, and it goes back to the point I was making earlier, just in terms of quantification.
Mm-hmm.
... the, if you're using a different control, right? There was a competitor of ours whose drug was very close to ours, and they said that they had a 5% expression.
Mm-hmm.
You know, when you look at the fold change.
It's Prosensa, right?
No, Enzastaurin.
Oh, okay. Yep.
When you look at the fold change, it's actually.
Yeah.
identical, right?
Got it.
Quantification has a big impact. Now, I do think, on some of the new therapies, the dosing frequency could be important, right? once monthly versus-
Mm-hmm.
A weekly, lessening the burden on a patient. I think that's where they could be more convenient from a competitive perspective. I think to your point around what is the team doing in advance of that, it's really educating around the long-term efficacy. The safety profile of the PMOs-
Mm-hmm.
... has been exceptional, and driving good benefit from a long-term perspective on all key major milestones of disease progression. Loss of ambulation, time to event, survival, mortality, we've seen good data coming out, you know, over 5 years from a, from a overall survival perspective, so very compelling data.
Mm-hmm.
Really making sure that everyone's aware of that data, educated, in advance of any competitive entries.
Have you met with FDA to discuss potential full approval of AMONDYS, VYONDYS, EXONDYS?
We haven't had the meeting yet.
Okay.
It'll be this quarter.
What's your base case and upside downside cases for this meeting?
I.
What's most likely?
Most likely?
Mm-hmm.
It's always challenging to navigate.
Mm-hmm.
regulatory landscape.
Yeah.
Look, I mean, I think the data, I'll say it a different way. I think the data wildly supports this drug remaining on the market.
This is in CDER. Like, all of this.
This is in CDER.
is being evaluated as CDER.
This is in CDER.
Yeah.
Obviously, there is a very close comp, in terms of Enzastaurin, and the last that they disclosed is that they're still discussing with the agency.
Mm-hmm.
... their protocol. That study didn't read out positively, and that was about 20 months ago. It actually is current in terms of, you know, the current regulatory landscape. I think it's as good of a proxy as one could.
Mm-hmm.
C ould possibly have. We'll see. I think the data from a scientific perspective and the way that both physicians and patients have responded, you know, you have not seen any change in prescribing patterns or enthusiasm or utilization of the therapy.
This data hasn't told anybody anything.
Didn't.
... didn't know already.
Exactly.
Okay.
We have a long history of experience.
Yeah.
... over 10- years, and the data's very consistent with that.
Got it. Next presentation's mine. I feel the ability to go over. Tell us a little bit about your 3rd generation PPMOs.
The team is actually working on a combination approach using the TRiM platform.
Mm-hmm.
in combination with the PMO. They're very excited about that potential.
Mm-hmm.
obviously very early, so.
Got it.
... keep it in perspective. We'll see.
Updates over 2026, potentially?
I think.
Or is it 2027 ?
It may be more 2027.
Got it.
You know, internally, I think we'll start seeing whether it's viable from a preclinical perspective.
Mm-hmm.
Depending on the data, we'll see if it makes sense to share it or not.
Great. With that, we are over time. Ian, thank you for all the insight.
Thank you for having me.
Yep. Look forward to the progress.