Conference Transcript - SRPT 2026-03-03

Ritu Baral, Analyst — TD Cowen

Awesome. Thanks, everyone, for joining us at the Sarepta Fireside Chat at the 46th Annual TD Cowan Healthcare Conference. I'm covering analyst Ritu Baral, and with us from Sarepta today is Ian Estepan, President and COO. Thanks, Ian, for joining us. Let's start with Elevitus and its current commercial ramp. On the Q4 call, Sarepta guided to 2026 net product revenue of $1.2 to $1.4 billion, noting it was comfortable with the current 2026 PMO revenue consensus estimate of $900 million. Now, this implies that 26 Levitas revenue will be between about three 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 for you guys to amend your estimates for 2026 at least?

Ian Estepan, COO

Well, first off, thanks for having me. It's a real pleasure. And, of course, we'll be making a number of forward-looking statements. So 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. So, for example, if you just looked at our current quarter that we reported, you know, they had $110 million, you know, times that by four, you should be at $440, right? And so you really have to understand the dynamic with a one-time therapy where you're starting it from zero every quarter. There is not a built-in install base.

Ritu Baral, Analyst — TD Cowen

It's all NRXs.

Ian Estepan, COO

Exactly.

Ritu Baral, Analyst — TD Cowen

It's a queue of NRXs.

Ian Estepan, COO

Exactly. Yeah. And so and then the other dynamic that's important to realize is the long turnaround time, which is around six months. So right now we're kind of working through start forms that were written during the summer.

Ritu Baral, Analyst — TD Cowen

Got it.

Ian Estepan, COO

And beyond. Right.

Ritu Baral, Analyst — TD Cowen

And so that's six months. Is that longer than it was previously? And if so, for what reason?

Ian Estepan, COO

It's traditionally been between four and six months. So it's still it's still within that range.

Ritu Baral, Analyst — TD Cowen

OK.

Ian Estepan, COO

Right. And so 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 and using that as a base case to set our guidance. So we don't from, 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 from start forms where we currently are and working through the start forms that are already in queue that's working for the next six months.

Ritu Baral, Analyst — TD Cowen

And then you extrapolate, like if you sort of map out the next six months and then you flatline that, that's your 300?

Ian Estepan, COO

Correct.

Ritu Baral, Analyst — TD Cowen

Okay. So if you accumulate, like you take the area under the curve for the next six months, but then you get an inflection, that's the 500 inflection of work.

Ian Estepan, COO

Exactly. And so 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, right, you wouldn't see that translate to sales until six months later. so you're running out of just time from a calendar perspective but from an opportunity perspective everything's intact you know um you know from the number of eligible patients who are available in the opportunity perspective so um 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 um like basically the the delta and the sales force expansion um how long it'll

Ritu Baral, Analyst — TD Cowen

take to train and deploy them any any color on where they're coming from um and is there i guess a unique element to expanding and detailing a you know billion dollar potential gene therapy that is different than you know billion dollar 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 AV approach going forward now that being said there's a wealth of

Ian Estepan, COO

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 so we're very pleased with the way that the data is panned out now from a sales so that's an important message these are the types of things um that so the data that your rep is reps are going out with is only going getting stronger time. Exactly. So that certainly balances the efficacy conversation. And then 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. So that's critical. And then obviously, just from, I know that you were asking about the sales force, they're just now kind of hitting the ground running so they're trained the first wave has been hired and has been trained but we're also doing a contract sales force that 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 so the the the 50 percent more the first the first wave are surrepta employees and they're they've hired a more technical detail is that fair to say and then the doubling is actually this contract force and you said their focus is is more on the peripheral sites and patient finding so the lower volume sites um what sort of patient finding activity um 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 around exon skip around um gene therapy or exon skipping and so it's getting those patients in front of the physicians and getting them to a referral site um and making sure they have balanced information Got it.

Ritu Baral, Analyst — TD Cowen

On your Q4 call, you guided to a slightly down Q1. What specific factors are driving that?

Ian Estepan, COO

Yeah. So 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? Filled for each child because it's a weight-based therapy. And so we have good line of sight into the quarter and the kits have to be done about two weeks in advance. So we have a good kind of line of sight from that perspective. However, what you can't account for is just the sicknesses, cancellations, and things like that. And so the down 15% captures that aspect of which we are just unknown until the patients actually get dosed.

Ritu Baral, Analyst — TD Cowen

So is that a conservative assumption of cancellations and sickness based on recent precedent? Yeah, so we just want to factor in everything. we don't want to be in a position where we don't disappoint the street so got it we factored in everything in giving that guy so you're assuming cancellations that maybe haven't quite happened yet correct okay got it got it that's very helpful um in january you emphasize that over the year surreptus commercial goal was to detail eleven's efficacy data sets now including the three-year embark data and less time on re-establishing 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

Ian Estepan, COO

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 there's there's questions around safety but it has to put be put in context with efficacy right risk benefit is always paramount whenever you're making any decision like this and even heightened as it relates to one-time therapy so I think the efficacy data is important to balance out but you know there could be any potential concerns around it and what has reception been to that three-year embark data I think it's actually one of the best receptions one could hope for and so 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 so they have been not surprised per se that they're seeing continued separation from what you would expect from natural history but also to see that it was very consistent with what they've experienced so 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 but it's not consistent with a larger data set so people have been very pleased to see that their experience is very consistent with a larger data set that they didn't necessarily have access to are you still seeing like new prescribers or really has everybody who's going to write a levitus at some point written at least one script we have seen new referrals so not new prescribers So sites that have not necessarily had a patient, that they're now referring them to one of the bigger sites.

Ritu Baral, Analyst — TD Cowen

I see. Okay. And is this post-three-year Embark data?

Ian Estepan, COO

This is post-three-year Embark data.

Ritu Baral, Analyst — TD Cowen

Yeah, Patrick just mentioned it on the call, that we're seeing two dynamics that are somewhat encouraging not to over-interpret very small numbers. but that a couple of sites who haven't written in a long time have written and then referrals from a couple of sites to existing administration sites got it so you previously guided to top-line cohort eight sirolimus pre-treatment data and non-ambulant patients for levitas treatment you'd previously guided to second half and then on the last call you noted despite high patient and investor i'm sorry my patient and physician interest also investor interest but patient

Ian Estepan, COO

and physician interest no non-ambulant patient had yet been dosed um but you received the green light to start enrollment in late november so is there are there gating items to that first treatment um is it site activation you know yeah exactly this is logistics right so there's a nuance to it so the agency agreed to the study design but you still have to go through the contracting process and IRB approvals okay so it's just logistics to get through even though the agency agreed in concept to actually get the sites to be in a position to be able to dose right now they're five they're five sites okay are they close to dosing yes okay and the five are open yes they're

Ritu Baral, Analyst — TD Cowen

five sites that are in the stages of opening I know one site is definitively open right as you think about that data what what do you want type 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 yeah the real primary endpoint is the rate of ALI yes as defined by the ALI definition is what on the other biomarkers uh it could be two times uh three times normal at ggt and will you also be looking at like alt ast yeah yeah we'll be looking at all but it's it's ggt defined ali okay um that's not usually how we think about drug induced like dilly right it's usually like bilirubin and alt is this a unique feature of an av associated liver injury that's sort of ggt focused yeah it's it's ggt focused especially because you often have variability as it relates to alt and ast so that's why you don't typically oh in dmd patients okay patients understood that makes sense what about um bilirubin or is it like by the time billy ruben moves yeah we look at it much earlier okay before the bilirubin starts actually having an impact got it um and then as part of this you will be doing a biopsy to see the impact of serolimus on potential expression how how are you um how are you taking the biopsy how are you assessing the expression levels and you know what what's the current standard for assessment of muscle content based adjustments to this analysis yeah so obviously from our perspective we want to different companies do it different ways which 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 that one uses and so that has an impact on on the overall quantification

Ian Estepan, COO

that being said we will do it in the exact way that we've done it always in terms of the embark readout and the like it's going to be completely consistent um with the way that we've always done now when could we get the first indications of impact on efficacy will it be um from that first top line data i don't know if um we'll have the biopsies just because as you know it takes time to um actually process and get it from both the western blot and if perspective um so i would expect that the 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

Ritu Baral, Analyst — TD Cowen

using an immunosuppressive regimen right that being said we want to 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 uh we feel good from an enrollment perspective obviously it's slated to the really back end of the year so could you always have some level of slippage yes but i wouldn't expect any major delay um was the non-ambulant indication in the label formally removed in the label update um and you know once you get that cohort eight data could it restore that language or what sort of restore it quickly without sort of

Ian Estepan, COO

a review process yeah a formal review process we haven't defined that with the agency now it was as you know you've seen the label so it was removed from the label um and 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 on um if the data is sufficient and and what the pathway is So we haven't had those formalized conversations. Now, obviously, it could be an SPLA, but we're just going to have to see. So step one is just getting the data. Hopefully, it has a significant impact on ALI, and then we'll engage with the agency to discuss kind of the pathway forward.

Ritu Baral, Analyst — TD Cowen

Have you ever had a, 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?

Ian Estepan, COO

Not formally with the agency.

Ritu Baral, Analyst — TD Cowen

Has it been a discussion topic?

Ian Estepan, COO

I think we want to look to reduce the risk by at least 30%. Got it. um but you know again we'll see you know we'll see where we net out from uh so moving on to the arrowhead assets um you noted that your initial fshd dm1 data is still on track for one q um could we please start by recapping which dose cohorts and what endpoints will be included in the first interim data set yeah so before i do that maybe maybe let me frame sure the the 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 sRNA space and in the with ASOS that I think there's a lot more information that we can glean specifically within DM1 and FSHD specifically right so when you take a step back and kind of look at the sRNA approach, which is currently in development, you did not see a dose response curve at all, right, with a MAP. And so there could be two reasons why that could be occurring, right? It could be the transferrin receptor, or it could be the MAP itself and the interaction with the transferrin receptor. Now, when you look at the ASO approach, you actually see a very good dose-response curve from a muscle concentration perspective right so and since that's using the transferrin receptor also you mean the transferrin ASO approach correct the dyne approach right mm-hmm I'm not calling people out by name I will so when you so when you see that you do see a very good muscle concentration perspective however because of the ASO approach that you're dependent on rna to be available for knockdown to occur you actually don't see that translate to a pd perspective right okay but with the srna approach with the mab you didn't see any dose response curve from a muscle concentration perspective so of course from a splicing perspective you don't see it because enough doesn't get in anyway and so it doesn't because there aren't enough doors open or whatever correct you're not getting enough into cells so you can't have more splicing so you've seen flat from that perspective also so what we really want to see is really focusing on the muscle concentration with an sRNA approach because if you're able to get more into the muscle what you've seen from a pre-clinical perspective then you is that you can get higher you can get a higher dose response curve which will drive more knockdown okay and i think from uh i think that's very important because as you know especially as it relates to dm1 the level of of repeats is correlated to disease progression right and so if you have the congenital form or over greater than a thousand repeats obviously incredibly severe if you have the classical form you're between 200 500 obviously severe but not as severe as the congenital form so 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 overall efficacy now whether you can differentiate that at a year or something who knows however but fundamentally if you're getting the best knockdown it will lead to the best clinical outcomes so with all that being said going back to your question you know what we're looking for and so it's very low doses but what we're looking for is a dose response curve from a muscle concentration perspective from a pk perspective to see because this is the big question is with uh using the trim platform and the s rna approach can we get more into the muscle which will actually lead to higher knockdown and then mechanistically the rna stuff is figured out exactly by precedent okay and then the the doses the doses that will so it's one and a half and three for DM1 and then for FSHD it's one three and six got it and how long are you treating them for so this is just a single dose so we're taking yep biopsies at 30 and 90 days got it and 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 and we'll see what the correct dosing regimen will be 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

Ritu Baral, Analyst — TD Cowen

with preclinical assays and sort of increasing knockdown with dose escalation in an intracellular basis with DM1 or FSHG? They don't really have good preclinical models. I mean, there's some preclinical models.

Ian Estepan, COO

I think we have good preclinical models, and that is certainly what we've seen from a preclinical perspective. The more you can get into the muscle, the more knockdown you end up getting do you have um do you are you gonna disclose any updated pre-clinical dm1 or fshd data before this no the big focus has been on the clinical data we haven't been doing a lot of pre-clinical work when you are 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 um but it's to the point that i was trying to make earlier where um because it responds quickly at 48 weeks i don't necessarily know if you can see differentiation but if you're driving the most knockdown you're going to see from a long-term perspective because this is so tightly correlated to the number of repeats you have And so, you know, I think knockdown and proof of concept from a functional measure, whoever has the highest knockdown will ultimately get the most share.

Ritu Baral, Analyst — TD Cowen

So, Serep denoted ongoing CASI 22 assay development delayed splicing data into second half. So, what work remains on that assay and what potential is there for further delays?

Ian Estepan, COO

Yeah, I wouldn't expect any further delays. this is just around the validation this validation work is going on the teams made good progress on that so we'll have that data with some of the higher dose cohorts so avidity before it was acquired indicated that it developed a proprietary ducts for related gene knockdown biomarker what bar do you see I'm sorry we'll get to the biomarker next but just what's the bar for the ducks for down regulation and we'll get to the biomarker um i mean you've seen where they've been in kind of that 20 range um so we'll just we'll just have to see how this translates again i think you can ultimately and you there you have to you know really to your point kind of compare how the assays that are being currently um reviewed and and how similar and different you know different companies are doing but 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 not and what about biomarker approach for they have yeah they have proprietary yeah so they have the the c-ducks our team's working on that right now obviously that's early so your team's working on using c-ducks I'm assessing I'm trying to validate it obviously we don't have you know all the

Ritu Baral, Analyst — TD Cowen

information so the team's working on that now and looking to potentially use that as an assay so that obviously just came out recently and 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 in the all the cohorts by the end of the year okay so besides top-line phase 1 2 data what else might gate a pivotal trial start in FSHD and DM1 oh it's gonna be your commercial manufacturing process how long do you think that will take into 27 to 27 so really a next trial maybe second half 2027 assuming success in 27 you know you

Ian Estepan, COO

know we don't have exact visibility into you know there's obviously more work to do from a commercial manufacturing scale perspective but things are on track and got it i do want to touch on your pmo franchise um recently a competitor announced what we see is kind of compelling pivotal data for a direct competitor xondas if that drug is approved what syrup strategy to counter their launch and maintain exonda's share and will you play on price uh just to answer your your last question first i think uh this isn't a glp1 market right i don't think prices is you know we have to make these viable and with such a you know small populations I don't think there's as much flexibility on price as as real large indications so have margins improved with your PMOs they've been relatively stable okay but as it relates to the competitive dynamic again and it goes back to the point I was making earlier just in terms of quantification you know 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 five percent expression you know but when you look at the full change so when but when you look at the full change it's actually yeah identical right so quantification has a big impact now I do think on some of the new therapies the top of the dosing frequency could be important right so once monthly versus a weekly lessening the burden on a patient I think that's where they can be more convenient from a competitive perspective but 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 has been exceptional um and driving good benefit from a long-term perspective on all key uh major milestones of disease progression so loss of ambulation time to vent uh survival mortality um we've seen good data coming out you know over five years from from a overall survival perspective so very compelling data so really making sure that everyone's aware of that data educated in advance of any competitive entries.

Ritu Baral, Analyst — TD Cowen

Have you met with FDA to discuss potential full approval of Amandas Viandas Xandas?

Ian Estepan, COO

We haven't had the meeting yet it'll be this quarter.

Ritu Baral, Analyst — TD Cowen

What's your base case and upside downside cases for this meeting?

Ian Estepan, COO

What's most likely? Most likely? You know I want to be very careful as it relates to it's always challenging to navigate the current regulatory landscape but um look i mean i think that the data i'll say it a different way i think the data wildly supports uh this drug remaining on the market and this is in cedar like all of this is being evaluated this is in cedar yeah and obviously there is a very close comp uh in terms of ns pharma and the last that they disclose is that they're still discussing with the agency their protocol that that study didn't read out positively and that was about 20 months ago so it actually is current in terms of you know the current regulatory landscape and so I think it's as good of a proxy as one could could possibly have so we'll see but I think the data from a scientific perspective in the way that both physicians and patients have responded you know you have not seen any change in prescribing patterns or or enthusiasm or utilization of the therapy this data hasn't told anybody anything they didn't didn't know already exactly okay we have a long history of experience over ten years and the data is very consistent with that got it next presentations mine so I feel the ability to go over tell us a little bit about your third generation ppmos so the team is actually working on a combination approach using the trim platform in combination with the pmo so they're very very excited about that potential um but obviously very early so let's keep it in perspective so we'll see updates over 2026 potentially um i think is it 2027 maybe a more 2027 got it you know internally i think we'll start seeing whether it's viable from a pre-clinical perspective and then 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

Ritu Baral, Analyst — TD Cowen

having look forward to the progress