Dyne Therapeutics, Inc. (DYN) May 20, 2026 Conference Transcript

All right. Great. Thanks. Hello, everybody. Luke AC, Senior Biotech Analyst here at RBC Capital Market. Today's our great privilege to actually have Dine as part of our 2026 Global Healthcare Conference. Representing the company, we have Eric Clucera, who's the Chief Financial Officer, as well as Ron Batra, Chief Scientific Officer. Thanks again, you guys, for joining us. How are you guys doing today?

Good. Thank you for having us. It's a pleasure and honor to be here. Look forward to that discussion.

Great. Great. Great. Great. Maybe, Eric, let's start big picture before we go into the specifics. Again, we have a long list of questions here, but maybe just, you know, a high level. Maybe just talk through some of the progress that the organization has made recently. And most importantly, what's next year for Dine?

Yeah, I mean, obviously, this is a great time for us at Dine. It's been, if you look back over the last couple of years, 2025 was a year of data de-risking. 2026 is a year of execution and preparation for commercial launches, not only with DMD in hopefully a year, but DM1 thereafter. And we're building a deep pipeline all based off the Force platform, which has been de-risked of DMD, DM1, FSHD, and four other exons following beyond that. So it's a great time to be at Dyn. Great. Great.

Super helpful. i do have a lot of questions on dmd but maybe before we go there if either of you can comment on kind of recent volatility at the fda what what's your take is there kind of any implications to the dying programs at this point or maybe eric i'll pass through to you and then yeah so maybe i'll start out with that at 30 000 feet as a reminder we have breakthrough therapy on on both of our products.

So what that allows you to have is a higher level and more consistent amount of dialogue with the agency. We've had a tremendous relationship with them over the time that we've been here. As you know, we recently had a pre-BLA meeting, which we have been aligned on our endpoint for Dystrophin for a while. And that was really something of an administrative meeting in terms of what do we need to do to get the application in. And we're on track for that BLA this quarter. So really just couldn't be happier with our interaction with the agency. Gotcha.

Maybe, Ron, if we can pivot to you. You know, we have seen in the broader field of DMD, you know, some of these skippers getting approved on expression. However, you know, the confirmatory trial for some of your competitors have not maybe played out the way we were kind of hoping for. is there a scenario where the FDA just look at you know expression as no longer kind of a good surrogate biomarker for accelerated approval and appreciate it again you guys are going after exon 51 versus some of these failures are going to be have happened in other exons and whatnot yeah what's your take on that

yeah you know beyond this amandes they'll tap so got accelerated approval they'll confirmatory studies it's unfortunate for the field but it does it's not a reflection of if dystrophin is a good biomarker for accelerated approval, accelerated approval pathway with the FDA remains open to us

based on dystrophin as a surrogate endpoint. We've shown STAT-SIG data in our DELIVER study with 0.0001% p-value for dystrophin. And to top that, we have robust functional improvement. Again, in the DELIVER study with 32 patients, 3 to 1 randomized, 24 on drug, 8 on placebo, We showed functional data with endpoints such as, you know, time to rise, rise from full floor velocity with nominal p-values of statistical significance. So, you know, that's great. We'll also be submitting that to the FDA for our accelerated approval. And lastly, you know, 24-month data, long-term data for us also is very robust. and we show durable functional improvement at 24 months. So, you know, we're very confident in the accelerated pool pathway for us.

Yeah, especially in the context of you obviously showing a materially high level of expressions versus some of your competitors, which I think is an important point there as well. You mentioned, you know, BLA. How should we think about standard review versus priority review? I mean, there's an argument to be made that there are technically therapeutic alternatives. out there but there's also an argument to be made this is remains a very very large on my medical needs so what's your level of confidence around priority review versus standard review yeah i mean as often is the case when you have breakthrough therapy designation there is priority review we have assumed the priority review in our timelines for guidance and and we feel good about where that is okay okay that's actually helpful um maybe ron if i can pivot back to you um this is fresh off the press your press release obviously came in earlier today um can you just maybe talk high level how you're thinking about the confirmatory trial here it sounds like you're going for time to rise here and you have a relatively sizable uh trial with 90 patients i believe 73 weeks is the timing of the primary endpoint like just walk us through why you decided to design the confirmatory trial the way you did

first of all very excited to say and you know announced that we have initiated Forzetto, which is, you know, our conformatory trial.

It speaks to the execution that the team is doing, right? We're on track, as you said, and Q2 will initiate the trial. And as you said, you know, 90 patients, one-to-one randomized, 72 weeks rise from floor velocity as the primary endpoint. We remain confident, you know, fully powered to deliver on this trial. Of course, this is a confirmatory trial. We are confident in our accelerated approval pathway with dystrophin as the biomarker. So this is a confirmatory trial that will test rise from floor velocity and will also be used for XUS applications. That was always our base case. And 18 months is the duration we chose and are confident in because in a disease like D&D, it takes time to improve the muscle so you see dystrophin as an early biomarker that's moving and then increase in dystrophin will lead to functional improvement not only at six months that we showed in this case you know at 218 months which i think is the right endpoint we have a lot of secondary endpoints also built into this trial that are very important for ambulatory assessment gotcha gotcha that's helpful um maybe you already articulated what's the primary point of confirmatory trial um why time to rise is the right primary endpoint it feels to me that the

broader field of dmd is walking a little bit away from north star and maybe just kind of looking at some other endpoints like why time to rise and not many of the other endpoints so you know if you You know, the disease in DMD, and I worked in DMD field and DM1 fields for about 20 years.

And in DMD, there's a Gower sign. So it's difficulty getting up from the floor. So rise from floor velocity is clinically meaningful. And also, there's now precedent that, you know, the field is moving in this direction. It's not the, I mean, we're not the only company that's using this endpoint. And lastly, I mean, which you said, from our delivered data, we're very confident in this endpoint showing robust functional improvement with nominal stat state values.

Is Novartis's and Avidity using time to rise at the primary point for the confirmatory trial for Exxon 44? And is that similar timeframe, like 18 months? I don't remember the details.

I think that is correct on the rise from floor velocity.

We chose this endpoint based on our data what we believe in terms of you know what we need to see in functional improvement in the in our patients um gotcha and the follow-up to maybe i can look it up later i guess but um is the follow-up for their trial somewhat similar or or yeah we can we can we can look it up later okay that's actually very super super helpful um maybe eric if i can pivot back to you um let's let's talk what a fun part which is you know commercial um absolutely i mean it's kind of still early days but like how you think about pricing at this point for this drug um you know obviously sarepta does

sets a comp for for better for worse so how should you think about pricing versus what they have been what they've done historically i mean first off from from 30 000 feet this is a great market to launch in there there's obviously established pricing as you mentioned there's established reimbursement already. The patients are very well motivated. The advocacy organizations are very strong. We just couldn't be happier to be launching into this and bring patients true functional improvement to their lives. So in terms of pricing specifically, it's way too early for us to comment on that. But I think as anyone that's been in biotech knows, we are bringing a dosing frequency advantage you know once a month versus once a week is a powerful thing for patients to have and also functional improvement so we'll see how that all plays out but you know right now it's just it's too early to comment on that but we feel really good about launching into this market with the data set that we're bringing.

Gotcha that's helpful in addition to exon 51 you guys are working on other exons as well whether it's 53 or 45 or 44 can just walk us through what's the plan there um and will you need to run separate trial on all of those or is there a scenario we can run kind of a quote-unquote basket study um given you know platform designations and some of the most recent uh you know uh effort from the fda to potentially speed up the development of uh you know just the molecules that shares a lot of the same properties except for you know the target.

Yeah, that's exactly right. I mean, from our standpoint in drug development and for me having been in biotech for 30 years, I've rarely seen assets that have as great of a risk reward profile as what you have with the other exons. Remember, it's the same fab, same linker, same oligochemistry, same patients, same centers, same physicians. I mean, from a risk adjusted basis, it's a tremendous opportunity. We have the ability to triple the total addressable market by getting these other four exons to the clinic. It's way too early to comment on what the regulatory strategy is. As you know, we have 51, which we're working to get that filed and approved. And then at that point, we can have discussions with the agency about how we can work together to bring these other exons to the patients and, you know, just anecdotally, when we put out the 51 data, you know, Doug and Ron, who have been in the field for a quarter century and know all of the KOLs, we're getting a ton of inbounds congratulating us for the data, but also saying, well, what about my boy that has a different exon?

So we think there's going to be tremendous interest in these and we're working with, you know, we look forward to working with the agency to find a pathway to get these to market gotcha gotcha that's actually super helpful um maybe if we can pivot to dm1 in the interest of time here um you know i think you recently increased the sample size a little bit in your in your trial that could potentially lead to accelerator approval obviously designed to show a benefit in vhat uh lots of debates with investors around your powering assumptions versus the avidity powering assumptions of artists and whatnot um again i think was originally 60 now you're saying is a little bit higher is that because you're less confident in the original

powering assumptions or is that not the way the right way to think about it yeah that you know we've always believed that we've been fully powered with 60 patients um as you know we had increased the number of of sites that we had been going to um and you get to a point where you get this influx of patients into the the funnel and and once they're in uh you know you have to analyze what is the screen failure rate how many more do you need and then at some point you you call it and any patient that's in the funnel you're ethically obligated to keep them in the trial so we feel like what we know that the number of patients that will be above 60 is not have anything to do with operational or statistical needs it's it's purely the the

patient demand that came in at the end and the ethical obligation that we have once they're in screening to make sure that they get drug and get in the trial sure i'm sure i'm pushing my luck but are we talking uh high single digits or low double digits uh incremental number of patients it's it's really impossible to say and you know until we see the screen failure right you just don't know many how many that are in the funnel make it to um to final randomization okay okay okay that's very helpful um i think you know for better or for worse the other important catalyst for your stock this year is going to be the Novartis' data is going to come in the second half of the year. Again, we already talked about some of the differences in terms of like, you know, powering assumptions that were not. However, you know, VHAT is obviously the primary point of that trial, as well as the primary point of your trial for the accelerator approval. Just walk us through how you're thinking about that data set and, you know, potential implications to Dyn as well.

Yeah, I think, I mean, we appreciate the investors are focused on the harbor data and you know the field is anticipating the harbor data but i have to caution everybody this you know making a direct comparison um with our drug with the last men um vasivarsin to novartis's drug because there's fundamental difference in mechanism of action in dm1 the mutant dmpk is located in the nucleus so we chose an antisense oligonucleotide that targets in the nucleus it recruits an enzyme RNAs H1 targets in the nucleus so that's a differentiation from the payload that Novartis is using which is an siRNA and largely is known to target in the cytoplasm right we are we are also using a fab compared to a mab based on published data the smaller size of the fab provides a better provides better tissue penetration so that's also different We don't see anemia in the clinic, so we're not dose-limited. We've been able to go to 6.8 mg per kg in our registrational cohort. So I think all of these things make it difficult for us to make a direct comparison with Harbor. You know, we're confident in our data, and that's that. Gotcha.

That's helpful. So, again, hopefully Novartis' result, the p-value is 0.0000001, and the rest is history. I think, you know, that would be very reassuring, I think, to the investment community that, you know, despite this whole debate about VHOD and whether that endpoint is sensitive enough to show a benefit or not, you know, I think that would be the ideal outcome, obviously, most important for patients. But should that not be the case, should they show a p-value that there's a little bit more in the margins, let's say you know 0.04 or something along those lines do you still have optionality in your trial design to maybe you know make the trial longer or bigger or reshuffling the endpoints and spend some of the alpha in the secondary endpoint like what what are the optionality that you have should their data be more mixed than many of us are hoping to see yeah so first of all i would say that we're very confident with, you know, our patient sizes to deliver on VHOT as the intermediate clinical endpoint.

And secondly, as I mentioned, with the differentiation mechanism of action, so it's hard to draw a comparison. So our trials and our designs are based on our data, our regulatory interactions. So we don't really anticipate doing anything, just to remain very confident in our, you know, our approach.

That's helpful. Especially because obviously at that time, the trial will be fully enrolled, right? Your trial will be fully enrolled, so maybe the optionality you have will be somewhat more limited if the trial is not fully enrolled, I guess. But that makes sense to me. Let's talk about CNS. I think it's always you highlighted some of the differences around your molecule versus your competitor. Again, it's an antibody fragment instead of a full-blown monoclonal antibody. So maybe the ability to cross the blood-brain barrier is a little different versus your competitors. Just walk us through why you think you can differentiate on the CNS side and what are some of the endpoints that you're actually using to potentially capture that benefit.

So Force Platform was designed to deliver the payload into muscle, CNS, ARC, and of course other muscles as well. And we do see that in our clinical data. and we also looked in our clinical data and we showed in deliver the md high which is a patient reported outcome or pro we looked at cns subscales of md high and showed improvement at six months and at 12 months so that's our first clinical signal in our phase three trial which is a harmonia trial we also have md high as a secondary endpoint we will we also have built into it our exploratory endpoints one is a digital endpoint so we're using an accelerometer called leap so to do actigraphy to look at circadian rhythms as well as heart and motion of course we also have fatigue and excessive daytime sleepiness scales in that and cog stage which tests cognition as you know in the dm1 world the cns endpoints are still emerging and as far as i know we're the first interventional study to use CNS endpoints. I think that speaks to the strength of the platform.

Gotcha. That's actually very helpful. I'm not sure I appreciated that dynamic. Can you maybe remind, let's pivot to HARMONIA, which is obviously the confirmatory trial here. Can you just maybe talk about why you decided to use five times sit-to-stand as the primary point is a whole debate around what's the kind of, again, we talked about VHOT earlier, and it's obviously a very heterogeneous disease. DM1 and there's a lot of different manifestations for those patients so why do you decide to use five times sit to stand as the primary point for the confirmatory trial and then how should we think about timelines here like again in a scenario where we will have to wait for this trial to actually get to market what's the lag between the trial that it's power to show benefit of VHAT versus harmonia how should we think?

Yeah I'll take the five times sit to stand I'll give the timing question to Eric. So, you know, VHOD, which is hand myotonia, when patients go into the clinic, the doctor will ask them to hold their finger. They can hold it, but can't let go, which is the hand myotonia. It's a good diagnostic tool, but it's not very clinically meaningful to DM1 patients as multiple muscles are involved, right? So it's an early clinical endpoint, which is why we're using it as an intermediate clinical endpoint, which may be a predictor of what's to come. for a more complete clinically meaningful endpoint we're using five times sit to stand that requires five times transfers of sitting and standing so acceleration and deacceleration of different muscles or patients are going through and that takes into account the strength in the leg muscles the myotonia in the leg muscle the strength in the trunk and the core muscles the posture it is also an independent measure of the risk for falls and dm1 patients are known to have falls so we're using this endpoint we think is clinically meaningful we also have shown in our

delivered data improvement in five times to stand so improving at six months and deepening into 12 months so you know confident using this more clinically meaningful endpoint true gotcha that's helpful i know we're already almost out of time here but maybe uh let's pivot to fshd what's the kind of latest thinking gun on that program you know when when can you potentially enter the clinic there um oh and then maybe i want to go back to eric maybe 30 seconds on the prior question i'm not sure if we gave you the opportunity to answer that question but love to maybe let's go there let's talk about the lag between the trial the potential lead to accelerate approval for vhat versus harmonia again that's question number one and then maybe going back to you ron give us an

update on on fshd so obviously you know we couldn't be excited more excited about having the harmonia trial up and running obviously we've had tremendous demand with achieve at the end particularly we've been kicking it off with as you would expect the investigator meetings and the enthusiasm is great and and we really look forward to moving this along as quick as possible we want that data we want that functional data but as quick as we can get it but we haven't commented on the timing yet and uh you know at some point we'll we'll say something more but it's a little too early sure if it just kicked off sure ron yeah for fshd very excited about

the program next one to enter the clinic we haven't really given any guidance on timing for this program but i'm very excited because one as i said for the platform the fab penetrates tissue better it's an you know opportunity to get into satellite cells which are important for the disease uh also since we don't see anemia we won't be dose limited but early days comment on that uh i mean not on i mean definitely definitely no anemia but depending on where we go with the dose um and you know we've also shown some preclinical data recently for our taos and just kind of giving a plug-in for that. But those programs, we're doing in a capital-efficient way such that we take them to a preclinical endpoint. We can do that very capital-efficiently and we're allocating our capital. And Eric can talk more about this and programs that are listed on our pipeline.

Gotcha. So maybe expand on that, Eric, a little bit and kind of capital efficiency and FSHD I guess what kind of go-no-go decision for FSHD? Maybe in the context of some of the commentary for Novartis, it felt to me that Avidity was always pretty vocal about potentially getting accelerator approval based on a circulating biomarker versus it feels to me that in the latest earnings call that were maybe walking back a little bit of commentary. So again, what's the urgency here to add a third program to the pipeline? What's go-no-go and timing?

Yeah, so in terms of the urgency to add a third program to the pipeline, obviously, FSHD is a massive unmet need. From an operational standpoint, it not only leverages our manufacturing, but also leverages the commercial infrastructure that we have. Talking about patients that are at the same centers as DM1 and DMD. So to put a third product in the bag has tremendous financial leverage as you get into that launch. You know, in terms of timing, obviously, you know, we haven't really commented on that, but it is something that is absolutely top of mind. We're very excited about the potential that we have in FSHD to bring something differentiated to the folks with that.

Gotcha. Any comment there, maybe, Ron, on the biomarker potential strategy for, again, I know super early program.

You know, we're excited to learn from Novartis' program.

Okay, that's helpful. And we're out of time. Maybe, Eric, big picture, last question, then we'll let you guys go. What do you think is the most underappreciated aspects of the dying story today?

Yeah, I mean, I think, you know, the story that we're telling is really one of execution and bringing DMD, DM1 to market, getting the other molecules in the clinic. We think we have a tremendous growth trajectory ahead of us in the coming years. And we're really excited to just answer more questions from investors and get moving.

Sure. And on that note, thanks again, Eric and Ron. Appreciate it. Fantastic conversation. I have a lot more questions, but no more time. So thanks, everyone, for joining. We'll talk soon. Thanks again. Thank you very much. Thank you very much.