Dyne Therapeutics, Inc. (DYN) September 2026 Conference Transcript

Brian Squarney, one of Baird's Senior Biotech Analysts. I'm really excited to have Dyne Therapeutics with us in a fireside chat. I think this is a really exciting company. They've got a number of awesome programs going on in the muscular disease space. Maybe to start, John, would you mind providing just a little bit of background on Dyne as a company, the broader approach on technology that sort of underplays your efforts in rare muscle diseases?

Yeah, happy to, Brian. Good to be here. Thanks for hosting us. I think dying was really built on the notion that the delivery of genetic medicines, oligonucleotides, and neuromuscular diseases needed to be done in a way that would broadly and fully distribute the oligonucleotides to tissue and across the blood-brain barrier, and to do so in a way that would be considered a safe way to do that. The intentional design of our platform, and it was very intentional, was that we would use the targeting of the transferrin-1 receptor, which others have used, which naturally transports iron into cells. And we would use that, target that particular receptor, not with a monoclonal antibody like most, but with a monovalent FAB. and the idea behind that was that what people had seen with MAVs is that you tended to block that transferrin receptor and you would be limited by anemia and we always had a concern that you didn't we wanted to avoid any cross-linking of multiple transferrin receptors particularly around the blood-brain barrier and so we intentionally designed a fab that would allow us to deliver to the CNS, broadly to tissue, a much smaller molecule than you, about a third of the size of a MAD, so that we could dose escalate in a way without seeing anemia and deliver high quantities of genetic medicines. That was always the, everybody knew the genetic basis for things like DMD and DM1. The challenge was being able to deliver enough of the payload. And the science this is a dying is before I came but this reason I came as we started this actually see pharmacology and ability to dose higher that you started to see kind of functional improvement and last year in 2025 we had actually I think validated this platform and two really tough diseases DMD and DM1 in both of those diseases across multiple functional measures we didn't just show slowing of decline, which is what most people would hope to see it best. We actually saw functional improvement from baseline and from placebo, both in DMD and in DM1. So this year has been all about execution, and we're hoping to launch our first product next year.

Great. So we've got a hot topic here, specifically in DM1. Novartis had like a really bad weekend, Labor Day weekend. And the company they acquired last year, Avidity, the two of you have sort of been in a competitive horse race over the last couple of years, specifically in DM1, beyond DM1, but in TFR1. And maybe kind of walk through what you see as the differences between ZBAS's role in treating DM1 and what the Avidity Novartis drug is able to do and sort of how to kind of compare and contrast some of the biomarker data.

I'm happy to do that. Listen, when we saw the announcement recently that they had failed to hit on their primary endpoint, the video hand-opening time for hemiotonia, we were surprised because that is a particular endpoint in DM1 that is, it moves early, it moves easily, and it moves with very little biological activity, meaning drug activity. So we had anticipated that they would hit on that. um we've gone back and really taken a look at it and I I think what we should first start with is the fundamental biology foundationally just foundationally we have a very different molecule and really I think in two ways one is the payload and one is a distribution if I start with the payload that's really important because I think you know Brian with this disease with DM1 the target has to be the nucleus. The target, more specifically, is the mutant DMPK that is causing the misplicing that cannot get out of the nucleus. Our payload is an antisense oligonucleotide because that payload gets to the nucleus. The other drug that you're referring to with Novartis is an siRNA. SiRNA acts in the cytoplasm. So getting, you know, kind of the first principle of making sure you're getting enough drug to the target to get sufficient splicing is key. So that's one point, and we can talk a little bit about the trial differences in a second. The second point is that it's not just getting to the target, but it's about enough payload to the target to drive enough of what we call splicing correction. And there's a way to measure that. It's called the CASI analytic. We measure that in every single patient. And when we did our dosing at a very low dose, the first dose in the multisending dose study, 1.8 mg per kg, we saw VHOP moving. It moves with very little splicing correction, but we didn't stop. We kept dosing higher. We went all the way up to 6.8 mg per kg. VHOT was taken care of, but then we started seeing potentially CNS effects. We started seeing broad functional improvement across multiple measures, and that's how we selected our dose. So that distribution, and what I described before with the fab, us being able to go to a higher dose without the kind of safety limitations that are referred to, allowed us, we believe, to get a very different level of targeting and amount of material to the nucleus unlike the other product. Now when we go back and just look at some of their early work and I really would like to I hope Novartis releases some of this data so we can all learn maybe there were just some some outliers things we can learn about VHOT but if you go back to their Marina study at their low dose their first dose two mg per kg they did not see much in terms of VHOT. They went to 4MIG and that's when they saw good VHOT response. But that was dosed every six weeks. And then they went into the phase three, spreading out the dose to every eight weeks. If you were sort of on the cusp of having enough and their splicing numbers were never very high, unlike what we had seen. Fundamentally, you have got to get splicing. That's where the truth lies. And if they were borderline on that, which would make sense if they're not getting the nucleus, you would expect with an endpoint like VHOT, which has variability, that you've got to be definitive about getting enough material there.

Great. Yeah, I mean, I never got the, I mean, I was always bullish on your program over avidity because of the CASI-22 could never understand how, you know, if you can't have an impact on the biomarker.

I remember you making that point before. I agree with you.

So, you know, why don't you talk to us a little bit about the Achieve data that you've shown so far, and as we're looking at potentially pivotal cohort data that's coming out early next year, you know, what data are you going to share, and what do you sort of anticipate both across, like, DMPK knockdown, CASI 22, and VHOP measurements sort of put you in a good position to file an accelerated approval with the FDA?

Yeah, I would get, I mean, in terms of the data, I'll go back a bit to, again, sort of the fundamental foundational biology here. We had presented some time ago, and I think it was actually at a J.P. Morgan conference the first time about a year and a half ago. We presented data from our MAD study, which showed at the 6.8 mg per kg registrational dose, we showed DMPK knockdown. then we showed splicing correction all at three months we saw about 25 percent splicing correction that's a very significant we think a biologically meaningful number and then what we saw at six months was across five or six different functional measures broad functional improvement strength five times sit to stand 10 meter walk run even on patient reported outcomes related to cns so those were that is basically all the biology adding up that was the data we had presented now that was for that cohort of 6.8 that was six patients so that brings me to what we're going to be presenting coming forward we actually Brian we had anticipated that Novartis at this time would be saying they hit on VHOT and we were looking forward to comparing our secondaries and functionals. And so we actually did a data cut on the long-term extension data from that group that was part of the AchieveMap. And we did that at 12 months, 25 total patients. We'll be presenting data from that. So you'll see the various functional measures, you'll see if they stand up compared to what we saw with the original N of six, you'll see MD high data, and particularly you'll also will show the CNS subscales, all of which will be, you know, in this disease, CNS is also a very important part of the disease and debilitating. And then the other piece, and it'll be compared with propensity matching to natural history. So I think it'll be a really a fulsome opportunity to look at that, but you'll also see VHOT, and you can look at VHOT at six months, and I remind you, we're applying for accelerator approval. So what we want to be able to say is, VHOT is a reasonable predictor of functional benefit downstream. So you'll have the six-month VHOT data, you'll see how that changes, and then you'll see the various functional measures and whether we have the kinds of trends. That gives people an idea, are we meeting the expectation for an accelerated approval package? And then the final piece of data that I think people are interested in is around VHOT. People want to understand, are the baseline characteristics of our patients in the registrational expansion cohort? That's what we're going to file on for the AA. Does it match up with what we saw in the MAD? So we'll show a VHOP baseline, compare that to the MAD, and people can come to their own conclusions about, you know, how they feel about the probability of success and the powering and so on.

Great. And then you're also running the confirmatory or start plan. It's start the confirmatory study as well. You have a different take in terms of primary endpoint. You know, how do you think about kind of the endpoint that you're utilizing versus sort of the primary VHOT endpoint that Avidity and Novartis views and how that translates into sort of like utilization and predictive functional?

You know, you've heard me say this before, all of us who've done this. We always felt that VHOT made sense as an intermediate clinical endpoint, not a great endpoint in terms of clinical meaningfulness for a Phase III. And we always said we will not use it for a Phase III, and that was in part based on conversations we had along the way with the FDA. Appropriate is an intermediate clinical endpoint for AA. for the phase three we said we are going to have a clinically meaningful a primary endpoint we liked and after talking to the FDA a timed function test five times sit to stand after talking to KOLs and looking at all of our data from the MAD study we came to the conclusion and with the FDA and for our phase three that this would be the primary endpoint it's clinically meaningful in multiple ways. It involves core strength, truncal strength, it involves quad strength, it involves the ability just from fatigue and so on to be able to follow instruction and get up and down. People know that five times sit to stand in other diseases relates to fall risk which is really important for morbidity. So we think we've got, I think it, we think it's a definitive endpoint for the future in this field and that's what we have in that study the only other point I make it's amazing how we've talked over the last couple of years Brian we've I think we've all assumed we were going to be second to market man did that change in the last week it's just so things have been so dynamic and now I think we're the only company with an actual phase three that is enrolling, it's actively enrolling around a primary endpoint that we think is the right endpoint.

Yeah, I mean, on one hand, it's given some caution around VHOT readings, but yeah, certainly a good point that, like, the stock would be up 20, 30 percent on positive VHOT data if Avidity was filed with positive data.

Yeah.

Now it's like 150 percent on positive data, right? Maybe moving on to, you know, the next leg, DMD. This is also a very interesting story. There's obviously a number of comparable drugs that have already been approved on much lower levels of dystrophin. So sort of walk us through, you know, what you've been able to achieve here in terms of targeted muscle dystrophin production and your current standing with the FDA.

Yeah, I'm glad we're talking about that. I mean, we're a company that is getting ready to launch our first drug in an area of massive unmet need, where the reimbursement pathways have been established, where the patients are known. It is a wonderful market for us to step into. And speaking of unmet need, I mean, nobody has really been able to show a functional improvement, maybe a slowing of decline on current treatments which brings me to the kind of data that we've had okay I think people have always wondered what dystrophin level everybody focused on dystrophin because that's that's clearly the protein that's missing what dystrophin level do you need to see an impact functionally that would result in efficacy and I really felt like we might be able to come be the company that can actually answer that question for the first time because nobody's gotten to the different numbers that would matter sufficiently and they certainly weren't distributing enough dystrophin deeply broadly to the tissue to have an impact I think with our fab we're getting that kind of distribution so we saw that with these patients exon 51 they have very low natural skipping meaning very low natural dystrophin less than half a percent we at six months we're over five percent that's a six months now it's a Adjusted for muscle content because they have fat and so on over five percent at six months And even at that level at six months, we saw that we had improvement from baseline on things like stride velocity ambulatory tests like NSA and time from floor Rise from floor velocity These are really incredibly important. They're all the standard measures. We even saw improvement on upper limbs strength and then we took data that went out even further and we saw further improvement we saw cardiac improvement pulmonary improvement so or at least stabilization and that's what you want as these boys go in when they go into a wheelchair you really need to stabilize around the diaphragm and the cardiac so the data was it's just remarkable data we even had taken a few biopsies that we presented mda they were just four optional biopsies you only want to take so many biopsies from the boys so you take them to six months we know that's not the peak discipline level we thought based upon our modeling that the discipline level would double so you get to kind of double digits low double digits over about i don't know 12 15 months we took four biopsies from boys the age 12 to 12 to 24 months after their dose of dosing the number had roughly tripled, roughly tripled. So people were 18, 19%. I mean, those are, it's just a remarkable distribution number. And we're seeing functional improvement across virtually every measure is six months, 18 months, 24 months. I really believe we have a chance to become the foundational therapy in this field. We need to get everyone with Exxon 51.

I hope they will get exposed to this drug and we're preparing to launch it in early next year yeah so on that front you have january 21st padufa day um i would assume at this point you're well past the mid-cycle review maybe knocking on a late cycle review um normally i wouldn't ask the recent sort of change in in leadership at fda with a permanent appointment to cedar uh if it matters but i don't think there's ever been a drug approved for dmd where there wasn't a center director intervention so i guess Does Michael's permanent appointment as CEDAR director, does that impact you guys? It would seem like that would be a positive, given his neuro background.

I think people had some concerns previously with some of the leadership about AA. We have not seen that kind of concern in our interactions with the FDA. I you know I don't okay our design of this trial was such that we should not have to get an exception we shouldn't have somebody intervene we're hitting on dystrophin where it's it's the sick change in dystrophin is statistically significant really significant you have to have trends on function you don't you don't need spectacles to see the trends that were shown in fact we have nominal p-values on two of those measures so and then we've got a placebo control group you've got 32 patients in the rec we had 50 plus patients in the mad all of that data in totality this is a this is how you should do percent an AA package and so we feel we feel very good about it and our interactions with the with the agency have been highly professional.

Great. So when we think about commercial launch here, I mean, Exondus 51 is obviously on the market. There's a number of, I don't know if I would say liabilities, but certainly things that you can counter detail on, whether it be from the dystrophin production, the frequency of dosing. How do you think about the addressable commercial opportunity in terms of patients who never took Exondus 51, patients who dropped off of Exondus 51 for one reason or another versus patients who are, you know, converting patients on Exondis 51 and like where's sort of the low-hanging fruit at launch for you guys?

Well, let me start by saying we started organizing with some confidence for a commercial launch over a year ago. And the investments, and I'll tell you one of the reasons Eric Lucero was sitting here with me, joined the company the CFO was because he saw the opportunity so near term with DMD even a broader franchise which we can talk about but so the commercial team we have built that with neuromuscular experts people working on market access and we have been studying that market deeply and to get to your question then, we see the market is having roughly 1,600 Exxon 51 amenable patients in the United States. There's only about 500, four to 500 that are on the current, if you want to call this standard of care, I guess Exxon 51, they have to get dosed every week. A significant portion of patients dropped off of that drug. They quit. You just don't see the results. They get discouraged weekly dosing so there's probably of the four to five hundred another three hundred or so that are quitters all of those are I think people that are astute to it they're aware and they're willing if you could if they could dose once a month like with our drug and when you see the kind of functional data I would expect them to switch and I sure I would hope they do for their sake. Now the other part of this I think that will be, I think you said low-hanging fruit or whatever, but I think that the group that will be very responsive are the clinicians. The clinicians who are the top clinicians around the country that have dosed patients with our drug, I think they see it as a foundational therapy. Like you get them on the drug. Maybe you use gene therapy on top of it, maybe you use some of the other anti-inflammatories, you obviously can use steroids. But those are people that really understand the drug. And I think it's incumbent upon us and our commercial team to make sure that this entire community is aware of it because there are so many people out there. I just left another 800 that are essentially maybe a few tri-gene therapy. Most have just used steroids. They just have not believed that anything is move on the needle. We need to make sure everybody's aware of what we have.

Right. And then just when we kind of look at CMC and commercial supply, no interruption to launch Exondus 51. Naked PMO had a much different cost of manufacture. There were supply limitations. Any of that here? Do you feel adequate that you could meet any demand that comes out? And how do you kind of compare and contrast cogs of like naked PMO versus TR-F01?

Well, the cogs have to be higher than just a naked PMO, right? Obviously, we're making a fab and a linker, and we're conjugating. It's a very different molecule than a naked PMO and has very different results, obviously. But I will tell you, I spent a lot of my life in CMC, tech ops, formerly of Biogen. I brought in some really great people. We have a chief technology officer, Rajman Chanda, who has worked with me in the past and in other places. We have been working on supply chain now for a couple of years, preparing for this moment, and all of that is on track. That includes scale up, that includes redundancy in certain nodes of the supply chain, that includes building inventory relative to the commercial forecast analysis with some potential upside. So I think we feel, I know we feel pretty good about where we are with kind of inventory build.

Got it, and then just last question on DMD, Obviously, there's a number of other exon-amendable subgroups that are targeted with commercial therapy right now. What are the plans upon successful approval and launch here in terms of expanding to other exons?

Eric, do you want to roll with that?

Yeah, I can roll with that. Obviously, the response we got from the patient community on the other exon, or DMD51, was tremendous. But following on that, a lot of people are like, well, what about my boy? They have a different exon. So I think we feel a tremendous desire, a need, a burden to get the other exons out as quickly as possible. So to that end, we were able to find some money in the budget this year. We accelerated IND-enabling tox studies. We accelerated some of the CMC. So that way we could get to the point where after we get approval for 51, knock on wood, we can have the conversation with the FDA about a development plan. Currently, if Doug were here, he would say he'd like to do a basket trial. I think that makes sense from an incidence and prevalence standpoint, and we'll get into that at the appropriate point. But this is a very high priority for us. We're moving it as fast as we can, and we look forward to getting those discussions going with the FDA post-approval of 51.

And you recently put in a program into the clinic in FSHD. I've been eagerly anticipating this for a while now. You know, Novartis, to give them some credit, they're not just trying to pivot to FSHD now with Avidity, but they were very enthusiastic about it on acquisition. Can you kind of walk through the compare and contrast in terms of your goals with the FSHD for them?

Listen, I think what is similar is we're both using an siRNA in this case. It is a cytoplasmic target. And so I think they have the right target. And what they did show was roughly 50% knockdown in the Dux4 transcriptome. and that uh that is a good indicator that there's activity now um we're going to use a fab that's our difference i think back to what i was saying at the beginning um we have an opportunity to dose higher reducing duct ducts four has this intermittent expression and so i think this distribution, broad coverage, and potentially being able to dose to a higher level to reduce that Dux4 even more could be an advantage for us. There's some other kind of design features and how we've designed our sRNA, which we haven't discussed yet. But that ability with our fab to dose in a different way may give us some advantages.

Whatever the case, this is a big market too sure is um maybe last question for eric cash was uh just about 900 million um in in june uh uh funding operations to second quarter of 28 does that runway assume revenue from xeros how does that kind of like yeah we have the full commercial build and commercial p l in there so okay um but the runway is not including revenue from xeros anderson oh yeah that was your question yeah Yeah, so it's only on the spend side. That could be a big offset there and I guess just last question would be kind of what are the key three or four catalysts to look for over the next year? It seems like there's a lot.

There's some good ones. Yeah, there's some good ones. So listen, I think the first is approval of the Russell Dersen. You know the Purdue for the January 21st. So for a company like us in a market like that and the opportunity to become the leading company in DMV that ought to be a that's a meaningful catalyst for us I'll tell you we're geared up for it internally. I think the other big catalyst is we've also told people in Q1 we will have the readout of that registrational expansion cohort so people are going to talk about VHOT a lot between now and then fortunately all that kind of gets settled in q1 and we present kind of the functional trends around that that that that really we talked that's a really important catalyst for the company and we're excited about it we also as you mentioned we've started we initiated the FSHD so you know that's about getting we need to get our first patient in and move forward with that program. And then I think this conversation that we just had about meeting with the FDA and start designing a basket trial, if we can make that, and I don't have dates for you around it, but we can do that, that will be, that really gives us an opportunity to essentially triple the market size fairly rapidly. And then, you know, we've talked about getting into later next year in terms of having our BLA for ZBASA-Barsan. So, man, those are, that ought to move the needle for a company like us.

Yeah, it's going to be a different conversation here next year.

I'm looking forward to it.

All right.

Eric, thanks so much for the time today.

Appreciate it.