Great. Thanks very much. Happy to be here with the Dyne management team. With me is Erick Lucera, CFO, and Ranjan Batra, CSO. Thank you both for joining. Appreciate it. And yeah, maybe we'll get started with Erick just giving some opening remarks and setting the stage on 2026 for Dyne, and then we'll do some Q&A. Thank you very much.
Yeah. Thanks, Paul. We're excited to be here and appreciate the support from Stifel, you know, not only with me at Dyne, but going way back to my first IPO many years ago. I've been at Dyne for about a year, and you know, really excited to come here, one, for the launch, but two, as many of you know, I spent 15 years on the investment side, on the buy side, and I really thought that this was an attractive investment opportunity as well. I still think like an investor, and I think 2026 is setting up for us as a breakout year, which might be, you know, a little bit surprising to some people. We see this as a year where we're gonna validate a lot of what we've done.
You know, 2025 was a year where we clinically validated all of our platform in humans across a couple different diseases. This year is the year where we're gonna transition towards a commercial company, be a fully integrated biotech company. We've got a couple of different events, whether it's the completion of the REC for DM1 enrollment, filing the BLA for DMD, and as you know, FSHD is our next product to be in the clinic. We expect this to be a busy year for us. You know, a year from now we'll be, you know, hopefully approved on the market with DMD and transforming that market. A year later, hopefully we'll be bringing another product to market for DM1. You know, we're really excited about what we have.
There are few companies in biotech that fully own all of their assets. We think we have a great platform that has allowed us to expand not only into DM1 and DMD, but also the other exons in DMD, FSHD and Pompe. In total, we'll have eight products in the clinic over the next couple years, and we think we can develop a real compelling, growth story over the next ten years.
Yeah
excited to be here, and thank you for your support, and look forward to taking some questions.
Okay, great, Erick. Thanks. Thanks so much. I mean, yeah, you guys just showed some updated data from the DMD program, which looks great. Do you wanna just maybe like walk through that data and like the high level key points on the case that you're making for accelerated approval here?
Yeah, happy to talk about the DMD data for our drug called Z-rostudirsen, Paul. In December, we announced some exciting positive top-line results for exon 51 DMD that we demonstrated for the first time ability of a treatment to deliver sustained functional improvement in this devastating disease. Currently, this disease area is quite underserved. The strong results represent a pivotal milestone for Dyne and also our FORCE platform. We believe that we have a clinical validation with our FORCE platform. Specifically on the results for the DELIVER data that we showed in December, just to remind you, the DELIVER study started with a MAD cohort, where we selected the registrational dose of 20 mg/kg, and this is dosed Q4W.
In the REC cohort, we enrolled 32 patients, 3:1 randomized, 24 on drug and eight on placebo. We chose dystrophin as our primary endpoint at six months. At six months, we saw statistically significant and robust increases in dystrophin expression, and this is both on adjusted and muscle-adjusted dystrophin and unadjusted dystrophin, and they both showed sevenfold improvement. That means that this meets the primary study endpoint. This is, just to remind you, this is tenfold higher than the PMO that's being used as standard of care, and that's dosed every week, so this is every four weeks. What's most important for the DMD patients is what we saw in terms of functional improvement. Function is what matters.
We looked at six functional endpoints, and this is for time to rise, ambulation, right upper limb function, as well as respiratory function and lung capacity, and we showed improvement in all six endpoints. We powered this study for stat sig on dystrophin, but showing that two endpoints that we have for function, time to rise velocity as well as ten-meter walk/run velocity, met stat sig, and we had the nominal p-value of 0.05, or less than 0.05. We're really excited about the data. I think also we saw preservation of lung capacity, which is huge, and this is at an early point of six months. We also shared long-term data at 24 months, and we show improvement in all six functional endpoints compared to baseline.
We also released some data recently at MDA, and we had an optional biopsy built into the cohort, so we were able to get biopsies from four patients at 12+ months, and we see adjusted dystrophin at greater than 18% and unadjusted at 9%. This really speaks to, you know, more time on drug leading to better dystrophin and better functional endpoints. Overall, lastly, I want to say the safety remains favorable. We have over 1,400 doses, 36 months of follow-up, and, you know, the safety is looking overall favorable with increase in dystrophin and functional improvement.
Yep. Okay. Great. Great overview. With that stage set, right, I think, you know, one of the big concerns that people have had, just not about Dyne, but the whole rare disease space, is just what's going on with the FDA, and is the FDA, you know, going back on certain agreements with different companies? It's a fluid process, right? Obviously, we saw changes now last week at the FDA. In the context of that, do you wanna just review, like, your regulatory alignment here, and the firmness of your confidence that you've met or exceeded what the FDA wants for accelerated approval for DMD?
Yeah, obviously one of the most important questions that we get asked almost every single meeting is the regulatory environment. You know, let me start by saying, you know, it's my view that not all submissions are equal. I think, you know, a lot of people will just assume that a filing goes in, and it's all perfect and all that. You know, there's a lot of things that go into this. When we started looking at some of the other Accelerated Approvals that have happened or not happened in the last year, you know, we saw a couple of patterns. You know, the companies that were getting Accelerated Approval, all of them had internal placebo controls. They were all in CDER. The ones that were not getting approval, they were using natural history comparisons, and they had small n's, right?
I think, you know, going back to what I said, not all submissions are equal, and you look at sort of what's going into our package and our submission. Again, reminding everyone, we have Breakthrough Therapy designation to start, which entitles us to a more frequent and higher level of interaction with the agency. You know, we've listened very carefully to what they're saying. We, you know, we have a very large data set that is in the range of the companies that have been getting Accelerated Approval, so we feel good about that. We do have placebo control arm, which again is in line with the companies that are getting the Accelerated Approval. You know, so we feel really good about the data that we've shown.
I think the feedback from the community has been indicative of the quality of the data that's going into this. You know, the other thing that I can say is recently within the DMD space, there was a competitor that recently announced that they had met with the FDA to talk about accelerated approval and using dystrophin as an endpoint and for accelerated approval, and that was all proceeding on track. We've said that, you know, we're doing all the things that you would expect us to do, all the meetings that you would expect, and we're confident that our filing for the BLA for DMD is on track for the second quarter.
Yeah. Yep. Okay. I think everyone talks about the alignment around efficacy, but in your conversations with the FDA, like how clear-cut was it as it relates to the exact safety database you need?
I mean, we have a pretty large safety database if you look at the number of patients that we have. You know, we have a total of 86 patients for Zros, and when you compare that to some of the other products that have gone in our database for safety is well in excess of what other folks have been submitting.
Right
I feel really good about that.
Okay, great. Okay, very good. Are you expecting Priority Review?
Yeah. Obviously.
Hopefully. Yeah, yeah.
It's obviously.
Priority Review
It's expectation, but we'll see what happens, right? Yeah.
Yeah. Okay. Fair enough.
We've always said that as long as it's
Yes. Okay, great. All right. Well, in the meantime, what are you doing to prepare for launch, and how much are you gonna, you know, make those investments like ahead of the PDUFA versus after?
Yeah, I mean, look, it's obviously really important to prepare for the launch. As you become commercial, the success of the launch is the single most important thing that investors are gonna focus on, and we're well aware of that. In terms of what we are doing, obviously about two years ago, a year and a half ago, we hired Johanna Friedl-Naderer, who led the launch of Spinraza at Biogen, which is another rare disease out there. She has built a team of people that have significant rare disease launch experience. Whether it's, you know, reimbursement or marketing, market research, whatever, we are bringing a team of people that have done this before, up and down the organization.
You know, one of the things about the market that I think which is great, you know, we're going into a well-defined market, right? We're bringing a great group of people with a differentiated asset to go into a market with existing reimbursement, where the patients are very well known and characterized, where the organizations, the patient organizations are very strong. The advocacy levels are really high. You know, from a return on capital standpoint, this is one of the most capital efficient opportunities that I've seen in 30 years of biotech, where, you know, we could have all of the products that we're pursuing going into about 100 muscle centers in the U.S. For example, in DMD, about 80% of the patients are in those 100 muscle centers. You're talking about a pretty capital efficient sales force.
That's what we're doing on sort of the commercial side. From a CMC inventory, you know, we've been building an inventory for as long as I've been here. We've got a dual source for every component of our supply chain from around the world. As you know, John Cox ran tech ops at Biogen, so he knows what he's doing. We're getting prepared on the commercial, the marketing, the reimbursement side with people that have done this going into a market that's well-defined. We know exactly where the patients are, and we've got the right people building inventory for us.
Awesome. Okay. Very good. When you think about the commercial market, is the right benchmark Exondys, or do you feel like you could get either deeper penetration or higher pricing? Any preliminary thoughts there?
Yeah, I mean, I think it's obviously too early to comment on reimbursement. I'd say, you know, in my 30 years of biotech, most companies don't talk about pricing until you have a label and you're starting to price for it. I think, you know, having said all that, if you look at the existing products, they're once a week or once a month, and most of them don't have any functional benefits. We're gonna bring a better product with a better dosing schedule to market, and we'll see at the time, you know, what that bears.
Yep. Yep. Okay. How fast can you move with other exons?
Well, I think that, you know, the other exons are a key component of our growth story. If you think about how do we build a company that can sustain growth into the next decade, the other exons are a key component of that. We're so lucky that the FORCE platform allows us to pursue this with the same linker, the same Fab, the same oligochemistry, you know. I'll give Ran a second here. In a moment I'll turn it over to him to kind of talk about how fast we can get there. This is a top priority for us. We think all four of these assets are significantly less risky than a typical preclinical molecule that's out there based on what I said earlier about the composition of the Fab being the same, the linker the same.
You know, the patients are largely the same, the measurements in the field are the same, the doctors are the same. With that, I'll turn it to Ran to kind of talk about how do we get to market.
Yeah. Hey, Paul. I've been in the DMD DM1 space for about 20 years, and I hear from a lot of KOLs, you know, patients, they're asking for Z-rostudirsen and exons beyond, right? There's a lot of excitement about our drug, but then leading into other exons. I'm really happy that the exons are in IND-enabling phase. You know, we had declared that we had development candidates. They're now in IND-enabling studies. We want to start GMP manufacturing. We wanna, you know, do IND-enabling studies and line it up strategically with the approval of Z-rostudirsen. You know, from there, we'll figure out an accelerated path to bring these exons to the market. Overall, very, like, very high excitement internally and externally for the exons.
As Erick mentioned, the probability of success for these exons are particularly high because it's the same backbone chemistry, right?
Right.
Same path, same linker. The PK and PD is not changing. For these exons, we've always said that exon 51's hardest to skip. With these other exons, we already, in our preclinical studies, see higher levels of exon skipping, so we're very excited.
Okay. Anything you can say on, like, where you're going next and the timelines?
No. It's too early to talk about timelines for that.
Okay. All right. Well, in the meantime, you just confirmed, or I guess firmed up your confirmatory study, for DM1. Maybe talk about that, and then, you know, you know Erick, right? There's, like, a lot of focus on the regulatory path in DM1, accelerated versus full. You know, should we interpret you guys firming up a confirmatory study as, like, adding more recent corroboration that the FDA is on board with accelerated, or is that not the right way to think about it?
I mean, look, I'll turn it over to Ran in a second to kinda talk about that. I think when you think of the totality of our development plan, again, Breakthrough Therapy designation, we're having conversations not only about the REC but also the phase III. It's all tied together. You know, again, we feel really confident about what we've been able to see out of the FDA over the last year or two. You know, Ran, if you feel like you wanna talk a little bit more about that.
Yeah. Happy to talk about the confirmatory study.
Just to remind you, Paul, we're using VHOT as an intermediate clinical endpoint for our REC cohort, and we cannot use this as our phase III endpoint, and we don't really want a myotonia label, and John will say that if he was here. We're using in the confirmatory study an endpoint that shows broad functional improvement in DM1. I think this is really the right endpoint. We're using Five Times Sit to Stand, which is already a secondary endpoint for ACHIEVE. We already have data on it, and we showed at World Muscle Society and thereafter that this improves at six months and then deepens at 12. We have alignment with the FDA on our phase III confirmatory. We have the sites already open for enrollment, like, the first initial sites.
We're fully powered to deliver statistical significance on Five Times Sit- to- Stand with 150 patients that are gonna go into the study at the registrational dose of 6.8 milligrams per kilogram every eight weeks, so Q8W. As we call it, this is a field-defining phase III Five Times Sit- to- Stand endpoint because it not only takes into account hand myotonia, but it takes into account whole body myotonia and strength. Strength in the core muscles, postural muscles, and going through acceleration, deceleration of repeated sitting and standing. It's very well correlated with independence on activities of daily living or ADLs in the patients, their respiratory functions, and prediction and predictability for the risk of falls. We think this is really the whole endpoint that we wanna use.
Yeah.
It's a phase III study, right? As you know that CNS is our big differentiator, so we also have endpoints to look at CNS function, you know, fatigue, excessive daytime sleepiness, as well as cognition endpoints. Finally, didn't talk about it, but our secondaries do include, you know, of course, myotonia, other timed function tests, strength, et cetera.
Right. Okay. Makes sense. Do you wanna talk about the data you already have on this endpoint from the phase I/II on the confirmatory endpoint? 'Cause you do have some data that trends favorably already.
Yeah. You know, we had registrational dose of 6.8 mg per kg. We showed data that at six months we see an improvement, and it deepens at twelve months.
Was that, like, data part of why you picked this endpoint?
That was yeah, one of the reasons we also looked at the natural history for DM1. We also, of course, are having interactions with the KOLs and taking advice from them, which is why we picked this endpoint. Myotonia is not very meaningful to the whole KOL community. It is an early predictor of change in what's about to happen in other muscles and other endpoints.
Right.
We are using myotonia as an early predictor, as an intermediate, clinical endpoint, and then using a more complete endpoint for our phase III.
Yep. Okay. Makes sense. Well, we'll get data likely from Novartis and Avidity later this year. You know, I guess, how would you frame that data in terms of how we should interpret those results and the read-through on to Dyne?
Yeah, I think, one, we should not really compare, like, you know, we should not do cross-trial comparisons. I would like to highlight that, you know, our mechanism of action is different. DM1 is an autosomal dominant disease, right? One copy is mutated, one is a normal copy. The normal copy escapes in the cytoplasm, the mutated copy is in the nucleus. Our drug ASO goes into the nucleus, recruits RNase H1 from the nucleus, and get degradation of these pathogenic RNA foci, and we see that in our preclinical models. We also see changes in splicing because of that in our preclinical models, which we also corroborate in the clinic. It's different in terms of mechanism of action on that, so we're directly hitting the mutant DMPK allele. That's one.
Of course, we get into CNS as well, and then overall in terms of our safety, we haven't seen more anemia compared to our placebo cohorts or DM1 natural history in our trial, whereas a recent paper from Avidity in MARINA trial showed some incidents of anemia. We're definitely, you know, in terms of safety as well differentiated. Overall, I wouldn't really draw any cross-trial comparisons, but we're, you know, it'll be an important data set for the field.
Yeah. Yep, okay. Makes sense. Anything else you wanna add on the DM1 program?
No, I think again we're really excited about, you know, getting the REC enrollment done in the second quarter and reporting out that data in the first quarter of 2027, so.
Yeah. Yep, okay. You know, maybe when you kicked this off, Erick, you, I think you said eight clinical programs in a couple of years. Is that right?
Yeah. I mean, we obviously have the DMD asset, which will be first to market in 2027, and then a year later, we'll have DM1. We've got the four other exons, which are all four separate products. We'll have FSHD, which is the next product we'll have in the clinic, and we have Pompe.
Yeah
As well.
Yep.
That actually is eight products.
Yep. Okay. For the other exons, I know you're not getting super specific, but there are other companies that are, you know, doing 53, 44, right? Like, you feel like there's enough white space there where you can go somewhere where either there's nothing or you can kinda clearly have a good chance at being best?
I mean, I think, look, the only thing we know at this point are two things, one about the FORCE platform and the way it was designed to hit the CNS and to get broad tissue distribution, which I think has shown in exon 51 a level of functional data that nobody else has shown to date. Exon 51, as you know, is the most difficult exon to skip. We feel really good about the differentiation that we will be able to bring to other exons as we get those to patients.
Yeah. Okay. And maybe one other question that I got from someone listening in is just related to VHOT in the Accelerated Approval cohort. I think people who followed the space closely have seen that, you know, VHOT effect size can be somewhat of a function of like finding the right patient baseline and getting it maybe kind of ±10 seconds put you in the best place to maximize effect size and not have too big of a placebo effect. I guess, well, one, do you kind of sort of agree with the premise of that? And then two, like, how are you selecting patients? How are you powered for VHOT in the Accelerated Approval cohort?
Yeah. I can talk about that, Paul. Look, first of all, we're fully powered to deliver on VHOT with the large sample size that we have in our REC, about 460 patient, and it should minimize potential bias due to baseline. For our MAD cohort, the total MAD cohort portion, there were 56 patients, and the average baseline value was 9.2 seconds. You know, we can expect a very similar baseline value for this REC cohort. We also do very well to control, you know, for multiple criteria when we're measuring VHOT or myotonia. We control for temperature as well as, you know, how a centralized reader would read it, you know, digitized voice prompts, maintaining anonymity, making sure that no unblinding happens, and so on.
Very rigorous control protocol. We also make sure that there's no massaging of hands in between. We're conducting this later in the visit. You know, there's a five-minute rest period. A lot of controls built into this. If you think about this statistically with what we have seen from the MAD cohort and total patient population coming in, we expect that the baseline's going to be around, going to be very similar. We feel confident, and we have power to deliver on this.
Okay. On enrollment, like, you know, how's that going, right? Can you just remind us when you expect to fully complete it?
Yeah. We've said that we would get enrollment completed in the second quarter, so we're sticking with that.
Okay. That would put data for what? 1Q 27? Is that right?
Yep.
Right.
Okay. Okay, great. I think we're pretty much up against time. Anything else you guys would like to highlight?
You know, again, thank you for having us. Thank you for the support, not only with Dyne but for, you know, for me personally and for a long time of working with Stifel. We think this is gonna be a great year for Dyne. You know, there's been a lot of things that we've brought in and, you know, we're expecting some big catalysts this year with the completion of the REC enrollment, with the filing and acceptance of the BLA for DMD. As we've always said, FSHD will be the next product that we get in the clinic. You know, we think this will be a great year for us, and look forward to speaking with everyone, and appreciate their support.
Awesome. All right.
Bye.
Thank you, guys, very much. Appreciate it.
Thank you, Paul.
See ya. Bye.