All right. Great. Thanks. Hello, everybody. Luca Issi, senior biotech analyst here at RBC Capital Markets. Today is a great privilege to actually have Dyne as part of our 2026 Global Healthcare Conference. Representing the company, we have Erick J. Lucera, who's the Chief Financial Officer, as well as Ranjan (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 the discussion. Thank you for having me. Great. Maybe Erick, let's start big picture before we go into the specifics. We have a long list of questions here. Maybe just a high level, maybe just talk through some of the progress that the organization has made recently. Yeah. Most importantly, what's next year for Dyne? Yeah. Obviously, this is a great time for us at Dyne. 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. 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. It's a great time to be at Dyne. 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's your take? Is there kind of any implications to the Dyne programs at this point? Maybe Erick, I'll pass it over to you and then. Yeah. Maybe what I'll start out with at 30,000 ft, as a reminder, we have Breakthrough Therapy on both of our products. 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. 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. Really just couldn't be happier with our interaction with the agency. Got you. Maybe Ron, if I can pivot to you. We have seen in the broader field of DMD, some of these skippers getting approved on expression. However, 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 expression as no longer kind of a good surrogate biomarker for Accelerated Approval? Appreciate it, again, you guys are going after exon 51, versus some of these failures have happened in other exons and whatnot. Yeah. What's your take on that? Yeah. VYONDYS, AMONDYS, VILTEPSO got Accelerated Approval, failed confirmatory studies. It's unfortunate for the field, but 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. To top that, we have robust functional improvement, again, in the DELIVER study with 32 patients, three to one randomized, 24 on drug, eight on placebo. We showed functional data with endpoints such as time to rise or rise from floor velocity with nominal p-values of statistical significance. That's great. We'll also be submitting that to the FDA for our Accelerated Approval. Lastly, 24-month data, long-term data for us also is very robust, and we show durable functional improvement at 24 months. We're very confident in the Accelerated Approval pathway for us. Yeah. Especially in the context of you obviously showing a materially higher level of expressions versus some of your competitors, which I think is an important point there as well. You mentioned BLA. How should we think about Standard Review versus Priority Review? There's an argument to be made that there are technically therapeutic alternatives out there, but there's also an argument to be made that this remains a very, very large unmet medical need. What's your level of confidence around Priority Review versus Standard Review? Yeah. 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 we feel good about where that is. Okay. That's actually helpful. Maybe Ron, if I can pivot back to you. This is fresh off the press. Your press release obviously came in earlier today. Can you just maybe talk high level how you're thinking about the confirmatory trial here? It sounds like you're going for a time to rise here, and you have a relatively sizable trial with 90 patients. I believe 73 weeks is the timing of the primary endpoint. Just walk us through why you decided to design the confirmatory trial the way you did. First of all, very excited to say and announce that we have initiated DELIVER, which is our confirmatory trial. It speaks to the execution that the team is doing. We're on track. As you've said, in Q2, we'll initiate the trial. As you said, 90 patients, one-to-one randomized, 72 weeks rise from floor velocity as the primary endpoint. We remain confident, 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. This is a confirmatory trial that will test rise from floor velocity and will also be used for ex U.S. applications or that was always our base case. 18 months is the duration we chose and we're confident in because in a disease like DMD, it takes time to improve the muscle. 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, at through 18 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. Got you. That's helpful. Maybe you already articulated what's the primary point of the confirmatory trial. 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. Yeah. Other endpoints. Why time to rise and not many of the other endpoints? If you know the disease in DMD, and I worked in DMD field and DM1 fields for about 20 years, and in DMD, there is a Gowers' sign, so it's difficulty getting up from the floor. Rise from floor velocity is clinically meaningful. Also there's now precedent that the field is moving in this direction. We're not the only company that's using this endpoint. Lastly, which you said from our DELIVER data, we're very confident in this endpoint. We've shown robust functional improvement with nominal stat values. Is Novartis' and Avidity using time to rise as the primary endpoint for the confirmatory trial for exon 44, is that similar timeframe, like 18 months? I think that is correct on the rise from floor velocity. We chose this endpoint based on our data and what we believe in terms of what we need to see in functional improvement in our patients. Got you. The follow-up to it, maybe I can look it up later I guess, but is the follow-up for their trial somewhat similar or? Yeah, we can look it up later. Okay, that's actually very super helpful. Maybe Erick, if I can pivot back to you, let's talk about the fun part, which is commercial. Absolutely. I love that part. It's kind of still early days, but how are you thinking about pricing at this point for this drug? Obviously Sarepta does set. Yeah. For better or for worse, how should we think about pricing versus what they have done historically? First off, from 30,000 ft, 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. 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, once a month versus once a week is a powerful thing for patients to have. Also functional improvement. We'll see how that all plays out, but right now it's too early to comment on that. We feel really good about launching into this market with the data set that we're bringing. Got you. 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 you just walk us through what's the plan there? Will you need to run separate trial on all of those, or is there a scenario where you can run kind of a quote-unquote basket study, given platform designations and some of the most recent effort from the FDA to potentially speed up the development? Yeah. mostly molecules that shares a lot of the same properties except for the target. Yeah. that they're going after. Yeah. That's exactly right. From our standpoint in drug development, 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 oligo chemistry, same patients, same centers, same physicians. 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, 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. Just anecdotally, when we put out the 51 data, Doug and Ron, who have been in the field for a quarter century and know all of the KOLs, were getting a ton of inbounds congratulating us for the data, but also saying, "Well, what about my boy that has a different exon? Sure. We think there's going to be tremendous interest in these, and we look forward to working with the agency to find a pathway to get these to market. Got you. That's actually super helpful. Maybe if we can pivot to DM1 in the interest of time here. I think you recently increased the sample size a little bit in your trial that could potentially lead to Accelerated Approval. Yeah. Show a benefit in vHOT. Lots of debates with investors around your powering assumptions versus the Avidity powering assumptions, and Novartis' and whatnot. Again, I think it was originally 60, now you're saying it's a little bit higher. Is that because you're less confident in the original powering assumptions, or is that not the right way to think about it? Yeah. We've always believed that we've been fully powered with 60 patients. As you know, we had increased the number of sites that we have been going to. You get to a point where you get this influx of patients into the funnel. Once they're in, you have to analyze what is the screen failure rate, how many more do you need, and then at some point, you call it. Any patient that's in the funnel, you're ethically obligated to keep them in the trial. We feel like, well, 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 purely 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. Got you. I'm sure I'm pushing my luck, but are we talking high single digits or low double digits incremental number of patients? It's really impossible to say. Until we see the screen failure rate, you just don't know how many that are in the funnel make it to final randomization. Okay. That's very helpful. I think, 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 the second half of the year. We already talk about some of the differences in term of powering assumptions and whatnot. vHOT is obviously the primary endpoint of that trial, as well as the primary endpoint of your trial for the Accelerated Approval. Walk us through how you're thinking about that data set and potential implications to Dyne as well. Yeah. I think, we appreciate the investors are focused on the HARBOR data, and the field is anticipating the HARBOR data. I have to caution everybody just making a direct comparison with our drug, zeleciment basivarsen, to Novartis' 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, RNase H1, targets in the nucleus. 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 also using a Fab, compared to a mAb. Based on published data, the smaller size of the Fab provides better tissue penetration. That's also different. We don't see anemia in the clinic. We're not dose-limited. We've been able to go to 6.8 mg/kg in our registrational cohort. I think all of these things make it difficult for us to make a direct comparison with HARBOR. We're confident in our data. That's that. Got you. That's helpful. Hopefully Novartis' result, the P-value of 0.00000001 and the rest is history. I think that'll be very reassuring, I think to the investment community that despite this whole debate about HVAD and whether that endpoint is sensitive enough to show a benefit or whatnot, I think that would be the ideal outcome, obviously most importantly for patients. Should that not be the case, should they show a P-value that is a little bit more in the margins, let's say 0.04 or something along those lines, do you still have optionality in your trial design to maybe make the trial longer or bigger or reshuffling the endpoints and spend some of the alpha on the secondary endpoint? What are the optionality that you have should their data be more mixed than many of us are hoping to see? Yeah. First of all, I would say that we're very confident with our patient sizes, to deliver on HVAD as the intermediate clinical endpoint. Secondly, as I mentioned, with the differentiation mechanism of action, so it's hard to draw a comparison. Our trials and our designs are based on our data, our regulatory interactions, so we don't really anticipate doing anything, just remain very confident in our approach. Yeah. 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 your trial was not fully enrolled, I guess. That makes sense to me. Let's talk about CNS. I think it's always, you highlighted some of the differences. Yeah. Around your molecule versus your competitor. 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 competitor. Yeah. 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? FORCE platform was designed to deliver the payload into muscle, CNS, heart, and of course, other muscles as well, and we do see that in our preclinical data. We also looked in our clinical data, and we showed in DELIVER the MDHI, which is a patient-reported outcome or PRO. We looked at CNS subscales of MDHI and showed improvement at six months and at 12 months. That's our first clinical signal. In our phase III trial, which is a HARMONIA trial, we also have MDHI as a secondary endpoint. What we also have built into it are exploratory endpoints. One is a digital endpoint. We're using an accelerometer called Leap. 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 Cogstate, 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. Got you. That's actually very helpful. I'm not sure I appreciated that dynamic. 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? Yeah. as the primary point? There's 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. Why decide to use five-times sit-to-stand as the primary point for the confirmatory trial? How should we think about timelines here? 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 is powered to show a benefit of vHOT versus HARMONIA? How should we think about that? Yeah, I'll take the five-times sit-to-stand. I'll give the timing question to Erick J. Lucera. vHOT, 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? 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 deceleration of different muscles patients are going through. 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. We're using this endpoint, and we think this is clinically meaningful. We also have shown in our DELIVER data improvement in five-times sit-to-stand. Improving at 6 months and deepening into 12 months. Confident in using this more clinically meaningful endpoint. Got you. That's helpful. I know we're already almost out of time here, maybe let's pivot to FSHD. What's the latest thinking on that program? When can you potentially enter the clinic there? Maybe I want to go back to Erick, maybe 30 seconds on the prior question. I'm not sure if we gave you the opportunity to answer that question, love to. Sure. Maybe let's go there. Let's talk about the lag between the trial that could potentially lead to Accelerated Approval for VHOT versus HARMONIA. That's question number one, and then maybe going back to you, Ron, give us an update on FSHD. FSHD- Yeah, Erick, go ahead. We're running out of time. Sorry Obviously, we couldn't be 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. 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. At some point, we'll say something more, but it's a little too early. Sure. Since 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 opportunity to get into satellite cells, which are important for the disease. Also, since we don't see anemia, we won't be dose limited, but early days to comment on that. Definitely no anemia, but depending on where we go with the dose. We've also shown some pre-clinical data recently for our tau, so I'm just kind of giving a plug-in for that. Those programs, we're doing in a capital efficient way. such that we take them to a pre-clinical endpoint. We can do that very capital efficiently, and we're allocating our capital. Erick can talk more about this in programs that are listed on our pipeline. Got you. Maybe expand on that, Erick, a little bit, and capital efficiency and FSHD. Yeah. 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 Accelerated Approval based on a circulating biomarker versus it feels to me in the latest earnings call, they were maybe walking back a little bit. Yeah. ...that commentary. Again, what's the urgency here to add a third program to the pipeline? What's go, no-go, and timing? 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. To put a third product in the bag has tremendous financial leverage as you get into that launch. In terms of timing, obviously, we haven't really commented on that. 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. Got you. Any commentary maybe, Ron, on the biomarker potential strategy for Again, I know super early program development? It's early. We're excited to learn from Novartis' program. Okay. That's helpful. I know we're out of time. Maybe Erick, big picture, last question, then we'll let you guys go. What do you think is the most underappreciated aspects of the Dyne story today? Yeah. I think 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. Got you. On that note, thanks again, Erick and Ranjan. Appreciate it. Fantastic conversation. I have a lot more questions, but no more time. Thanks everyone for joining. We'll talk soon. Thanks again. Thank you very much. Thank you very much.