Jefferies Global Healthcare Conference in New York

We're gonna get started with our next session. I'm Andrew Tsai, Senior Biotech Analyst at Jeffries, and it's my pleasure to have the Dyne team with me today. To my direct left is Eric Lucera, CFO, and to his left, Ron Bastra, CSO. Welcome, both of you. So there are some people who might not be as familiar with the Dyne story or they are just revisiting, so can you just give us the latest and greatest about Dyne, what programs you're working on, maybe you how you're differentiated, and then milestones over the next 12 months could be helpful.

Yeah, thanks. Thanks for having us, and it's an honor to be here, and thank you very much for the support. In terms of Dyne, Dyne's a company that's maybe five, eight years old, and was really created to solve one of the quintessential problems in biotech, which is delivery, particularly delivery to the CNS and target tissues like that. The company has several products in development from DMD, DM1, several other DMD, Exxon assets, FSHD, and Pompeii. And it's all based on the Force platform, which was designed to solve the problems of delivery. To date, we've got data in multiple programs, all de-risked with human data. And if I were to characterize where we've been over the last couple of years and where we're going, 2025 was a year of clinical validation. We presented data on hundreds of patients, proving that we get to the CNS, that we can create drugs that deliver functional improvement. That is the mantra of Dyne, functional improvement. 2026 is a year of execution. I think you may have seen recently we filed the BOA for our first drug, DMD. We filed that about a week or so ago, and today we're pleased to announce that we completed the enrollment of the registration cohort for our DM-1 trial. So excited to get that done, and we'll have data in, you know, first quarter of next year. And we're also on track for approval, hopefully, with DMD assets around the same timeline. So in terms of the second part of your question and the catalyst, you know, we think this This is a catalyst-rich year in terms of preparing for commercialization, which is what next

year will be. Great, great. And so maybe to start, we'll start with the DMD program, maybe DM1 after. So starting with DMD, help us, Exxon 51 specifically, help us frame the market opportunity for this. Like you said, it could be approved, maybe launched around Q1 of next year. I mean, I can think of, you know, patients currently on Exondis, patients who have discontinued Exondis, patients who have never tried Exondis. So how many patients are there is the bottom line.

Yeah, well, just for those who are unaware, DMD Exon 51 is just one of many mutations that result in issues for boys with DMD. Exon 51 is the largest, and it's the most difficult to skip. We believe there's about 1,600 patients out there in total, spread into basically three buckets. Those that are currently on treatment, about 500. Those have tried treatment and failed, similar, about 500. And then there's another 500 or so that have never really tried anything, maybe steroids, but that's about it. So we think that we are going to be the first drug, knock on wood, that can deliver functional improvement. and we hope that we can get as many boys as possible on this drug. It's a really difficult disease, and we think we're going to be the first company that brings true functional improvement to the field.

Yep, and as investors think about the peak sales opportunity, I mean, in theory, it could be large, but help us think about pricing, bookends. You don't need a guide today, per se, but bookends of a rare disease asset could be helpful, too.

Yeah, I think one of the great things about launching in Exxon 51 DMD is it is, as you mentioned, an existing market that does not have to be built. You know, the physician community, the advocacy groups are all in place, and reimbursement is in place. Obviously, there's a benchmark out there of about a million dollars a year from another company, and that's sort of where pricing is at the moment. You know, it's way too early for us to comment on pricing, but I would say, you know, in the 30 years that I've been in biotech, any time that you can bring a drug to market that has a dosing advantage, we're going to be once a month versus once a week. And something that brings true functional improvement, that's usually something that people can get a premium for. But again, way too early to start thinking about pricing.

Yes, and then, you know, even the biomarker dystrophin, to be clear, it's, I don't know, way higher. than Sarepta's, Exondis. So there's that too. And so then let's just say if you were approved and launched, what is the low-hanging fruit? Which of the three sub buckets are we talking about?

Yeah, so happy to answer that, Andrew. I think it's going to be a mix of the three populations, ones that are currently on treatment, ones that have discontinued treatment, ones that have never been treated. I just wanted to remind you, this community remains unserved and underserved in terms of what is available to them so I talk to these SCPs all the time I you know grew up in the neuromuscular world and the patients and community are really excited about what we are the profile of the Rastodersen it we have dystrophin we have functional improvement we have dosing convenience including safety so patients are really

excited I think it's gonna be a mix of the patients okay I guess for those who have never tried they I guess your reason would be the maybe then feel what is the reason they've never tried Exontas for instance what yeah yeah I

think the variety of reasons right so perceived lack of efficacy the dosing burden access limitations and those are some of those issues that patients may

not have tried available therapies okay and so when let's just say you're approved when exactly would you be prepared to launch I mean presumably you're already planning and hiring people maybe walk us through that so

far yeah I mean obviously being a commercial organization is a big endeavor and something that you don't take lightly about two years ago we We hired our chief commercial officer, Johanna Friedel-Nader, who was principally responsible for launching rare disease drugs over at Biogen, and she's brought several of her team members with her. So, you know, the first year or so has really been what we used to call the thought experiment of bringing in the VPs and all of those folks to really understand the market that we're getting into. As we continue to de-risk the program with the BLA filing and hopefully BLA acceptance, and as we get closer to launch, we'll continue to start building out the field presence. Okay. And then would you expect an adcom in the meantime or? I think it's way too early to speculate on whether you would need an adcom.

Sure. So then 2027, I took a peek the other day where consensus is, I think it's around 50 million for 2027. I mean, hypothetically, if you price aside a million, that's 50 patients, assuming they all start day one, but they don't necessarily all start day one. So maybe let's just say you need like 75 or 100. Out of 1,600 patients, do you feel confident, I guess, you can get them? We believe there'll be no shortage of demand

for the drug based on the feedback that we've been getting from the patients and the community out there. There's no lack of interest in the product. I think with any biotech launch, any rare disease drug, the gating factor which affects the slope of the launch curve is gonna be access and coverage. So that's really something that we're working really hard on. We've got a great advocacy and reimbursement team that is in place that is getting those storyboards ready. But it's way too early to start commenting on what consensus is. But nevertheless, you know, we do see a lot of demand and a lot of interest in our product. And how many sales reps do you need ultimately?

How concentrated are these patients?

Yeah, it's a great market to launch into. Again, just as a reminder, it's an existing market with existing reimbursement. If you look at where the patients are, about 80 percent of the patients are at 100 or so centers in the U.S., and Europe is actually even more concentrated. So if you think about a prototypical specialty pharma, rare disease marketplace that's serving 100 different centers, you don't need hundreds of people to go out and service that market and bring the drug to patients. It's not a big number, which is something that I found attractive when I was looking to come here. And it's also something that as we get into DM1 and FSHD, it'll be the same sales force. Right. You can scale.

Okay.

A lot of economic leverage.

Right. So to be clear, even those who have discontinued Exondis, they are found at those, most of them are found at the 100 centers, to be clear. Yeah. Okay. should we think about cost of goods COGS yeah we haven't yet commented on COGS as

you know I spent a long time on the buy side and my intention is to give COGS guidance at some point but I'd say it's it's not too far from what you would expect from a you know a rare disease biologic in terms of COGS and gross

margin okay and as we think about going back to approvability of this I mean the data congratulations it's strong on efficacy on the safety side some investors wonder sometimes you know do you have enough just be you know it's pretty accelerated of a pathway that you have so how many patients do you have in your safety database especially out to one year and is that enough yeah I mean

I would just do first of all to and as you said and what Eric said that we were really excited that we've submitted our BLA and as you know we have breakthrough therapy designation so we have a lot of conversations with the agency. We had a pre-BLA meeting where the agenda was mostly administrative in terms of the contents of the submission. We have dystrophin data which we've shown in our delivery trial. We have functional data so and two end points were nominally statistically significant. We also have a large safety database in context of rare disease so we feel pretty good and

confident about our submission. Okay great and to be crystal clear the FDA agreement for to support an accelerated approval for your six-month study was STAT-SIG on dystrophin positive trends on function we don't need STAT-SIG per se on function is that? Yeah so through through our breakthrough therapy

designation that I said we had consistent dialogue with the agency you know based on that we think that dystrophin is the agency is aligned with us we think that if they're aligned with us for accelerated approval based on dystrophin of course we submitted other data as well but that was the alignment

okay and then in the meantime as this is going on you've started the phase three confirmatory study for Zetto it's a global study maybe talk us through that

design yeah so for Zetto study we chose the primary endpoint as rise from floor velocity DMD is a disease which shows our sign it's hard for these kids to get up from the floor so it's a very clinically meaningful endpoint there's precedent for this you know Roche-Levitas and other companies are also using rise from floor velocity most importantly we have data on rise from floor velocity in our delivered trial this was one of the endpoints that was nominally statistically significant and we hope to be able to replicate this the study duration is 72 weeks and for a progressive disease like DMD this is a good time point to show clinically meaningful and durable improvement and And I think Harmonia is, no, sorry, Harmonia. So is fully powered to show rise from flow velocity at a statistical significant endpoint. OK.

And then out of curiosity, when could we get the confirmatory data? I mean, it's at 90 patients, but it doesn't seem, it's only, quote, unquote, only 90 patients. It's too early to say. very good so then shifting gears to DM1 also exciting like you said completed enrollment was it today that's right the press release went out this morning okay so data is in q1 2027 so big picture market opportunity how many patients are there in the u.s. how are you intending to price this if this was

approved so I think in the u.s. there's about 40,000 patients I think it's way too early to even think about pricing in this one as well okay very very fair and

so in my notes it sounds like 60 patients have been enrolled is that

correct in the sheets the original target was 60 but as we announced this morning we had 71 patients in the rec enrollment 71 patients so if I this is a

six-month time frame so I guess okay so you've completed enrollment at six months some data cleaning hence Q1 data readout

yeah if you just go back to the precedent we set with DMD it was a very similar setup with with the same amount of follow-up and it takes a couple of months to do the database lock and the cleaning and then get everything all ready for presentation okay and so

powering wise the the primary endpoint is VHOT. How did you exactly power the study drug versus placebo? What are you

assuming? Yeah I mean we have we know we believe that the trial is is well powered and I think in terms of the question that you're answering like we do plan to release some of those numbers you know by the end of the year in terms of the assumptions that went into that but nevertheless we're very

confident about the powering of the trial. And I think you know based on the phase one two data there are some analyses done on a MMRM adjusted basis non non MMRM can you remind me the the primary endpoint will be adjust or a non-adjusted basis or both I don't know how it truly works yeah it'll be MMRM okay and so placebo behavior for V hot what we have seen from mad data is that

there's a worsening in placebo of about 0.4 seconds. And so do you expect the

same in this registration study? I mean I can only comment on the data that you've seen. Okay all right and so for to support and accelerate approval do you need a hit what do you need to see on the functional side in addition to VHOT

as a primary endpoint yeah so we think that the VHOT is an incomplete measure in terms of supporting a full approval for a heterogeneous disease in manifestations such as DM1 so we had proposed VHOT as an intermediate clinical endpoint so we we expect in this study to hit on VHOT which we are fully powered to do and we expect to show trends on the secondary endpoints as

well okay and then splicing is also secondary Cassie is fully powered so

splicing is fully powered in in the achieve study okay and I think what was

notable personally is this here here you've started the harmonia study which is a confirmatory study, but the design of which was informed by your recent FDA discussions. So in your recent FDA discussions, how did the FDA view VHOT as it relates to an accelerated approval versus full approval?

Yeah. FDA acknowledged that VHOT is an incomplete measure of the DM1 heterogeneity. And also, the improvement on VIHOT alone is incomplete for heterogeneity in DM1. It's not as clinically meaningful. So we discussed using VIHOT as ICE, or Intermediate Clinical Endpoint, which is reasonably likely to predict the clinical benefit. And that's how we powered the Achieve Study for VIHOT. And as you said, that we're empowered to deliver on CASI as well, which is splicing.

Okay, very clear.

And so we used five times sit to stand, which is a clinically meaningful endpoint for the confirmatory study harmonia. And this is five repeated sit and stand transfers that takes into account the leg strength, the leg myotonia, trunk strength, posture, and is also predictive of falls in DM1. So we think that's a comprehensive endpoint for a study like harmonia. We were fully powered for five times to stand in harmonia.

Got it. In the meantime, your competitor Novartis Avidity has a data readout in the second half, 2026. Phase three, VHOT as a primary endpoint as well, but going after full approval. But presumably it's a 12-month readout, so they'll share presumably the other functional endpoints. But like what is the most optimal scenario in your view?

Yeah, I think it would be interesting to see the data. Of course, you know, as the DM1, in the DM1 market, there's ample room for multiple players to come in, and if there are multiple therapies in this field, the market will grow. We are very excited about the differentiated profile for our drug. As you know, in DM1, the mutant DMPK that causes the disease is stuck in the nucleus, So we're using an ASO as a payload, a GAPMAR ASO that goes in the nucleus and targets the mutated copy. So we see reversal or correction of splicing. And with our FAB and force platform, we also get into the CNS, which is an important aspect of DM1. And further, lastly, we don't, you know, our FAB is designed not to interfere with the transfer in function, and we don't see anemia in the clinic.

Got it. So it could be, point being is superior potentially on efficacy and safety compared to adidity is your view.

I mean, we're excited about the differentiated profile. We hear from HCPs. I was at IDMC last week, the DM1 conference, and we're hearing from the patient community and the HCPs that they're very excited about the profile of the drug and the data you've shown so far.

And back to your phase 1, 2 data, remind us, like, what kind of functional improvements, including cognition, did you show that makes you feel convinced you have a differentiated asset to be more specific?

Yeah, so at WMS last year, we showed multiple data points. We showed, of course, five times sit to stand, which is our own data, and we're using that as an endpoint. We saw that it gets better at six months than it deepens at 12 months. We showed other mobility endpoints as well. We showed improvement in CNS subscales of the patient-reported outcome called MD-high. So these are six CNS-related subscales that cover cognition, sleep, fatigue, and so on. So that's differentiated as well.

And bottom line, one more time, stat sig on VHOT functional trend on any one of your key secondaries and you should be able to get accelerated approval. Like you have multiple shots on goal is my point on the secondary.

I think what we intend to show and what the Achieve trial is set up to show is that VHOT is reasonably likely to predict the clinical benefit.

And then, again, both programs, DMD, DM1, the confirmatory studies have started. Do you have alignment, ex-US, with ex-US regulators? Maybe talk about that, which region specifically.

Yeah, so both Phase III studies are serving as confirmatory trials in the U.S., and they will support marketing applications ex-US.

Okay, ex-US, okay. And then, I guess, then you mentioned you're working on a more, you know, as we think about the earlier stage in the pipeline, you're working on FSHD, Pompeii, a basket study in DMD. Maybe talk us through the timelines for that and maybe any color on what you're seeing for any of those programs, what makes you differentiated, for instance.

Yeah, and we can tag team this, Eric. I know you're excited about these topics as well as I am. So we're very excited about the differentiated profile of the FORCE platform and products such as FSHD. So FSHD, we think it's going to be next in the clinic. And then Eric was able to, Eric's team was able to fund our DMD exon. So, you know, being in the patient community, being in the ECB community, we got a lot of demand for other exons based on the data that we showed for Z-Rostedersin. People wanted drug for, you know, their kids and their patients. So we have four development candidates for four different exons in DMD with the same fab, the same linker, the same payload chemistry. So even though these are preclinical products, we think the probability of success is really high based on what we've seen with Z-Rostedersin. So Eric's team was able to fund this in a capital-efficient manner. Eric, if you have anything else to add.

Eric H. Yeah, I'd say we're really excited about DMD as a franchise. You know, we believe we have the opportunity to have a significant position, not only with, you know, with Exxon 51, but the other four exons that we're pursuing and truly build a DMD franchise. You know, when we released that data, you know, as Ron mentioned, we were getting a lot of inbounds from physicians saying, well, this is great data, But what about my boy? They have Exxon 44 issue or whatever. And, you know, so we looked hard and we found the money. And the opportunity to triple the total addressable market by going from Exxon 51 to now having five different exons was really something that we thought we had to do in the interest of the patients because, as Ron mentioned, these are all high probability of success products. We're just tweaking a little bit of the oligochemistry. But everything else is exactly the same, fab, linker, same physician, same disease, et cetera. So it really felt to us like we had a moral obligation and to the shareholders as well to pursue these products, particularly, you know, as fast as possible. So we're doing that. Okay. And FSHD seems first.

Yes, that's correct.

When could it enter the clinic? Yeah, we haven't given any guidance on that, but I can assure you it is an absolute top of mind for both Ron and I. We're constantly in communications with the team about timing, and, you know, when we have a development point that we can announce, we'll say it, but, you know, we are very excited about FSHD.

And then DMD, conceptually, I think you've mentioned you've wanted to run, like, a basket-type study. I guess, how does that work? Is there a shared placebo arm?

So currently, after, you know, announcing the development candidates, We're working on the manufacturing piece and we're also working on non-clinical studies. We don't want to waste time, but based on the Rossiderson approval, that's a good time and provides us an opportunity to have further conversations with the agency to think about clinical trial designs for these other axons.

I see. And then lastly, Pompeii, what kind of preclinical data makes you excited about this program?

Yeah, Pompeii is very exciting, again, leverages force platform, which is truly modular. I mean, if you think about DMD, DM1, FSHC, and Pompeii, there are four different payloads that are attached to the fab, and it can also deliver to the muscle, to the heart, and to the CNS, where in Pompeii the glycogen storage issues exist. So we're in preclinical development for Pompeii, also very excited. Eric would put it there's like eight products in development so I'll hand it over to Eric but that's excited about Pompeii as well yeah no we're excited

about all the products that we have okay very good and then maybe a last question for me is just cash runway at the moment yeah we've stated that we

have cash into the first quarter of 28 so we're you know we've have almost a billion dollars on the balance sheet we have a great relationship with Hercules capital for non-dilutive sources of capital. And, you know, the FORCE platform has opportunities outside of our core focus. Our intention is to focus on muscle and things that can leverage the same commercial organization. But we can use this in other areas, and those could be sources of out-licensing candidates where we could get non-dilutive capital from that as well. So we think we're in a great position financially, and, you know, look forward to developing these eight products and coming up with a portfolio that can drive growth into the next decade.

Very good. I think that's all the questions I had today. So thank you and for sharing the progress. Congratulations on the execution. But big milestones coming up. Yeah. Yeah.

We're very excited. Thank you very much for the support. Thank you very much for having us. Thank you.