We're going to get started with our next session. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies, and it's my pleasure to have the Dyne team with me today. To my direct left is Erick Lucera, CFO, and to his left, Ron Batra, CSO. Welcome, both of you.
Thank you.
There are some people who might not be as familiar with the Dyne story or they are just revisiting. Can you just give us the latest and greatest about Dyne, what programs you're working on, maybe how you're differentiated, and then milestones over the next 12 months could be helpful?
Yeah, thanks for having us, and it's an honor to be here, and thank you very much for the support. In terms of Dyne's a company that's maybe five, eight years old, and it 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 exon assets, FSHD, and Pompe, 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. 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 BLA for our first drug, DMD. Filed that about a week or so ago. Today, we're pleased to announce that we completed the enrollment of the registration cohort for our DM1 trial. Excited to get that done, and we'll have data in first quarter of next year. We're also on track for approval, hopefully, with DMD asset around the same timeline. In terms of the second part of your question and the catalyst, we think this is a catalyst-rich year in terms of preparing for commercialization, which is what next year will be.
Great. Maybe to start, we'll start with the DMD program, maybe DM1 after. Starting with DMD, help us, Exon 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 can think of patients currently on EXONDYS, patients who have discontinued EXONDYS, patients who have never tried EXONDYS. How many patients are there is the bottom line.
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, 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, there's another 500 or so that have never really tried anything, maybe steroids, that's about it. We think that we are going to be the first drug, knock on wood, that can deliver functional improvement, we hope that we can get as many boys as possible on this drug. It's a really difficult disease, we think we're going to be the first company that brings true functional improvement to the field.
Yep. As investors think about the peak sales opportunity, in theory, it could be large, but help us think about pricing at bookends. You don't need a guide today per se, but bookends of a rare disease asset could be helpful too.
I think one of the great things about launching in Exon 51 DMD is it is, as you mentioned, an existing market that does not have to be built. The physician community, the advocacy groups are all in place. Reimbursement is in place. Obviously, there's a benchmark out there of about $1 million a year from another company. That's sort of where pricing is at the moment. It's way too early for us to comment on pricing. I would say, 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. Something that brings true functional improvement, that's usually something that people can get a premium for.
Right.
Again, way too early to start thinking about pricing.
Yes. Even the biomarker dystrophin, to be clear, it's, I don't know, way higher than Sarepta's EXONDYS there's that too. 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, 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. Just wanted to remind you, this community remains unserved and underserved in terms of what is available to them. I talk to these XSPs all the time. I grew up in the neuromuscular world, the patients and community are really excited about the profile of zeleciment rostudirsen. We have dystrophin, we have functional improvement, we have dosing convenience, including safety. Patients are really excited, I think it's going to be a mix of the patients.
Okay. What is the reason they've never tried EXONDYS, for instance? Why?
Yeah, I think there are a variety of reasons, right? 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. Let's just say you're approved, when exactly would you be prepared to launch? Presumably, you're already planning and hiring people. Walk us through that so far.
Obviously, being a commercial organization is a big endeavor and something that you don't take lightly. About two years ago, we hired our Chief Commercial Officer, Johanna Friedl-Naderer, who was principally responsible for launching rare disease drugs over at Biogen, she's brought several of her team members with her. 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 hopefully BLA acceptance, as we get closer to launch, we'll continue to start building out the field presence.
Okay. 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. 2027, I took a peek the other day, where consensus is, I think it's around $50 million for 2027. Hypothetically, if you price this at $1 million, that's 50 patients, assuming they all start day one, but they don't necessarily all start day one. Maybe let's just say you need 75-100. Out of 1,600 patients, do you feel confident, I guess, you can get that?
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 going to be access and coverage. 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. It's way too early to start commenting on what consensus is. Nevertheless, we do see a lot of demand and a lot of interest in our product.
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% of the patients are at 100 or so centers in the U.S., Europe is actually even more concentrated. 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.
Yeah. A lot of economic leverage.
Right. To be clear, even those who have discontinued EXONDYS, most of them are found at the 100 centers, to be clear.
Yeah.
Okay. How 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. I'd say it's not too far from what you would expect from a rare disease biologic in terms of COGS and gross margin.
Okay. As we think about going back to approvability of this, the data, congratulations, it's strong on efficacy. On the safety side, some investors wonder sometimes, do you have enough? It's pretty accelerated of a pathway that you have. How many patients do you have in your safety database, especially out to one year, and is that enough?
Yeah. I would just do, first of all, too, and as you said, and what Erick said, that we're really excited that we've submitted our BLA. 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 stat sig in our DELIVER trial. We have functional data, and two endpoints were nominally statistically significant. We also have a large safety database in context of a rare disease, so we feel pretty good and confident about our submission.
Okay, great. To be crystal clear, the FDA agreement 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 correct?
Yeah, through our Breakthrough Therapy designation, as I said, we had consistent dialogue with the agency. Based on that, we think that the agency is aligned with us. We think that they're aligned with us for accelerated approval based on dystrophin. Of course, we submitted other data as well. That was the alignment.
Okay. In the meantime, as this is going on, you've started the phase III confirmatory study for FORZETTO. It's a global study. Maybe talk us through that design.
Yeah. For FORZETTO study, we chose the primary endpoint as Rise from Floor Velocity. DMD is a disease which shows Gowers' sign. It's hard for these kids to get up from the floor. It's a very clinically meaningful endpoint. There's precedent for this. Roche, Elevidys, and other companies are also using Rise from Floor Velocity. Most importantly, we have data on Rise from Floor Velocity in our DELIVER 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. For a progressive disease like DMD, this is a good time point to show clinically meaningful and durable improvement. I think FORZETTO is fully powered to show Rise from Floor Velocity as a statistical significant endpoint.
Okay. Then out of curiosity, when could we get the confirmatory data?
It's too early to guide on any time.
It's like 90 patients, but it's only "only 90 patients.
I think it's too early to say.
Very good. 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. Data's in Q1 2027. Big picture, market opportunity, how many patients are there in the U.S.? How are you intending to price this if this was approved?
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 fair. In my notes, it sounds like 60 patients have been enrolled. Is that correct, in ACHIEVE?
The original target was 60, but as we announced this morning, we had 71 patients in the rec enrollment.
71 patients. This is a six-month timeframe.
That's correct, yeah.
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 the same amount of follow-up. It takes a couple of months to do the database lock and the cleaning, and then get everything all ready for presentation.
Okay. Powering-wise, the primary endpoint is vHOT. How did you exactly power this study, drug versus placebo? What are you assuming?
Yeah, we believe that the trial is well-powered, and I think in terms of the question that you're answering, we do plan to release some of those numbers by the end of the year in terms of the assumptions that went into that. Nevertheless, we're very confident about the powering of the trial.
I think based on the phase I/II data, there are some analyses done on a MMRM-adjusted basis non-MMRM. Can you remind me, the primary endpoint will be adjusted or non-adjusted basis or both? I don't know how it truly works.
Yeah, it'll be MMRM.
MMRM. Okay. Placebo behavior for vHOT?
What we have seen from MAD data is that there's a worsening in placebo of about 0.4 seconds.
Do you expect the same in this registrational study?
I can only comment on the data that we have seen.
Okay.
Yeah.
All right. To support an accelerated approval, what do you need to see on the functional side in addition to vHOT as a primary endpoint?
Yeah. 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. We had proposed vHOT as an intermediate clinical endpoint. 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.
Secondary endpoints. Okay. Splicing is also a secondary-
Yeah. CASI is fully powered, so splicing is fully powered in the ACHIEVE study.
Okay. I think what was notable personally is here you've started the HARMONIA study, which is a confirmatory study, but the design of which was informed by your recent FDA discussion. In your recent FDA discussions, how did the FDA view vHOT as it relates to an accelerated approval versus full approval?
FDA acknowledged that vHOT is an incomplete measure of the DM1 heterogeneity. Also improvement on vHOT alone it's incomplete for heterogeneity in DM1. It's not as clinically meaningful. We discussed using vHOT 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 vHOT. As you said, that we're powered to deliver on CASI as well, which is splicing.
Okay. Very clear.
We used Five Times Sit-to-Stand, which is a clinically meaningful endpoint for the confirmatory study, HARMONIA. 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. We think that's a comprehensive endpoint for a study like HARMONIA. We're fully powered for Five Times Sit-to-Stand in HARMONIA.
Got it. In the meantime, your competitor, Novartis Avidity, has a data readout in the second half of 2026, phase III vHOT as a primary endpoint as well, going after full approval. Presumably it's a 12-month readout, so they'll share presumably the other functional endpoints. What is the most optimal scenario in your view?
Yeah, I think it'd be interesting to see the data. Of course, as a 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. We are using an ASO as a payload, a gapmer ASO that goes in the nucleus and targets the mutated copy. 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. Further lastly, our Fab is designed not to interfere with the transferrin function, and we don't see any immune in the clinic.
Got it. Could your point being a superior potentially on efficacy and safety compared to Avidity is your view?
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 we've shown so far.
Back to your phase I/II data, remind us 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. 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, then it deepens at 12 months. We showed other mobility endpoints as well. We showed improvement in CNS subscales of the patient-reported outcome called MDHI. These are six CNS-related subscales that cover cognition, sleep, fatigue, and so on. That's differentiated as well.
Got it. Bottom line, one more time, stat sig on vHOT, functional trend on any one of your key secondaries, you should be able to get accelerated approval. 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.
Understood. Okay. Then again, both programs, DMD, DM1, the confirmatory studies have started. Do you have alignment ex-U.S. with ex-U.S. regulators? Maybe talk about that, which region specifically.
Yeah. Both phase III studies are serving as confirmatory trials in the U.S., and they will support marketing applications ex-U.S.
Okay, ex-U.S. Okay. I guess then you mentioned you're working on as we think about the earlier stage in the pipeline, you're working on FSHD/Pompe, 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. We can tag-team this, Erick. I know you're excited about these topics.
Oh, yeah.
As well as I am. We're very excited about the differentiated profile of the FORCE platform and products such as FSHD. FSHD, we think is going to be next in the clinic. Erick's team was able to fund our DMD exon. Being in the patient community, being in the DMD community, we got a lot of demand for other exons based on the data that we showed for z-rostudirsen. People want a drug for their kids and their patients. We have four development candidates for four different exons in DMD with the same Fab, the same linker, the same payload chemistry. Even though these are preclinical products, we think the probability of success is really high based on what we've seen with z-rostudirsen. Erick's team was able to fund this in a capital-efficient manner. Erick, if you have anything to add.
Yeah, I'd say we're really excited about DMD as a franchise. We believe we have the opportunity to have a significant position, not only with exon 51, but the other four exons that we're pursuing and truly build a DMD franchise. When we released that data, 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 exon 44 issue" or whatever. We looked hard and we found the money, and the opportunity to triple the total addressable market by going from exon 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 physicians, same disease, et cetera. It really felt to us like we had a moral obligation, and to the shareholders as well to pursue these products, particularly, as fast as possible. We're doing that.
Okay. 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 when we have a development point that we can announce, we'll say it, but we are very excited about FSHD.
DMD, conceptually, I think you've mentioned you've wanted to run a basket type study. I guess, how does that work? Is there a shared placebo arm? I don't know.
Currently after 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. Based on the z-basivarsen 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 exons.
I see. Lastly, Pompe, what kind of preclinical data makes you excited about this program?
Yeah. Pompe is very exciting. Again, leverages FORCE platform, which is truly modular. If you think about DMD, DM1, FSHD, and Pompe, they're 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 Pompe the glycogen storage issues exist. We're in preclinical development for Pompe. Also very excited. As Erick would put it, there's eight products in development. I'll hand it over to Erick, but that's excited about Pompe as well.
Yeah, no, we're excited about all the products that we have.
Okay. Very good. Maybe last question from me is just cash runway at the moment.
We've stated that we have cash into the first quarter of 2028, we have almost $1 billion on the balance sheet. We have a great relationship with Hercules Capital for non-dilutive sources of capital. 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. We can use this in other areas, those could be sources of out licensing candidates where we could get non-dilutive capital from that as well. We think we're in a great position financially and 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 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.
Thanks for having us.
Thank you.