Avidity Biosciences, Inc. (RNAM) Earnings Call Transcript & Summary

Great. Thanks, everyone, for being here. It's -- my name is Yanan Zhu. I'm one of the biotech analysts here at Wells Fargo. It is our great privilege to have the Avidity Therapeutics management team here for a fireside chat. And with me on stage, CFO, Mike McLean; and Kath Gallagher, Program Manager for the muscle disease programs. Thank you for being here.

Thank you, Yan.

Thank you.

Great. So I was wondering if, Mike, could you provide an overview for the company's platform and key programs and talk about the achievement so far and your vision for the future.

Absolutely. Happy to do that. And first of all, thank you for having us at the conference. It's always wonderful to kind of start out the fall here at the Wells Fargo Conference in Boston. And so look, first, I'd just start with the fact that our vision is to profoundly improve people's lives through the delivery of RNA therapy. And as I look back on the 5 years since we IPO-ed at a time where we had no programs in the clinic. And as we sit here today, we have 3 programs in late-stage development. And it just is so profound to me that we can be sitting here having this conversation today. So really look forward to the conversation and talk about these programs. We have over this 5-year period of time, shown consistent and reproducible data across our programs in the neuromuscular space. We've shown delivery to muscle, knockdown of the target, the favorable safety and tolerability and functional data -- or functional data that proves that there's a benefit to these drugs for FSHD and myotonic dystrophy. And soon, we'll be showing our functional data for the DMD program coming up here in the very near future. So that sets us up to be on track to file 3 BLAs in a 12-month period, starting this year with the DMD -- del-zota program for accelerated approval in the U.S. and then in the second half of 2026 to file BLAs for our FSHD and myotonic dystrophy programs. And so that will be the second half of 2026. FSHD, the del-brax program will be for accelerated approval in the U.S. And for myotonic dystrophy, our Harbor program, that is a global full approval study, right, in U.S., Europe and Japan. So that's really what we are focused on in the near future and as we head to commercialization. We look at all of these drugs as first-in-class, best-in-class. And just quickly to touch on the data catalysts that we see coming up. The first will be functional data for our del-zota drug in DMD44. And as I said, that's coming soon. Then we will be presenting OLE data for the participants who are in the MARINA trial in the fourth quarter of this year. And in the second quarter of 2026, we're going to have 2 data readouts. One is going to be at the 30-week mark for our HARBOR trial. So that is going to be pretty much midway through the study. We will be disclosing what we're seeing on a top line basis there. And then also in the second quarter of 2026, we'll be showing the data from our FORTITUDE biomarker trial.

Right. Yes, that's a lot of very exciting data catalysts and also regulatory -- on the regulatory front, also a very busy calendar. So congrats on all the achievements. I do want to ask you about your thoughts on, a, commercial strategy; and b, business development strategy, including thoughts around partnership or even M&A.

Okay. That's a pretty meaty question. And I'm just going to assume that maybe on the M&A front, it may allude to some rumors that have been out there in the marketplace. So I'll tackle that first. As we look at where we sit in the cycle of our company's development going into the commercial phase, with 3 potential launches by the end of 2027 and 2 of those drugs being potential blockbuster indications in terms of financial opportunity. It's not surprising to us that we're in the spotlight of what people might perceive to be an M&A target. So we have had different flavors and types of rumors. And as we looked at this and we've dealt with it from the internal point of view, the 2 things we're focused on is to make sure our team has their heads down and are in the game. And then we're known for our execution, so we need to continue to execute. And that's what you're going to see us do. I just told you a lot of things that we have in front of us that we have to focus our time and attention to. And we're really excited as we head to these approvals and eventual launches. This is something this team is able to do, has done in the past, and we're really excited to do that. So now moving on to the commercial opportunity. We are well along. We have really a great situation where del-zota is our first drug indication. And as we move into accelerated approval and launch in the U.S., it gives us the opportunity to build a foundational commercial infrastructure that we can easily leverage across all 3 of our drugs. So as we sit here today, we have a patient services organization stood up. We have MSLs and patient -- I'm sorry, payer reimbursement folks in the field. We're working on site of care. And the last piece we'll put in place is a field force. And so those are right where we want them to be. We've built the hub. We will start to kind of build the field next. And we can leverage that foundation across all 3 of our product opportunities. And we're feeling really good about where we stand from the commercial perspective.

Got it. Thank you. So let's delve into del-zota, the DMD44 program. So you previously reported very impressive exon skipping and dystrophin expression data from the EXPLLORE44 study. And you will be presenting functional data in the fourth quarter of '25. So can you review the previous data and talk about what new data might be presented?

Sure. I can take that one, Yan. So we have previously presented data before -- one little spoiler alert. We have said this week that this data is going to come sooner than Q4. So it will be really by the end of this month that we'll be sharing the del-zota data. And if you look back at what we have presented before, we have shown unprecedented levels of dystrophin increases as well as decreases in creatine kinase. And so the key data that was important -- and of course, we've also had a great safety profile, and we presented all that data as well. But the key thing that was important was that we had a 25% increase in dystrophin in these patients on average. And what that is, is really an increase from a baseline of 7% to 32%. So it's a really significant jump. And on the CK side, what we have seen is a decrease to near normal levels. And so what we're really excited about, Yanan, for this upcoming data readout is that we're going to, for the first time, be able to show what does functional improvement look like when you've actually had these significant impacts on the biomarkers that are really so significant for DMD.

That -- yes, that's very intriguing because for the first-generation exon skippers, we all know they struggle to show any functional benefit. What insights or learning do you hope to contribute to the field?

Oh gosh, of course, I mean that's a responsibility we think of actually every day in terms of how we present this data. And we know that the patient community is listening as well as, of course, the investment community, the health care community. So as we look to the exon skippers, they pave the path, right? They pave the path for this accelerated approval pathway. And what -- the major difference for our programs in these next-gen exon skippers is delivery to muscle. And I think at the very core of what we are doing is we are delivering the PMOs directly where they need to go. And so that again comes down to why we saw this increase in dystrophin and this decrease in CK. And it's an exciting piece now to see that while the exon skippers have shown some increases, they're much lower percentages, right? So we're looking really at 1% increase in some cases in dystrophin. And so this is kind of uncharted waters to see what actually happens in functional data when you are really having a significant impact on the biomarkers. So we're kind of looking forward to seeing all of this with everyone else.

Okay. I was wondering what drove the decision to report the data ahead of schedule?

Ahead of schedule. One, you know how we are, and we do like to beat expectations. But I think, two, when we set out these milestones, Mike reminds me this morning, that was December of last year. So some of this is just a timing thing. We are still pretty close to Q4, but it's just coming in a little earlier than we anticipated.

Got it. Got it. Would it be a company release, typical question or medical meeting?

So it's going to be a company release. You should probably expect that we'll do a webcast. The way we think about this is it's not normal in this disease indication for companies to report functional data. So we think it's appropriate to do a webcast.

Got it. Well, can you also give us a sense of patient number, follow-up time and perhaps what functional endpoints because there are a few, right, you could report on.

Sure. So what we're going to be looking at is the -- I think it's 17 patients that have been on the EXPLORE44 trial that were on drug. So remember, we had placebo patients. They will not be included in this because we wanted to look pretty far out so that we could actually get a sense of what this functional data looks like at around a year. So it's going to be those 17 patients, and they'll have been on both the 5 mg per kg and on the 10 mg per kg. And then as you may remember, when we moved everybody to the open-label extension, they've all now shifted to the 5 mg per kg every 6 weeks. making sure I got that right. But yes, 5 mg per kg every 6 weeks. In terms of the functional measures, so we have quite a number of them actually in the EXPLORE44 program and then carrying over into the EXPLORE44-OLE. So you should expect to see time to rise, 10-meter walk run. The pull is one that is important for the non-ambulatory patients, so that's performance of upper limb. And we'll also be looking at the 4-stair climb. We are, of course, looking at the NSA as well, but the North Star is one that we're planning to show, but it hasn't been our major area of focus in terms of looking at functional.

Great. Yes. One interesting observation is that the median age of your patients is much -- I think it's much older compared with other trials. I think the median age is 16 years in your 5 mg group and 10 or 11 years in your 10 mg group. Could you talk about the reason for that difference? And what implication might that have on the data?

Yes, of course. So we did very purposefully design this trial to be a broad age range. We wanted to get a sense. I mean, this is our first AOC that's PMO delivery. And so we did really want to get an understanding of what that looks like across the broad age range because our goal from the very beginning was that if this was a good proof of concept, we want to move into additional exons down the road. So we were intentional on that age gap there. In terms of what it means for the data, I mean, what we've seen so far is that, that age range has not impacted our biomarker data. And so we'll have to see how that impacts functional. But one thing we will know is, for example, not everyone will be able to do the ambulatory assessments because we have patients that are non-ambulatory, for example. But beyond that, we're kind of seeing this dystrophin and CK impact across all of these patients. And so it will -- it remains to be seen, but it's not something that we're anticipating having a massive impact on our functional outcomes.

Okay. I feel it's fair to say that older patients, it's harder to show improvement. At least on NSAA, we saw that the gene therapy is more difficult, even adding 1 year of age. So certainly, it will be very interesting to see your data on these patients. So maybe moving into the regulatory realm, you plan to file a BLA by the end of this year. Is that still the timing? And can you remind us of -- this is -- will be an accelerated approval pathway according to what you discussed with FDA. Can you talk about the main filing requirement and give us a sense of your progress towards meeting those requirements?

Sure. So I'm going to kind of take us back to the end of last year, we had a meeting with FDA where we aligned with them that the dystrophin data that we had at the time was sufficient for us to move forward for an accelerated approval. So what we actually did was remove biopsies. So since that data, what we have done is also decide we needed more patients to really increase our safety database, but we did not need more patients to prove the dystrophin that we have shown. So all of the new participants that have enrolled in EXPLORE44 did not have to have biopsies, for example. And so what we -- really, the major checkmarks here are dystrophin. And from -- for our perspective, CK remains incredibly important for this data package and safety. And we have got -- we've kind of got the box checked on all of those things. And what we are very much on track to file at the end of this year.

Sorry, did you say CK is also important in those trials.

Yes. CK has become -- I mean, for us, it's become something that is really a critical marker in terms of how we're looking at this because it really is looking at muscle preservation as well.

Remind me, was CK present in any of the other labels for approved dystrophin?

I don't think so. I'm not aware of it being there.

Yes. Yes. Certainly, when we talk to some of the KOLs, they were very impressed by the CK findings from your previous data.

I guess what I'd say is I think it's less important. I'm not necessarily speaking about the label per se on CK, but really the fulsome data package that they could get. Those are the 2 pieces that we really see as incredibly compelling.

Right, right. Got it. Got it. I have a curious question. There is this new FDA Commissioner's National Priority voucher. I was wondering, do you have any thoughts on del-zota could be a candidate?

Sure. So I'm happy to answer that one because Yanan, in my -- when I'm not working on the programs, I also cover all of corporate affairs. So I've been doing all of our government affairs work as well. So I pay close attention to all of this. We have been advocating for things like examples like this accelerated pathway for a couple of years now. We've been really involved in the government affairs side and on the policy piece as well. So we are thrilled to see some of these things coming up. When you kind of look at the things that are important for this voucher, we actually believe that not only del-zota, but any one of our programs really kind of fit the bill for this. And as is typical for Avidity, we are going to go forward and explore any of these options to really deliver these drugs to patients as soon as we can.

Got it. Got it. Perhaps let's talk about the market opportunity for Exon 44 and your go-to-market strategy.

Yes. So basically, the way that we're thinking about this is there's about 900 boys and young men in the U.S. that are DMD44 patients. And so those -- of that population, we see about 50% of them go to the same 40 treatment centers or centers of excellence as they would call them. And so we think that with the infrastructure that we've built up and that I described earlier with patient services that central infrastructure added with the field force of probably about 50 people, we can really be able to go after this patient population. Remember, in the DMD space, these people know they have DMD, they are identified. There's a process that they go through to figure out which exon variant they have. But people who have DMD pretty much know it and are getting seen by the doctors that we see both in the DMD space and also in the myotonic dystrophy and FSHD space. We expect DMD44 will be first-in-class, best-in-class. And as Kath has kind of laid out, we see a reduction of CK to near normal levels, and we can connect the dots because we think that CK level as Cas said is a preservation of muscle. So as we go to the market, we think we'll be the first therapy available to these patients as well as the best therapy available.

Right, right. Maybe thinking on a broader level, but still within DMD, to what degree do you think the results achieved with the DMD44 program could be translated to other exon targets? What strategy do you see as most effective for leveraging from the del-zota to other programs?

Within DMD?

Within DMD.

So look, I mean, we've already -- there's going to be definite leverage, right? We are -- our drug creates near normal length dystrophin and we think that, that's really important for the chronic treatment of the disease. And so we have identified and disclosed that DMD45 is our next target. That program is in pre-IND-enabling studies. And we have done work to identify other sequences that -- for PMOs that would be meaningful to other exon skipping variants. So we look at DMD as a franchise. We look at it as one patient population as they do themselves. And so it will be important to kind of build out this technology for all the patients that could benefit from our treatment.

Got it. Got it. Given that del-zota will be the first antibody conjugated oligonucleotide to reach market, could you give us a sense on COGS? How might it differ from traditional siRNA?

So the way that I would think about COGS, and we've spent a fair amount of time on this across all of our programs because remember, it's important to know that the del-zota drug conjugation is different than the other 2. So with del-desiran and del-brax, it is an siRNA, single siRNA conjugated to a full-length monoclonal antibody. With del-zota, it's approximately 4 PMOs conjugated to a single monoclonal antibody. And so as we move from clinical manufacture to commercial manufacture, we will scale up from 2,000 liters to 10,000 liters to 15,000 liters to 20,000 liters to 25,000 liters. So these -- as we kind of go to commercial COGS, if you will, we are going to experience the benefit of larger scale batches. And so as we hit run rate across all of them, even with the complexity introduced with the del-zota 4 PMO conjugation, our COGS is going to be 10% to 15%.

Got it. Maybe pivoting to the del-brax program for FSHD. There, you had recently announced exciting accelerated approval pathway on a novel biomarker endpoint. Could you remind us of that arrangement? And have you had any additional interactions with the FDA on this AA path since the last announcement? And what might be the update?

Sure. So importantly, I think people have to remember that we actually had 2 conversations with the FDA and our first conversation was about the confirmatory pathway, so a full approval pathway for the approval of del-brax. And that was really important to us to make sure that we were kind of off and running on the full approval strategy. We had in late 2024, already started the biomarker study, right? And we actually fully enrolled the biomarker study in March of 2025. So that was the second conversation. What's the accelerated approval pathway in the United States based on a biomarker. And so the same people that were in the room on both sides of the table were reconvened, if you will, after the confirmatory study to talk about the accelerated approval path. So the regulators knew that there was a confirmatory study. In fact, at the same time we announced the accelerated approval pathway, we had already begun the confirmatory study. So it was a deep conversation with the regulators on what the accelerated approval pathway would be. And so what we've announced on that is that the primary marker is cDUX which is a circulating biomarker that we discovered that is -- we can prove to be highly present when somebody is exhibiting DUX4, which is an aberrant expression of a gene and is not so present for people who are not expressing DUX4. We were able to kind of show that if you reduce this biomarker, functional benefits could accrue. And those are the things that we're working on now in the accelerated approval pathway. So this is the -- so the accelerated approval study is the one that I talked about at the beginning, where we'll announce the data from that in the second quarter of 2026, and we expect to be filing a BLA in the second half of 2026 for that study.

Got it. Got it. So let's talk about the data that you plan to share in the second quarter. Can you give us a sense of patient number, the follow-up and the endpoints there?

Yes. It's just over 50 patients, right? It's a 2:1 randomized trial. It's a 1-year follow-up. And so we expect to be showing the impact that we've had on the biomarker, which we call cDUX because it's really hard to say all the letters of the actual one, but it is in our corporate deck. And secondarily, we'll be measuring CK. And Kath just talked about in DMD, what an important marker CK is in our minds in terms of muscle preservation. Remember also in the biomarker study, because we started it before the conversation with the FDA, we actually are tracking everything. So that study did have a biopsy, and we are measuring, obviously, cDUX and CK, and we're actually also measuring the functional benefits, which would be 10-meter walk run, timed up and go and QMT. So it will be a fulsome data readout when we get there.

Got it. Got it. Speaking of your filing in second half of '26, will there be a pre-BLA meeting? What will be the focus for that meeting?

So yes, we would typically have a pre-BLA meeting for really any of these. And the major goal for that, Yanan, is the FDA really -- they gave us very fulsome feedback when we talked with them earlier this year. The pre-BLA meeting is basically an ability for us to go back to them and say, okay, here's kind of what we've pulled together based on what you've told us to do, and let's make sure that the package we give you is actually what you're asking for. So it's an important step in the process. But pre-BLA meetings are not -- they're also not gating in any way to actually filing your BLA. They're important and helpful along the path.

Got it. Got it. Do you have a sense of -- for the secondary endpoints for the accelerated approval path? Do you need to hit a certain trend or statistic or in one or more of the endpoints? Any sense on that front?

The accelerated approval is really based on the cDUX and really, that is the key thing. The secondary endpoint is actually CK. So all of the functional tests are actually more exploratory endpoints. I do not think that they are required. And with this disease, we're kind of paving the path here. And as you can see from the design of our FORTITUDE trial, we also are paving the path on what it means for FSHD to see progression and to see a change in that based on a drug like del-brax. So you'll see in that trial design is 18 months. This one is 12 months. And so I think we are hopeful, as we've already shown some very interesting data, right, on the functional improvement side, but I do not believe it is required for the filing.

Got it. And the confirmatory study that we were -- that you were alluding to earlier has started -- has been initiated recently, right? I'm not sure -- can you give a sense of patient physician interest or enrollment timing and momentum? Any color there?

Well, you've worked with us long enough to know Yanan, we do not go slowly on things. So we will enroll that program. The one thing that we're being very thoughtful about, and we did this also with the HARBOR study is these are the first phase -- like -- well, actually, in FSHD, that's not the case, but this is the first disease-modifying therapy. We really want this to be a global trial. And so we are -- one of the things that's going to drive that time line in terms of when we actually get to our last patient in for that trial will be when we are able to get Europe up and Japan as well. But we are actively working on doing that now. And that trial is open and ongoing. And as far as the patient community, I mean, FSHD is an incredible -- all the ones we work with are really incredible. FSHD is incredibly organized. And when I tell you there really isn't a day that goes by that we don't hear from patients about the excitement behind this, that is true. I mean this community is very excited and waiting for something.

Great. Definitely looking forward to further update. In the remainder of the time, let's definitely talk about del-desiran for DM1. You have completed enrollment back in July for the 159-patient study. Congrats on that. Top line from the study are expected in the second quarter of next year. Primary and secondary endpoints are measured at week 30, which will be around March 2026, if I do the math correctly. But the study will continue towards week 54 for safety follow-up. So the question we get from investors is that do you need to unblind the study when you do the week 30 analysis? And if that's the case, how you handle that?

We do not need to unblind the study. Patients and investigators will remain blind to the study. We'll have an internal process that keeps that true internally, too. But -- so the reason for this is we can -- we are powered to meet all of our primary and secondary endpoints by week 30. And we do need more safety data than 30 weeks. So this is the reason we go from 30 to 54 weeks. Of course, we'll maintain the trial with all the measures during that time. But what's going to be important is the 120-day safety data beyond the week 30. And so what we'll be doing is working on the efficacy data from week 30 on and then update with the safety data at week 54 when we do the filing for the BLA. So it is still a blinded study. At week 30, we do intend -- we would expect that we will be announcing whether or not we've met the primary endpoint and what the p-value is. Obviously, that would be important.

Got it. Got it. And on the vHOT primary endpoint, what would be your expectation for the data? And what is the bar for approval?

Sure. So I think if you take the high-level view for HARBOR, Yanan, so of course, video hand opening time as a measure of myotonia is our primary endpoint. But we are looking at this study in its totality. So we are looking to measure all of the different endpoints that go from myotonia to strength to patient-reported outcomes as well. We have to hit the primary endpoint. I think there's no question, right? We -- of course, that's the goal. We're very confident in that. And in terms of how we need to do that, we've just ensured that we've really powered the study quite well that we really feel confident going into this data readout.

Got it. And for the secondary endpoints of hand grip and QMT, is there any requirement there for the approval?

Obviously, the primary is the most important one. We do view the secondaries as important as well. I'm not sure that there's a regulatory requirement for that so much, but we have designed this study for reimbursement as well. And so we are looking to have a really fulsome package that covers a number of the challenges for patients living with myotonic dystrophy with the study.

Great. I have one last question. You plan to report the MARINA-OLE data in the fourth quarter, as you mentioned. What would be the incremental learning from that readout?

So what we are planning to present is you've seen our 4 mg per kg patients. So these are the patients that started on 4 mg per kg in MARINA. We've shown the 1-year data. What we're looking to show this time is our 24-month data and the package that we're putting together or that the team is putting together will focus really around safety, but also around consistency, really trying to see that consistency from what we saw in year 1 following through that these patients are still having a good experience on del-desiran.

Got it. Got it. With that, I think we're out of time. Really thank the team for this very wholesome update and all the insights.

Thank you, Yanan.

Thank you.

Thanks, everyone.