If you have any questions, please reach out to your Morgan Stanley sales representative. Today we have the pleasure of hosting the management team from Avidity. Thank you so much for coming. I know this is a busy conference season, so appreciate you coming. Perhaps before we get started, would you mind doing a quick round of introductions, please? Sure. Hi, I'm Kath Gallagher. I'm the Chief Program Officer at Avidity Biosciences. I'm Michael MacLean. I'm the Chief Financial Officer. I'm Kat Lange, Chief Business Officer. Great. Before we jump into your various programs, could you remind us where your pipeline currently stands and the most important catalysts you're looking forward to in the next 6 - 12 months? Yeah. First of all, thank you very much for having us here at the Morgan Stanley Conference. This is our inaugural Morgan Stanley Conference, and we're very happy to be here. As we sit here today, I kind of just remember back like five short years ago where we went public and we were a preclinical company. Now, I'm about to walk you through what our next 12 months look like. We actually sit here with three late-stage clinical trials, and we're looking forward to three BLA filings in a 12-month period starting this year. At the end of the year, we'll file a BLA for our first product, Del-zota, for patients with DMD 44. This will be eventually our first launch product. We expect to launch that product in 2026. We'll have two other BLAs for our Del-zota product in myotonic dystrophy and our FSHD product, which is Del-brax. Those will both be filing BLAs in the second half of 2026. It's really amazing to be sitting here, five years later, looking to three potential launches by the end of 2027. More near-term, what we're looking for is, or what we're going to execute on, is data readout from our Del-zota trial this month. This data readout will be for functional data in our EXPLORE44-OLE. It will look at participants that have been on drug for 12 months, six months in the Explore 44 trial and another six months in the LLE. That adds to really unprecedented dystrophin data that we showed earlier, as well as bringing down CK to near normal levels and sustaining it there. Also, in the fourth quarter, we'll be disclosing our data from our MARINA-OLE. This will be for participants who have been on the drug for 24 or more months. What we're looking to show there is consistency in terms of our ability to reverse disease progression and sustain it. Also, in the first half of 2026, particularly Q2, we will be showing the 30-week cutoff data for the efficacy in our HARBOR trial. Our HARBOR trial is for myotonic dystrophy. It's for our drug Del-zota. It's a 54-week trial, but at 30 weeks, we will have completed all of the efficacy testing or measurement. We expect to disclose that we have met our primary endpoint in the p-value of that. Of course, the trial continues since there will only be week 30 and it continues till 54. It will still be a blinded study. We will be able to disclose more once that study is completed. In Q2 of 2026, we'll have completed our Fortitude biomarker cohort. This is for our FSHD program with the product Del-brax. This is going to be a completed study for a biomarker accelerated approval program. In Q2 of 2026, we will show all of the data from that study. As we do all that, we continue to progress forward with other neuromuscular programs, our precision cardiology franchise, and bring forward our next-generation products. Great. Thank you. Over since, you know, long before going public five years ago, what have you learned across your muscle programs about their product design, long-term safety, and dosing? Kath, would you like to answer that? Sure. I'm happy to. It's always fun. Thank you for the question on the AOC platform. We don't get it all that often. For people who are not as familiar with Avidity, AOC stands for Antibody Oligonucleotide Conjugate. For all of our programs that are currently in the clinic today that Mike was just going through, they all utilize the same monoclonal antibody and the same linker. What changes for each is the actual therapeutic. For two of those programs, in FSHD and DM1, we're using an siRNA. For DMD, we're actually using a PMO for exon skipping. In terms of what we've learned, it's been a pretty incredible amount. I guess we're both relaxed and philosophical today because I'm also looking back on being here four and a half years. Almost to the day, four years ago is when we started to dose our first patients in the Del-zota trial of MARINA. We went into that with this incredible set of information, but we also went into it knowing nobody's ever done this before. We were the first AOC ever to enter the clinic. There were a lot of lessons that we did have to learn in order to kind of keep the platform going and also to learn from so that as we think about our next generation of technologies, we'll build upon that. Some of the key things that, four years later, we are now dosing, and this is a really important statistic. I don't think people fully appreciate this, but we are now dosing about 30 patients a week on average across our platform. That is a tremendous amount. We have also over 250 patient years. We've learned a lot in terms of safety. I think one of the other big learnings that we have taken in is our understanding of how siRNAs work slightly differently when they're going with delivery to muscle. When we went into the clinic, we anticipated, for example, that we'd be doing every three-month dosing. That was based off of what we saw in non-human primates, what we knew about siRNA therapies beforehand. What we learned through the heart, through the Marine program, and what we've also now seen with the Del-brax and Del-zota program is that we're dosing more frequently. Thanks to the safety profile that we have all this data on, we're able to do that. For HARBOR, for example, in our DM1 program, we're dosing 4 mg per kg every eight weeks. For Del-brax, 2 mg per kg every six weeks. For Del-zota, 5 mg per kg every six weeks. We've really been able to learn a lot and kind of leverage that knowledge across the program. Just last year, we started talking about our next gen as well. The data we have collectively across these three programs is really helping us to figure out, now that we've had this kind of leading-the-field pace with our first three programs, what are the things we want to do and insert into our later-stage programs as well. Got it. Thank you. Maybe now starting to get into some of your programs, and I know we just touched on a lot of it. For maybe starting with DM1, what's the primary in HARBOR and Hand Grip, QMT, and DM1 Active as secondary. What is the right composite to capture the disease change in progression, and what magnitude would you consider clinically meaningful based on your MARINA- OLE learnings? First, before we get into answering the question directly, I just want to kind of point out that this was our first program that we launched. Of course, I talked about Del-zota and DMD being our first product. DM1, and what we're going to talk about here in terms of influences where we've been blazing the trail into an area where, although there's been some understanding of the biology of the disease, we've been part of figuring that out and figuring the biology out and how to treat the disease. Really, dealing with the ambiguity of the biology, the regulatory pathway. Now we're starting to think about, you know, how to bring it to market. With that, I'd ask Kath to answer the question. Sure. We designed the HARBOR program so that we are really looking at the key aspect. I love that you call it a composite because not to be confused with the composite endpoint, but we really have always looked at this as a totality of data. The HARBOR trial is the first ever global phase III study in myotonic dystrophy. To some degree, there is a fair amount of responsibility in that, right? When you're leading the field, you want to make sure that you're really testing the right endpoints and that you're getting the right patients in that trial. We spent a tremendous amount of time with the patient community, with the physician community, the global physician community. How we came to these endpoints was really an understanding from the DM1 community itself that myotonia is, of course, important. I think a key point in thinking about VHAT is that VHAT is not just measuring hand function, right? Myotonia is throughout the entire body. People have it in their tongue. It makes it difficult to swallow. They have it in their legs. It makes it difficult to walk. They have an impact from sleeping. It is a truly systemic challenge. The easiest way to really measure that is through video hand opening time. VHAT, while it is measuring the hand, has really given you a lot more information because it's also helping us understand systemically, are we targeting the splicing changes required to make an impact on myotonia? We put that as our primary endpoint. We had a tremendous amount of input on it. It's really a key hallmark of the disease. In addition to that, in it being a really great functional endpoint, we also wanted to look at strength, which is another really important piece of this disease. That's where we have our Hand Grip coming in, as well as QMT. Of course, there's a big deal in all of this, which is how do the patients feel on drug? Our other endpoint is the DM1 Active, which is a PRO that's in the study as well. When you kind of look at these together, collectively, it's a total package for the DM1 community. We believe, and we designed it this way, that it's not only going to help us with our regulatory path, but it's also a reimbursement path too. Key to all of this was getting regulatory input. We have done that across the U.S., Europe, and Japan, and have gotten full alignment around this design and VHAT as the primary. Got it. Thank you. From your perspective, what secondary endpoints are you most confident in hitting stat sig and least likely to hit stat sig? I'm confident in hitting all of them. I really do feel strongly about that. Within full disclosure, I was the global program head for this program. It is near and dear to my heart. When you really look at the MARINA data, which is our phase I/ II data, we saw something that you just don't expect to see in a muscular dystrophy, which is reversal of disease progression. We saw that across all of these endpoints. We do have, you know, we're pretty bullish going into our phase three top line, based on the data we've seen and also based on, you know, we have a tremendous amount of natural history data that we've been able to use to help us look at that and also to power it properly. The study is really well powered for all of these endpoints. Okay. With DM1's cardiac burden, how are you tracking all the cardiac endpoints or biomarkers as part of the HARBOR trial? You know, somebody asked me earlier today if there's one thing I wish I could do differently. My answer was I would love to be able to track cardiac, but the HARBOR trial is not the place for us to do that. We had a lot of discussion around that. The reason is that cardiac is a huge piece of the disease for these patients. Part of why I'd love to track it is because we know we deliver to the heart. We know Del-zota actually can get there and can have an impact. You know, this is a rare disease. These patients have nothing today. As we designed this trial, it was about getting to the market as fast as possible. I do look forward to actually studying some of those things in the post-marketing setting for sure. Got it. Thank you. Can you talk a little bit around your decision to use an siRNA in this indication as well as your choice of dose and the dosing interval? Yeah, actually, Kat, would you like to talk? Yeah. This is something that we actually have a lot of experience with. This team has a lot of experience with from prior companies. siRNAs are just really good at knocking down genetic targets. One of the things that was really missing from the field and one thing that Avidity has really been the leader in is taking the siRNAs into tissues outside of the liver. We had a very strong hypothesis that if you get sufficient concentration into the muscle tissue, these siRNAs would work incredibly well in these types of diseases. In this case, with DM1, it's all about the DMPK knockdown, which then leads to the freeing up of the muscle-blind protein that has all of these downstream effects on splicing and really fixes the splicopathy that is a hallmark of the disease. What we're seeing with the AOC deliveries is a very nice increase in the muscle concentrations of the siRNAs. That was really the choice that we made. As Kath touched on in the preclinical models, we thought we could really get to a quarterly dosing schedule for every 13 weeks. One thing that we noticed in the MARINA phase I/ II study is that that was not quite frequent enough to really get the benefit to these patients on a consistent basis and really sustain that benefit. It's something that we even heard anecdotally from patients that a couple of weeks before the next dose, they would feel a waning of effect. It's really important for us that we took the anecdotal evidence together with some of the biomarkers that we've seen into account to really optimize the dosing interval. That's how we've ended up at an every eight-week dosing interval here for the Del-zota program. siRNAs are extremely safe. They're also potent and durable, and they are the right oligos to pick for this disease. Got it. We've touched on some of the upcoming milestone events already. Maybe we can just talk a little bit around the disease prevalence. You've framed the opportunity as 80,000 individuals across the U.S. and Europe now, but there are much higher estimates. At the same time, there's an argument that some of these individuals may not be motivated to seek treatment. How will you segment the population while addressing awareness, building awareness, and also the diagnosis rates? I'll take that one. Look, this is a very large rare disease, right? 40,000 patients in the U.S. as rare diseases go is pretty significant. What we're finding in terms of, is that number appropriate and, you know, is the size believable? Everything that we've seen is that, yes, this is approximately the size of things that we look to, you know, the major medical centers where these people end up. There's a DM1 study that has enrolled over 500 patients into a natural history study. As we conduct our clinical trials, MARINA and HARBOR, the level of interest and the engagement in this patient community to be part of these trials is pretty healthy. We're not finding apathy in terms of trying to come into the trial. You can see our HARBOR trial was enrolled on target and on time in a 12-month period. Everything we've seen is that that's the right patient size. This is an engaged patient population. Is there a symptomatic apathy for the patient? Yes, we understand that's part of the disease, but it's really not part of their behavior toward treatment. That may not be solely related to the patient. These patients are part of families that have this disease in their family. That is, it's a community that helps this patient deal with the disease through their lifetime. When we talk to the patient advocacy groups, they're passionate about getting treatments. They deserve treatments, ours and others. As we kind of go forward on that basis, we see this as a patient population that's actively engaged. The uptake as we look at commercialization and the opportunity here, we're really pleased with the fact that we're going to be launching this drug globally, right? By globally, initially, what I mean is the U.S., Europe, and Japan. In all of those markets, we found great enthusiasm for the uptake. This will be our first global launch. We're preparing for that. Del-zota is our first U.S. launch, but we'll be launching Del-zota in the EU and Japan first, right, as a company. We're setting up everything for that: the supply chain, the commercial organization, the patient services function. We're really excited about, you know, not just the 40,000 patients in the U.S., 80,000 includes Europe, but I don't believe that anything brings in Japan. That's a market that we've started the clinical trials there a year ago. The KLLs there are thrilled that we've launched our global first full-approval clinical trial in Japan, simultaneously. Great. Thank you. With most companies, we'd be done with the presentation now. We've got to get through the rest of your program. Maybe shifting to Del-brax in FSHD, can you talk about your biomarker approach? Kath, do you want to talk about? Sure, of course. Just this past June, we announced that we have a circulating biomarker, which we refer to as cDUX. cDUX is targeting a gene, oh gosh, KHDCL1. Pretty close. We named it cDUX because it is quite challenging to remember the actual name of the gene, but it is a very well-known gene in the FSHD space. It is something that people have been studying for quite some time. We had been looking at it in our muscle biopsies as well. The thing that Avidity really discovered is that you can also measure it in blood. That really is a very exciting thing for the community. The real insight around cDUX is that when patients have high levels of cDUX, they actually have a more severe version of the disease. We're kind of looking for an inverse correlation here. We want to decrease cDUX so that we can see more improvement with Del-brax. What we did last year is we wanted to look at FSHD as a whole. We got our first data set back in June of 2024, looked at that, and said, we need to move this drug forward as quickly as we can. What we did, as we call it at risk, is we initiated the Fortitude biomarker cohort, which is about 50 patients. That one is our accelerated approval trial. We initiated that last November, and we fully enrolled it this past March. That is what we are looking to have read out next year. A lot of the questions we've been getting are around what functional data do you really need to show. The functional data is not necessary, right? This is an accelerated approval pathway. It's not that we have to hit statistical significance on our functional measures here. What is important is that we're able to correlate cDUX with function. That is the work that our team is doing right now and paving the path for FSHD to really bring this treatment to patients. At the same time, we have launched our global phase III study called Fortitude 3, and that has just opened and started enrolling this year. That will be our functional trial that we would go for a global approval with. Got it. Thank you. While we're on the point about cDUX and functional improvement, can you elaborate on what additional work you still need to do to prove or show that correlation works by the time you go for a BLA submission? Of course, sure. We've already done a fair amount of the work using the Fortitude data that we have, which is the dose escalation cohorts that we presented earlier this year. We've also utilized our natural history data, which we have a tremendous amount of. In FSHD and DM1, the investigators have just been an incredible source; they were really strategic in setting up these natural history studies. There is a tremendous amount of data we can utilize from RESOLVE, MOVE, and MOVE +. What we are really waiting for now is the data from the actual biomarker cohort, which will allow us to really fulfill the work that we're trying to do. The other things that we have to do between now and the BLA are things that you just need for an accelerated approval pathway, like what CMC do we need to have, things like that to make sure that our submission is fulsome and ready to go. Got it. Thank you. In case you didn't bump into Commissioner McCauley, what feedback did you receive from the FDA when you learned that the accelerated approval pathway was opened and announced that you had achieved significant, you had achieved alignment with the agency around the regulatory strategy? Maybe I'll take that one and add if. I think one thing that people haven't focused on is Kath just talked about how we were already doing the biomarker cohort. The way that we set up our conversation with the FDA was we actually went and got approval of the confirmatory study design. I guess one other thing that's important is that the part of the agency that we deal with, Neuro Division 1 and CDER, works with us across all of our programs. We had a conversation with the team at the FDA on confirmatory trial design. When that was approved, we then went back and had a conversation with them on the biomarker accelerated approval design and process. A lot of the questions that you would typically have had been answered as part of our confirmatory study. We were able to spend time on really the two pressing issues, which is how do you prove that the surrogate can be linked or correlated to benefit? As Kath just said, how do you show that you're going to be ready to produce commercial-level inventories in time? Most of our discussion were deep in those areas, which is really what we call alignment with the FDA. Got it. Thank you. What are the planned disclosures around the Fortitude biomarker cohort in the second quarter of 2026? Kat, can you talk to that? Yeah, absolutely. In the second quarter of 2026, this trial would have been completed. If you recall, we completed the enrollment in March of 2025. By the time we get to the Q2 readout, all of those participants would have rolled over into the OLE if they so choose. At that time point, we can actually disclose all of the primary and the secondary endpoints, including the p-values, and, of course, all of the safety profile. That is really the totality of the data package that will go into the BLA submission in the second half of next year. Yeah. Maybe one more on FSHD. You've provided a wide range for the prevalence in the U.S. and Europe. What sort of data support both the low-end and the high-end of the range? Can you speak to the interest in Del-brax from the FSHD community, both here and abroad? Kath? Absolutely. This is, I think, out of the three indications that we're pursuing, probably the least well-illuminated prevalence figures, as you can imagine. The ICD code has been around for about five years. It was launched right around the time of COVID, which is very unfortunate, just in terms of gaining data from the ICD-10 databases. We believe in the U.S., there are about 5,000 patients that have already been identified and diagnosed with FSHD. That is actually a pretty good number for the total size of the indication that we're looking at, which we believe to be at least similar to DM1, if not slightly larger. If you look at the genetics studies, there are a lot that would tell you there's at least 40,000 in the U.S., if not higher. We're doing a lot of that work at the moment in order to prepare for the launch that we're anticipating here relatively soon. The interest has been just tremendous. We're getting multiple emails per day, not just for FSHD, but also for the other programs. I think FSHD really has been notable in just the motivation and the excitement from the patient community. A big part of that is also the patient advocacy group. The FSHD Society has been very, very active as well. They're very good at getting the patients organized, educated about potential clinical trials, treatments that will be available soon. They're also driving a really big diagnosis effort that we think is going to really help us here. Overall, as you would expect with a lot of rare diseases, as treatments become available, you will start finding even more patients. Got it. Thank you. Now, shifting to Del-zota and DMD. The Explore 44 showed an increase of 25% of normal in dystrophin at four months and almost near normalization of CK. How are you thinking about how to translate this into functional signals? Interesting you should ask. We have guided, as I said at the top of this meeting, that we're going to be giving functional data this month. We think that that's really important for the community to really understand how this therapy could benefit them and how they can live their lives. With the strong dystrophin, a 25% increase from 7 to 32 that we demonstrated, and bringing down and sustaining CK to near normal levels, we should see functional benefit. The original trial went six months, and we didn't think that we would see functional benefit that soon. Back last December, we said, why don't we look at it at one year? We had guided to the fact we would be looking to functional and are presenting, sharing functional data around this time for participants who had been on Del-zota for one year. Here we sit at the eve of that disclosure. We're really hopeful that we can actually connect the dots, that dystrophin leads to near normal CK levels and near normal CK levels so that you can see functional benefit at that point in time. Importantly, we're applying to the FDA for accelerated approval based on a dystrophin biomarker. We're submitting the BLA at the end of this year. The functional benefit is not part of the requirement to submit that BLA. We do think showing that functional benefit will be, could be important to the patient community to understand the power that the therapy could have. Thank you. Now, shifting to your commercial strategy, when it comes to your pre-launch commercial preparations, what elements are Del-zota or DMD specific? What are anticipated to support all three programs? Can you maybe discuss the top priorities between now and the Del-zota approval? Yeah. Literally, Rok, we've started building our commercial organization quite a while ago. We've actually built the patient services organization. We have MSLs in the field. We have payer reimbursement specialists who've been talking to those parties. We're in the process of building the flight of care teams, so that's all either built or underway. The next thing is the sales force in the field. We have done the market research to understand that 75% of these patients are seen by 100 doctors, 100 specialists in the U.S. We know where to go. We know what size team you need to get there. We're ready to go on Del-zota. It's a bit of a gift to be able to launch your first drug in your smallest indication. Remember, Del-zota will be U.S. only, right, because it's an accelerated approval here in the U.S. What it allows us to do is build that center hub with things like patient services, build the field team, get them to develop the relationships and understanding of the patients, the doctors, where these people go for their treatments. When we're ready to, hopefully in relatively short order, launch our next two drugs for FSHD and DM1, these sales reps and others have developed relationships with the caregivers. They're going to just be adding into the conversation these other diseases that they treat because these caregivers, these docs, actually, there's pretty much 100% overlap between FSHD and DM1 in terms of their patients they treat. Most DMD 44 patients are treated by these docs too. Some DMD 44 patients are treated by pediatrics, right, so there's not necessarily an overlap there. This is really powerful in terms of helping us build the infrastructure, helping us test the infrastructure, that it's sound, that people are doing the right things, developing the right relationships. Then to leverage that for really incremental investment, even though FSHD and DM1 are much larger populations, those potential drugs are going to be blockbuster in nature. The investment on top of the infrastructure is going to be relatively modest. Thank you. Maybe that's a good place to get to the last question. Now, with $1.4 billion in cash and a stated runway to mid-2027, could you talk about some sensitivities in your assumptions? Just, I guess, conceptually, what is the shape of your financing trajectory once these products launch? Kat, would you like to take that? Yeah. Rok, you're correct. It's a very strong cash position to be sitting on today. Runway is to mid-2027, so that means we do not get all the way to profitability. However, once we launch these drugs with the market opportunities that we see, we do believe we're going to reach profitability relatively quickly. There's really, you know, a lot of things you can test in the sensitivity, but all of it means you get to profitability very quickly post those two big launches. I'm talking about Del-zota and Del-brax specifically. With that being said, we are in a very strong position today, but we do also emphasize, you know, all the time that we just want to maintain a strong balance sheet, be able to execute on all of these drugs, in the clinical trials as well as the commercialization globally. We will be continuing to assess additional pools of capital that we can tap into. We're very blessed in the sense that we are going towards three commercial launches, and a lot of different pools of capital will be available to us. Great. Thank you so much for your time today. I hope you enjoy the rest of the conference. Thank you. Thank you.