Conference Transcript - RNA 2026-11-11

James, Analyst — on behalf of Steve Volkmann)

There we go.

James, Analyst — on behalf of Steve Volkmann)

Welcome, everyone, to the next session here. Happy to be with Atrium Therapeutics. I have CEO Kath Gallagher here to discuss their story. You're going to do a presentation, and then with whatever time is left there, we can do a Q&A. So thanks for being here.

Cass Gallagher, CEO

Sounds great. Well, thank you, James. Thanks for including us. It's wonderful to be here at the Stiefel Conference. So thanks, everybody. I'm actually joined here by a number of my team members who are also in the audience. So thank you. I'm very excited to introduce you to Atrium. Um, let's start, of course, I'm going to be making some forward-looking statements today. Um, let's just start with what Atrium's vision is. So Atrium is here to pioneer precision RNA medicines for the heart and to profoundly improve people's lives living with cardiac disease. Now that is a big and bold statement. And the reason that is the case is because RNA therapeutics have really not made a big impact in the cardio space. Now, with the exception of really the TTR programs. RNA has been limited because of the fact that it hasn't been able to deliver to the heart. And so a big piece of what Atrium is bringing to this is our ability to utilize our platform to deliver to the heart and really impact these diseases that historically have been very difficult to treat. I'm going to take a second just to kind of step back and say what we've done, because Atrium, we are just shy of nine months old. So our first day trading was February 27th, 2026 of this year. Atrium spun out of the Avidity Novartis merger and acquisition. We launched with $270 million, and we launched with the RNA delivery platform from Avidity, as well as a pipeline of precision cardio programs. So it's an incredible way, frankly, to get to start off, and we were able to bring a number of our team members with us from Avidity to Atrium. And in the time since we have launched, we have had a very productive period of time. So First and foremost, we are cleared to run our clinical trial, the Corventus study, for ATR-1072 in PRKAG2 syndrome. We cleared that over the summer, and we just dosed our first patient in the last few weeks, so very exciting times there. In addition, we've done a lot of work to truly understand what the real potential is for, of course, G2 syndrome itself, But also looking at these programs as a whole and thinking about ways to expand into other rare cardiomyopathies and, frankly, ways to expand our pipeline as well, which are all things that we are doing and excited to talk to you about today. So if we take a step back here for a minute, there have been a tremendous amount of advances in the cardio space. But one group that has really been left behind is the genetic cardiomyopathy, the genetic cardiomyopathy patients. And, you know, when you think about the space of cardiomyopathy, there's about 2 million people in the United States with cardiomyopathy, about half of them, so about 1 million, are said to be genetically driven. Of that 1 million patients, there are only 1% of them today that are getting genetically tested. So a lot of these patients are really just kind of living with the disease, but they're going under the radar, and they don't necessarily know what has caused their disease. In the cases of the programs we're working on, these are areas where it's really impacting this person's life in the prime of their life. So in the case of PRK-AG2 syndrome, symptoms start for that in the late teens and early 20s. So it's quite young. And in the case of phospholamine cardiomyopathy, it's in your 30s and 40s. So these are, you know, unfortunately, the stories you hear, and we hear them probably all too frequently, of someone passing away, you know, a runner that passes away from a heart attack. These are very likely driven by underlying genetic conditions that have not been caught. And that lack of genetic testing that where we are today is both a really important thing for us to move forward because, of course, it will help us to identify patients, but also it's helpful for these patients themselves to really understand what is the cause of their disease and do they need to be treated or seen. And it's really an exciting time for the cardiomyopathy space because alongside Atrium, there are also a number of other companies that are really starting to look at this space. But it is really a blue ocean, if you will, in terms of how people are doing this. And Atrium is very excited to really be at the tip of the spear on this. Patients today are really getting symptomatic management. They don't have anything that actually treats the root cause of their disease. So that is really where we hope to come in, at least for our first two patient populations, and really bring something that can actually help to stop, ideally, their disease progression, and maybe even reverse some of that. From an execution perspective, we understand the urgency in which we need to execute, because these patients, again, they are progressing. And eventually, these diseases lead to heart failure and, in some cases, heart transplant. And those are clearly very serious. And so we are moving quickly, again, dosing our first patient in Corventus, but also moving our pipeline forward. And the tools we're using to do this are both our RNA delivery platform as well as our focused precision cardio pipeline. So I'm going to start for a second just talking a little bit about the RNA delivery platform. For any of you that followed Avidity, this would have been what we call the AOC platform, antibody oligonucleotide conjugates. What we are doing is utilizing the same monoclonal antibody and the same linker that we were utilizing at Avidity in the neuromuscular space, but we are now applying that to the precision cardio space. Where we have made some changes is, of course, in every disease, there's a different oligo based on the gene you're trying to approach. But in this case, we are also using some of the next-gen technology that we have developed, which is a chemical modification that makes our oligos. More durable, as well as more potent. And so, you know, this is a technology that we understand quite well. We understand the antibody, we know how it works, and it's been shown already to deliver to skeletal muscle. We've also shown in a lot of our preclinical studies that we can deliver to the heart. We now need to show that in humans, but we have a lot to work with in terms of this technology platform. And then spending a minute on our pipeline. So we're going to spend most of our time today on PRK AG2 syndrome or ATR 1072, our program targeting that. We also touch on ATR 1086. Behind that, we have two additional rare cardiomyopathy programs. The first one we're hoping to put into development candidate in 2027. So we are moving. And again, we just see this as an incredible space with so much opportunity. From a balance sheet perspective, you know, surprise, surprise, it's earnings time. So our numbers are going to be coming out in the very near future here. This is quite an outdated number at this point. But we will be putting that out shortly. And I think the important piece is twofold. One, we have a collaboration with BMS and one with Lilly. And over the last few months, we have actually gotten multiple milestones from that. And in addition, we were able to close a pipe last month, which we were thrilled to do with a number of really high quality investors in the biotech space. So we have a very strong balance sheet as we head into 2027. We have cash through the end of 2028. So now let's spend a minute on ATR 1072. So PRK-AG2 syndrome, this is an inherited and progressive disease. These patients show up with a thickened heart or it's a hypertrophic cardiomyopathy. They also have glycogen storage challenges. And what this leads to is heart failure. In cases where people are undiagnosed, there's a higher incidence of sudden cardiac death. And the real thing that is exciting about helping these patients is that today there is no therapy targeting the root cause of this disease, and we really see ATR 1072 as an opportunity to do that for these patients. Right now, we have an estimated prevalence of 1,000 to 2,000 patients. We feel very confident that this is quite a conservative number, and that's due really twofold. One, to the lack of genetic testing that I mentioned earlier in the cardio space, but in addition, this is rare disease, and rare is almost always significantly underdiagnosed, and that might be more so here because of the fact that that genetic testing number is so low. So, if we spend a minute just talking about the disease, so what is happening in this disease is that there's a mutant PRK-AG2, and that is leading to overamplification of AMPK. That ends up leading to this HCM as well as the glycogen accumulation in the heart. We've recently, just this past weekend, actually, so hot off the presses, showed some new non-clinical data in a mouse model with a pretty aggressive form of PRK-AG2 syndrome. And in that mouse model, we were able to show that the mice did have glycogen accumulation in the heart, and the mice treated with ATR 1072 were actually able to go back to close to control in terms of their glycogen. So this was very, very reassuring data as we think about really targeting the root cause of the disease. In addition, we also saw some other key parameters like improvement in ECG parameters and including the PR interval. In addition, that other key hallmark I mentioned earlier is the hypertrophy. And what we were able to show through echocardiogram in this non-clinical model is that we were actually able to decrease wall thickness in these mice as well. So very encouraging in terms of what we have been able to see preclinically. In addition to our work in mice, we have also been able to show activity in monkey, and you can see here we were able to show knockdown with ATR 1072, and in addition, we've done a tremendous amount of work on the safety side of this as well, and so we've completed our chronic toxicology studies with no dose-limiting toxicity. So now I want to spend a minute talking about the Corventus trial. So while, of course, this is a huge milestone for the Atrium team, this is our first clinical trial as a company, this is a bigger milestone for the PRK-AG2 community because this is the first trial ever to really bring them a potential therapeutic that could be disease-modifying. So this trial, it is a dose escalation trial with an expansion. We're looking at three doses first. We're looking at 40 mg per kg, 80 mg per kg, and 100 mg. I'm sorry, not mg per kg. We're doing flat dosing in this. So 40 mg, 80 mg, and 160 mg. We're doing that dose escalation first, and all of those participants are able to actually move into a long-term extension. Through that portion of the trial, we will actually identify our phase two dose, and then we will enroll an additional 25 participants into an expansion cohort. One of the ways that we really were quite thoughtful in designing this Corventus study is that we've had a very flexible design. So we have the ability, for example, if we get a tremendous amount of information and we want to really think about that expansion cohort as even a potentially registrational expansion, for example, We have the potential to do that. But again, since this is the first trial in this disease, we also have a lot to learn. And that's part of the work here in the dose escalation portion. The primary endpoint, of course, is safety. And in addition to that, we're looking at a number of secondary and exploratory endpoints. Importantly, we're looking to prove through this study that we can, in fact, in humans deliver to the heart and knock down the target gene there. And then, of course, we're looking at a number of different parameters to really understand what are the ones that make sense for us to continue tracking as we look ahead and registrational endpoints down the road here. And so we're looking at all sorts of exploratory endpoints, including echocardiogram, ECG. We're looking at ones that measure arrhythmias as well. So doing quite a bit of work in this study. Um, you know, as we think about the next steps for this program, you know, we've just dosed our first patient, but our next big milestone for ATR 1072 is our initial proof of concept data that we're anticipating in the second half of next year. What we're looking to report out on in that proof of concept is that, yes, indeed, we do deliver to the heart. We do knock down our target and given, and of course, safety. And the way we will look at this is we will do it by cohort. So we would be looking at full cohorts of data. And of course, we will be reporting on safety from all the participants that have been dosed with ATR 1072. So we have quite an exciting time ahead for this program as we continue to recruit and bring sites up and running. So now let's turn to ATR-1086. This is our program for phospholambin cardiomyopathy. Again, this is a rare genetic and progressive disease. It has a frequent family history. And in fact, in this disease indication, there are founder populations in the Netherlands and Greece. And so, you know, you have some little strings to pull there in terms of where to look for the patients that might have this disease. Majority of the patients with this are driven by the PLNR14 DEL mutation. And again, this is an area where we actually have a dilated cardiomyopathy as well as arrhythmias. And this disease can be very serious and, in fact, can often lead, when it gets to late levels of progression, to an actual heart transplant. One number that always sticks with me is that in the Netherlands, this is one of the top reasons for a heart transplant in the country. And so it is, you know, quite an impactful disease. There are no treatments today targeting the root cause of disease either. Everything is symptomatic management. From a prevalence perspective, again, we have a relatively conservative estimate of 2,000 to 4,000 patients. We have to do a lot of the same work we've been doing around PRK-AG2 to truly understand what this prevalence might be. But again, with the fact that we have a low genetic testing number and the fact that... It's rare. We do anticipate that these are pretty conservative numbers. As we think about the mechanism of disease here, what we are doing is knocking down phospholamin. Phospholamin is mutated in this case, and that is leading to form protein aggregates. Those aggregates are what lead to this dilated and arrhythmogenic cardiomyopathies. And what we've been able to show so far in our early mouse studies is one, of course, we're able to knock down the target in mice. But interestingly, we've actually been able to see the impact of ATR-1086 on functional improvement, and in this case, survival in mice. So as you can see here, we had tested a number of mice, and the ones that went without treatment actually died around eight weeks. What we were able to show is survival in the mice that were treated with ATR-1086. And importantly, what we also saw is a real improvement in ejection fraction, which is clearly quite important for this heart failure population. In terms of next steps for ATR 1086, we are filing our IND next year and really looking forward to that as well. So one differentiator for these two programs, so again, if you think about a lot of genetically driven RNA therapeutics are one therapy, one disease area. In the case of ATR 1072 and 1086, we actually believe that there are multiple opportunities for indication expansion for both of these programs. And so if you think about the reasons why, both ATR-1072 and ATR-1086 play a central function in cardiac pathways. So in the case of ATR-1072, it's impacting AMPK, which is the energy sensing pathway. And in the case of 1086, it's calcium handling, PLN inhibits circa two. And so looking at both of those, we believe there are a number of rare cardiomyopathies where we could do indication expansion for both of these programs. That is something that our research team is working on actively today to really think about where we would like to go next for these two programs. So as you can see from the atrium story, we are really firing on all cylinders. We've been in execution mode since we launched earlier this year. We've achieved a number of milestones, but importantly, we also have quite a few ahead of us with our initial proof of concept data next year, as well as filing our next program and identifying our next development candidate, all in 2027. And as I mentioned earlier, a number of my management team members are here with us today. We really have a phenomenal team that has deep expertise in rare disease as well as RNA therapeutics. In addition, we have a phenomenal board with really some of the leaders in the biotech field supporting us in this. And really, this team is what is making this happen. You know, we went through a tremendous amount this year in terms of transitioning into being an independent company. We only had four months from the beginning of the announcement of the Novartis transaction to us being a publicly traded company. And we basically started at a standing stop and created a company and a vision. And we have our lab set up and we've been able to achieve all of our milestones for the year. So I am incredibly proud of this team, of course, our management team, but also, frankly, every team member that has done a tremendous amount of work to get us to where we are just nine months after our launch. And, you know, we really look to the future, and we are well set up for success here. We have a platform that is well understood. We have a pipeline of focused therapeutics that have indication expansion opportunities, as well as looking at adding additional programs to our pipeline as we move forward. Our team knows how to execute, and we have a balance sheet that allows us to get through a number of milestones ahead. So thank you all so much for listening, and now I will open it up with James for Q&A.

James, Analyst — on behalf of Steve Volkmann)

Do you want to?

James, Analyst — on behalf of Steve Volkmann)

How is this administered?

Cass Gallagher, CEO

Yeah, it's a great first question. Thank you. So the first question is around how do we administer this drug? This is an IV infusion. And so patients get an IV infusion every six weeks. The way to think about delivery here is that the monoclonal antibody, you know, I kind of jokingly have used this reference, but it really works, especially on Capitol Hill. It's kind of like the magic school bus. So basically, the Magic School Bus delivers to where we're trying to get it to, but then it drops off the actual medication, and that's really where it does the work. And that's the important piece, because SIRNA Therapeutics have really shown to be so promising, but getting them to where they need to be was always the challenging part. And so that's why the AOC technology has been, you know, really a game changer, of course, for these programs, but also, frankly, just in the field in general, bringing so many more people into this idea of delivery. I don't think we've gotten into that level of detail. I mean, it's targeting PRK-AG2 in the case of G2 syndrome, but I don't think we've specified. Oh, I'm sorry, the antibody. I was going right to oligo. Sorry about that. We are targeting the transferrin receptor. So similar to what we were doing at Avidity, we're utilizing the transferrin receptor, which is ubiquitously expressed throughout the body, and that is bringing it to the heart and then delivering the siRNA there for treatment. Thank you. Sorry, I'm so focused on the oligo. I was, like, not even hearing the fact that this was an antibody question. Thank you.

James, Analyst — on behalf of Steve Volkmann)

Yeah, maybe just on the platform, obviously, you know, disappointing outcome for the DM1 program, obviously an entirely different indication and context, but there's obviously been a lot of sort of history here with this, you know, with Transfarin. There's a lot of other companies with Transfarin. Maybe just in terms of these programs specifically, how different, if at all, is it from what was used in the DM1 program? And was there further optimization to bias this towards cardiac tissue versus muscle? Just curious, the differences with this versus what's been done in the past.

Cass Gallagher, CEO

Yeah, no, it's a great question. Listen, the Harbor results were, they were devastating for all of us. We really believe in the technology and that patient population will always stay very near and dear to my heart. Having said that, you know, I don't really see any read through from the Harbor results to the atrium, the platform that we're utilizing. There's still so much to be learned from that trial, including really what happened. We just haven't seen the data yet. So I think we need to see that data to really understand what was driving that. But in terms of delivery, we have shown that, of course, obviously in FSHD as well, DelZota has a BLA filed. So there's actually quite a bit out there beyond the DM1 story that really shows the strength of this platform. Um, in terms of what we have done, so yes, we have made some changes to the oligo itself. So a question we get quite frequently is what kind of target this is. This is a cytoplasmic target. Um, and in addition, um, What we have done is we did a chemical modification to really optimize for cardiomyocyte delivery for the siRNA, and that's really where the increased potency and durability comes in. And you can kind of see that also in even our dosing. We are doing flat dosing, and we're able to do that based on all the work we were able to do in the neuromuscular pipeline. But you'll see even if you were to convert that to MIGs per KIGs, it's almost about half of what we were doing in the neuromuscular programs.

James, Analyst — on behalf of Steve Volkmann)

Makes sense. And yeah, that's funny. Stytoplasmic versus nuclear in that whole debate.

Cass Gallagher, CEO

I don't know if you've heard, but there's a bit of a debate about that.

James, Analyst — on behalf of Steve Volkmann)

So maybe just on AG2, your lead, you've talked about 2,000 patients. You know, do you think all those would be addressable? And I know it's hard to probably be quantitative, but, you know, how much upside do you think there is to that number in terms of a prevalence for this population?

Cass Gallagher, CEO

Of course. Well, let me walk you through, you know, the work that, you know, Rocio, who's here, her team has been doing since we launched Atrium. I do think there is quite a bit of upside and to kind of start at the end. We really look at that 2,000 as almost our floor now. And the question really is, how do you understand what the ceiling might be? The reason for that is really threefold. So the first thing that we did was we... I contacted some genetic testing labs to really understand how many patients have had a cardiac panel done and how many of them are positive for G2. And so with Rocio doing all that work, what we've already identified through the handful of labs that we've contacted is close to 2,000 individuals with the PRK-AG2 gene mutation. Now, those 2,000 are either pathogenic, likely pathogenic, or they're what's called a VUS. And so the likelihood of those converting to patients eventually is quite high. Now, it doesn't mean that we know who those patients are or where they're being treated. It just tells us that that's a pretty significant number, especially when you're in the ultra-rare space, you're not intending to find that in a short period of time. I think another thing that gives us quite a bit of confidence is... The fact that as we are starting to enroll these patients, we have already identified through the sites that we are getting up and running right now more than enough patients to complete the dose escalation portion of the trial, and that would include if we had, for example, a really high spree failure rate, which I'm not anticipating, but if we did, we have a number of patients, and patients kind of lined up for the study. So those two things, you know, I think the third is really, again, I'm going to come back to it, but this low genetic testing number, you know, these patients got a cardiac panel for a reason. Most likely that reason is because they were having some sort of symptoms. If it wasn't symptom-based, it was most likely they were getting cascade testing and their family member had it. So, you know, all of that together really tells us that this is a rare disease where we are just starting to understand what that patient's size looks like.

James, Analyst — on behalf of Steve Volkmann)

Yeah. Makes sense. And that was going to be one of my other questions, just how enrollment has sort of kind of played out so far, but sounds like favorable. And kind of, you know, on that point in terms of screen failure, this study. How variable are these symptoms, and is there a specific kind of, you know, patient population or segment of this kind of, like, broader disease presentation that you're trying to, like, enrich for in these studies that, you know, is maybe better suited for this drug?

Cass Gallagher, CEO

Yeah, so we are not doing a lot of enrichment, actually, at this point in the trial. I mean, this is early days, right, in terms of a phase one, two study. So, for example, even patients with a VUS right now are eligible for the study. We have very purposefully left the criteria quite open because we really want to explore this patient population and understand, you know, what is really driving this disease. And so as we look to that, we don't anticipate that we're going to have a heavy screen fail rate. In addition, the way we design the drug is that it's not allele specific. So it really, it's covering a number of, it's really covering a number of the mutations on the PRKG2 gene. And that allows us to really target, you know, a broad set of patients with the G2 mutation as well.

James, Analyst — on behalf of Steve Volkmann)

Yeah, yeah, makes sense. You know, in that study, second half next year, totally understand it's early. But how are you sort of framing what a win looks like? And, you know, you're testing a lot of these other sort of like exploratory measures. Do you expect to see anything on, you know, like EKG or the Holter monitor or anything like that?

Cass Gallagher, CEO

Yeah, I mean, so for us, the success looks like a great safety profile or a great safety profile in rare disease in particular, right? It also looks like we are able to show delivery to the heart. We're able to show our target knockdown. That is a huge win from our perspective. And again, putting that in the context of where I started at the beginning, cardiologists have not worked with RNA therapeutics a lot. They don't really have a baseline reference. And most of the time when they have in these genetic spaces, it's been with gene therapy. And so this is a really big data readout for us, but also for the community, because it will hopefully show we can deliver. And we can deliver to the heart, and we can knock down our target. Now, anything beyond that would be fantastic. I think the real question is, given that this is the first trial in this disease, we just don't know how long it will take. Given the preclinical work we've done, we have a lot of confidence that we're going to be able to impact things like glycogen accumulation. But what we don't know is how long it'll take to show that.

James, Analyst — on behalf of Steve Volkmann)

Yeah. Yeah. No, it makes sense. And then maybe just in the last minute here or so, in terms of these expansion opportunities, just curious if you could kind of provide additional color of sort of what that might look like. You know, you mentioned hypertrophic cardiomyopathy. There's hypertrophy in the heart. Is that like HCM is sort of like an opportunity for this? Just curious what that expansion opportunity looks like.

Cass Gallagher, CEO

No, it's a great question. So we're not looking like broadly necessarily at HCM as like a whole, right? What we're really looking to do, I mean, we're focused on precision cardio, right? And so part of being precision is that it's got to be a really well-defined biological thing that we're going after. So in the case of, for example, PLN, we'd be going after cardiomyopathies where calcium handling is the issue, and we think we could actually define a patient population and actually measure that in the clinic, because, of course, that will be really important as well. And so what we're thinking about with this is that it's probably multiple rare genetic cardiomyopathies that we are looking at for potential indication expansion opportunities. And the reason that's also important for us as a company is that also matches our business model, right? We can actually develop those programs and eventually commercialize them. And so there is quite a bit of opportunity there and a lot of synergies if, in fact, we are able to do these indication expansions as we look down the road.

James, Analyst — on behalf of Steve Volkmann)

Yeah, makes sense. Great. Well, we're just about on time. Anything else to quickly highlight?

Cass Gallagher, CEO

I just want to thank you guys for having us. It was great to be here. And thank you to everybody who came in to listen.

James, Analyst — on behalf of Steve Volkmann)

Of course. Thanks for joining. Thank you.