Atrium Therapeutics Stifel 2026 Healthcare Conference

Thanks for being here. Sounds great.

Well, thank you, James. Thanks for including us. It is wonderful to be here at the Stifel Conference. Thanks, everybody. I am actually joined here by a number of my team members, who are also in the audience. Thank you. I am very excited to introduce you to Atrium. Let us start. Of course, I am going to be making some forward-looking statements today. Let us just start with what Atrium’s vision is. Atrium is here to pioneer precision RNA medicines for the heart and to profoundly improve people’s lives living with cardiac disease. 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. With the exception of really the TTR programs, RNA has been limited because of the fact that it has not been able to deliver to the heart.

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 am going to take a second just to kind of step back and say what we have done, because Atrium, we are just shy of nine months old, so our first day trading was February 27, 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. It is 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.

In the time since we have launched, we have had a very productive period of time. First and foremost, we are cleared to run our clinical trial, the Corventis 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 have done a lot of work to truly understand what the real potential is for, of course, PRKAG2 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.

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 patients. When you think about the space of cardiomyopathy, there's about 2 million people in the U.S. with cardiomyopathy. About half of them, 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. 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.

In the case of PRKAG2 syndrome, symptoms start for that in the late teens and early 20s, so it's quite young. In the case of phospholamban cardiomyopathy, it's in your 30s and 40s. These are, unfortunately, the stories you hear, and we hear them probably all too frequently, of someone passing away, a runner that passes away from a heart attack. These are very likely driven by underlying genetic conditions that have not been caught. That lack of genetic testing, 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.

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. 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. 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. We are moving quickly, again, dosing our first patient in Corventis, but also moving our pipeline forward. The tools we're using to do this are both our RNA delivery platform as well as our focused precision cardio pipeline. 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 called 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. 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. 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. Then spending a minute on our pipeline. We're going to spend most of our time today on PRKAG2 syndrome, or ATR-1072, our program targeting that. We'll 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. We are moving, and again, we just see this as an incredible space with so much opportunity. From a balance sheet perspective, 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. 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. Now let's spend a minute on ATR-1072. PRKAG2 syndrome, this is an inherited and progressive disease. These patients show up with a thickened heart or 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.

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 one 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. If we spend a minute just talking about the disease, what is happening in this disease is that there's a mutant PRKAG2, and that is leading to over-amplification of AMPK.

That ends up leading to this HCM as well as glycogen accumulation in the heart. We 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 PRKAG2 syndrome. 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. This was 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, including the PR interval.