Good morning and welcome to the Milestone Pharmaceuticals Investor Education Series Part One. At this time, all attendees are in a listen-only mode. A question- and-a nswer session will follow the formal presentations and fireside chat. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player, or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this event is being recorded and a replay will be made available on the Milestone website following the conclusion of the event. I'd now like to turn the call over to Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. Please go ahead, Joe. Thank you, Tara, and good morning everyone. I'm, as Tara said, Joe Oliveto, the CEO of Milestone, and super excited to welcome you all to our investor key opinion leader call today. I will be making forward-looking statements, so we'll direct you to our SEC filings and our 10-K for full disclosure of risk factors. I'll also make a point and take this opportunity to let everyone know and emphasize that etripamil is an investigational new drug that is currently under review by the FDA, so it is not approved yet. We are looking at an FDA review period that should come up towards the end of March of next year. At Milestone, we are dedicated to helping patients suffering from two very common cardiac arrhythmias, paroxysmal supraventricular tachycardia as well as AFib. The pictures on these slides are not stock photos. These pictures bring us a lot of joy because they are just some of the many patients who we speak to and learn from when we look to develop our interventions for PSVT and AFib. We've come close to these patients, we've learned from them, and they provide us a lot of insights, as well as a lot of motivations to do what we do every day. What we do is, our goal is to develop interventions that provide these patients and others the opportunity to self-treat their attacks of PSVT and AFib. These attacks occur in many places, and our goal is to have them treat them wherever or whenever they occur, and help lead better lives. A part of our work is also trying to find ways to inform investors about the conditions that we work on, and our goal for today is to do that and focus our discussion on PSVT, which is the lead indication for etripamil. Here's today's agenda for the call. The primary point of the call is to have a fireside chat with two key opinion leaders. Following the fireside chat and a short recap, we'll then open up the call for questions. Joining our call today are two key opinion leaders, Dr. George Mark and Dr. Vivek Sailam, who I'll introduce in a minute. The fireside chat will be moderated by Lorenz Muller, Milestone's Chief Commercial Officer, and other members of the management team. Dr. David Bharucha, our Chief Medical Officer, and Amit Hasija, our Chief Financial Officer, will also be attending and will be available for the Q&A session of the call. This call is envisioned to be the first in a series of calls in which we plan to highlight for investors views on the management of PSVT from experts in the community-based setting. Different calls will include practitioners from different geographies. We'll work on trying to include different specialties. On today's call, you'll learn about the fact that we have a cardiac electrophysiologist and a clinical cardiologist. Other calls we're envisioning may include cardiologists from other regions. We have East Coasters today. We're gonna maybe head out to the West Coast on our next call. Also potentially including other healthcare practitioners such as nurses, nurse practitioners, physician assistants. We've learned a lot, and we've been very thoughtful about our development program, and we feel that different practitioners really provide a holistic view on the management of PSVT, and our goal is to provide that holistic view to our investors. The one common denominator that we are gonna try to focus on is the community-based setting. The reason we feel that's so important is really threefold. First, community-based providers really manage the majority of PSVT patients. This is not to take anything away from those providers in the academic institutions, but our thought is really to expose investors to those providers who are seeing the majority of patients. We figure there's no better way to get educated around the needs of those providers in managing the majority of patients. The second reason is community-based providers and leaders, of which we have two today, are really the initial evaluators in new interventions once they come to the market. Their views on the medical needs that they have for their patients in their practice, we feel is very apropos for giving investors a view as to what needs are most important for a new intervention, and hence, we feel very important to provide that aspect to our investors. Lastly, I would say that, again, community-based leaders, once they form their opinions based on experience with a new intervention, are instrumental in helping extend education to their peers. Not every healthcare provider, especially those in busy clinical practices in the community, are able to attend every conference, read every publication, and they learn many ways from their peers, whether it be in grand rounds or journal clubs or hallway conversations in their community-based institutions or in their community. Doctors like Mark and Sailam will be go-to people for the rest of their colleagues in their practices. Having, again, an impression from these people about the condition, and then once they get experience with the intervention, they'll be able to answer their peers' questions about how it's working for them and their patients in their practice. Not only from an efficacy and safety standpoint, but from a very practical standpoint of, are their patients responding well? What are the issues with the drug? Is it easy to get? These very practical matters that come into play when you figure out whether an intervention is truly helpful or not. Both Dr. Mark and Dr. Sailam are colleagues joining us from The Heart House located in Southern New Jersey. It's a suburb of Philadelphia, so we have some Eagle fans on the call today. The Heart House of New Jersey was founded more than 40 years ago and has a long history of providing cardiovascular care in the region, by a talented team of trained medical professionals and includes 30 cardiology specialists. The Heart House is also affiliated with, and members of The Heart House hold privileges at many leading hospitals in New Jersey, including Cooper University Health Care, which I believe is in Camden, New Jersey. I'll start by introducing Dr. George Mark. Dr. Mark is a cardiac electrophysiologist. He specializes in treating rhythm disorders of the heart, such as medical device implantation for the prevention of sudden cardiac death. Apropos for today, performs cardiac ablations to treat abnormal heart rhythms. Dr. George Mark obtained his medical degree from Temple University and his undergraduate degree from Wesleyan University with a course of study in molecular biology and biochemistry. Dr. George Mark completed fellowship training in cardiovascular diseases and clinical cardiac electrophysiology at Thomas Jefferson University Hospital and was the chief medical resident at Temple University. Additionally, Dr. George Mark was also a principal investigator in two of the Milestone-sponsored etripamil studies, RAPID and NODE-303, and as many investors are aware, NODE-303 was recently published at ACC this year. Congratulations, Dr. George Mark, on that achievement of that study. His disclosures are listed here on the slide. Joining Dr. Mark today is his colleague at The Heart House, Dr. Vivek Sailam. Dr. Sailam is a clinical cardiologist with more than 16 years of experience in cardiology. Dr. Sailam completed his medical residency with additional training in cardiovascular diseases at Hahnemann University, also in the Philadelphia area. Dr. Sailam is the recipient of multiple awards including South Jersey Top Docs, Guardian Angel Award, and New Jersey Top Docs. He is passionate about community health programs including Walk with a Doc, Work out with a Doc, Eat with a Doc, and Shop with a Doc. Dr. Sailam's disclosures are listed on the slide here. Dr. Mark, Dr. Sailam, thank you for joining us today, and I'd now like to turn the call over to Lorenz Muller to moderate the fireside chat. Lorenz. Thank you, Joe. Let me take the opportunity on behalf of Milestone to thank our audience for tuning in relatively early on a Thursday morning here, and also to thank our two physician opinion leaders, Dr. Sailam and Dr. Mark for taking time away from their busy clinical practices to help educate our audience on PSVT. Maybe let's jump right in, gentlemen. The audience heard your background academically, but I'd love for you to share in a few minutes each. Give us a little sense of your clinical practice, your research interests. Talk to us a little bit about the day in the life of an electrophysiologist in the case of Dr. Mark, and then we'll go to a day in the life of a clinical cardiologist, with Dr. Sailam. Let's start with you, Dr. Mark. Good morning, everybody. My name is George Mark. I'm a cardiac electrophysiologist in practice for about 18 years so far. I think I have an interesting job, combination of clinical care as well as opportunities to involve myself in clinical research and the teaching of residents and fellows. I think that's been a very fulfilling opportunity for me, particularly because of our close relationship with Cooper Medical School of Rowan University. I would say that 90% of my time is spent either in the office or in the electrophysiology labs performing procedures, with a smaller percentage devoted to doing clinical research in structural cardiology, device implantation, ablation technology, and opportunities like these to work with new medications. It's a pleasure to be here this morning. Thank you, Dr. Mark. How about you, Dr. Sailam? Why don't you give us a sense of your day-to-day practice? Well, yes. Hi, good morning, and excuse me. Thank you for having me this morning. My name is Vivek Sailam. I'm a clinical cardiologist. I have about 17 years of experience. As a clinical cardiologist, I spend most of my time either rounding in the hospital, seeing patients in the acute care setting, and also in the office setting where I see a lot of patients for clinical evaluations, whether they come in for general cardiac evaluations for chest pain, shortness of breath, palpitations, which is very common, and other general cardiac entities that we see as kind of the first line for dealing with cardiac issues. As Dr. Mark had mentioned, we also are involved with teaching residents and fellows in the hospital setting, which is a great opportunity to share our experience and kind of lead the next generation into this healthcare field, which is fantastic. We have a very busy practice, and I spend probably 95% or 98% of my time in a clinical setting. Obviously this morning, we're involved in this research event, so we're very thankful for this. That's kind of my day-to-day activity. Great. Thank you for that background. Let me now introduce the topics for the fireside chat today. We thought we would look at five different areas that we'll cover over the course of the call. We'll start with talking about the magnitude of the problem and looking at how many patients you folks manage with PSVT, both of you. A little bit of the burden of disease as you perceive it, both on the patient, and of course, on the healthcare system and you as physicians. We'll talk a little bit about kind of the tools that are currently available to you to treat patients with PSVT, and perhaps explore some of the unmet needs, as you see them existing, and gaps in care relative to your armamentarium. Then we'll close out the discussion by looking at the potential opportunity for some novel additions to the armamentarium to better manage patients with PSVT. We're going to do this in a format that we've selected here, where I'll present you both with a statement that Joe and I, and the rest of the members of the management team here at Milestone have heard not uncommonly or not infrequently from investors. We've done that. We're going to do this with the intentionally sort of provocative prompt of perception or misperception to try to get at understanding what's truth in the eyes of clinicians and what is perhaps things that are not as true, in your experience. Our goal for this engagement is really to hear, as Joe mentioned at the onset, really, so to speak, from the front lines, and hear the views of both Doctors Mark and Sailam on all of these topics with the goal of trying to help investors out and better understand the dynamics of the disease state of PSVT. With no further ado, we'll start with the first. This is the first topic for discussion. Here we're looking at the magnitude of the problem and really understanding how PSVT manifests in a clinical setting. The prompt here is that PSVT is not very common and is managed primarily or exclusively by electrophysiologists. Let's start this part of the discussion by exploring how the two of you collaborate on patient cases involving the treatment of arrhythmias in general and then SVT in particular. What are your respective roles in the diagnosis and management of patients, and how and when do you hand patients off to each other? Maybe here we'll start with Dr. Mark. Yeah. I think PSVT is a very interesting disease process because for over 85% of patients with that diagnosis, the root cause is a electrical abnormality or innate predisposition that they carry with them since birth. There are patients who are 15, 16, 17 that come into my office, but there are others that are 80 and 85 that have had maybe episodes throughout their life. Typically, I think that is the general theme, is that most often people have some episodes, they're infrequent, they're self-terminated, they're hard to catch on an EKG. People are often told they're anxious by their general doctors. It's certainly been an advance with the wearable technologies like wristwatches, that we are starting to identify a lot of these patients at earlier stages. Maybe it's not until someone has an episode that brings them to the emergency department or into the primary care doctor's office with an abnormality on their EKG that they're referred to cardiology. There's this large patient population that are undiagnosed, frustrated by symptoms, but eventually do often come to the cardiologist, where there's an opportunity for education into predisposing triggers like caffeine or alcohol or other things, and also maybe discussions about the ways to manage this without medications. Most commonly, people are given some sort of medication by their general cardiologist. Comprehensive cardiac evaluations, including stress tests and echoes, are performed. It really is only at the very end of this path when maybe lifestyle modifications or changes in patient activity is unsuccessful. Maybe when people are failing medications that they end up in the electrophysiologist office, where we talk about more potent and often drugs with more side effects or invasive procedures like cardiac ablation. It's a path, and it's a long path for many, and I think there's more people out there than we know. Thanks, Dr. Mark. Same question to you, Dr. Sailam. Now, obviously, you're a little bit upstream, based on the paradigm here on the screen. Talk a little bit about how you manage these patients and how they appear to you and the types of patients you might hand off to Dr. Mark. Right. I want to echo a lot of what Dr. Mark has expressed so far. I'm pretty much first line or kind of the point guard of the situation. I'm the one who gets into the field first. When a lot of these patients come in, before the advent of a lot of the monitoring devices that we have now, like wearable devices such as the Apple Watch or Fitbit or things like that. A lot of these patients were told that they have anxiety, and part of the issue was that these irregular rhythms were not caught on any type of objective data. Now that we have more technology, we're able to capture more of these patients. The key is trying to actually identify the irregular rhythm, which we can't always do. Most of these patients, just like Dr. Mark said, they come in at a younger age. I've also met patients who are in their 80s who have never been officially diagnosed until we catch them in the ER with an SVT. It is a very long process. I think that we have more technology on the market now to identify these people more frequently and earlier. It is a common problem that doesn't get picked up until we can have some objective data on the situation. As for me, as a first-line person, I obviously will try medications for the patients or lifestyle modifications first and see how that works out for them. I follow patients for years and years and years before I will refer them to the electrophysiology colleagues. If they have a change of symptoms or a change of clinical etiologies, we'll refer them out. There's been a very, very long path for these folks. Thank you, Dr. Vivek Sailam. Dr. George Mark, as we heard earlier on, obviously, you've been involved in the clinical development program here at Milestone in both the RAPID phase III pivotal trial and the large open label safety outcome study, NODE-303. Can you comment a little bit on your experience? I believe you sent me a couple of slides, so let me pop those up, and you can use those, reference those as you sort of talk about your experience in these studies, actually using etripamil in patients. Yeah. Thank you. We began talking about RAPID and NODE-303 kind of in that strange time of COVID. Interestingly, we did some internal querying as we were trying to identify if we would be good enrollers. We always want to be good enrollers for clinical trials. It was interesting. We pulled for the last two years prior to initiation of the RAPID and NODE-303 trials, our EMR's documentation of diagnosis codes, and we found that there were over 1,600 patients identified, unique patients in our practice with a I47.1 SVT diagnosis code attached. Interestingly only 600 were seen by electrophysiologists. Over 1,000 were only seen by general cardiologists in that two-year window. We thought we had a robust population of patients who would be candidates for immediate acting drugs such as etripamil, give people immediate relief in a fashion that was unavailable through oral medications at the time. We said, we're going to do this. What we need to do as an institution, as a group, was to educate my general cardiology partners about it and ask them to help us find these patients. Because, again, not always were they the ones coming directly to the electrophysiologist. They were almost always seen by general cardiologists and maybe managed for some time by general cardiology without being seen by an electrophysiologist. We were successful and that really spoke to both the desire of patients to look for alternative options than what they were doing right now, not being particularly happy with what was available on the market. it was a combination of that and good results that these individual cardiologists saw from their patients who were enrolled that led them to refer more patients for the study. Could we go to the next slide? most often, I would tell you the reasons people decide to participate in clinical research is just a dissatisfaction with their current management status. I will say that in the patient population of SVT, the worst or the most alarming feature of it for patients is they feel like they have no control over their symptoms, that there is not necessarily a reproducible, oh, if I do this will happen, therefore I can avoid it. Or, if I drink enough water, or, if I avoid caffeine, I know I will be safe. It's a little bit like that beaten dog syndrome. They're never quite sure when that next hit's gonna come, and that anxiety makes them very uncomfortable with the idea of doing things like getting on an airplane or maybe, God forbid, they go to Mexico and something happens. There's just generalized anxiety about, if this arrhythmia happens, I may not have control over it. That may mean I may need to come to the emergency department. That's probably the number one complaint I hear from patients with SVT. The close second is they're dissatisfied with medical management because the most commonly prescribed medication for patients with SVT are beta blockers. Beta blockers are blood pressure medications that block the effects of adrenaline. Certainly adrenaline can be a source for irritability. It can be a source for more rapid heart rhythms under the effects of adrenaline, and blocking adrenaline in the form of these medications is a treatment used to hopefully minimize the number of episodes and definitely slow it as it is present, so it is less symptomatic. Beta blockers, as you might imagine, have side effects because they block adrenaline. They cause fatigue, they cause weight gain, they cause depression, they cause erectile dysfunction. Most 25-year-olds with SVT don't want to be on beta blockers. While there are opportunities for some to take them on an as-needed basis, medications like these take hours to kick in, hour, two hours, three hours, four hours. To have a tachycardia at a rate of 200 for three, four hours is enough that people are already in the emergency room by the time their medications kick in. To take it regularly every day for something that may only happen once a year or twice a year or something like that, then people are very dissatisfied with this idea that I'm going to be on a medication for the rest of my life. As a proceduralist, I will tell you, certainly there are opportunities to get to the root of the problem with a procedure called ablation. Like any carpenter who sees a nail, they want to hammer it. I think that electrophysiologists are very happy to offer ablations as they do offer an opportunity to eliminate this problem at the root. The fact is that most patients are not interested in rushing towards a procedure, particularly because there is the small but real chance of injuring the normal electrical system of the heart. A 26-year-old with a pacemaker for the rest of their life is just a horrible thing. While thank God it is rare, the concerns about the risks of procedure generally point people away from interest in invasive procedures until they've lost the ability to really see themselves going on, moving forward in their life in the current state. It is really a kind of a last-ditch thing in patients' minds, although the electrophysiologists are very happy to offer it. I think that might be a lot about why people decided to participate, and we had great responses from the patients who did enroll in the trial with the etripamil. It was a very positive experience on our side. Thanks for sharing that experience. Back to you, Dr. Sailam. Maybe to kind of come to the crux of this topic, can you give us a sense of how common SVT is in your practice? As you're thinking about a typical week, are you seeing patients monthly? Are you seeing them weekly? Are you seeing them daily? How much of a burden is this on your time as you're trying to manage your diverse set of cardiovascular patients? I think for myself, for someone who spends a lot of time in the office also, I see these cases several times a month. We have a very dense population here in South Jersey, so we have a lot of patients that come in for an evaluation of palpitations. we do have monitoring that's available to us, and we do identify this, I'd say a handful of times a month. I can't say it's six times a month or seven times a month, but it is quite frequent during my monthly practice sessions. it is a common occurrence. again, we do have a dense population, so there's a very high population of patients in this area. it can be identified more frequently than some of the more sparsely populated areas. We do see it quite often, and I deal with it quite a bit in the hospital setting also. Just because it may come up later on this call, how would you compare that timeframe that you're seeing at patients or managing patients with SVT relative to patients you treat with atrial fibrillation? Is it more or less the same? It's less. AFib is something that we deal with every day, several times a day. AFib is much more common. With the population aging as it is, you're going to see the preponderance of AFib increasing tremendously. AFib is more common, but however, PSVT or SVT is certainly something that we see. It's less common than AFib, but it's something that we see on a frequent basis. Great. Thanks. In the interest of time, let's move on to our next topic for discussion. Here, we're looking a little more detailed on the burden of disease on patients primarily, but also on the healthcare system and on physicians. Here the perception or misperception that we commonly hear when talking with investors is that PSVT is more of a nuisance than a life-threatening condition, and therefore perhaps not as important to manage actively. Here, let's get a bit more specific and talk about patients with SVT that you have both recently treated. Here, I believe, Dr. Mark, you had prepared a case that you'd sent over to me. It'd be great if you could kind of get into some detail about how this patient presented and how you managed them, and perhaps we can derive some insights from that on the burden that that caused on that patient. Sure. That's great. I picked a relatively recent patient who had come through our office and wanted to recount to you guys her path through this disease process. There was a young woman with a history of SVT diagnosed back in 2020 when she arrived at the emergency department with symptoms of chest pain and shortness of breath. She knew the heart was doing something crazy, but it really was a surprise to her when they put her on the heart monitor and her heart rate was over 200. Initially, the emergency department will try vagal maneuvers. These are ways to try to activate a reflex in the body that slows the heart rate. Things like holding your breath and bearing down or rubbing on the neck arteries or. I just had a patient actually last week, who when those things didn't work, they dunked her head in a bucket of ice water, and for her, that one worked. Now she's at home every once in a while, dunking her head in buckets of ice water. It's a trigger. It triggers a reflex in the heart, which stimulates the vagus nerve and slows the heart rate down. It did not work for this patient. Through an intravenous line, she was given adenosine. Adenosine is a way to stop all electrical conduction through the heart for about seven or eight seconds, and that is enough to terminate SVT in, I would say, 99.5% of people. Patients describe it as if the world's about to come crashing down on them, but it is immediate relief. They did this for her to terminate this rapid heart rate. They said that there was a full set of labs drawn. There were abnormalities seen on the cardiac troponins. Cardiac troponins are muscle enzymes that are released into the blood when heart muscle has been injured or strained, or in the worst case, infarcted or dies. These abnormalities on troponins led her to going to a hospital like Cooper, where she underwent heart catheterization. They checked for any evidence of blocked arteries, which were all normal. Really this enzymatic leak, this evidence of heart muscle injury or strain was really just from the heart going too fast for too long. She was discharged on a low dose of this metoprolol, recommended to be seen in a cardiologist's office. Can we move to the next slide? She got an appointment, but it took seven weeks, and I'll tell you, in South Jersey, that's probably pretty good. There is a density of cardiologists in this area, but there's still a long waiting list often. She sort of lived on eggshells waiting to get this cardiology appointment. She had some other testing done, and she actually related a history that stretched back since her teen years, but it never had lasted as long or been as intense. She talked to the cardiologist about not being on medications because she wanted to get pregnant, and was eventually convinced to take the medicines on an everyday basis due to this evidence that there had been heart muscle injury on the blood work during the event. Can we move to the next slide? She was seen by the EP team in that regard about two months after that, so a total of about four months since diagnosis. She had not had a recurrence, but she did state that she had stopped taking the medications due to complaints of fatigue and, oh, by the way, I recently identified that I was pregnant. When discussing her treatment options, the opportunities were limited because medication's different than the beta blockers that were causing fatigue, and in pregnant women cause what's called intrauterine growth retardation, which basically is a reduction in fetal size. The babies maybe would've been eight pounds upon delivery or five pounds, and while safe, nobody wanted to take medications. Other medicines at my disposal similarly had side effects that were unacceptable during pregnancy. A treatment like ablation, while possible, to use radiation like X-ray during pregnancy is again, nobody wants that. The thought was, you're just going to have to bite the bullet and let us know if we're having problems. After pregnancy, when you're done breastfeeding, we can talk about reinitiation of medications or a procedure. Prior to the full term of her pregnancy, she started to have more palpitations, no ED visits, but she was just sort of being driven mad by the heart racing, and she agreed to take beta blockers again. Can we move to the next slide? Four months postpartum, lined up with us still being in the NODE-303 trial, and we talked to her about whether she would be interested in participating, and she jumped at the opportunity to have a medication that she could take on an only as needed basis, something that she could have in her pocket, whether she was at the grocery store or at home by herself with her child. She was just desperate to be off of the beta blockers and really not interested in a procedure due to her new role as a mother. This was an easily offered and accepted opportunity to have an alternative treatment for the management of her symptoms or symptomatic arrhythmia. Can we go to the next case? Next slide. Excuse me. Over the following 12 months, she did have two episodes of SVT. In that study, the protocol of the study would say, try the vagal maneuvers, do everything that you can to avoid needing to give the drug. If you need it, you can give the drug. Then both times she had episodes that were not terminated by these vagal maneuvers. I'm not sure she dunked her head in the ice bowl, but she tried the other ones, and she ended up taking this nasally applied medication that gives rapid onset of an action similar to that adenosine, although, you know, not to the degree where all cardiac electrical activity stops, but she was given this medication, and it was successful, and it prevented her the need to go to the emergency department or call the EMTs. She reported back that she was just so happy to know that she had this in her pocket all the time. It was almost like a lucky charm in her pocket. She wouldn't go anywhere without it. It just gave her confidence and peace of mind. I think where a lot of people are just driven kind of to the edges, frayed nerves, anxious, she felt she had some control. As the study wrapped up after its conclusion, she petitioned to have continued access given the medication's success. She was really one of my favorite patients to share with you guys. Thanks. Thanks very much for sharing that. Over to you, Dr. Sailam, to kind of your reaction to this case. Is this sort of, I wouldn't use the word typical, but is this representative of the kinds of patients you treat? And if not, can you give us some additional observations on how patients present to you and kind of how you think about managing them? Well, this is a very typical patient, and the timeline that Dr. George Mark illustrated is very common also. I have a very similar patient that I took care of for years who was a surgical resident at one of the local hospitals who had a similar clinical scenario with her being pregnant and not wanting ablations. I think if etripamil was available at that time, this would have been an outstanding alternative for her. These episodes happen maybe a couple times a year, and to have this agent in your pocket to use and is very effective by stopping the calcium channels, which propagate a lot of these abnormal rhythms, is really an advantage for these folks who suffer from this type of clinical situation. Yeah, this is a common case. The timelines were spot on, and etripamil, I think would be very, very effective for a lot of folks who have this type of situation, which again, is a common presentation. I had an attending physician back in 2001 who was a cardiologist who would go into SVT on rounds, and he would reach into his pocket and take a flecainide tablet out of his pocket and take the tablet during rounds to terminate his arrhythmia. A pretty unorthodox way of dealing with rounds. Again, if we had etripamil back then, 25 years ago, it would have been something I think he would have used himself. I think this is a great method and something to be hugely advantageous in the clinical scenario. Maybe as a follow-up to that, Dr. Sailam, I know I mentioned earlier sort of the typical patient, but one of the things we often hear when we do market research is the heterogeneity of this disease and that even across the population or even within a given patient, how this disease manifests differently over time, the time course of it. Could you speak a little bit to your experience there with whether it's duration or frequency or symptomatology, how different patients present to you and how heterogeneous that truly is? Well, it is very heterogeneous, right? Because the textbooks always talk about young men or young ladies or pregnant ladies who have this type of situation. In the real-world setting, we see this in all populations. Again, it was something that before we had monitoring devices that doctors would say that patients were anxious or patients were not really having any true clinical manifestations. Now that we're able to identify the PSVT, we see this in all populations. I had met a patient who was 86 years old in the ER with SVT who had never been formally diagnosed. He's been dealing with this as a diagnosis of anxiety over the years. He's been having SVT all along, and we finally caught it. It's something that we see. It's in all shapes and sizes of people, and it is a relatively common entity that is present in the clinical setting. Yeah. Thank you. Let's move on to the third topic for discussion today, which is looking at the current treatment landscape. We'd heard earlier about ablation being a tool here that is available to manage these patients. As we talk to investors here on the management team at Milestone, we often hear this idea that, well, yeah, you're developing an interesting drug, but isn't this disease generally just always managed by ablation? Highly successful, largely curative, very safe, et cetera. Maybe obviously starting here with you, Dr. George Mark, as an ablationist yourself, how would you typically introduce the option of ablation to a patient? How do you describe and counsel them on the procedure? Then, how do you determine who are the best candidates? Yeah. It's a great question. I think back to the very first visits I have with patients who have been diagnosed with SVT. Most commonly, that's something that had led to an emergency room visit where they required intravenous treatment of adenosine to terminate that arrhythmia. The discussion starts with first reassurance, because thank God, SVT does not cause people to drop dead. It's not that kind of an arrhythmia, but it does significantly affect people's ability to enjoy the quality of their life. After sort of trying to ease people's initial concerns that they're going to drop dead at home in their sleep, we talk about the treatment paths. One choice, medications. Other choice, procedures. We talk about the limitations of medications due to basically that lack of immediate onset of oral medications, which means we can try it, but we may have to suffer from arrhythmias for hours to see if the medicine's even going to do anything. Or we have to take that medication on an every day basis, accepting whatever drug-related side effects there may be with that medication, not really knowing whether the medicine's going to really do anything, honest to God. I don't tend to point people towards ablation after their first episode of SVT. Sometimes another episode of SVT doesn't come around for two years. Ultimately, those people, if I did an ablation, I'd think I was pretty successful, but maybe it wasn't going to come back for two or three years anyway. We tend to talk about being a path, a movement that sort of starts with medications or starts with more conservative care, ends up with a procedure, if we are finding medicines are ineffective or are associated with side effects, or if episodes are just happening too often and leading to too many trips to the emergency department. That is something, excuse me, that I think that we have to respect, that there's no procedure without risk. Ultimately, when you tell people you're going to be moving wires around inside their heart, there is definitely some anxiety produced by that idea. I think that where etripamil would definitely fit in is in that situation where you are offering people opportunity to control their arrhythmia. Maybe we don't need to talk about anything beyond this ever. Maybe if we're finding we have to use the etripamil 3 x a month or 3 x a quarter, we have to then think maybe we should do something. Keep the ablation as the backup to the backup plan, and now have an opportunity to use a medication with rapid onset, high effect, low side effects, as a means to control something that otherwise might be unable to be controlled. Dr. Sailam, so of the patients you manage with PSVT, what% would you estimate do you refer to ablation in your practice? Well, I think it really depends on their clinical situation. Like if Dr. George Mark was saying, if they have SVT once or twice a year, then I'll try to medicate them with medications, and they usually do pretty well, as long as they don't have any serious side effects of the SVTs, like passing out or anything like that. However, if their SVT becomes more frequent and they start to have it a couple of times a month, or they're becoming intolerant to medications because of side effects with a lot of the younger folks, their blood pressures tend to be low, and they don't tolerate taking the oral medications on a daily basis, in addition to the other side effects that they have with the medicines, with fatigue and hair loss, weight gain, all these things. If the frequency of SVT becomes much more burdensome and it's affecting their lives, then I certainly will be happy to refer them to Dr. Mark and his colleagues for ablation consideration, as the success rates nowadays are very good with ablation, so it'll be a curative procedure for them in their lifestyles. Just as a follow-up to that, can you give me a sense of from the time when you refer patients to Dr. Mark until the procedure is actually performed, how long does that typically take? You mentioned earlier it could be seven weeks. The case that Dr. Mark presented, there was a seven-week lag just to be seen by a cardiologist. The time course from the time you start talking about ablation to the time they actually can get to one, how does that work in your practice? Well, I think it could be several months, actually. Again, it's because of the density of population in this area. There's a lot of cardiologists here, but we're all very busy just because there's so many people to be seen. It could be several months. Again, if patients are having symptoms on a frequent basis, we'll certainly make them a more urgent evaluation by the EP doctors. If they're a patient that has SVT infrequently, like once or twice a year, maybe every six months or so, then that's somebody that we can kind of watch and wait with. Those people that are symptomatic, we certainly will make sure that they're evaluated in a faster manner. We have avenues to get that done. Yeah. Can I jump in? Yeah. I would just say that as of right now, my backlog for ablations of all kinds pushes about eight weeks. If I see somebody in the office and they are desperate to do something because they just are besides themselves that this can't keep going on the way it's been going on, I have to tell them, it's going to be eight weeks. If you end up in the emergency room between now and eight weeks, I promise I won't send you home. I'll find a way to get you to the EP lab on an emergency kind of basis. It's not a rapid path from agreeing to doing something to actually getting it done. I think the path that gets to me is even a longer path. It's certainly a longer timeframe than you might imagine. Yeah. Thanks for that. Let's move on to the fourth topic for discussion, just in the interest of time. Here we're talking about some of the unmet needs as you gentlemen perceive it and the gaps in care. Here the prompt is that there is really, we often hear a low unmet need or a perceived low unmet need for the unablated patient, the patients that we can't convince her that it's not safe to perform an ablation, that the current medications that Dr. Mark, you started to describe in your case are good enough. Just as an anecdote here, our research that we've done over the last four or five years has shown that around two-thirds of patients with PSVT have tried to use beta blockers or calcium channel blockers chronically to reduce the frequency of their episodes, so prophylaxis. Dr. George Mark, you mentioned early on the call that some of the side effects from that route, but can you expand a little bit on your experience with this form of treatment, chronic prophylaxis, and its effect on the frequency of episodes and how much that fills the need for these patients? Yeah. I would say that when I talk to people about medication treatment like beta blockers, I often describe it on a scale of one to 10 as being like a two in terms of its power or effect or ability to terminate or reduce the possibility of an arrhythmia. It really is a blood pressure pill. It's a blood pressure pill that happens to slow the heart rate down, and we use it because it's safe. Heart doctors love beta blockers. We treat patients with all kinds of cardiac conditions with beta blockers, kind of calms the heart rate down. Pretty much everyone feels that they're safe. They're not a very effective treatment. People all the time have arrhythmias on beta blockers. When they come into the emergency room, and they've already been on beta blockers, but they're having SVT anyway, typically, they just increase the dose, in which case people tend to have more symptoms, but not any more benefit. I do describe that there are these other medications, and Dr. Sailam mentioned one that his cardiology attending in 2001 took called flecainide, which is something that's been around since the 1960s. We have about seven different, what I would call anti-arrhythmia medicines that people can take to reduce the likelihood of arrhythmias, and they may be more between five and 10 in terms of the potency, but they have a long list of side effects associated with them. There's generally a dissatisfaction from the cardiology standpoint, at least the electrophysiology standpoint, of the usefulness of medications in this scenario. Maybe that's why if you talk to an electrophysiologist, they would say, don't mess around with medications. Just go for the ablation. That's more so I think what's an equal part dissatisfaction with the medications and the opportunity to do something for somebody to get to the root of the problem. Always you pat yourself on the back when you're able to do that. I think if there was a medication alternative that had the benefits of etripamil, then that balance, that decision-making process gets swayed. Yep. Thank you. Dr. Sailam, maybe in the interest of time, pivot over to the other treatment that we've heard about on this call. I'll just give some context here that our research with physicians has also suggested that almost all cardiologists at some point in their career have prescribed AV nodal blocking agents like beta blockers or calcium channel blockers as a so-called pill in the pocket for patients with PSVT. Currently around a third of patients actually have that available to them and use that episodically or periodically to manage at least some of their episodes. Can you share your experience with using that treatment approach to manage episodes of SVT? Yeah. I think that, I have a few patients who have a pill in the pocket. The pill in the pocket is a little bit. You have to be very careful as the patient has to be very knowledgeable about a situation and also have the awareness to take the pill in a timely manner and things. The issue with the pill in the pocket is that with oral pills, there is an absorption delay, correct? When you take the pill, it may take an hour to take effect. As Dr. Mark mentioned earlier, if your heart rate's 200 bpm, you're not going to tolerate being in that type of rhythm for an hour and a half, two hours. It's very unnerving. It's very uncomfortable, and most of these folks will end up in the ER. The pill in the pocket method can work in certain circumstances. I do have some patients on it. However, the onset of action is delayed, so it's not always effective in terms of treating their condition in all situations. We don't use it as often as we used to in the past, but it's certainly something that is implemented, but not very common anymore. Great. Let's move on to our final topic for discussion before we get to the Q&A. Here we're looking at another way to fill the gap, the opportunity for novel additions to the armamentarium. Given what we talked earlier about the perception or misperception that there isn't a significant unmet need with these patients, the companion perception here as well, if there's not much of a need, then there really isn't a high need for a new tool to add to the armamentarium. Here, maybe we'll start with Dr. Mark. Let's go back to your experience in the clinical trials with etripamil. Maybe talk a little bit about why did patients decide to enroll in a study like that versus the other options that they had, including an ablation? How hard was it for you to recruit patients into a study like this, given the perception that maybe the need for new therapies is low? I have, in the last 18 or 19 years, had opportunity to be PI for a number of studies. I think convincing someone to participate in clinical research. There has to be a strong motivator for people to do that, because the ideas of taking medications that are not FDA approved yet, or in other situations, doing a procedure that has not been around for long. It takes a couple of things. It takes certainly some trust in their physician. I think that's super important. It takes a generalized dissatisfaction to where they are and what alternatives they have. There's no doubt that when people come to the office and see me and we discuss treatment choices, what they want me to tell them is either that this arrhythmia is never going to happen again, and therefore they don't have to worry about it, or that I have a pill that I can offer to them that's going to do the job, and it's going to avoid them ever having to go to the emergency department. When I tell them that it's certainly going to happen again, and that I have a pill that'll maybe take hours to do the job, they get very frustrated and concerned, and anxious again, to talk about a procedure which carries with it some risks. I think people are in a state where they were looking for an option, like the trial became a very easy option for people to listen to the discussion of the study and decide to participate. We had very high patient satisfaction as a result. It was good. That's great. Over to you, Dr. Sailam. I know you haven't had the opportunity to use the etripamil in the clinical program or gain experience that way, but based on what you know from the literature and from the published studies on the drug, what do you see as the role of an acutely acting self-administered treatment in your practice, just based on what you know from literature? Well, yeah like you said, Lorenz, just based upon my reading of the literature, I think it's going to be very effective in the clinical setting. I tend to use calcium channel blockers more often than beta blockers because of the side effects from the beta blockers. I tend to lean towards calcium channel blockers for the use of treatment of PSVT. I think for those folks who have the PSVT in a relatively sparse occurrence, who have the wherewithal to use this inhaled device, I think it's going to be very effective. I think it's going to be great. For me, as a person who had asthma when I was younger, when I ran track for my high school, I had to use an albuterol inhaler to prevent wheezing and things like that during events. I think a device like this or an agent like this is going to be extraordinarily useful for a lot of people and help them in their clinical situations. Great. Maybe the last question back to you, Dr. George Mark. Obviously, you mentioned at the onset that the majority of your practice is performing ablations as an electrophysiologist, but you've had a positive clinical experience with the drug in the pivotal trials. How are you thinking about using this in the context where most of what you do is perform ablations? Well, I think it'll affect the path to getting to me to some degree. I think that my expectation is that it'll be the mainstay choice of initial treatment out of an emergency room visit. Like if someone was gonna come home from their ER visit on a medication, I suspect it would be something like this that would be like that asthma inhaler. That's a great analogous kind of situation which people can have as that opportunity to protect them while they're waiting six, eight, 12 weeks to see a general cardiologist, and then further on to talk to an EP after that. I think a lot of people are going to be on it already by the time they get to me, or probably even by the time they get to Dr. Sailam. I think that if they were not, if they ended up coming to me and said, what are my options? I certainly would say, here are our paths. And while we could do something like invasive, why not try a medicine first? If it has that opportunity and gives you peace of mind and you say, oh, now I can take that trip to Europe and not fear being something I'm going to end up in a German emergency department or something for. I think people have a lot of satisfaction with it. My suspicion is it will be a more commonly, most commonly chosen first-line agent. That's terrific. Well, that's all the time we have today for the fireside chat. Again, I want to thank our audience for their engagement here and listening, and very much to Dr. Sailam and Mark for sharing their clinical experience. At this point, we'll turn it back over to Joe for some observations before we move to Q&A. Yeah. Thank you, Lorenz, and thank you, Doctors Mark and Sailam. I was feverishly writing notes, but you guys did such a great job providing a wealth of guidance around these areas. I think what's just fundamentally clear is that there's dissatisfaction and need, and that there's an opportunity to do better for these patients, which is great to hear because this is what we're hearing directly from the patients themselves. I'm not going to go point by point and try to recapture or summarize in the interest of time. We have a lot of questions that have come in. I want to make sure our audience has the chance to ask as many as possible, and I think we'll probably go 15 or 20 minutes to allow these questions. Operator, I'd like to turn it over to open up the question period and allow our analysts to start asking their questions. Great. Thanks, Joe. At this time, we'll be conducting our Q&A with our speakers. As a reminder to the audience on the webcast, please use the Q&A text box at the bottom of the player, and to our analysts in the queue for verbal questions, please raise your hand to indicate you have one. I'm going to read our first question from Ritu Baral at TD Cowen. What percentage of your patients elect for ablation, and what is the median age of your patients who elect for ablation? Right. Thank you, Tara. Dr. Sailam, let's start with you on this one. Ritu is an analyst at Cowen who knows our story quite well and probably trying to help her modeling as to how she should think about the percentage of patients that you would elect to refer for ablation, and then the age, if there is a median that you can think of. Then Dr. Mark, I'll ask you the same question. Well, I have to say that my patient population tends to have a lot of comorbidities, and they may be more complicated than some other areas of the country. I deal with an older patient population here, a very large Medicare population. I actually tend to refer more frequently for ablation therapy because a lot of my folks are on several medications, and they tend to have a higher burden of arrhythmias or abnormal rhythms. Usually for them, because they're so complicated, coming from an inner city population or an elderly population, I will refer them for ablation more frequently than I think that a cardiologist who deals with the younger population may. I don't know if there's a median age group, but I would say that most of my folks are probably over age 60 that I deal with. Again, a large Medicare population, so that would take them into the mid-60s to start with. I hope that's reasonable in terms of answering that. Makes sense. What's the percentage that you send over for ablation? I would say personally, probably 30%-40% of my patients will get referred over. Again, I have easy access to George Mark, so it's something where I have this luxury of having him close by as a colleague and accessibility. Okay. I think it's sometimes referred to as like, just listen to what he's got to say. Get his point of view. It's not like Vivek says to me, ablate my patient. Occasionally that does happen, for sure, but most often it's like, maybe we should let you talk to someone with expertise. For completely separate reasons, I was looking through my last five or six clinics and all that, which I do clinic one day a week. It's the last five or six weeks. I saw five consultations for SVT, and of those, I think I offered ablation to four, with relatively high frequency. The ages of the patients were predominantly low 40s to high 70s, more in the younger range, but there was one older patient. I would tell you, of the four that I offered ablation to, one opted for it. The other three said, let's see how the next six months goes. I say, I'll catch up with you in six months. We'll see what happens. If you end up in the emergency room in the next six months, we know we got to do something. It is not something I push and offer to people, but all the options, they decide what they want. Of them, the majority were like, no, I'm not interested in a procedure right now. That would not be what I want. That was my most recent six weeks. Okay, that's perfect. Data behind the assessment. Tara, I could see Ritu's question. I'll just piggyback and maybe go to Dr. Mark and then Dr. Sailam. We knew we would get this question, what's the ideal patient for ablation versus etripamil treatment? Out of your diagnosed patients, what percentage of them would you prescribe an etripamil? Now, before I ask you, Dr. Mark, I do have to caveat this, that e is not approved. We have data on etripamil from the study, but it is not approved. We don't have a product profile or a label or anything. Want to make sure we have that caveat right up front. If you're comfortable thinking about a percentage of patients for an innovation that could have the type of profile from the data, that's the caveat that we have here. Just to repeat the question, it is the ideal patient for ablation versus an etripamil treatment and then the percentage that you would prescribe an etripamil for. We'll do Dr. Mark and Dr. Sailam. Etripamil, it's not prophylactic. It doesn't stop the arrhythmia from its initial rapid rates. People typically will then try the vagal maneuvers and use it if they fail. If someone is very uncomfortable and it's even 10 minutes of SVT, it's just like it's happening too often. It's like affecting my ability to live my life, then that's not a good etripamil patient. They need to have something done to nip it in the bud. I think that the ideal etripamil patient would probably be someone who really needs something here and there, 2x, 3x a year, 4 x a year, something like that, where they have that opportunity to avoid emergency room visits, but they don't mind waiting 20 minutes or 15 minutes or whatever the onset of action between identification of a problem and the treatment kicking in. That's kind of the differential for me. I think frequency and how people can tolerate that initial portion while they're waiting for medications to do their effect, that would probably be the decision-maker as to whether I would try it or just move right to ablation. Otherwise, though, why not try it? Why don't I just offer it to people while they're waiting for their ablation? Because it might be eight weeks before their ablation. Maybe they take the etripamil home with them from the office, or I give them a script for it so they can have something while they're waiting. There's low downside to offering it to people. It's just if it's something that is happening with frequency and they're not tolerating even the beginning parts of it. Now we need to do something more final. Right. No, thank you for that. A lot of patients we hear that from. Why not just go for the ablation? Dr. Sailam, you're in a very different spot right in front of Dr. Mark. How would you think about either the ideal patient for etripamil versus sending them to Dr. Mark and the percentage you might want to send to Dr. Mark? Well, I guess we already got that. The percentage you would want to prescribe etripamil for. Well, I think the ideal patient for me is somebody who's, again, has a structurally normal heart with no significant comorbidities in the sense that they don't have severe diabetes or hypertension or issues with congestive heart failure, et cetera, or coronary artery disease. If you have a relatively low-risk patient who has a structurally normal heart and their episodes are relatively spaced out, like Dr. Mark was saying, 2x, 3x a year, 4x a year, I think that that patient will be ideal for this situation. I had a nurse who had SVT probably twice a year, and I think etripamil for that person would have been outstanding in that they knew when they went into SVT, and they were able to tolerate it for the time for a few minutes, and if they took the etripamil and it terminated the arrhythmia, it would have been a great treatment plan for them at the time. This is going to be something that I think we can use. In terms of percentages for it, I would say for these lower-risk patients who have this type of situation, I would say I could use it 20%, 30%, 25%, 30% of the time with a lot of these folks that we identify. Maybe even more depending on the identification rates. Thank you for that. Thank you. Operator, who's next? Yes. Thanks, Joe. Our next question is Ted Tenthoff at Piper. Please go ahead, Ted. Great. Hi, everybody. Thanks so much to the doctors for the time and their perspective today. I think I have a question both for the company and also for the docs. Joe, I've asked you guys, you and Lawrence this before, but when it comes to packaging, how do you envision delivering the etripamil nasal units? To the doctors, how do you envision real-world use? Is this something they would kind of carry around with them and have two in case they needed it? How do you think this would actually be used by your PSVT patients? Thanks, guys. Thank you, Ted. Really appreciate the question. I'll start with the first, and as you know, Ted, our treatment dosing regimen that we will propose or have proposed in our NDA, and it is under review by the FDA, is that the dosing regimen is upon symptoms and a failed vagal maneuver, a patient would dose themselves with etripamil, and then if after 10 minutes symptoms persist, they are to take a second administration or second dose of etripamil. It will be packaged in a two-unit pack so that they have two available to them. In the studies, approximately one-third of etripamil patients had their symptoms resolved with one dose. Within 10 minutes, they did not have to take the second dose. Two-thirds of patients, about 66%, wound up taking the second dose. It would be packaged in that two-dose regimen, if you will. Really with that, maybe you could offer it to Dr. Sailam and then Dr. Mark, any view as to how your patients would use it in the real world if it's out there, once it's out there? Honestly, I see this kind of, for me, this is going to be very analogous to back in the day, we would have patients take sublingual nitroglycerin, which was a tablet of nitro that they would put under their tongue if they were having angina or chest discomfort. If the symptoms didn't subside, they would take a second tablet in five minutes, and then if their symptoms didn't subside, they would go to the ER. To me, this agent is very similar to that. If you have symptoms of the PSVT, then they would be able to use this in a similar fashion. I think that with what I've seen so far from the literature and talking to George, that a lot of times the calcium channel blockers, again, are very effective with some of the most common episodes of PSVT we have, and they would get terminated, and the patients would go on with their daily activities. I think that this type of modality has been used several times in our clinical practice with various agents. This is going to be a very easy thing to adopt for patients. Thank you. Dr. George Mark? Yeah, I think it would be something they carry around with them all the time. I think it would be like your asthma inhaler. I think when they were going to go on vacation, they'd want to bring two or three probably. You know what I mean? Because they're single-use. At least in the study, they were single-use inhalers. You had to get a new one when the treatment was completed. Each episode would require renewal, and I think, like inhalers, even if you didn't use it, you'd probably have to get a new one after a while just to make sure the drug was still effective, like nitro, which stopped having effect after four or five months. I think that it would be something people would carry around with them, and they'd be happy to carry it around with them because that meant they wouldn't have to worry about ending up in the emergency room. I think that is the way it would be. Attach it to the keychain, maybe. Yeah, we'll work on different approaches to carry this in a convenient way. Great. Well, thank you, Ted. Operator? Yes. Thanks, Joe. Our next question comes from Dennis Ding at Jefferies. Please go ahead, Dennis. Hi. Good morning. Thanks for taking my questions, and thanks to the doctors for their great comments this morning. For the doctors, maybe comment around the willingness for your patients to use etripamil for every episode that they get and maybe their willingness to pay the copay each time. I'm just wondering, would some patients kind of wait it out, given some of these episodes self-resolve? How would the copay situation, I guess, potentially impact that? Thank you very much. Well, thank you, Dennis, for that. Before I offer the doctors to answer that question, I guess the big question that we won't know yet or won't know until after the FDA approves the product, and if it were to get on the market, obviously, the one big question is pricing. Our philosophy is our goal is to not trade one set of issues for another. We're hoping to price it in a way so that payers will enable it to be accessible to patients. Depending on the plans, our goal is to have patients have out-of-pocket expenses that are reasonable, depending on the plan, under $50 or under $100. Sometimes Medicare is a little higher. Doctors can't answer that question without having that at least bit of guidance. It is not confirmed right now. We'll have to see what happens in the market. That's how we're thinking about this. We want this to be a readily available drug for patients and not too many hurdles for physicians to be able to prescribe it. That's the company's desires and what we're working towards. Doctors, can you, to Dennis's point, ask about, Dr. Mark, you said why not use it, right? Why not have it available? Once it's in their hands, how do you think they'll think about it, using it? Will they wait? Will they jump to use it? That sort of question. Maybe we'll start with Dr. Mark and then Dr. Sailam. Yeah. I think that it's going to be very patient-dependent because there are some who do, like you say, have episodes that self-terminate, and they're not sure when one happens, is this going to be one that does self-terminate, or is this one that doesn't? Those people will probably wait. There's at least an equal number of people that when they have it, they know it's not going away until they do something about it. That might be the vagal maneuvers, or they know that they're going to have to end up calling the EMTs or go to the hospital. Those people may just say, why wait? I do think that it's a conundrum because too fast for too long is a strain on the heart. Like Vivek said so clearly, there are some people out there have blocked arteries, had bypass surgery, have weak heart muscles, have sticky valves. Too fast for too long, it can be a dangerous situation in patients with a lot of comorbidities. There may be people that we say, we just don't want to fool around with this. If you're going to do this, we want you to do it early. I think it'll be individualized based on people's previous experiences with their arrhythmia. That's the best probably I can say to that. Okay. Dr. Sailam, your views? I think just going back to the financial aspect of this, I could tell you that, as Dr. Mark mentioned earlier, SVT has a large mental component to the clinical scenario. If patients know that they've got this, essentially a security blanket in their pocket, that is priceless. I think that they're going to be willing to pay the copays for this security, as it really affects their daily activities and also affects them to be fearful of travel, fearful of being with their children, fearful of driving, et cetera. To have this security, in my opinion, and the mental peace that it's going to bring to them, knowing that it's going to cure or terminate their irregular rhythms, is really something that folks are going to be very enthusiastic to get involved with and pay for in this sense. Okay. Well, thank you. Thank you. Operator, thanks for the question, Dennis. Operator? Yes. Our next question comes from Patrick Trucchio at H.C. Wainwright. Please go ahead, Patrick. Thanks. Good morning. A couple of questions for the KOLs. First, I'm wondering what proportion of PSVT patients do you believe would be eligible for treatment at the time of approval? Of these, what proportion consists of those patients that may be readily identified? To what extent do you believe having an at-home treatment, if it's approved, may improve diagnosis or identification of new patients? In other words, what we're trying to better understand is how large an addressable patient population there is today, and how it may trend in the future if etripamil is approved. Secondly, I'm wondering if you can discuss the number of PSVT episodes patients experience on average per year? Of those, for the patients where you see etripamil as being appropriate, how many of those episodes would actually end up being treated with etripamil on average annually if it's approved? Thank you. Okay. I can tell Patrick's really trying to get into his model and figure out, and Dr. Mark and Dr. Sailam, this is how we help the investors get their hands around the condition. We try to identify an addressable population. That's not all PSVT patients. Just so you know what we've got at the street, too, and then maybe it'll help you compare and contrast. Milestone's guide at the street, too, of the PSVT patients are out there, about half of them are probably candidates for etripamil. Right? About half of them have it either so infrequently or so non-burdensome that etripamil is not going to be for them. In also that half not for etripamil, there's those that are having it with either really serious events like dizziness or so frequent that it doesn't make sense to be treating with an acute-use therapy. The half is the way we think of the target addressable market, and then we try to figure out, of the half that could use etripamil, how many of them. Well, what's the average number of events they have, and then how often will they use it? We've got it that we've heard from patients that the median patient has about 12 events per year, of which they use it on about half. We guide the analyst to model about four or five uses per year of etripamil, knowing that the median patient would have one a month type of thing. We have seen that patients actually report more events than do physicians telling us they have. That's not so unusual. Patients are at the forefront of their condition. Anyway, that's a little bit the guidance that Patrick has and what's behind some of his questions. Just come back to the questions. If you could talk about the eligibility of your population for etripamil and then cascading down, how many would you, if you own a practice, would you try to prescribe for? And then ultimately, how many would use it, actually? That's what he's asking for. Dr. Sailam, maybe I'll start with you. I think, John, I'm going to have to agree with you in terms of the folks that identify, probably 50% of these patients would be eligible for the medication if they fit that model of having the SVT 3x to 4x a year or in that general ballpark of SVT. I think we have a very good opportunity here to treat folks. As again, as I mentioned earlier, a lot of these folks do not tolerate taking daily medications for these episodes that may happen just a few times a year. This is going to be a unique opportunity for them to have relief for the arrhythmia and give them peace of mind. Dr. Mark, any thoughts? Yeah. It's an interesting question because the population is so diverse in terms of how they present and how they experience their symptoms. I think the wearable monitoring kind of information is so interesting to me. It is bringing a lot more patients to our awareness than it used to. I think that with a defined SVT episode on a wearable monitor, I think a lot of people are going to get this drug, like a high percentage, like 80% or 90% or something like that. Then the question as to whether they're going to use it as their mainstay of treatment, like that's the way they're going to treat this ad infinitum forever, depends a lot on how much they have to use it and how often those episodes are occurring. There's going to be some people with rarer episodes that are probably going to be happy to have a medicine for their episodes for the foreseeable future. Then there's going to be some where maybe episodes start to happen more often or last longer, or do something where they are like, now I need to do something about this. A percentage number is probably a really hard thing for me to wrap my head around. I just think that it's going to be an early stage, high percentage option instead of beta blockers, instead of drugs like that. One of the vascular surgeons here at Cooper sent me his son, who's like a 25-year-old consultant in D.C., whose smartwatch tells him every six weeks his heart rate hits like 210. I think about that, and he tolerates it, and we talk about medications. There's just a lot more. I think the pie is bigger than we might be aware of, and I think that this will be the early stage option for people, and it'll be more consideration for procedures when their frequency of events are too many. That's the best way I can answer that, I guess. It is hard. We've been working on it for years as a way to try to figure it out, but really value the comments. Operator, any other questions you could- Sir, there's a BTIG question. No, I think we're actually running up against. They've adjusted that one. Oh, okay. All right. Let's do one more, and then we'll close on this last one. Who do we have here? Tara, do you want to read the BTIG queue? Yes, definitely. Bhavin Patel at BTIG is asking, as both KOLs discuss the widespread incorporation of wearable technologies are helping finding patients earlier with PSVT, exactly how many more patients from an estimation standpoint are you diagnosing earlier on versus historically before the widespread adoption of these technologies? Okay. Doctors Mark and Sailam, our investors need details and numbers. Very clear from both of you that wearables are bringing more patients to you and shortening the diagnosis path. That was very clear throughout the story. Any sense as to how to think about numbers there and expanding the correct diagnosis of SVT? Dr. Mark? Yeah. It's a great question. I would say that AFib monitoring via wristwatches, I've noticeably seen a rise in that. That's probably because AFib's a usually asymptomatic arrhythmia, so people aren't even aware they're out of rhythm unless their wristwatch tells them. For SVT, I would tell you this. When you do a few hundred ablations a year, it's hard to do more than that. I just know EP is growing, and I think that we're identifying people more at earlier stages, than we would've at other times. It's probably a 20% increase, something like that. It's really hard to gauge it just because as an EP in 2024, things are coming at me from every angle. A lot of reasons why is because we're doing better at identifying it with wearable technology. Great point. Dr. Sailam? That's a tough question. I'd have to say as a frontline guy, wearable technology really is increasing the evaluations or consultations that we're seeing in the office. AFib is the most common thing that we see in the office from the wearable technology. The accuracy of the wearable devices is very good with detecting AFib. Now with PSVT, it becomes a little bit more tricky. I tend to have a lot of younger patients who come in now, who have wearable devices that have alerted them to higher heart rates, but I can't say a specific number. I can't say if it's 25%. I can't say if it's 30%. I can just tell you that with the advent of wearable devices that have come on the market over the past several years, we've had a very high increase of consultations based upon various alerts that they've gotten from their watches. Again, there's a lot of variables that go into the identification of PSVT on a watch or a Fitbit. I don't know if I have a concrete answer for that, and I apologize, but it has increased in terms of identifying patients and led to further testing on our part for more medical-grade devices. The larger, better increased patients, just hard to get the percentage. Okay. Right. Bhavin, that's what we got. All right, great. Well, with that, I'd like to close the call here. We're at an hour and a half now. I first and foremost want to thank Dr. Sailam and Dr. Mark for their time. Going forward, I mentioned this is the first in a series. We were going to see how we did here. I was just so impressed, and it was a phenomenal event. Our next one, we're going to go to the West Coast and see if we can find some, I guess, L.A. Charger fans to help us explain the management of the SVT out there. A little bit of teaser for our investor friends that are online. I also want to thank all who called in and for our analysts for asking those questions. I really appreciate it, and I want to wish everyone a great rest of the day. Take care, everyone.