Good afternoon. My name is Amit Hasija, and I am the CFO and Executive Vice President of Milestone Pharmaceuticals. I'd like to thank you all for joining our KOL event focused on etripamil for the treatment of PSVT. Before we begin, I'd like to address our legal disclaimer. This is a forward-looking statement disclaimer and our safe harbor provision. I will direct you to our SEC filings for a full disclosure of risk factors. Joining me on today's call from our team at Milestone is Joe Oliveto, our Chief Executive Officer, Lorenz Muller, our Chief Commercial Officer, David Bharucha, our Chief Medical Officer, and Francis Plat, our Chief Scientific Officer. In addition, we're joined by two of the preeminent rhythm disorder specialists in the field of cardiovascular medicines. First is Dr. Bruce Stambler. Dr. Stambler is board-certified in cardiology and cardiac electrophysiology. He currently serves as Director of Cardiac Arrhythmia Research and Education at Piedmont Heart Institute in Atlanta, Georgia. Dr. Stambler earned his medical degree from Duke University School of Medicine. He completed his internal medicine residency and his clinical research fellowship at Beth Israel Hospital, Harvard Medical School. He then completed a clinical and research fellowship in cardiac electrophysiology at Massachusetts General Hospital. Prior to joining Piedmont Heart Institute, Dr. Stambler practiced at University Hospitals Cleveland Medical Center, where he served as Director of Clinical Electrophysiology and Pacing and Director of the Electrophysiology Fellowship Program. He's also a Professor of Medicine at Case Western Reserve University in Cleveland, Ohio. Dr. Stambler has been an integral part of the etripamil phase II and phase III clinical trials, having treated more patients with etripamil than anyone else to date. He is the principal investigator and presented as the primary author of both the NODE-1 phase II and NODE-301 phase III studies. Second, we have Dr. Sean Pokorney. Dr. Pokorney is board-certified in internal medicine, cardiovascular disease, and clinical cardiac electrophysiology. He currently serves as Director of Arrhythmia Core Laboratory at the Duke Clinical Research Institute and Assistant Professor of Medicine at the Duke University School of Medicine in Durham, North Carolina. Dr. Pokorney earned his medical degree and completed his internal medicine residency at the Feinberg School of Medicine at Northwestern University. Additionally, Dr. Pokorney completed his fellowships in clinical research, cardiovascular disease, and electrophysiology, all at the Duke University School of Medicine. In addition to Dr. Pokorney's years of treating patients, he has done extensive research and has published broadly on the characterization, epidemiology, and cost burden of PSVT. With that, I'd like to run through our agenda for today's call. We will begin today with an introduction of Milestone Pharmaceuticals and an overview of etripamil. Following a brief video, Dr. Stambler will walk us through the characterization of etripamil and the data set to date. Joe will then outline the status of our etripamil development plans and the next steps for the program. Later, Dr. Pokorney will walk us through PSVT as a condition, including epidemiology and the burden of the condition on the healthcare system. Lorenz will round out our prepared remarks with an overview of the etripamil commercial opportunity. At the end of the call, we'll open the line for a Q&A session. Now I'd like to provide a brief overview of Milestone. We are a phase III cardiovascular company and are focused on advancing our lead program, etripamil, which is a novel calcium channel blocker. As you'll see in the middle of the page, the concept of etripamil from the outset was to change the treatment paradigm for patients living with cardiovascular conditions, shifting the treatment setting from the emergency department to patient self-management. On the left, you'll see two areas of large unmet need that we are initially focused on. The first and farthest along is paroxysmal supraventricular tachycardia, or PSVT, which will be the main focus of today's program. We are also advancing etripamil in a phase II trial in patients with atrial fibrillation with rapid ventricular rate. We are driven by our belief that etripamil has the potential to overcome the limitations of the current standard of care for PSVT, which is invasive, anxiety-provoking, and costly. We believe etripamil will serve as a meaningful new therapeutic option for patients. With that, we will now play a brief patient video. The episodes are scary because your heart is beating so rapidly. Feels like a marathon runner, that you've been running as hard as you can run for an hour or more. A year or so after that one, with my SVT acting up, oh, I'm gonna call it very severely, several times a day, and each time it acted up, I was very close to passing out, if not passing out. I was very frightened and worried that something more drastic, it could lead to something more drastic. It's not only uncomfortable, but it's the fear and the anxiety that that comes along with it as well. Emotionally, it was horrible. I can tell you that much because o nce you got used to having those episodes, it was like, "Oh, here we go." You know, this was going to take at least 20 minutes-30 minutes for me to just move through the episode itself, let alone knowing the exhaustion that comes with it after. We were driving to the airport to drop off my sister, and we stopped for lunch at a Chipotle, and the episode was actually triggered by hitting a bump in the road. Nothing, no stress, nothing. It was actually that bump, and I was in the passenger seat. It was really emotional that way, because it affected my family. It really affected them. If I went into an episode, my partner at the time, he would be at work, and he'd come racing home from work to help me because we didn't know how long it was going to last for. You know, do you get to the hospital on time? Are they going to catch it? Are they going to actually see what the rhythm is on the screens for them to be able to even diagnose you, b ecause a lot of the times, by the time you get there, it's gone. For me, it was difficult, physically, emotionally, mentally. Something as simplistic as going for a walk in my neighborhood, I think about if I have you know, do I have my phone with me? Do I have, you know, a way to do something with the dog? I think in the beginning it caused me a lot of anxiety, and I didn't know how long it was going to last or what I could do to convert the episodes. The most worrisome time for me when I was getting the episodes was, again, playing ball and I had a fear that if I would pass out, then other people that don't understand what's going on, other ballplayers or whatever, would run away, you know, kind of panic and call an ambulance. I could not get on a plane for nine hours or almost any length of time because I'm very afraid that I would have an episode while I'm flying. Every time I experience my SVT, when it starts, I immediately go to the ER because the nearest hospital to us has no available adenosine. I mean, receiving the adenosine shot for me is quite physically because you can actually feel that it restarts your heart. I first had PSVT in my late 40s, which means I've had it for about 20 years. I heard about ablations. It took me about five years to make the decision to have one. Within weeks, I started having episodes again. They started me on medication to try to control it, but it kept coming back and with a vengeance. I feel the same, too. Talking to the specialist, I think just the word pacemaker came up, and I absolutely recoiled with horror. Oh, it would mean so much to me if I had an at-home treatment procedure so that I would not have to go through the embarrassment of calling 911 and having all of the neighbors know. If there was something that I could do myself within my home, I would be so grateful. Now I will turn the call over to Dr. Stambler. Hello, everyone. My name is Bruce Stambler. I'm a Clinical Electrophysiologist. What we're talking about today is supraventricular tachycardia, SVT, and an unmet need in the treatment armamentarium of SVT. Arrhythmias that are under the category of SVT that include those that are based in the atrium, atrial flutter, atrial tachycardia, and atrial fibrillation. These are categorized as supraventricular arrhythmias, but they have their mechanism based in the atrium. SVT also includes arrhythmias that have their mechanism and their maintenance based in the AV node. An AV node is a necessary part of the reentrant circuit. In SVTs known as AV nodal reentrant tachycardia or AVNRT and AV reciprocating tachycardia or AVRT. These last two arrhythmias, AVNRT and AVRT, are often referred to as PSVT, paroxysmal supraventricular tachycardia, as they are AV node dependent and often present with patients complaining of a rapid, regular heart rate, often 150-250 beats per minute. Patients with SVT often report impaired quality of life and a feeling of loss of control of their health, importantly because these episodes of SVT can occur suddenly, often without triggers or warning, and can be associated with increasing frequency and burden of arrhythmias in patients frequently who develop sudden onset of symptoms of palpitations, shortness of breath, lightheadedness, chest pain, fatigue, and anxiety. These symptoms and the sudden nature and unpredictable nature of the arrhythmia can result in impaired quality of life and often increasing need for healthcare utilization, especially urgent care visits and emergency room visits. What is the current treatment paradigm for PSVT? How do we typically manage these patients, and what are the unmet needs in management of PSVT? Given the recurrent but episodic nature of this condition, in general, there are three long-term management strategies. Number one, no treatment, or which I call off and watch and wait for recurrent episodes. This is really based on patients' acceptance in terms of the frequency and burden of episodes. Some patients with relatively infrequent episodes can tolerate this strategy. Others with more frequent episodes are not willing to tolerate the unpredictable nature and symptoms associated with PSVT. We can often prescribe chronic oral medications, including calcium channel blockers, beta blockers, and antiarrhythmic drugs on a chronic basis to prevent an episodic condition to reduce the burden or frequency of these episodes. We can recommend an invasive but potentially curable catheter ablation procedures. If recurrences of PSVT, which are common even in patients on chronic oral therapy occur, in general, patients have one of three management options currently for an acute PSVT attack or episode. They can try what's called a vagal maneuver, where they bear down or they press or rub on their belly, trying to terminate these episodes. If a vagal maneuver doesn't work, some patients can try what is called pill-in-the-pocket therapy, where they take an oral beta blocker or calcium channel blocker on demand as needed, and they wait sometimes one, two, or three hours at a time for the medication to be absorbed and for the arrhythmia to terminate. If the arrhythmia doesn't terminate, patients are often forced to go to an emergency room or an urgent care setting where medical personnel can insert an IV and give intravenous therapy, such as a drug called adenosine or intravenous beta blockers or calcium channel blockers. There really is an unmet need in PSVT management as there is no currently approved therapy that's safe and effective that will rapidly terminate episodes of PSVT on demand without the need for medical intervention. The availability of such a effective therapy to rapidly terminate PSVT would potentially change the treatment landscape for both the acute and chronic management of PSVT. Etripamil was conceived and developed and is being developed to meet this unmet need that I alluded to in the acute management of PSVT. Etripamil nasal spray is designed to be fast, convenient, and empowering. It's a novel compound that is based on a clinically validated known mechanism of action. As a calcium channel blocker, it prolongs the AV nodal refractory period and conduction time, which is the mechanism of how other drugs terminate PSVT by acting on the AV node electrical properties or potentially slow rapid conduction during atrial fibrillation. As a nasal spray, it has a rapid onset of action as it is rapidly absorbed into the bloodstream after the nasal spray. You can see on the right in the figure showing that it's absorbed rapidly within a few minutes in a dose-dependent manner. Within five or 10 minutes, there are peak effects of the drug. Again, dose-dependent shown here, three doses. It's metabolized by serum esterases, resulting in a short duration of pharmacokinetic effect, lasting about 45-60 minutes. The initial phase I studies conducted in 2013 demonstrated the pharmacokinetic and pharmacodynamic profile of etripamil nasal spray. As you can see on this slide shown in purple, again, there is a rapid increase in plasma levels within a few minutes, within five minutes. That again shown in purple that begin to decline after 10 minutes following the spray. This is paralleled by a pharmacodynamic-mediated increase in the PR interval shown in light blue, which is the surface ECG marker of AV nodal conduction time, which increases rapidly, as you can see in blue, a 10% increase in PR interval above baseline within five or 10 minutes. This effect persists for up to an hour. The initial proof of concept that etripamil could actually terminate PSVT and do it rapidly was conducted in phase II in electrophysiology or EP labs in the United States and Canada. I participated in those studies, and we presented the results of those studies both at the late-breaking clinical trials and in the Journal of the American College of Cardiology. These were dose-ranging studies compared to placebo of PSVT induced in the EP laboratory, atrial dependent tachycardias, AVNRT, and AVRT in patients who were undergoing catheter ablation procedures. Doses of etripamil 35 mg, 70 mg, 105 mg, and 140 mg were selected based on observations in phase I that indicated at least a 10% increase in PR interval in sinus rhythm. Around 100 patients were recruited and enrolled in these studies. They received either placebo or one of the four doses of etripamil. Importantly, the three highest doses of etripamil, 70 mg, 105 mg, 140 mg, rapidly terminated induced PSVT with conversion rates ranging from 75%-95% within two to three minutes. We did look at effects on blood pressure in the EP lab. We did find that the two highest doses, 105 mg and 140 mg, did have a transient effect on systolic blood pressure with a transient decrease in systolic blood pressure that began about five to eight minutes after the dose, again based on the pharmacology, that returned back to baseline within about 20 minutes. Importantly, the reduction in blood pressure was not observed at the 70 mg dose shown in green here. The 105 mg and 140 mg dose with reductions in blood pressure shown in blue and yellow. Therefore, since 70 mg had a high efficacy for conversion of PSVT and did not show a reduction in blood pressure, 70 mg was selected as the best dose based on the balance of efficacy and safety to take to the next phase III studies that were conducted outside the hospital. This is the study design for the initial phase III study which we called NODE-301. NODE-301 recruited patients greater than 18 years of age with a documented history of PSVT with episodes lasting more than 20 minutes. 97% of these individuals safely received a test dose of etripamil in sinus rhythm and then were subsequently randomized 2: 1, 70 mg etripamil versus placebo in a double-blinded fashion. Patients then waited for a suspected episode of PSVT, and when they had symptoms they thought were due to their typical PSVT that were sustained, they applied an ECG event monitor to their chest. They attempted a vagal maneuver to terminate the episode. Then if the episode did not terminate, they themselves administered on their own outside the hospital without medical supervision the study medication nasal spray based on the double-blind 2:1 randomization. In total, 156 patients experienced a vagal maneuver refractory sustained episode of symptomatic PSVT that was adjudicated by an independent blinded ECG events committee as AV nodal dependent PSVT. Based on the double-blind randomization, 107 patients administered etripamil and 49 patients self-administered placebo. The primary results were not significant between etripamil versus placebo over the five-hour observation period p < 0.12. Therefore, the NODE-1 trial, after 156 events, failed to meet its primary efficacy endpoint over the first five hours. Notably, as you can see from these curves early on, there clearly is a treatment effect that favors etripamil over placebo. When we analyze this effect using a post-hoc analysis, in fact we did find there was a significant effect of etripamil versus placebo in terminating PSVT 54% versus 35% p = 0.02. You can see the early portion, so to speak, of the curve shown on this slide over the first 45 minutes where the curves clearly separate within five minutes. There is a treatment effect favoring etripamil over placebo that remains separated by 15%-20% absolute difference in efficacy of etripamil over placebo, again over the first 45 minutes. It was decided based on these data to continue the trial but have a new efficacy primary endpoint in part two of the trial, which is called the RAPID trial, with a primary efficacy endpoint of 30 minutes comparing etripamil versus placebo. In addition, patients in the part two of NODE-301, again called RAPID, will have the option of using a second dose of 70 mg after 10 minutes. Recall that the pharmacokinetic effects of etripamil begin to wane after 10 minutes or decline, so to speak. Therefore, we're allowing patients in RAPID an option of self-administering a second 70 mg dose of etripamil if after 10 minutes if their symptoms don't resolve. In terms of safety, this to me was the primary take-home message, importantly, that etripamil was well-tolerated and safe. During part one of the trial, there were no important adverse cardiovascular safety events seen. Remember, this was the first in-human study of etripamil administered by patients themselves outside the hospital during PSVT, where their heart rates are very rapid from 150 - 250 beats per minute. Importantly, it was safe and well-tolerated. The most common adverse events with etripamil compared to placebo were related to the nasal route of administration, with symptoms such as nasal congestion, rhinorrhea, cough being the most common symptoms, adverse symptoms associated with etripamil. Other important observations in part one of NODE-301 were that etripamil had a significant effect to reduce heart rate during PSVT, even in patients that did not convert from PSVT to sinus rhythm. These are data shown here. During PSVT, there's a decline in heart rate during PSVT, about 10-15 beats per minute that begins to occur within one minute and persists for up to an hour. We also looked at other key secondary endpoints, including relief of PSVT-related symptoms, and there was a marked improvement favoring etripamil over placebo in improvement of PSVT-related symptoms, including rapid pulse, palpitations, dizziness, shortness of breath, anxiety and chest pain. I think the key take-home messages for the etripamil nasal spray development program that I've been involved with now for nine years is that AV node dependent PSVT occurs frequently and in all age groups. PSVT negatively impacts patients' quality of life and leads to increased emergency room visits and need for healthcare utilization. Etripamil nasal spray would be a novel addition to the PSVT treatment armamentarium, satisfying an unmet need for a safe, effective and rapidly acting therapy that can be conveniently self-administered by patients on demand during PSVT at home. Etripamil nasal spray, the phase I through III data demonstrate a mechanism of action and effects on the AV node, based on targeted PR prolongation and heart rate during PSVT. This demonstrates its mechanism of action with the reduction in heart rate being an AV nodal effect. Demonstrated were tolerability and safety during at home dosing of self-administered etripamil during PSVT. Rates of PSVT termination in placebo-controlled blinded trials were potentially clinically meaningful, and PSVT symptom relief and reduced need for other medical interventions, including emergency room visits, is also potentially important. The current phase III RAPID trial should yield even more definitive data on safety, efficacy and the clinical impact, including the potential utility of repeat sequential dosing. Thank you for your attention. Thank you, Dr. Stambler, for taking us through the SVT condition, treatment options for characterizing etripamil, and for reviewing the phase II and phase III studies. I'll take this opportunity to provide some background on interactions with the FDA and how that has led to the RAPID study design and the clinical program path forward. I'll then transition the presentation to Dr. Sean Pokorney for a further characterization of the size of the PSVT condition and recent learnings on burden of the condition. Shown here is the NODE-301 primary endpoint. Upon reviewing this endpoint, we quickly realized the learnings around the analysis and specifically that earlier observation windows in the range of up to one hour would be ideal for studying etripamil for this condition. As we show here in the statistics for the analysis over the first 30 minutes, conversion rates for etripamil and placebo results in conversion rates in the range of 54% and 35% respectively. We immediately followed that finding with speaking with our key opinion leader advisors as well as 250 practicing cardiologists to gain an appreciation for the clinical benefit. We were comforted to learn that cardiologists would value conversion rates of 50% within an hour of dosing as a key deliverable, and with etripamil delivering 54% at 30 minutes and the low 60s percentages by one hour, we believe we had a commercially attractive profile based on the results of the NODE-301 trial. With that understanding, we approached the FDA with a discussion of the data and the path forward. The FDA largely agreed with our learnings around the observation window for the primary endpoint and agreed that 30 minutes was an appropriate window. The FDA felt that NODE-301, complete with this post-hoc analysis over the 30 minutes, would be valuable as part of the NDA efficacy package, but that another study would be needed. We also agreed, and that study is now RAPID study. Second major discussion point with the FDA was around clinical benefit and if there was potential to increase the dose, given the tolerability profile in the NODE-301 data which Dr. Stambler had presented, was really quite remarkably unremarkable, if you will, somewhat benign, and offered us the chance to approach increase in conversion rates that we had originally envisioned for etripamil, more in the range of 70% rather than the 50% or 60% that we saw on the NODE-301 study. We originally discussed an increased dose, for example, moving from 70 mg to 105 mg or 130 mg. Upon further discussion with really the rhythm disorder specialists, we agreed with the FDA on including a repeat dose regimen that Dr. Stambler explained, but just to refresh, would instruct patients to take a second dose of study drug, same dose of study drug, if they were experiencing symptoms 10 minutes after their initial dose of study drug. The next slide provides a picture of the PK of such a regimen. What I'm showing here is the plasma concentration for 30 mg dose of the etripamil over time. What you see with the first peak is a characteristic Cmax occurring at approximately five minutes. We consistently see that whenever we show etripamil PK studies. That's followed by the characteristic drop in plasma levels that is designed into the molecule. When the second dose is delivered at 10 minutes, notice the plasma levels are still present from the initial dose. The second dose is starting from a higher base of drug and resulting in a second Cmax that's likely a bit higher than the first Cmax seen with the first dose. What is important according to key opinion leaders is the second peak resulting in the second impact on the AV node and a second chance to break the tachycardia. Not necessarily that the second Cmax is larger than the first, although I think that's somewhat of a benefit. The approach mimics a common practice in current treatment paradigms with IV drugs, where practitioners often deliver a second dose of, for example, adenosine in the emergency room if the first dose does not convert the tachycardia, and that second dose of adenosine is often the same dose as the first dose and not necessarily a higher dose as the label calls for. With that agreement with the FDA on the repeat dose administration, the RAPID study was formed. What you see on the next slide here is the RAPID study design. Notice it is remarkably similar to the NODE-301 study design. Key differences are highlighted in yellow. There are three main differences, the first being the repeat dose administration, 70 mg followed by 70 mg, should symptoms persist for 10 minutes. That repeat dose administration is seen both in the test dose as well as the administration of study drug during the event. The second key change from the NODE-301 study is the re-randomization. In this study, we're randomizing 1:1 drug to placebo compared to the 2:1 randomization we had in the NODE-301, which resulted in a small number of placebo patients and which ultimately hurt our analysis. The third major change between RAPID and NODE-301 is the observation window that we've already previously discussed, and in this case would be a 30-minute observation window compared to the five hours that we had invoked in the NODE-301 study. Finally, the sizing of the study for RAPID is 182 PSVT events. Sorry for that. This is driven by the assumptions of trying to replicate the difference that was seen in NODE-301 study, namely a 19% delta between drug and placebo at 30 minutes, remembering that it was 53% for drug and 35% for placebo. We of course believe the repeat dose administration has a good chance of increasing the efficacy of the drug group compared to the placebo group, an increased chance of a higher delta, a hope for a higher delta. However, we powered the study and sized it not to require any additional efficacy coming from the repeat dose. We believe that if we can replicate the NODE-301 study results in the RAPID study, we have a winning profile and would be well-positioned to deliver an NDA filing to the FDA. In the next slide we provide a Gantt chart and an overview of the program. We've recently updated our guidance on the timing of the expected top-line results from the RAPID study to the middle of the second half of this year, 2022. For our NDA, the efficacy portion will be comprised primarily of the NODE-301 study, which we've presented here, including the post-hoc analysis at 30 minutes, as well as the RAPID study efficacy results. The safety package will add to those two studies the NODE-303 study. The NODE-303 study is an open-label study, adding new patients to the program. It does not have the test dose associated with it, so it's more of a real-world experience. The combination of NODE-301, RAPID, and NODE-303 will make up the majority of the safety data set for an eventual filing. Turning our attention back to the PSVT population, I'd like to remind the audience of what we faced when we first started learning about the PSVT condition. The literature was sparse with only one epidemiology study, which we call the MESA study because it was done in a population of 50,000-person area in Marshfield, Wisconsin. The study was published in 1998, and while valuable for characterizing patient characteristics, we believe significantly underestimates the size of the overall PSVT population. From there, we set out to learn a lot more. I'd like to introduce Dr. Sean Pokorney, who has been instrumental in advancing the field and understanding a great deal about the size of the PSVT population as well as the medical burden. Thanks, Joe. I appreciate the opportunity to talk about PSVT burden of disease. This is an area that I found extremely interesting because we see these patients very frequently in clinical practice, and there has not been a lot of research and data and understanding of how prevalent PSVT truly is in our patient population, as well as how the disease really affects them in terms of symptom burden. This has really been an opportunity to explore this in greater detail. There previously had been two studies, MESA and PREEMPT, that looked at the prevalence of PSVT, but there were some significant limitations to those studies. We felt that a better approach was to do a claims-based analysis to provide a better estimate of the prevalence and incidence of PSVT in the United States. To do this, we analyzed a U.S. commercial and Medicare claims data set over a nine-year period, and patients had to be included in that data set for a continuous five years in order to be analyzed. For patients to be identified as having PSVT, they needed to have at least one or more claims billing code for PSVT in the emergency department or inpatient setting. If those claims codes came in the outpatient setting, then patients had to have at least two or more diagnosis codes for PSVT. What we really set out to do was to try to understand what the ranges of PSVT were, the ranges of prevalence and incidence. The reason I say ranges is that patients have sometimes PSVT only. Sometimes they have concomitant atrial fibrillation and atrial flutter as well as PSVT. Some of the concern is that when patients may have concomitant atrial fibrillation and atrial flutter, some of those patients have true PSVT in addition to their atrial fibrillation and atrial flutter. Another portion of those patients may inappropriately be labeled as having PSVT in combination with their true atrial fibrillation and atrial flutter. We considered the ceiling for the incidence and prevalence to really be the population of patients that had PSVT and concomitant atrial fibrillation, atrial flutter, and the floor for the prevalence and incidence of the PSVT population to be the patients with PSVT alone and with no codes for atrial fibrillation and atrial flutter. Probably the true incidence of PSVT really lies somewhere in between. When we looked at the numbers within this claims data set, we found that the floor or the number of patients who had... Were identified as having PSVT and did not have concomitant atrial fibrillation or atrial flutter, the prevalence of those patients was 1.3 million, and the prevalence increased up to 2.1 million when we included the patients with concomitant atrial fibrillation and atrial flutter. Even these floor and ceiling estimates that I'm giving may actually be low and underestimated. Part of the reason that I say that is that when you look at data from MESA, 39% of patients that had adjudicated PSVT were labeled and had a claims code for PSVT. We're only identifying patients in this claims-based data set who had a billing code for PSVT, and that may actually even underestimate the population. We know that when we look across age ranges and across male versus female sex, we see that PSVT is prevalent really across all age ranges and across sex, which is demonstrated here in this figure. One of the things that's important to understand in this patient population is the disease burden that these patients experience. The reason that is that clinically, the way that we decide to manage and treat these patients is really based on their disease burden or symptom burden that they're experiencing with these episodes. An interesting analysis here that I'm going to go through now is some patient-reported outcomes, and this was prospective longitudinal data that was collected among 247 patients in the United States and the U.K., and these were unablated patients with PSVT. The average number of days covered in the study was 257, and there were over 5,000 surveys that were completed by these patients over that time period. We collected episode symptom surveys when patients had episodes of SVT, and we had over 2,500 episode symptom surveys that correlated with over 5,000 SVT episodes that were collected in this data set. There were over 2,700 quality of life surveys that were also collected among these patients. When we look through the data, one of the ways that patients and clinicians characterize the severity of episodes or the impact that the disease has on the patients is the duration of the episodes themselves. What this figure shows on the left-hand side, we have all episodes. Towards the right-hand side of the slide, we have mild to severe episodes, with the more severe episodes being on the right-hand side of the figure. In this stacked bar graph, we show the color coding related to the duration of the episodes, with the bottom of the bar being shorter episodes and the top of the bar and the darker colors being longer episodes. What we see here is that when you look at all episodes, 35% of all episodes lasted 30 minutes or more. When you look at more severe episodes, you see that the duration of the episodes are actually longer on average. That's demonstrated here when you look under the moderate episodes. We see now 40% of the episodes last 30 minutes or longer. That increases even further when you look at the severe symptom episodes. 75% of those episodes last 30 minutes or longer. Another way to characterize the burden or impact on patients is the severity of the symptoms that they actually experience. We collected a number of symptoms in these surveys, but one of the things that I wanted to focus on here on this slide is four of the symptoms that we focus on and care about most clinically. Those are palpitations, difficulty breathing or shortness of breath, dizziness which may predict patients who are going to experience near syncope or syncope or passing out, as well as chest pain. And again, those aren't all the symptoms, but those are some of the symptoms that we focus on most often. When you look along the bottom, what we show is that when you see patients with all episodes on the left-hand side, the average number of symptoms with an episode is three. That average number of symptoms increases in more severe episodes. Among the moderate severe episodes, three and a half is the average number of symptoms for a moderate episode. Within the severe episodes, it goes up to six. Again, more severe episodes are associated with greater number of symptoms. Furthermore, within those four symptom categories that I mentioned that we focus on the most clinically, you see a similar pattern where the prevalence of each of those symptoms increases across more severe episodes of SVT as reported by patients. Another thing that's interesting and important for society is the cost of PSVT to the healthcare system. What I'm showing here on this slide is a cost analysis looking at healthcare utilization for patients under age 65. The blue bars demonstrate the year before the PSVT diagnosis occurred, and the orange bars demonstrate the healthcare -related utilization and cost in the year after the PSVT diagnosis. There are matched controls on the left-hand side of the figure and the PSVT patients on the right-hand side of the figure. What you can see is that for the PSVT patients, the cost in the year prior to the year after the PSVT diagnosis more than triples for these patients. When you compare this to matched controls, although the year prior to diagnosis of PSVT is relatively similar in terms of cost, $6,000 versus $9,000, there's a $23,000 increase in the cost comparing matched controls to PSVT patients when you look at the year after diagnosis. Along the bottom, the table at the bottom shows the rates of different healthcare-related utilization across this patient population. For PSVT patients, what you see is that these costs are really being driven by emergency department visits and inpatient stays. This is the data for patients that are 65 years and older, and the data really shows a similar story. For the PSVT patients, there's a near doubling of their cost of care in the year following diagnosis, and the patients with PSVT relative to the matched controls have a significant increase of $13,000 of their cost of care in that year following. Again, this is being driven by inpatient stays and emergency department visits. One of the ways that we treat and manage these patients is when we treat them with ablation. We wanted to better understand what portion of these patients really get treated with ablation therapy. When we looked at the data, the answer was that about 15% of patients received a catheter ablation during the three-year follow-up period after receiving their diagnosis. The rates of ablation were highest among the younger patient population and were more prevalent among male versus female patients. We also looked at the rates of reablation because we know that although catheter ablation can be curative for these patients, it's not 100% curative. The rates of reablation were about 7%, and that was again highest in the youngest patient population. What this tells us is that a significant portion of patients with PSVT are not ablated, and so there is a high unmet need for acute at-home treatment. In conclusion, I wanted to go through a few takeaways of the scope and impact of PSVT. What our data and research has shown is that AV nodal dependent PSVT occurs frequently. We know that AV nodal dependent PSVT is prevalent across age ranges and sex, as I showed. Patient perceived severity of PSVT episodes appears correlated with episode duration and number of symptoms. PSVT management is costly and leads to increased emergency department visits and healthcare utilization. Finally, catheter ablations occur in about 15% of the population. Thank you. Thank you, Dr. Pokorney, and thanks to everyone for your attention this morning. I'm Lorenz Muller. I'm the Commercial Officer at Milestone Pharmaceuticals, and it's my pleasure to briefly review with you this morning the commercial opportunity for etripamil to help patients with PSVT. What you see on the slide here is a summary of literally thousands of interviews over the last four or five years with the important stakeholders that ultimately will be engaged with etripamil, whether it's patients, physicians or, of course, payers. Across the board, what this slide summarizes is the receptivity that these key stakeholders have for a product like etripamil to treat episodes of SVT. Starting with the patients, which is the most important. Patients have repeatedly and consistently told us how excited they are about the profile of this drug, that it will allow them to empower them to self-manage this disease, something they really haven't been able to do. They've been wholly dependent on the healthcare system to be able to manage episodes if they last longer than they can tolerate. They're also very excited about not having to go to the emergency department to be able to manage these episodes. Physicians, another key stakeholder, are always looking for a new tool in the armamentarium to help with patients. In this particular disease, there aren't that many choices once a patient is in an episode of SVT. They're very excited about the, certainly about the safety of the product, about the efficacy. They would use it in a number of different types of patients, not just patients with very high disease burden, but also potentially as a bridge to an ablation or other types of treatments within this disease state. The insurance companies, the payers, have also expressed interest in etripamil, partly because they see the clinical need within this patient population, but also because they see the potential for some cost savings, based on hopefully a reduction in emergency department visits that we're able to show in our clinical program. They're also very interested and more and more being measured by changes or impressions of patient satisfaction with a particular treatment. I wanna come back to something that Dr. Stambler showed earlier. When we got the results of NODE-301, you'll recognize this slide from his presentation. One of the questions we asked is, are the results of this study clinically meaningful to practitioners? With converting roughly half of the patients within 30 minutes that take the drug, would that be important to physicians? Would it make it compelling for them to use it? We did a lot of research back in 2020 after we got the results of NODE-301, which are shown on this slide. What we learned from that research with both opinion leaders and also rank and file prescribing general cardiologists is that what they care about related to this product profile is first and foremost the safety of the product, which is not shown on this slide. Beyond a safe profile, they really like the rapid onset of the drug, and you can see the divergence of these curves in the first five minutes. They found that the conversion of the majority of patients, so more than half the patients within 1 hour, as clinically meaningful very consistently because they guide patients who are in an episode to try to wait out the episode for 1 hour before seeking additional care, before calling them, before going to the emergency department. That was a very important finding for us because it meant that we knew we had, even with the NODE-301 results, an important product for physicians to add to the armamentarium. When we pushed physicians in this research and asked them, "Is there anything you would like to see more?" They said, I mean, broadly, they're very happy with the profile, but if you really press them, they had hoped for a little more efficacy. Hence, the design that was reviewed by Dr. Stambler for RAPID to try to take a second dose at 10 minutes makes sense in terms of trying to increase the efficacy, the percent of patients that convert at 30 minutes without increasing any safety concerns. As we think about this commercial opportunity, in summary, we've identified and done a fair bit of work, and Dr. Pokorney, as you saw earlier, has led a lot of that work in terms of the epidemiology. We're very comfortable that there's around a little more than 2 million patients in the U.S. currently diagnosed with PSVT and perhaps more that are in the process of being diagnosed, given the time it takes to diagnose patients. Of those, Dr. Pokorney reviewed the patient reported outcomes market research that we conducted that gets us very confident that about 60% of the patients who have been diagnosed with the disease are actually eligible and would benefit from a product like etripamil because they have sufficiently long, sufficiently frequent, and sufficiently severe in terms of symptoms, episodes where they would wanna take an action. They've told us when we show them the profile of etripamil that they would use the product on these types of episodes. Roughly 60% of the diagnosed population is what we define as our target addressable market, or around 1.6 million patients. When we conduct market research and show physicians, cardiologists, electrophysiologists, and primary care a profile of etripamil that's similar to what we achieved in NODE-301 that I showed you a minute ago, we consistently get almost independent of the type of patient profile we show them as stimuli, an adoption rate, a stated adoption rate of around 50%. It goes, you know, 40%-60%, but it's in that range. That gives us a confidence that we have, you know, a peak share of around 800,000 patients that we can help at peak with this product. The same research that Dr. Pokorney reviewed in some detail also gives us confidence that of the 12-15 episodes that patients are experiencing a year of SVT, that four to six of them would be significantly burdensome enough that they would be willing to use a product like etripamil, should it be available to treat them. That gets us to an average of five per year. When you do the math, going vertically down the column on the left, you can see a peak opportunity on the order of 2.5 million-4 million episodes a year treated. Which we find is a very attractive opportunity for us as a pharmaceutical company. Also very importantly, it gives us the opportunity to help hundreds of thousands of patients with this extremely burdensome disease. As we think about commercializing and bringing this product to market and to patients, one of the very important insights that we gained from our research is that the majority of these patients are diagnosed and managed by cardiology. For a company like Milestone launching its first product, that was a very important finding because it means that we have a very focused call point. We can, by targeting 150-200 sales representatives on roughly 20,000 cardiologists and some small percentage of high-volume primary care physicians, we can get at roughly 60% of the revenue opportunity that's available here. That becomes very important from a financial standpoint, from cash management, and also from just achieving a break-even in a reasonable timeframe. Equally importantly, there's an opportunity to get at the remaining 40% of the revenue opportunity here by targeting primary care, and that's something we could do in a partnership with another pharmaceutical company that already has sales reps on the streets promoting other products. This product, etripamil, would be easily laid into the bag that the reps are carrying. It would give them something new to talk about. The overlap, importantly, between the targets they're currently calling on and the targets we would wanna call on is very, very high for many disease states. Think about oral anticoagulation, diabetes, heart failure, just to name a few. There's a real opportunity here to partner as we launch and actually get at more than just the 60% of the revenue opportunity that we think we can get to on our own. Lastly, there's an important use case for electrophysiologists, as I mentioned earlier, as a bridge to ablation. That is important. It's not a lot of volume, it's not a lot of revenue for us, but it does help a certain subsegment of patients. Most importantly, it gives electrophysiologists, who are the thought leaders in this therapeutic area, a chance to have experience with the drug and therefore advocate for it, with the knowledge that they've actually had some actual hands-on experience with the drug. That in a short summary captures the commercial opportunity as we see it for etripamil. On behalf of Milestone and our two physicians, Dr. Pokorney and Dr. Stambler, I wanna thank you all for your attention. At this time, if you'd like to ask a question, please press star one on your telephone keypad. If you wish to remove yourself from the queue, please press the pound key. You can also submit a question via the question submission via the webcast. I will now turn the call back over to the Milestone team. Thank you operator, and thanks everyone again for following the story here. I have a couple of just starter questions to get us rolling. Again, we'll monitor the incoming emails via the chat system as well as we had mentioned earlier, opening the lines up for direct questions. Maybe this first question I'll ask Dr. Stambler to take the lead on, followed by Dr. Pokorney. It's surrounding Dr. Stambler, your explanation of the treatment options available that you have now for your patients that you listed earlier in the presentation. If you could provide your experience on use of pill-in-the-pocket for treatment of these acute episodes of PSVT. Thanks, Joe. In general, I would say I often don't recommend pill-in-the-pocket therapy for PSVT episodes. First off, there is not a large, medical evidence database on which to assess the efficacy and safety of an oral pill-in-the-pocket therapy such as a beta blocker, such as metoprolol or a calcium channel blocker such as diltiazem. There are a few studies, but they're quite old, maybe 20 or 30 years old. We don't have a large database, a large evidence base showing that this is effective and safe. In addition to which, it doesn't make a whole lot of sense for me, since oral pills oftentimes can take 60, 90, 120 minutes, number one, to be absorbed, number two, to have a pharmacological effect. In general, I don't recommend pill-in-the-pocket therapy for PSVT. I tell patients that if the episode is ongoing and it doesn't terminate with a vagal maneuver, that they need to think of some other alternative after about 30 minutes, which generally means proceeding to an urgent care or an emergency room setting. Thanks, Dr. Stambler. Dr. Pokorney, any thoughts? Yeah, no, absolutely. I completely agree with Dr. Stambler with really everything that he said, and I might just add on top of that a little bit. You know, when these patients go into the emergency department or into an acute care setting, they don't do IV beta blockers or IV calcium channel blockers. Certainly, I've had a number of patients where they go to to an acute care setting, and they do give those medications IV, and even those medications IV don't terminate these arrhythmias. Then they end up ultimately going on and getting adenosine to terminate the arrhythmias. I would say that, you know, my experience is that even these medications by IV don't terminate the arrhythmia acutely. Certainly, you know, as Dr. Stambler said, when you take them orally, it takes much longer for them to potentially have an effect. Even once you do have a therapeutic drug effect, those drugs just aren't effective for terminating these arrhythmias. I think that's unfortunately been a misunderstanding among the general medicine and cardiology community that beta blockers and AV nodal blockers in general are effective at preventing or treating these episodes. Well, thank you. Thank you. Moving on. I have maybe a couple more that are in here so far. Maybe this is with regard to trying to understand the value of the 30-minute treatment window that's being proposed. Maybe to say it specifically, again, maybe I'll start with Dr. Stambler and then move over to Dr. Pokorney. You know, how will an endpoint assessed at 30 minutes of treatment provide clinically useful information, and how does that dovetail into your approaches with patients? Yeah, I can start off, Joe, and say I think it is clinically important because that is, in general, dovetails well with my clinical practice. First off, it's important to understand that these are not life-threatening arrhythmias. They're not life-threatening tachycardias, but they can cause significant troublesome symptoms and impair quality of life. As such, I tell patients to try a vagal maneuver. If it doesn't stop, just sort of wait it out on the couch. If it doesn't stop after 30 minutes, that's a time point where I would certainly define the episode as sustained, and that the episode is less likely to spontaneously terminate in the next 30-60 minutes, and they need to make a decision about what their next option's gonna be, which generally means figuring out a way for them to get transported to an emergency room. I tell patients not to drive themselves, so it's either they need to call a friend, a loved one, a companion, or call 911. 30 minutes is a time point where I think patients have to make clinical decisions about how they're gonna get themselves back into normal rhythm. If we can terminate the episode quickly within less than 30 minutes, that would relieve a lot of the anxiety associated with the rhythm. Patients tell me they enjoy the fact that they can control their clinical condition, and they can avoid the inconvenience and cost associated with an urgent care and emergency room visit. Great. Thank you, Dr. Stambler. Dr. Pokorney, maybe I'll adjust the question a little bit for you and get your opinion. In addition to the 30-minute component, you know, I'll just relay what I get asked a lot, which is, you know, these patients will, or at least half of them, according to your study, will convert naturally within an hour. Can you also layer in this idea of, you know, if they're naturally gonna convert within an hour, help me understand the clinical utility of etripamil converting more of them earlier. Yeah, absolutely. I think it's an important point. You know, one of the challenges is one of the things that patients often express to me when I'm talking to them in clinic is that they never know when the episode is gonna happen that they're gonna end up in the emergency department. Or even when the episode starts, they still don't know if that's the episode that's gonna stop or that's the episode that's gonna land them in the emergency department. I think that it's really important to, you know, number one, focus on shortening the duration of an episode for a given patient because any amount of shortening of an episode for a patient is meaningful to them since they're the ones that are suffering during the episode. Beyond shortening the individual episodes, taking a portion of these patients, again, if you're saying 50% of patients terminate on their own in 50 minutes to an hour, that means 50% don't. Giving those 50% of patients an option to take control of their condition and prevent having to go to emergency department, prevent having to experience it, that delayed suffering because, again, even if they make the decision to go to acute care in the emergency department, that whole process by the time they get there and get checked in and get an IV and get everything else, you know, that can be a prolonged process that can take an hour or more time. Again, I think that we need to somewhat shift the focus away from just shortening the episodes and actually focus in addition to that on converting more patients who otherwise wouldn't be converted without emergency department or acute care type of treatment. That's great. Thank you, both Dr. Stambler and Dr. Pokorney. Here's another question that's in. You know, what results would you ideally like to see out of the RAPID study that would make etripamil compelling for you to prescribe for your patients? Dr. Stambler? Sure. Thanks, Joe, again. I think the key take-home message from part one, the first 156 patients, was that etripamil is well-tolerated and safe. Certainly, if we would like to see that be reconfirmed in RAPID, the safety and tolerability. Number two, I would like it to show that it's as good as, if not better, the efficacy in terms of PSVT conversion within 30 minutes. As you suggested, if we can boost that 54% within 30 minutes that we saw after one dose up to 70% or even 80%, as we saw in the EP lab studies, that would be clinically meaningful and a wonderful outcome, so as good as better. We'd like to know whether or not this repeat dose sequential regimen makes sense from an efficacy, safety point of view as a therapeutic strategy. I think those would be the three things that I'm looking for, reconfirming safety, reestablishing efficacy as good as better. Answering the question whether repeat dosing makes sense from an efficacy and safety point of view. Great. Maybe I'll go with the next question here, and I'll ask Dr. Pokorney this one. It says here that only 15% of the U.S. patients with PSVT get an ablation. The question is, does this surprise you given that ablations seem to be so successful? Maybe I'll ask both of you, but ask Dr. Pokorney to start off with that one. Yeah. I think it's a really interesting question, Joe. I think that this is, you know. It was maybe a little bit lower than I had even expected when we looked in the data. I probably thought that it would be closer to 20% or maybe 25%, but I figured it was going to be low. Part of why I figured it was going to be low is that, again, as specialists, we're a little bit skewed in our perspective because of the patients that I see for PSVT, you know, I would say that a large portion of those patients end up undergoing ablation. That's because they're sent to me by their cardiologist to get an ablation most often. You know, I would say even among the patients that I'm seeing in clinic who are sent to me for an ablation, it's still not 100% of those patients that go on to get an ablation. It's probably about 2/3 of those patients go on to get an ablation. I would say within the remaining 1/3, there's still a portion of patients, even after they hear about the success rates of the procedure, that are concerned about the risks and are looking for alternative options to replace ablation. That's even among the patients that are sent to me specifically for that reason. We have to keep in mind that there's a whole group of patients that are managed within the cardiology clinic that don't make it to me. There's an even larger group of patients managed in the primary care setting who never even make it to cardiology. I wasn't surprised that the number was low. I would say that I was expecting it to be low. That's just often what we end up seeing in therapies that require an invasive approach. It takes a certain bar for those patients to get referred on. Although, I will say it was even a little bit lower than I was expecting. Gotcha. Dr. Stambler, your thoughts? In general, I agree with Dr. Pokorney. In my clinical practice, I think it's about 1/3 of patients who go ahead with an ablation. Among the three strategies I outlined, watch and wait, chronic medical therapy or ablation, about 1/3 decide for themselves that it makes sense for them. Again, when you consider an invasive, although potentially curable procedure for SVT, many patients are not particularly inclined to undergo an invasive procedure and would prefer a medical treatment option. The 15% is a bit lower, as Sean indicated. I would've guessed 20%-25% in advance. In my own clinical practice, it's only about 1/3 of patients who make it to me with PSVT agree to undergo an ablation. Just by way of anecdotal experience, you know, I've participated in the phase II and phase III clinical trials. We had really no difficulty recruiting patients in the sense that patients were eager to participate in these clinical trials with etripamil, even recognizing that they might get a placebo. We approached patients, and they were very interested in this option. Dr. Stambler and Dr. Pokorney, thank you for the answers. Maybe we'll go to some of the questions that are coming in on the chat before we open the line. We got one from Leland Gershell here. Maybe I'll take a stab at this and ask my colleagues for any help if I miss it or don't answer it fully. Questions along the lines of what plasma concentration is etripamil essentially at the target saturation, and to what extent can you expect the higher peak after this potential second dose to enable conversion? It's a great question, Leland, and we did just come out just a month or so ago at ACC with some PK data, updated PK data around that happened to be around the study where we were trying to evaluate ethnic differences between people of Japanese and non-Japanese descent. Some of those PK is in there, but we will be getting out a full manuscript shortly. To answer your question directly, probably in the range of about 180 ng/mL is where we max out. For etripamil, that's at 140 mg, 180 ng/mL for 140 mg. My colleagues will correct me. We do see dose proportionality all the way up to 140 mg. We are dealing with quite a bit of issues with regard to really the volume of the drug in the nose is something we think about quite often and whether we're overwhelming the nose with volumes. When you ask about the repeat dose, though, and trying to improve Cmax there, we do think of it as being higher, as we explained when we showed the representative at 30 mg, at the 35 mg dose. Let's put it that way. We do think it will be higher, but we haven't gone and disclosed publicly with how much we think it's based on modeling. We are in the process of doing those studies, and we'll include it in the NDA. I'd rather pivot to how, you know, how did we come up with the repeat dose administration, and why do we think it'll be giving extra efficacy? The first component is we actually did wanna be very careful about safety. As Dr. Stambler had mentioned, safety is a hallmark of what we wanna deliver here with this molecule. If you recall, in the phase II study, there were some drops in blood pressure at the higher doses. They came in at around five minutes and lasted for up to 10 minutes. The idea of giving a repeat dose at 10 minutes, we believe protects the safety profile of the drug, and any additional efficacy would be better, even if it's a small increase in Cmax. The other thing we think about is there's variability within the actual tachycardia itself. Some of them could be more difficult to break than others, regardless of plasma concentration, if you will. We thought that having that second impact on the AV node, second prolongation of the PR interval would allow for a chance to break those more difficult tachycardias, if you will. That was the rationale behind the repeat dose administration rather than simply increasing, you know, from 70 mg to 140 mg, for example. Maybe, is there any other questions? Yeah. Maybe direct this one to Lorenz. This question is, why is the healthcare cost lower in age less than 65-year-old patients versus greater than 65-year-old patients? I think you meant the other way around, why is the increase- Sorry. Greater than 65 year old patients. Basically, the older patients had less of an increase in cost. That's actually a simple answer. There are two components to that. One is, it won't be a surprise to anyone that Medicare reimburses at lower rates than commercial insurers. When you look at dollars, you're gonna have a lower reimbursement rate for the same procedure. Secondly, Dr. Pokorney mentioned that 15% of patients get an ablation, but he also showed that it skews younger. Younger patients have a higher rate of ablation. Dr. Pokorney in the numbers actually showed that the under 65 had about a 14% ablation in the window that he studied, whereas the elderly, the over 65, had a 3% rate. Less ablation equals less cost, too. It's both a utilization and a dollar difference that leads to that difference in total. Okay. We got another question here from Patrick Trucchio at H.C. Wainwright. Can you discuss the data generated to date regarding the reduction in emergency room visits? How do you view the potential for etripamil to reduce emergency department visits? How important is this potential in terms of commercial uptake if etripamil is approved, sorry? Lorenz, do you wanna start with that, and then I'll offer to Dr. Pokorney? Yeah. Obviously anything that reduces healthcare resource utilization and cost is important. It's disproportionately important to payers, but it's not unimportant to patients. You heard me say in the video that patients don't like to go to the emergency department, and they would do a lot to try to avoid that. Physicians also tell us, and I've asked Dr. Stambler and Dr. Pokorney, you know, for a non-life-threatening condition, do we really want these patients seeking care in an emergency department when there are other patients there that perhaps have greater needs? I'll ask that question in a minute. The short answer is, it is important. It's not the most important characteristic of the profile. The most important thing is just terminating these episodes quickly and with a rapid onset and the other things I've mentioned earlier. The emergency department piece of it would be a nice additional attribute, and it certainly would be something in our value proposition as we approach payers for reimbursement. Let me ask Dr. Stambler and then Dr. Pokorney your view on, you know, patients that habitually go to the emergency department or often go to the emergency department to treat these episodes. Yeah. I mean, patients don't want to have to go to the emergency room if they don't have to. In addition to which, there are many patients in my practice who live far away from emergency rooms, especially in rural areas where they might be an hour or more away from the emergency room. Yes, the reduction in emergency room visits, I think, is certainly very important, certainly very meaningful. In the pre-specified analysis in part one, after 156 events, we did see a numeric reduction by 50% i n the need for emergency room visits in etripamil versus placebo-based patients. If that didn't reach statistical significance, mostly I think because of the sample size. We're hoping and expecting to see more data in the future in RAPID, which is a well-designed, well-powered trial, and we may be able to fully address that question about emergency room visits. Thank you. Then maybe Dr. Pokorney, if we think about this idea of PSVT being non-life-threatening disease and patients having to go to the ED versus those that have a stroke or a heart attack. How do you think about when you get an inbound from a patient saying, "I'm in an episode, it won't stop." How do you think about instructing that patient to go to the emergency department versus some of them might have chest pain or other conditions that you would frequently encounter? Yeah. I think it's an important question. For all the reasons that Dr. Stambler mentioned, you know, in addition to the patients not wanting to go to the emergency department, I don't want them to go to the emergency department. The goal is always keeping our patients out of the emergency department. I think that, you know, my patients with ventricular tachycardia, those patients, you know, end up having to go into the emergency department. Unfortunately, patients with sustained PSVT also often end up having to go to the emergency department because we don't have another option to treat them at home. If patients have AFib with RVR, I can at least adjust some of their heart rate control medications and I have some degree of confidence that I'll be able to control their heart rate and their symptoms. That's less the case with PSVT, where I really have very little in the way of options. We already talked about earlier how neither Dr. Stambler nor myself really feel that pill-in-the-pocket strategies are effective ways to control this. You know, I think it's a source of frustration for providers and patients that these patients oftentimes end up having to go to the emergency department because, you know, we and the patients themselves feel helpless in terms of what else we can do to offer them other than vagal maneuvers, which again, frequently don't work. That's why I do think that etripamil has such an important place in the marketplace. It's really gonna be critical to have something to offer these patients to prevent these emergency department visits. I think that, you know, in addition to what Dr. Stambler said earlier about things that he's excited to see from upcoming clinical trial data. I think that in addition to that, it's as well preventing emergency department visits. Because I really think that that's a critical issue as well as seeing how the symptom burden is affected by the dosage of etripamil in terminating these arrhythmias sooner. Because I think, you know, I presented earlier some of the patient-reported outcomes data, but there'll be a lot more symptom data that'll be available and be really exciting to see from the clinical trials. I might also add that, there are patients who really prefer to avoid the current standard treatment option in the emergency room, which is IV adenosine. IV adenosine is the first-line treatment, given rapidly. It produces some very disconcerting symptoms, that patients really desire to avoid. Patients feel like they're about to die almost. I have many patients who say, "I'll do anything to avoid that, IV adenosine medication." Therefore, I think, the tolerability of this is, very acceptable, of etripamil and actually quite enticing for patients. Thank you both. Maybe I'll ask the operator. We have quite a few questions coming on the chat, but I do know that there are people on the line. Operator, if you could open up the line, and maybe we could take some questions from those that are listening in and wanna ask them directly. Yes. Once again, that is star one to ask a question. We'll take our first question from Patrick Trucchio from H.C. Wainwright. Your line is open. Hi. Good afternoon, and congrats on all the progress. I have a follow-up question for Dr. Stambler and as well for the Milestone team. In the RAPID program, I'm wondering if there's an assumption for how many patients would be expected to administer a second dose, and how is that decision, you know, to administer the second dose being decided or conducted? Is the patient solely deciding when this second dose is administered, or is there some guidance on when and how to do so? Yeah. Let me start out. I guess there's three parts to that question. The last part is the easiest to answer, which is, it's patient determined. Patients are instructed, educated, that if their typical PSVT symptoms persist after 10 minutes, they should give themselves the second dose. It's patient self-determined and self-administered. The other two parts of the question, which I'm forgetting, and my apologies, about how it was decided. Could you just repeat the other two parts? Yeah. Just, is there an assumption of how many or what proportion of patients would be expected to administer the second dose? And then I just- Yes. You know, how that decision is being kind of evaluated. If you look at the curve. I don't know if we can put the slides back up. One dose in part one, 10 minutes. I think my recollection is the conversion rates with etripamil were about 30% in that range after 10 minutes. One would expect that, 180 events, 1:1 randomization, so at least 70% of the 90 patients would be, my rough math would suggest, would probably give themselves a second dose. Got it. Maybe know where the other Milestone folks could. Yeah. Yeah, no, I think that's on target. You know, the number you quoted, Dr. Stambler, 30% of etripamil patients convert, and given that half of the patients you would suspect would be on etripamil, that maybe 70% of the etripamil patients would take the second dose. Placebo is not doing as well, right? I think only 10% convert. So you would think more placebo patients might take the second dose. The long and short of it is we are expecting the majority, some 70%+ to take the two doses. That's great for the study because then we get a picture of the safety of the repeat dose in the at-home setting, which is ideally what we're looking for to eventually move to an NDA filing. Right. Yep. That's helpful. Then just maybe one follow-up for Dr. Pokorney. I'm wondering if in your research, what proportion of the patients would be anticipated to self-manage or self-treat PSVT? If there is a severity of an episode or threshold at which the patient would be expected to self-treat, you know, versus not treat or versus going to the emergency room. Yeah. I think those are two excellent questions. You know, one of the challenges of working., a lot of the work that we've done has been in claims data. In claims data, it can be more difficult to tease out exactly who is performing the management of these patients and all the different providers that are really seeing them. I think that there is the ability to use NPI numbers and other things to dig into some of those issues. You know, we've talked about doing that as future research follow-up studies. I would say that clinically, my impression of this is that the majority of these patients are not managed by electrophysiologists or even cardiologists, and it's probably less than 50% of these patients that make it on to cardiologists at all. You know, again, to me, one of the important aspects of this research that we're doing and I think one of the benefits to the clinical community that will come out of the commercialization of etripamil is an awareness of the disease state, and hopefully the ability to more accurately identify these patients and diagnose these patients. You know, we see this all the time in clinical practice where patients get to us eventually, a cardiologist, an electrophysiologist, and they've seen, you know, five different providers over the last two years, and they've always been told that it was just anxiety or something else that they were dealing with and it wasn't anything that needed to be treated or managed. Again, we're hoping that by getting more of this research out, we'll continue to highlight the prevalence of the disease so that more people or more providers are aware we are diagnosing a large portion of these patients. I think right now it's a small portion of patients that are ultimately getting referred and referred on to electrophysiologists, which is partly why the ablation rate is low. I think it's probably about 50% of these SVT patients that end up making it to, you know, cardiologists. In terms of the question around symptom burden, again, this is where I think that we don't have a lot of data. I mean, there's not a lot of patient-reported outcomes data available. The data set that I presented to you is really the first one that I've seen around the issue of SVT and symptom management. I think that it's another area where we need to make sure to get a better understanding of. I think that, again, as Dr. Stambler said, too, clinically, when we're talking to these patients, you know, we think that in general, an episode of 30 minutes is the time point when most patients, you know, become frustrated and become more fearful, to be honest, that the episode is gonna be ongoing and continue to sustain. We think that episodes that are moderate or just severe in terms of symptom burden to the patients and duration burden of 30 minutes are the time point when these patients really want treatment. Yeah. That's helpful. Thank you very much. All right. Thank you, Patrick, for the questions. Operator, do you have any others online or? It appears we have no further questions at this time. Okay, great. Well, I think we're getting towards the end here. Maybe we could come back to some of these questions that are in the queue here on the chat. Amit, do you have anything? Absolutely. The next one is: Among those patients presenting to emergency departments with PSVT episodes, what fraction are mid- and post-op patients? Presumably, they are on a monitored unit. Are they typically discharged the next day? Lorenz? I mean, I can quickly summarize what we've seen from some of the claims analyses, but I'd then ask Dr. Stambler and Pokorney, who routinely admit these patients what their experience is. The broad data seems to suggest that the minority of patients who present in the ED with symptoms of SVT ultimately converted, a ctually get admitted, but it's a big minority. It's like 30%-40%, meaning they get admitted. Majority of patients present at the ED nationally and then are discharged. We know that north of 150,000 times a year according to HCUP data. Then a subportion of those, roughly 30%-40% once they're admitted to the ED are actually then admitted for their PSVT. I don't know, Dr. Pokorney or Dr. Stambler, if you have any additional comments on that. Yeah. I would say that there's a number of reasons that these patients get admitted, and I'd say that the numbers that you're quoting there, Lorenz, seem pretty accurate. That again, once patients get to the emergency department, you know, especially when they're complaining of chest pain and some of these other things, lab work starts getting drawn. They start evaluating other factors, and there can be sort of downstream effects of the episode of SVT that lead the emergency department to be concerned and require, you know, admission and further workup from their perspective. I would say that the vast majority of those patients that get admitted, get admitted for observation overnight. They sort of get these underlying conditions, such as making sure that patients aren't having a heart attack. They get those ruled out, and they mostly end up going home the next day. Now some of these patients, if they've come into the emergency department a number of times, may be admitted and ultimately, you know, get an ablation procedure while they're in the hospital, and those patients may have, you know, a two or three day stay. That would be the minority of the minority. you know, among those 30% of patients that get admitted, it would be a small portion of those that stay for longer than an overnight visit. Great. Thank you. Another question. Of diagnosed patients with PSVT seen by a cardiologist at any time, what percent are likely to seek an ablation in the next one to two years? Sorry. Could we read that again? There was some subtlety to that that I wanna make sure I understand. Of diagnosed patients with PSVT seen by a cardiologist at any time, what percent are likely to seek an ablation in the next one to two years? Yeah. Dr. Pokorney, you can describe the results that you showed that were the 15%. The majority of those are seen by cardiologists, and then I can make a comment on the broader timeframe. Would you remind the group? Yeah. I think that's absolutely right. I think that probably those numbers—I really think those numbers are accurate that we represented. I think it's about 15% of patients that see a cardiologist end up getting an ablation procedure. You know, you heard Dr. Stambler say that in his practice about 1/3 of patients, about 30% of patients that see an electrophysiologist go on to get an ablation procedure. I think that it ends up being the minority of patients, again, for a number of reasons. Oftentimes patients are hesitant to pursue an invasive procedure, as we talked about earlier. It ends up being the sizable minority of patients that go on to get an ablation even that see cardiologists. Thank you. The next question is on commercial preparation. Can you discuss how you think about the commercial launch and ramp up with the understanding that the uptake will depend on outcomes from RAPID and safety trials? How quick of an uptake do you expect? That's a big question, isn't it? First, I would remind folks that one of the attractiveness or attractive characteristics of treating patients with PSVT with this type of an intervention is, as we've been saying all along, it's all about cardiology. The majority of these patients are identified, managed, treated by cardiology. From a commercial lens, that's what we call a focused call point. We can interact with, educate, you know, 18,000-20,000 cardiologists with a sales force that we can afford to deploy 150-200 sales representatives. Then that would allow us to generate about 60% of the revenue opportunity that's represented by etripamil. That allows us to, in an economic way, deploy our resources and gain uptake and achieve a break even within a reasonable timeframe for our company launching its first drug so that our, you know, investors are also happy with the performance. In terms of speculating on the actual uptake, that has so many other factors in it and more and more nowadays also payer uptake, you know, commercial payers, Medicare payers, the review cycles and then pricing strategy and all that. I wouldn't speculate on a specific uptake curve, but I can give you an analogy given this is symptomatic disease, and you look at other disease states, pain and others. You know, uptakes for new entities where there's significant unmet need is not trivial. There's a decent uptake curve given that patients that are symptomatic, in this case episodically symptomatic but have symptomatic disease, a decent subset are often looking for a new way to treat it. You can see decent uptake again compared to something that's an asymptomatic disease, maybe a preventive condition in cardiology where you're taking a tablet to prevent something, but you really don't feel any different. Okay. We have enough for one more question. Yep. One last question here. Can you discuss the status of NODE-303, the safety program, and what the expectations would be around this trial and when you expect top-line data? Sure. Maybe characterize NODE-303 again for the audience. NODE-303 is an open-label safety study, and it's kind of designed without any particular sizing in place at the moment. It is designed to fill out whatever else is needed from a safety perspective to be able to deliver an NDA filing and a filing for the European regulators. Maybe I'll talk about the process rather than give the specifics of the size, since there really is none at the moment. Our plan is to, once we receive top-line data from RAPID in the middle of the second half of this year and can digest that, both safety and efficacy, we'll be prepared to go to the FDA and have a discussion about an NDA filing and what the overall size of the safety data set would be. As we approach that time, we'll probably come out with guidance to the street as to rough estimates on an NDA filing with the caveat that it will be based on whatever that discussion with the FDA results in. It's logical to think that should the repeat dose administration look like or be similar to the single dose administration, we would require less safety data because they would obviously bridge both. If they're dramatically different, then the FDA may request us to have more of the repeat dose administration, and NODE-303 would be open and stay open to deliver that amount of safety data. Our expectations are based on data that is being generated as we speak and will be generated through the RAPID trial that comes out in the middle of next year. We'll come to the street with more definitive plans after that. Listen, I think we're at the end here. I really want to thank everyone for joining us today for this event. This is our first key opinion leader event, and we'll digest how this went and get feedback and look forward to advancing the field and educating everyone in future events should we find these are useful. Of course, I wanna thank Drs. Stambler and Pokorney for joining us today and sharing their expertise both with regards to their practice and what the field looks like. Again, I wish everyone a great rest of the day. Thank you so much.