Good day, ladies and gentlemen, and welcome to the Milestone Pharmaceuticals virtual key opinion leaders call. As a reminder, this call is being recorded. I would now like to turn the conference over to Joseph Oliveto, President and CEO of Milestone Pharmaceuticals. Please go ahead. Thank you, Betsy, and good morning, everyone. Thank you for taking the time out to join us today. As a reminder, a slide webcast accompanying today's remarks is available on our website at milestonepharma.com. During today's call, we will be making forward-looking statements, so we'll direct you to our SEC filings for a full disclosure of our risk factors. Joining me today, making prepared remarks, will be Dr. David Bharucha, our Chief Medical Officer. Additionally, we are honored to be joined by two leading cardiac electrophysiologists and atrial fibrillation experts. First, I'd like to welcome Dr. Paul Dorian, Professor of Medicine and Pharmacology at the University of Toronto and Staff Cardiac Electrophysiologist at St. Michael's Hospital. Additionally, we are joined by Dr. Jonathan P. Piccini, Professor of Medicine and Population Medicine and Director of Cardiac Electrophysiology at Duke University School of Medicine. I'd like to thank both of them for being on today's call with us. During the Q&A portion of today's call, we will be joined by Amit Hasija, our Chief Financial Officer, and Lorenz Muller, our Chief Commercial Officer. I'll now provide a brief overview of the agenda for today's call. In just a moment, David will provide a brief overview of atrial fibrillation with rapid ventricular rate and the characterization of etripamil, our lead investigational product. We will then turn the call over to Dr. Dorian for a review of promising data from a subset of patients experiencing AFib with RVR from our NODE-303 study, which we recently presented at Heart Rhythm 2023. As a reminder, the open-label phase III NODE-303 global safety study sought to evaluate etripamil in patients with paroxysmal supraventricular tachycardia, or PSVT. We estimate that approximately 20% of PSVT population also has atrial fibrillation. It's not surprising that some patients with PSVT who were entered into the study ended up treating an attack of AFib with rapid rate. These data represent the first direct clinical evidence of the impact of etripamil on heart rate in patients experiencing AFib with RVR. Following Dr. Dorian's remarks, we will turn the call over to Dr. Piccini to provide his additional perspectives on these data and the potential use case of etripamil in AFib with RVR. We will close out today's prepared remarks with an overview of our ongoing program for etripamil and atrial fibrillation with rapid rate and highlight a few key next steps. At the conclusion, we'll be opening the call for questions. Before turning the call over to David, I'd like to provide a brief overview of Milestone. At Milestone, we are committed to developing and commercializing innovative cardiovascular medicines. Our two main arrhythmias of focus are PSVT and atrial fibrillation with rapid rate, both of which are common heart conditions with a high burden on patients and on the healthcare system. We are targeting these conditions with etripamil, our novel calcium channel blocker nasal spray. Etripamil has been designed and developed to be a fast-acting, well-tolerated, portable, and on-demand treatment option to give patients ability to self-manage their conditions. In October of 2022, we announced positive results from our phase III RAPID trial evaluating etripamil in PSVT, and we expect to submit an NDA to the FDA for this indication in the third quarter of this year. We believe AFib with rapid ventricular rate represents an opportunity to expand the market for etripamil, and we look forward to discussing this further in today's call. We are currently evaluating etripamil in patients experiencing AFib with RVR in our ongoing phase II ReVeRA study, which we expect to report top-line data from in the second half of this year. We'll discuss this trial in greater detail on today's call. With that, I'll now turn the call over to David for some more background on AFib- RVR and etripamil. David? Yeah. Thank you, Joe, and thank you all for joining us today. If we could go to the next slide 7, please. Over the next several slides, I'll provide a context for Dr. Dorian's and Dr. Piccini's upcoming presentation of data and their observations. Particularly, I'll give background on, one, atrial fibrillation and problems which result, particularly when this cardiac arrhythmia occurs with symptomatically rapid heart rates. Two, currently available treatments for control of AFib and unfortunately, the limitations of these currently available treatments. Three, I'll describe some basic physiology as to how acutely administered drugs can provide a potential opportunity for AFib treatment. Last, I'll provide some background on etripamil, the drug itself, as Joe mentioned, Milestone's lead asset. On the slide in front of us, this describes atrial fibrillation with a rapid ventricular rate, or, as we say, AFib- RVR. This is a heart arrhythmia in which patients experience markedly symptomatic episodes of increased heart rate that can be incredibly disruptive to their lives. Some of the most commonly reported symptoms, bulleted here, include heart palpitations, fatigue, chest pain, lightheadedness, and difficulty breathing. These episodes can occur at any time, leaving patients with uncertainty between episodes and feeling like they have little control over their condition. Moving ahead to slide 8, we outline that currently available therapies for managing acute attacks of AFib- RVR are burdensome, and these current therapies are often limited to the emergency department setting. For patients and family members, the emergency room can be a difficult and time-consuming experience, and obviously, it's unfortunately very costly. For context, the Healthcare Cost and Utilization Project, a publicly available database, has estimated there being approximately 800,000 annual emergency department visits or hospitalizations in the United States each year for atrial fibrillation. As well, that estimate of 800,000 annual visits was made in 2016. As I'll show in a moment, all indications are that those numbers have since increased substantially. Overall, it's clear that there is, and there will be, a need for a simple, fast-acting treatment that patients can utilize outside of the emergency care setting. On the next slide, as I just mentioned, AFib represents a growing area of concern in the United States and worldwide. This data summary, which is about to come up, shows AFib prevalence in the U.S. on the Y-axis and time on the X-axis. As one moves up the graph line from left to right, there's a clear illustration of the rapid growth in the incidence of AFib over several decades, and as well, the strong expectation of further growth in atrial fibrillation. As illustrated by an extrapolation of this line, there's going to be an expected annual prevalence of 8-10 million by 2025. Furthermore, the CDC has published further projections of an AFib prevalence of 12 million Americans by 2030, underscoring there being a large patient population inevitably with significant medical needs. Thus, there is, and there will be even more in the future, an unmet need in AFib- RVR that I'll describe on the next slide. The slide that you're about to see, number 10, summarizes the point that available care for AFib- RVR has significant limitations. When considering current treatment options for AFib- RVR and when focusing on the left column of this slide, it is important to recognize that most patients receiving chronic medications still experience acute events despite that prior therapy. For example, current oral therapies for rate control, calcium channel blockers, which we abbreviate as CCBs, and beta blockers, or oral therapies for rhythm control, such as cardiac anti-arrhythmic drugs. None of these prevent breakthrough episodes, or as Joe phrased it, attacks of AFib- RVR. Patients can opt for a catheter ablation, an invasive approach. However, efficacy and duration of efficacy for AFib ablations varies depending on patient characteristics. Focusing on the right column of the slide, to reiterate, for the acute treatment of AFib- RVR episodes, oral drugs for rate control or rhythm control can be used, but they all have problematically delayed response times and do not routinely deliver effective rate control. Intravenous treatments such as CCBs or an electrical DC cardioversion require an emergency department or hospital visit. We believe that etripamil, as a rapid-acting, self-administered drug, could potentially overcome some of the shortfalls that I just described of existing therapies, either as a standalone treatment or as a bridge to additional treatment options. Let's talk on the next slide about why acutely acting AV nodal drugs such as intravenous CCBs can serve as a meaningful intervention for these patients. On the right-hand side of the slide, there are points that are made, and I'm on the right-hand side of this slide. Intravenous CCBs have been shown to slow and to attenuate conduction signals from the atria to the ventricles through the AV node. This results in a rapid reduction in the ventricular heart rate, which is the rate of the heart's lower or main pumping chambers. Such a slowing controls heart rate and reduces symptoms. Etripamil, which is a CCB and a rapidly acting CCB, has the potential to provide the same rate slowing and symptom control that I just described, but without the need for intravenous administration or for a costly ED trip. On the next slide, I'll summarize some further details of this drug. Etripamil is a new chemical entity. We have developed the drug to be a fast-acting nasal spray, and it has a rapid onset of action with a CMAX of approximately seven minutes following dosing. As shown in the pharmacokinetics plot in the upper right panel, the drug has a very rapid onset. This particular pharmacokinetics plot, shown in the upper right panel, is very much akin to what would be observed with an intravenous administration. However, the drug here has been delivered non-invasively via nasal spray. As well, the drug's impact on the critical AV node part of the heart is shown in the lower right panel with the light blue line showing this substantial impact, namely PR interval prolongation on the ECG, concurrently with the quickly increasing etripamil levels. In a moment, Dr. Dorian will also be showing this graph of PR prolongation as context for the data that he will be presenting. This concludes our overview of AFib with a rapid ventricular rate and of etripamil. I'd like to now ask Dr. Paul Dorian to summarize the phase III NODE-303 sub-study presented two days ago at the Heart Rhythm Society 2023 annual meeting, titled "The effect of etripamil nasal spray on ventricular rate in patients experiencing symptomatic atrial fibrillation." These data represent the first clinical evidence of the impact of etripamil directly in patients experiencing AFib -RVR. With that, I'll turn the call over to Dr. Dorian. Paul? Good morning, everyone. Thank you very much. You have in front of you slide 13, which is the title slide for the presentation I'm going to make, entitled "Review of AFib- RVR Data," presented just a couple of days ago in New Orleans at the HRS 2023 meeting. The next slide is just a title slide from our abstract presentation. You can see that there's a number of colleagues who were participants in this particular research study from across North America and Europe and other countries. The presentation was entitled "Effect of etripamil Nasal Spray on Ventricular Rate in Patients Experiencing Symptomatic Atrial Fibrillation." Just for the record, these are identical in format to the slides that were actually presented at this international meeting of experts on cardiology and cardiac electrophysiology. As background, as you have heard, atrial fibrillation is the most common sustained rhythm disturbance we find worldwide, North America and worldwide. Its prevalence is increasing because of both increasing aging population as well as the risk factors for atrial fibrillation, including obesity, inactivity, diabetes, hypertension, are increasingly prevalent, unfortunately, in our society. We know that when patients develop atrial fibrillation, almost always outside of hospital, that they feel, in most cases, very unwell, and there is a general understanding that the cause of the symptoms is because of the rapid and irregular heart rate as a consequence of atrial fibrillation. We know that even when the strategy employed is to try to get rid of this rhythm disturbance, the immediate initial treatment is generally to try to slow the heart rate until such time as the normal rhythm either spontaneously recurs or it's made to terminate with drug therapy or cardioversion therapy. Slide number 16 illustrates the information that you have just heard from Dr. Bharucha, and it basically reminds us that the pharmacodynamic effect, in other words, the effect of the drug on heart tissue, as opposed to the presence of drug in the blood, which is in the purple. The effect of the drug on heart tissue in light blue is expected to last approximately 60-90 minutes, although the effect is greatest in the first 10-20 minutes after drug administration. There are no available drugs that can be used by patients to be administered or self-administered that work this quickly and this effectively. There are drugs that they can take by mouth, including drugs with a similar chemical profile to etripamil, but these take somewhere between 30 and 60 minutes to begin to take effect, and the onset of effect is much more gradual. We have here in the light blue a drug that is expected to work within about five to 10 minutes and whose effect is expected to last somewhere between 30 and 60 minutes. Slide number 17 tells us a little bit about how the trial was designed and how it came about. Again, just to remind all of us, the original research study was designed to investigate the effect of etripamil on a different arrhythmia, not atrial fibrillation. This is called SVT, which is a common heart rhythm disturbance associated with very rapid heart rates. The drug was successful in its attempt to prove that the drug does work in terminating SVT. That was the primary trial. As it turned out, a little bit unexpectedly perhaps, a minority of patients, you'll see in a minute the data, developed a different rhythm disturbance from originally anticipated in this SVT trial, and this is atrial fibrillation. We know this because all patients, as part of the trial, self-applied a heart rhythm monitor at the first onset of symptoms before they actually took the medication. That was the design of the trial. After the fact, when we looked at all of the data, we found that in a small number of patients, but not trivial, 21 patients, or 21 episodes, excuse me, in 18 patients actually had this other rhythm than anticipated, which is called atrial fibrillation with a rapid ventricular rate. We took advantage of the fact that these patients then self-administered etripamil according to the study protocol, and we could see the result of the administration of etripamil on atrial fibrillation. There are some limitations to this analysis, which is, I suppose, proof of concept. It wasn't designed this way, as you heard. The limitations are that we don't know exactly how long after the monitor was applied that the patients actually self-administered the drug. They were instructed to do this within a few minutes, and the best information we have is that the timing of drug administration was, in general, between five and eight minutes after the onset of arrhythmias, but we don't know exactly. Second limitation of this is that although we are certain that the arrhythmia being treated in this particular presentation is in fact atrial fibrillation, the kinds of patients who develop SVT and atrial fibrillation may not be identical to patients who develop atrial fibrillation by itself. Slide number 18 is a summary of the results. Not unexpectedly, this is what we generally observe in clinical practice. The average heart rate was quite fast, about 130 beats per minute. We know from experience that rates faster than 100-110 beats per minute tend to be quite bothersome. This is pretty much average for patients coming to the emergency department with acute onset atrial fibrillation, generally with severe symptoms. We had 21 episodes analyzed, and 17 of these episodes, the vast majority, had a fast heart rate of greater than 110. All patients had some degree of symptoms, which is why they applied the monitor in the first instance. The mean heart rate in these episodes was 138 beats per minute, the ones that were slightly more rapid. Of the total episodes, some of them, as would be expected, stopped by themselves 60 minutes following etripamil administration, and Professor Piccini will talk about this phenomenon in his presentation. We did see slowing of heart rate, as you'll see in a minute in detail. The slowing of heart rate was very rapid after the administration of the drug and lasted approximately 60 beats per minute. We had, as would be expected from the known pharmacology of this drug, a reduction of approximately 28 beats per minute. This is roughly 25%-30% reduction at the 22 minutes, which is around the time of peak effect. This effect persisted, although waned to some degree, at 60 minutes. There were no severe adverse effects from this drug, as has been previously shown in other research studies. The most common treatment-related side effect was related to the irritation in the nose, but there were no serious side effects reported in this study. Slide number 19 is the figure or pictorial representation of our data. You can see on the far left, at time zero, the Y-axis here represents the delta change in heart rate averaged over the patients. So this is not in beats per minute. This is the reduction in average heart rate as a function of time in the beats per minute. You can see at time zero, of course, we're starting at no reduction. By approximately 10 minutes, there's an average 20 beats per minute reduction in heart rate. By 22 minutes, there is approximately a 28 or 29 beats per minute reduction in heart rate. The curve is a little bit unstable because of inter-patient variability. As you can see, there is a slight waning of effect but persistent drug effect, the desirable effect of slowing heart rate, which goes on up to about 60 minutes after drug administration. Slide number 20 is our conclusions. We know that from the study, patients experiencing episodes of atrial fibrillation and rapid ventricular response, self-administration of etripamil, this investigational new drug, resulted in ventricular rate that sustained over 60 minutes. As we would've expected, the timing of response aligns with the known pharmacological profile of the drug. We believed in our presentation, and continue to believe, that these findings are clinically potentially important but clearly warrant further study and do suggest a potential role for the drug in the acute treatment of rapid ventricular rate in patients with atrial fibrillation. Thank you very much for your attention. Thank you, Paul, for both your presentation and all your thoughtful observations. Now I'd like to turn the call over to Dr. Jonathan Piccini for his perspective on these data and for his perspective on a potential use for etripamil in AFib -RVR. John? Thank you, David. Just to review, we've heard about how big a problem atrial fibrillation is and the unmet need for therapies that can actively and quickly lower heart rate. You've also heard from Dr. Dorian about the post hoc analysis and findings of etripamil use in persons who are having episodes of atrial fibrillation with rapid ventricular response. In the next few minutes, I'm gonna integrate those data together and highlight how specifically etripamil might be used and potential use cases in different varied groups of individuals with atrial fibrillation in different clinical care settings and problems. If you'll follow on slide 22, there are many unmet needs within this overall broad need for rate-lowering medications that act very quickly. Regardless of how a patient is being managed, whether the patient is allowed to stay in AFib with an attempt to control their heart rate, or whether their care team is trying to keep them in normal rhythm and limit episodes of atrial fibrillation, all patients are susceptible to breakthrough episodes of atrial fibrillation with poorly controlled rate. Unfortunately, these episodes can be frequent, highly symptomatic, and burdensome, and disruptive. Many times, these persistent, uncontrolled, and bothersome symptoms lead patients to seek emergent care. Thus, current treatment of many of these attacks occurs in emergency departments across the world, and these visits are burdensome and costly, as Dr. Dorian has pointed out. This leads to an expensive and inefficient use of healthcare system resources. If patients actually were armed with a technique and method to arrest these episodes by lowering their heart rate and dramatically improving their symptoms, we could avoid a lot of excess healthcare utilization. Tying all these things together, the missing piece, if you will, is a simple, fast-acting, well-tolerated treatment that can be self-administered at home outside of the healthcare system and can reduce the burden of episodes, not only to patients, who are obviously the most important, but also to healthcare providers, healthcare systems, and other healthcare-related resources. If you go to slide 23, this is not a small problem. The lifetime risk of atrial fibrillation in the United States is between one in three and one in four. As you've already heard, the frequency of atrial fibrillation in the general population is expected to accelerate even more rapidly in the future. Just to give you some brief ballpark numbers, if you look on slide 24, we know in 2030, there are an estimated 10 million persons in the United States afflicted with atrial fibrillation by 2030. We know that in 2016, there were over 785,000 visits to the emergency room and hospital admissions for atrial fibrillation. It's estimated that by 2030, there will be 3-4 million patients who will require some treatment of AFib with rapid ventricular response during the course of the year. On slide 25, I just want to emphasize what the other speakers have alluded to, which is the very unique property of etripamil with a non-oral, non-IV and easily administered spray, which leads to a significant reduction in heart rate in about five to 10 minutes. Moreover, this effect is sustained for up to an hour. These timing data are critically important to understand how powerful an addition to the medical armamentarium etripamil can be for atrial fibrillation. In slide 26, we try to illustrate this paradigm. Consider a patient who has either suddenly develops an episode of atrial fibrillation or is staying in atrial fibrillation, and because of stress or acute illness, their atrial fibrillation rate suddenly spikes, say, to the 138 beats per minute we observed in the post hoc analysis of NODE. In the current situation, a patient would need to elect to do one of two things, generally. They would either take an oral agent which has been prescribed for them, and they would need to deal and tolerate with the symptoms for a long time, 30-60 minutes for sure before the oral medication would start to take effect. Its maximum effect may not even be achieved till later than that. During this time, they could be short of breath. They very likely have very rapid palpitations, uneasiness, and anxiety. even if they've had prior episodes and know that at some point they may subside, this is a very uncomfortable time for the patient. This patient is the patient highlighted in yellow. Many patients, however, cannot tolerate these symptoms at all or out of fear or concern, they go to the emergency room. that's a patient highlighted here in red. What etripamil gives us the opportunity to do is take the path and experience of the patient in blue. They have etripamil. They can administer the medications by themselves at home. They don't even need to contact their medical provider because they've already been instructed on its use. With five to 10 minutes, they get a significant decrease in their heart rate. They can avoid going to the emergency room. They can contact their medical care provider if needed in a much less urgent fashion, and potentially allow the opportunity for additional titrations, changes, or additional actions in a purely outpatient setting. To date, we've never had a therapy like etripamil that offers to change this very frequent paradigm that many of our patients find themselves in. Dr. Dorian and I have discussed this. This is one of the most frequent calls we get when we are on call on the weekend, is someone who has a very elevated heart rate and has significant symptoms with atrial fibrillation. At present, the only choices are an oral medication that takes a very long time to act or sending the patient to the emergency room. In slide 27, let me summarize again. There are several potential use cases of etripamil for atrial fibrillation complicated by rapid ventricular rates. It can provide acute standalone treatment for rate control and symptom control. It can serve as a bridge to longer-acting medications, including oral rate control agents or the administration of anti-arrhythmic drugs, so-called because they try to act and change the rhythm back to a normal rhythm. Use of etripamil surrounding periods of time where someone may be having more than normal events of AFib with RVR, including periods of time around ablation, but you could also imagine other medically stressful events, like recovery from surgery and other situations. Finally, really any time there's a need for acute control of heart rate without access to an IV or situations where that might be inconvenient. That could even include in ambulatory clinics where putting an IV in is time-consuming and often difficult. Again, to summarize, etripamil is a drug that is rapidly acting and self-administered outside of a medical setting, and these characteristics lead to its ability to solve an unmet need in many different patient and clinical scenarios. Thank you. Thank you, John, and thank you both, Paul and John. We really appreciate your perspectives on the data and your thoughts about needs for acutely administered treatments for AFib. Now, if you could go to the next slide, I'd like to direct our attention to Milestone's current etripamil program in AFib- RVR and our next R&D steps. On slide 29, you'll see an overview of our current ReVeRA study, a phase II double-blind randomized controlled trial of etripamil versus placebo in patients presenting to an ED, an emergency department, with AFib -RVR. The objective of this study is severalfold and is focused on how etripamil impacts ventricular rate in AFib. Specifically, one, by how much does the drug reduce the rate? Two, how quickly do we reduce the rate? And three, how long does that rate reduction last? I'm pleased to state, very pleased, that ReVeRA is now enrolling strongly, and we expect to be able to report top-line results in the second half of 2023. On slide 30, which we'll see in a moment, there's a summary of data demonstrating the effect of etripamil on the AV node to slow conduction. On the left panel, you'll see a tachycardia heart rate reduction during SVT, a plot of tachycardia rate reduction. Shown in green in this left panel are the patients who self-administered etripamil at home in response to symptoms of a rapid heart rate. Placebo control is in blue. This tachycardia heart rate reduction, the difference between the green and the blue, reflects etripamil's impact on the AV node during SVT and with a timing consistent with the known pharmacology of this drug. To emphasize, what's shown here in the left panel is that etripamil is reducing heart rate compared to placebo, and importantly, this reduction comes on quickly, within 10 minutes or so, and is maintained for the whole hour that we observe here. On the middle panel, we reiterate the findings from Dr. Dorian and colleagues' presentation that etripamil has been shown to reduce ventricular rate following self-administration in patients with AFib -RVR, and this reduction is apparently sustained for at least 60 minutes. On the right-hand panel, you'll see a descriptor of our current ReVeRA study. As I just mentioned, we expect to report top-line results in the second half of this year. We look forward to leveraging data from the ReVeRA study to inform the design of what we're planning for pivotal and registrational phase III AFib- RVR study. On the next slide, and to conclude today's remarks, I'd like to reiterate some key points that have been made. Number one, based on etripamil's known pharmacology and the reported data from our PSVT program, investigating the drug in atrial fibrillation with RVR is a rational next step for this asset. Two, recently released data directly from patients with AFib support the potential for etripamil's utility in the cardiac arrhythmia, atrial fibrillation. Three, to briefly summarize these data that Dr. Dorian presented for us, in patients experiencing episodes of AFib- RVR, self-administration of etripamil resulted in a reduction in the ventricular rate that was apparently sustained over 60 minutes. The timing of this response was aligned with the known pharmacokinetic profile of etripamil nasal spray. These findings warrant future study and suggest a role for the drug in the acute treatment of RVR in patients with atrial fibrillation. Next slide. Point number four, we believe, and we've heard today, that etripamil represents a potential opportunity to provide a clinical benefit to patients experiencing AFib- RVR as a standalone treatment or as a bridge to other treatment options. We've also heard that this represents a true opportunity to overcome limitations of currently available treatments for AFib -RVR. As has been mentioned, current treatments, unfortunately, are time-consuming, potentially expensive, fraught with delay, and can be an inefficient use of resources. What would be really helpful to patients and other stakeholders, and is currently missing, would be a simple, fast-acting treatment that could be self-administered at home. Such a treatment would provide an important opportunity to reduce the burden of episodes, trips to the ED, and calls to on-call physicians. To reiterate a very important point, there is a need here. As Dr. Piccini already pointed out, at least one in four Americans will have AFib in his or her lifetime. Points numbers five and six. As we look ahead to the next steps in the program, we are focused on completing enrollment in ReVeRA and sharing top-line results later this year. Furthermore, we are working with clinical trial investigators and key opinion leaders to align on a phase III program in this AFib indication. To go to slide 33, please. To reiterate, we appreciate the perspectives of Dr. Dorian and Dr. Piccini, and we look forward to continuing our evaluation of etripamil in AFib -RVR. With that, I'll turn the call back over to Joe Oliveto, Milestone CEO, for final comments and for Q&A. Joe? Thanks, David, and let me just reiterate my thanks to Dr. Dorian and Dr. Piccini for their comments and their time today. I'll ask Brendan to open up the line for any questions. We will now begin the question and answer session. To ask a question, you may press star then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question today comes from Ted Tenthoff with Piper Sandler. Please go ahead. Hey, thank you. Good morning, everyone. Can you hear me okay? We can, Ted. Great. Hey, Joe. Firstly, this was really compelling, really interesting initial proof of concept. I appreciate all the doctors' times and perspective. I have two kind of high-level questions. The first is, would this resolution of acute symptoms, would it actually have any impact on risk for stroke? In other words, do these patients is the higher risk of stroke that's associated with AFib during these atrial fibrillation events? My second question has to do with durability. Is AFib a condition where you take a patient out of fibrillation? Or could it simply either persist afterwards or reignite after etripamil wore off? Maybe those are unfair questions because of the data set we have so far, but I'm trying to understand that impact on the underlying disease. Thank you. Yeah. Thanks, Ted. I think, so two questions. Maybe I'll start the first one with Dr. Dorian to maybe comment on the resolution and the risk of stroke, and if there's higher risk when patients are in elevated rates. Then for the second question, maybe we'll start with Dr. Piccini and then go to Dr. Dorian after that for the durability question. Thanks. Thank you very much. This is Dr. Dorian. With respect to the risk of stroke, the risk of stroke is probably not directly related to the actual rate. So that we would expect the risk of stroke is the consequence of the atrial fibrillation itself, not necessarily the rate, although it certainly is possible that with a more rapid ventricular rate, there's lower blood pressure, there's other hemodynamic consequences. This is highly speculative. There's going to be more hemodynamic consequences of atrial fibrillation, which potentially indirectly could increase the risk of stroke. I think, at least from what is known today, all of these patients, however they're treated, if they're appropriate candidates for anticoagulation, would need to receive anticoagulation. This treatment is clearly for symptomatic reasons and not necessarily to prevent stroke. Although, obviously, if we can avoid hospital visits and other downstream events, that would be desirable. For sure. Yeah. Okay. Ted, with regard to your second question, with regard to the durability, are you asking in general about these events, or with these events with a drug like etripamil on board? What was- With a drug like etripamil. Maybe to clarify, etripamil is so successful at bringing patients out of PSVT. I'm wondering whether AFib is a similar thing, where sort of the heart has to be reset, the pacing or the beat has to be reset. I think the answer is yes, because of the underlying mechanism of the AV resolution. I just wanted to ask to make sure that that's mimicking what we're seeing there. Thanks. Okay. Dr. Piccini, maybe if you can comment on that. Yeah. Dr. Dorian. This is profoundly complicated, and we'll try and make it as simple as possible. There are different types of atrial fibrillation. Typically speaking, atrial fibrillation has a tendency to progress, where patients go from intermittent episodes of atrial fibrillation that stop on their own and allow the patient to go back into normal rhythm, to longer and longer episodes where patients progress to a point where they stay in atrial fibrillation unless something is done to get them out of it, like sedating them and applying a shock to restore normal rhythm. There's the first important point to your question is that there are different stages of atrial fibrillation, some that are intermittent and some that are sustained, and the patient stays in it for days and weeks. The second point is that there's two ways to manage atrial fibrillation. One is to try and keep the patient in normal rhythm all the time. Another way is if the patient has fewer symptoms or no symptoms, one can leave the patient in atrial fibrillation and just make sure that the heart rate is controlled, say, 80-90 beats per minute, no higher over a 24-hour period. It is important to note that etripamil is not what we consider an anti-arrhythmic agent or something that is expected to necessarily bring the patient out of atrial fibrillation. All patients, whether they're having intermittent AFib or they're in AFib all the time, are at risk for having attacks where they have AFib with high rates. That's where etripamil comes in, because it can calm the heart rate down quickly and effectively. I hope that makes sense. It's very helpful. Very, very helpful. Thank you so much for that answer. Thanks, Ted. Operator? As a reminder, if you would like to ask a question, please press star then one to enter the question queue. Your next question comes from Patrick Trucchio with H.C. Wainwright. Please go ahead. Thanks. Good morning and congrats on the data update. Just a couple of questions for the KOLs. Just earlier noted that the differences in patient population in NODE-303 of those with atrial fibrillation alone. I'm just wondering if you can discuss how the patients in the subgroup would compare to those patients solely with AFib and RVR, and if the response seen in the subgroup in NODE-303 would be expected to be representative. How the AFib with RVR patient group would be expected to respond to etripamil. Maybe we'll toss that one over to Dr. Dorian. Opinions on the difference between this subpopulation, which you would assume is comorbid with PSVT, versus if they were AFib alone. This is with respect to the effect of the drug in different patient populations. I think we would expect, knowing the pharmacology of the drug, to have a very similar effect in all patients when they have a rapid ventricular rate. It is true that in this subpopulation that we presented, the patients tend to be a little bit younger than the average patient in atrial fibrillation, and we know that ventricular response is somewhat related to age, so younger patients tend to have faster heart rates than older patients. You've heard that there's going to be, fairly soon, 10 million people in the United States with atrial fibrillation in a given year. Not all of these patients will have rapid ventricular rates. Probably a substantial minority will. The total patient population eligible for this treatment may be somewhat less than 10 million, largely younger patients of the type we saw in the sub-study of NODE that we presented. We can expect that any patient, regardless of age, if they develop a rapid ventricular rate, would respond in exactly the same way from the known pharmacology of the drug. That's helpful. Then can you discuss how long an AFib- RVR attack would be expected to last? If etripamil's expected duration of effect is 60-90 minutes, is that sufficient or would you expect the patient would have to redose at some point? If I may answer that. Yeah. Sorry. No, I was going to say, Dr. Dorian, if you could, and then maybe Dr. Piccini would love your thoughts on this as well after Dr. Dorian. Sure. Yeah. My apologies for cutting in. That's an excellent question. I think there's something very important that we need to know. The very substantial minority, perhaps up to half of these patients with intermittent atrial fibrillation, the episodes are destined to self-terminate. That self-termination often is within 30, 45, 60 minutes or two hours, let's say. It's within an hour or less or a little more than an hour. We would anticipate that in these patients, all they will need is short-term rate control. That is how we use currently somewhat ineffective and slow-to-act oral drugs for acute rate control. I tell my own patients, when you have acute atrial fibrillation with a rapid rate, take an oral medication understanding it's not going to work very quickly, and just hang out and see what happens over the next hour or two. In many of these patients, the arrhythmia will then stop spontaneously, and then they don't have to seek further immediate medical care. We obviously look after them days or weeks afterwards. In these types of situations, one would anticipate that the only treatment that would be needed is temporary rate control. The other use case would be in situations where the arrhythmia does not stop immediately. The immediate or almost immediate or rapid onset symptom relief would allow some time for other interventions to be applied. They might be oral medication for rate control, and they might, in some cases, be hospital visits for subsequent treatment. Dr. Piccini, how do you think about this? Yeah, I would completely agree. I think, if you think about another cardiovascular medication that we use intermittently is we use sublingual nitroglycerin for patients with chest pain and ischemic heart disease. Has a very active onset. Its effect doesn't last terribly long. I personally was very pleasantly surprised to see the data from NODE with action out to one hour. That's kind of an ideal. A drug that's going to give you action within minutes and lasts as long as an hour is really ideal. As Dr. Dorian pointed out, there's multiple options for the patients who have longer episodes, whether it's an oral medication or it's potentially another dose of etripamil. Those are things that we're going to need to sort out. The timing of effect is really ideal. I'd also want to point out that the nice thing about it is that sometimes in an attempt to rate control a patient, for patients who are extremely symptomatic, we may be very aggressive and then leave the patient with too low a heart rate. Because by the time the oral medication kicks in, they may be back into normal rhythm and their heart rate gets really low. Etripamil is also theoretically should reduce our vulnerability to that effect. My own suspicion with this is that when patients experience this new treatment mechanism, I think they're going to react to it very favorably. This will probably become a highly patient-centered form of therapy. That's helpful. Thank you so much. Thank you, Patrick. The next question comes from Rohan Mathur with Oppenheimer. Please go ahead. Hey, guys. Thanks for taking my question. Rohan Mathur speaking on behalf of Leland Gershell. I just wanted to ask, given the multiple treatment settings in which AFib- RVR and etripamil could be used in, which do you see as the most attractive, taking into account the drug's innovative profile and the various market opportunities that can be offered here? Thanks. Yeah. Maybe, Dr. Piccini, if you could start there, and Dr. Dorian, I would love to hear your views. I personally would love to hear also about maybe in the role of it in your rate control patients and your rhythm control patients, and how you think about the potential for etripamil. Just adding to Rohan's question. Dr. Piccini? Yeah. I guess the answer to this question kind of depends on whether you're a lumper or a splitter. All of the situations have in common that what they have in common is you're treating patients with acute elevations in rate due to AFib. I think you can kind of view this like an EpiPen for people with allergies. It's something that they know they have a condition that can be extremely bothersome. In the case of anaphylaxis, it's fatal. This may not be fatal, but it certainly could lead to an emergency department visit. I think patients having this available will develop reassurance. Again, for the patient who has these episodes. I would say the best use case, in my opinion, is the patient with atrial fibrillation who has intermittent or sustained episodes of AFib with high rate that currently has a short-acting medication, oral medication prescribed for that purpose. To give you a sense of how frequent that is, I run a electrophysiology clinic where 70% of my patients have atrial fibrillation. I would say the vast majority, probably 75% or more of those patients, currently have a prescription for an oral short-acting AV nodal blocking agent. In my clinic, the potential use case is up to 75% of all patients that I see for atrial fibrillation. I'm not sure if that answers your question optimally, but that's my gut reaction. Yes. Thank you. Thank you, John. Dr. Dorian, thoughts on your ideal patient, who you would first think about? Should etripamil be there for you? Thank you. I would just add to Dr. Piccini's excellent comments, the following observation. This is yet to be proven in clinical trials, but it's clearly been my observation. Many patients with atrial fibrillation anticipate that they're going to have highly symptomatic events, and this restricts their quality of life. Many of my patients don't like to travel, don't like to go on cruises, don't like to go on airplanes, and don't like to take long-distance trips because they're concerned that if they have the sudden onset of symptoms, particularly if they're not at home or they're far from hospitals, we can see many situations like this, that they will not have immediate relief available at hand. They tend to have kind of restricted lives in anticipation of future events. I think we can expect, this has certainly been my observation clinically, that if a patient has in their pocket, so to speak, an immediately effective treatment, this then allows them to undertake activities they otherwise would have been concerned about. Thank you, Dr. Dorian. Thank you, Rohan, for the question. This concludes our question and answer session. I would like to turn the conference back over for closing remarks. Well, again, I want to thank Dr. Dorian and Dr. Piccini for their time and their excellent thoughts today. Thank everyone for taking the time to listen in to the Milestone Key Opinion Leader Day, and I wish everyone a great rest of the day. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.