Good morning, everybody. Thank you for joining us at Milestone's corporate presentation. I am Athena Chin, an associate at TD Cowen. Joining us today, we have CEO of Milestone, Joe Oliveto, who will be giving a corporate presentation and update on their pipeline and really exciting etripamil PDUFA this month. Joe, please take it away.
Thanks a lot, Athena, and also thanks to the colleagues at Cowen for inviting us. We're always big fans of this conference, hoops and shoes included. Thanks so much. We do have two disclaimers today. CARDAMYST is a conditionally approved trade name for etripamil, but it is not yet approved. It is under review by the FDA with a PDUFA of March 27th. Of course, we will be making forward-looking statements. 2025 is really shaping up to be a potentially transformative year for Milestone with this PDUFA, and hopefully the approval on or before March 27th really allows us to take this drug, etripamil, that's been a labor of love for us through development to the market and really serve a lot of patients that are in need.
It also allows us to start building the commercial organization and realize all the opportunities that come with that. We are really super excited about it, and the majority of this presentation is focused on that approval and that launch. An approval in PSVT also opens the opportunity for our second indication with the same compound. It is in atrial fibrillation with rapid ventricular rate. The approval will enable what is called a supplemental NDA pathway. That is a pathway, a regulatory pathway with the FDA where you are allowed to leverage, if you will, the wealth of safety data that has been generated on the SVT program, over 2,000 patients' worth of safety data, to apply it to your second indication and allow for the potential for a single study approval in that second indication, which, again, is atrial fibrillation. Our plans are to start that study this year.
The team is working very hard and has reached agreement with the FDA on that study protocol. We will expect to start it in the second quarter, which is really shortly after the PDUFA date for PSVT. Obviously, AFib represents a much larger market and potential opportunity for etripamil, and we believe provides a nice extension for us once we are on the market for PSVT. I will say a word about the finances of the company up front and then close with that as well. We have in place already a royalty financing agreement with RTW. They are our largest, excuse me, investor. That royalty financing enables a $75 million Milestone payment upon approval. Our expectation is that funds, plus what is on the balance sheet at the time of approval, would enable runway into 2026, mid-2026.
We think of it as PDUFA plus about five quarters or so of runway. The other thing we do like to mention is, given these two programs, the start of Phase III alongside of a launch, we will highly prioritize the launch. PSVT is really at the forefront of our minds right now. AFib will start, but it will start at a lower burn just to enable full commercialization of PSVT. Lastly, we did just announce two weeks ago a notice from the U.S. Patent Office of a patent extension for our patent portfolio. This extends our market exclusivity potentially out to 2042. That enables even more value to come from the compound based on that being peak year sales for PSVT, as well as opens up AFib even further, given it is a second indication, giving that more runway to help more patients.
I'll say a few words about the arrhythmias that we work on, PSVT and atrial fibrillation. They're very common in certain ways and with some differences. The commonality is that these patients wind up having events or episodes, or as they call them, attacks of a rapid heart rate. These rapid heart rate events result in highly symptomatic problems for the patient. You could see them listed here at the bottom of the slide. Get this to work. Almost always will they feel their heart, palpitations. They often report things like shortness of breath, lightheadedness, a lot of fatigue, especially if the event seems to go on for some time. We hear words like, "It feels like I've run a marathon." Even when the event stops, the patient is really fatigued and has trouble going on, if you will, with the rest of their day.
The physiology behind why these events start is slightly different, but they both do involve the AV node of the heart. The AV node of the heart is a gatekeeper between the atria and the ventricles, and it's where calcium channel blockers work quite well. IV calcium channel blockers are approved for both of these indications, PSVT as well as atrial fibrillation. The role in PSVT is to convert the patient back to a normal rhythm, and their role in atrial fibrillation with rapid rate is to reduce the heart rate while this patient stays in atrial fibrillation. They are both highly successful, and again, in IV form, they're approved, but not in oral form. We'll talk about that in a minute. Here are the available options for patients who are currently suffering from PSVT.
On the left-hand side of this chart are chronic or preventative measures for their attacks. These are either in the form of oral drugs like beta blockers or calcium channel blockers. They're used off-label, and they do suppress episodes, but they don't eliminate them. Catheter ablation is an invasive procedure performed by a specialist called an electrophysiologist. These electrophysiologists will go in there and either burn or freeze parts of the heart to try to cure this condition and prevent future episodes. On the right-hand side are the options available if a patient is actually in an attack. They could try to, if they have oral meds, they can take another one. Doctors will often tell them, "Try to take another one if you're in an event.
Try to do that before you go for your second option, which is a trip for an IV drug at the emergency department. The pill in the pocket, again, is not available with any real data. It's all anecdotal data. It's not approved for this use, but it is used because there really is very little else available for these patients once they're in the event. Going to the emergency department involves, obviously, the cost and time to get there, but it also involves getting a drug called adenosine, which actually stops your heart. It fully blocks that AV node, maybe for seconds, but it's very disconcerting for the patient. This is what's available for them right now. A little bit about the condition here, some of the characteristics. It is a chronic condition. These patients are born with these pathways of SVT.
It presents at first, either in your teens, your 20%s, 30%s, 40%s. We're not exactly sure why it presents at different times, but once it does present, you're living with it for the rest of your life. The incidence and the duration of these episodes are quite unpredictable and variable. Could happen once a year, could happen once a week. The duration of the actual event could be minutes, tens of minutes, or hours. What we find is that it's this uncertainty that's really quite disconcerting for the patient, very anxiety-provoking. 50% of the patients are under 65%, 50% are over 65%, and it tends to skew more towards women. As you can probably imagine, it's mainly managed by cardiology. On the right-hand side is a little bit more about the impact.
I think you could probably understand why a patient that has their heart going at 200 beats a minute and is very symptomatic is a problem. The other issue, though, is because of the uncertainty of when these events will occur, how bad they'll be, or what the patient will be doing also impacts their lives. We hear reports 80% of patients report feeling anxiety about their condition, even when they're not in an episode. That's that worry about the next episode. We also hear of patients adjusting their lives. We hear of patients giving up driving, not wanting to get on planes, not wanting to take vacations when they go to a city, mapping out where the emergency departments are. It really is top of mind quite regularly, even when they're not in an event. Approximately 2 million patients in the U.S. with PSVT.
Very importantly, up to half of them, 650,000- 1 million, are engaged in the healthcare system every year. About half are not. They have given up. They have kind of settled with the lack of options, and they have kind of disengaged from the system. The beauty for a company coming to launch is about half of this market is already engaged and activated, word we use, and that is the market we are going to target when we come out with CARDAMYST. Eventually, we are going to wake up the rest of the market and bring them back into the system. The drug is called CARDAMYST. It is a nasal spray. It is a new chemical entity. It is designed as a very fast-acting and short-acting, or relatively short-acting, calcium channel blocker.
That's all so that it can be delivered conveniently with good efficacy and safety and be able to be administered by the patient without any medical oversight. That's the whole concept of the drug. When we show you, and I'll show you some efficacy and safety data, obviously, I think it's seen why it's convenient. It's in a very convenient packet nasal spray. Importantly, the attributes that are here convey the results on the right-hand side, why patients would appreciate having something that's rapid and reliable to actually deliver results in the event, whether it happened at this conference, at your home, or at your job, et cetera. They feel empowered by having this. They don't have to worry as much, or our belief is they won't have to worry as much about their next episode because they have something in their purse or in their briefcase.
Finally, maybe it would allow them to take that trip to Europe to get on that plane, right, to bring driving back into their lives because they have something available to them. Here's some data from our pivotal trial. What you can see here is the conversion rates of patients over time going from tachycardia to normal rhythm. Quite simply, what you're able to see is the primary endpoint is at 30 minutes. We think that's a great amount of time to be able to allow a patient to judge whether the molecule is effective or not. Twice as many patients convert on drug compared to placebo. The other thing is it works quite fast. You can see separation happening as early as five minutes, and half of the patients convert before 20 minutes, whereas placebo takes closer to an hour.
Three times faster and twice as many. We think those are very valuable data for physicians to be able to feel comfortable and for patients to have something reasonably confident that'll work. You could see that out over an hour and a half, 80% of the atrial patients convert. That's normally the amount of time anyone would be able to get to an emergency department anyway to be treated with that lovely drug called adenosine. The other thing that's not shown here, but worth noting, is that in this trial and its sister trial, about 40% fewer atrial patients went to the emergency department. After the trial or after a period of time in the trial, patients were told to seek care as you normally would, i.e., the drug didn't work.
We saw that 40% reduction in emergency department visits, which will be valuable as we come to the market as well. That's really the whole point of this drug. Here's the safety data from that trial. What's reported here is anything with an incidence of greater than 5%. You see very few events here, and they're all kind of in and around the nasal cavity and the nose and the eyes. It is an acidic spray. These are generally mild adverse events. There's a few moderate. There are really no severe adverse events. We view this as an incredibly valuable piece of the puzzle for the label. These tolerability issues are really more nuisance-oriented issues. The drug kind of feels like having some vinegar in your nose, if you will.
Importantly, there are no adverse events that the FDA or cardiologists are concerned about, and those are things like having too much AV nodal blocking or blood pressure drops that would result in, for example, lightheadedness or falls. We did not see that in this study at all. Again, very opportune to have this profile. Let's switch over to how we're going to think about marketing the drug and commercializing it here. I think everyone understands from the previous comments why patients would value the empowerment, a little bit more about why prescribers would want to use it. I'd mentioned two or three times we have data. The other available options, pill in the pocket, really no data. Cardiologists, we believe, will value this data that we're showing here. We have it published. It will be prominent in the label.
The fact that it's a calcium channel blocker, which cardiologists are quite comfortable using over many decades, we think allows early trial of the drug more earlier than you would normally have if you had a new mechanism that needed to be explained to cardiologists. The other important thing is these cardiologists are in busy practices. They're often seeing these patients on a weekly basis. They're seeing many other types of patients on a daily basis, whether it's diabetes, lipid management, heart failure, AFib, right? It's a busy practice. These patients, when they get calls from these patients about these events, it's really disrupting their practice, whether it's the cardiologists or their nurse practitioners. We feel that this could really help the cardiologists, again, help that patient manage their episode and take time and allow them to better manage their other patients and not get behind.
On the payer side, every drug that comes to market needs to think about their payer strategy. Our approach here, and we've been in front of payers now for the better part of four or five years, more actively in the last year and a half with the key account management team. We've learned and educated them on this condition and learned what they want. What they're looking for is rational pricing around this drug. They see the value. They want to provide it for their customers. They guide us to price it rationally. What that means is keeping it below specialty pricing. In today's world, that's about $900 per month, think of it per episode. They've guided us to keep our net pricing below there. We think it's very rational to do that. We could easily do that.
This will be distributed through a normal retail distribution model, no special handling, no special pricing, no special bells and whistles, is our opinion of what we'll need. They value that it's a well-known mechanism like the cardiologist. They value that it's prescribed by a specialty audience. Very valuable to them is also this idea of emergency department utilization being reduced and the cost offset that comes with that. We think that causes them to potentially review it a little earlier than they might otherwise review other drugs that are completely cost additive. I mentioned before the available options to these patients. You see it here, whether they're orals, taken chronically, or pill in the pocket, ablation. When we ask cardiologists where they would use CARDAMYST, they give us answers across the board.
Really, all patients, depending on the actual events that they have and what they're taking, are candidates for CARDAMYST. Cardiologists tell us that they will use CARDAMYST in all these situations. That's really attractive for the breadth of use of the drug. Now, how much will it be used? We envision about half of the market is our target addressable market. I'd mentioned about 2 million patients with PSVT. What you see here on the right-hand side is really based on those patients that are getting it with a certain frequency and a certain amount of burden. Not every event is bad and not every event is long. For those events that are short or not too burdensome, not candidates for the drug.
For those that are having this every day or every week, or if they're worried about fainting, probably not a great candidate for the drug. It's this middle group. It's this 50% is our target addressable market. These are patients having events in the range of a handful of times per year that are burdensome events where they want to treat and they would be using CARDAMYST. They may have more than that. They may have two handfuls of events per year, but we think the average patient, if there is such a thing, would use the drug about, you know, call it 3x-5x per year. That's how we model the pricing, and that's how we model our uptake. When we ask cardiologists how they would use it, again, this is on the left, the available options, where they would use it in place of them.
At the end of the day, we're looking at a 50% penetration according to these cardiologists. A couple of the characteristics as to what makes us bullish on why this is an important and compelling commercial opportunity. There is no competition that we can see. That allows two important things. First is, like many competitive markets where you have multiple companies counter-detailing against each other, you don't have that here. You have one simple message. It's a calcium channel blocker with data behind it, and you don't have another company counter-detailing against you. We think that's a simple message that gets uptake. Secondly, when you're in front of payers, you don't have competitors raising their rebates against your rebates, right? You don't have this escalation and price deterioration. We think that helps. I already mentioned we think there's a low bar to prescribing for the cardiologists.
They already want their patients to manage this. They already know about calcium channel blockers, and we think the data kind of speaks for itself. We'd like the opportunity, as I mentioned before, that there's already 650,000- 1 million patients already very active in the system. Half of them are commercial patients. Commercial patients and payers will review the drug sooner, and we have greater opportunity to help those patients by bringing the copays down to, you know, tens of dollars, if you will. Where are we in our launch right now? Three main goals: build awareness and demand generation. The second is to work on access with payers, and the third is to develop a great patient experience. On the awareness and demand generation side, we've been successful in recently hiring sales leadership.
We've hired the head of sales, two regional directors, and eight district managers, and they're in the process right now of interviewing sales reps. We will hire sales reps after approval. March 27th is the PDUFA date, and our goal is to have those sales reps in the field with promotional materials that are approved by the FDA by middle of the year. On the access side, we've been in front of these payers. We've educated them. We have developed our distribution channels, and we've developed what we call fit-for-purpose reimbursement support programs. Every new drug goes through payer hurdles. When it's launched, we're going to have those support services available to both the physician and the patient when they show up at the pharmacy to make sure their copays are reasonable. That's included in the patient support services.
In addition to that, what we want to do is develop that relationship with the patient. We don't feel in the launch year we need to drive patients into the cardiologist. They're already going there. Once they get that script, we want to build an engagement with them, support them so that they feel well empowered to use the drug and to refill the drug. We'll do this in a staged way. What you see here from left to right, Phase I is pre-launch, which we've been very active in for the last few years with KOL engagement and payer profiling. We're in the process of preparing for the launch, which I explained the number or how we're commercializing. The sales force will be in the range of 50-60 sales representatives.
That should allow us to cover in this range of 10,000-12,000 prescribers, which represents about 50% of the potential in the commercial patient population. We'll obviously target the high-value prescribers. In years two and three post-launch, we'll monitor what goes well in year one, and we'll be in a position to either expand our sales force or adjust our other marketing tactics to enable continued growth and more expansion to greater than 50% penetration or coverage here. You see us going to 17,000-20,000 HCPs and eventually 25,000-30,000 HCPs, which we feel represents 70%-80% of the commercial potential. Just in the last few minutes, I'll move over to AFib. AFib, as I mentioned before, a much larger opportunity potentially, about 10 million-12 million AFib patients projected for 2030.
AFib with RVR as a subset of the AFib population, about 30%-40% as best we can judge. You could see the target of adjustable market here about three to four times what we think it is for PSVT. Now, for AFib, I'll bring you back to the start of the presentation, similar presentation, elevation of heart rate and highly symptomatic. What happens with these patients, similar to PSVT, is either on the dotted line across the top, they make their way to the emergency department. They typically receive here IV diltiazem, an IV calcium channel blocker. The first objective of treating this is to bring the rate down before you work on other aspects of their AFib, and IV diltiazem does that quite well. Same issues, though. It takes time to get to the emergency department. It's costly to get there.
IV diltiazem at least does not stop your heart. It is a more comfortable treatment. Nevertheless, you have to make your way to the emergency department. In the middle patient here, if you will, the yellow one, you can take an oral calcium channel blocker or beta blocker. They work better than they do in PSVT, but you can see they do not work for all. It does not get the heart rate down for everyone. The other main problem is it takes time for them to kick in. What often happens is patients will start on their journey, find out that it is not working fast enough for them, and then the dotted line kicks in and they will head over to the hospital along that path.
Many of the people that wind up at the emergency department are on background oral drugs, either because they just took them or they haven't been working for them. What we'd love to have available to these patients is this profile on the left here where you deliver IV-like rate reduction that you have with diltiazem, but do it at home in the nasal spray. That would be CARDAMYST. That's our whole concept here. That would allow them to relieve symptoms quickly and not have to make that weight of how long is it going to take for my symptoms to go away and should I go to the emergency department. Same value prop as we have for PSVT. Like for PSVT, there's many use cases, whether it's on top of oral drugs, in place of oral drugs, around the ablation. Same applies to AFib with RVR.
I have two slides on data. This is the design of our Phase II study that was conducted and already published. This was an inpatient study. We always start inpatient, and this was in the emergency department. This study studied a single dose of etripamil, 70 mg I forgot to mention, but I'll do so now, that the dose that will be used and that was used in the RAPID study for PSVT and will be used in the market is what we call a repeat dose. This is where the patient doses themselves. If symptoms don't resolve in 10 minutes, they dose themselves again. We found that to be highly successful, as seen in that prior data, and we'll use that in the Phase III program going forward for AFib. However, this study was done with only the single dose.
The study had a main objective of seeing a reduction in the heart rate for these patients of at least 20 beats per minute within an hour. That was our objective. It was about a 50-patient study. We also wanted to see how long it lasted and how quickly it took to kick in. This is the primary result from that ReVeRA Phase II AFib study. What you see here is the gray placebo really did not move much at all. It had a five beat per minute drop over the course of that hour. The etripamil group in purple here saw a very fast response with it maxing out at around 35 beat per minute drop. Remember, we are looking for 20. That difference of 30 beats per minute was well beyond our expectations, became a highly statistically significant result.
We also saw that it started to separate very quickly within three to five minutes, with a max reduction happening within 15 minutes. This was really great results from this trial. What's not shown here is that these results actually carry out beyond this hour to the point of two to three hours, which was also a nice, pleasant surprise for us. Again, this was a highly successful study that's causing us to go into the Phase III program. The second aspect of this study, you know, this is all about symptom relief. It's one thing to bring your heart rate down, but why does it matter if the patient doesn't feel better? This is a patient-reported outcome that was in that Phase II study on AFib RVR. You could see how satisfied they were or dissatisfied they were with their symptom relief.
You could see the purple bar, etripamil had a 1.5 unit increase in terms of its delta over the placebo group. Again, highly statistically significant with only 50 patients. We took these results to the FDA. We got agreement on a Phase III trial. Looks like this. It's a single study registration trial, as I mentioned before, via an sNDA pathway. The design, conduct, and operations looks a lot like our PSVT program. It's going to be done in the outpatient or at-home setting, not on their medical care. It'll be that double-blind randomized etripamil versus placebo using the repeat dose regimen. Again, the opportunity to improve over the results that we had from the Phase II study. The primary endpoint is that reduction in ventricular rate. We're going to make it over a half hour, not an hour, that we saw in Phase II.
We saw most of the activity there in the first half hour. Again, because it's a repeat dose, and if they're going to dose again at 10 minutes, we give that second dose a chance to kick in. Very importantly, a key secondary endpoint will be symptom relief. FDA has guided us that we need to hit that endpoint to get the approval. The study is actually powered off of showing that result in addition to the ventricular rate. It's about 150-200 of N trial. Looks a lot like our SVT trials, and it's powered at 90%. I'll finish with cash. We finished in September with $76 million. We'll be releasing our Q shortly. We think, as I said before, that plus the synthetic royalty payment of $75 million on and around approval will deliver a runway into mid-2026.
With that, I'll close and thank everyone for their attention.
Thanks, Joe. We have about 46 seconds left if anybody has any questions on the floor. Yep.
Curious about CARDAMYST. When I think of the program, I think of it almost like an EpiPen, but PSVT. Thinking of it in that way, what is the formulation stability? What is the shelf life? If people have this, let's say, in their purse when they're going around, what is its temperature stability?
Great question. We're expecting at launch at least 18 months of stability and shelf life. It'll probably be longer, but that's the minimum. We feel that if a patient doesn't use it within a reasonable amount of time, they have it and they won't waste it. There's no special handling. We ask them not to have it be in like frozen conditions or leave it in your car in Arizona, but normal room temperature handling is available for this product.
V ery stable.
Thank you, guys.
Okay. All right. Thanks, all.