Milestone Pharmaceuticals Inc. (MIST) Earnings Call Transcript & Summary

Greetings. Welcome to Milestone Pharmaceuticals CARDAMYST FDA Approval Call. [Operator Instructions] Please note, this conference is being recorded. I will now turn the conference over to Michael Wood at LifeSci Advisors. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to Milestone's conference call and webinar to discuss the FDA approval of CARDAMYST nasal spray. On a Friday evening, the company issued a press release on the approval. This can be accessed on the News & Events page of the company's corporate website at milestonepharma.com. During today's call, the company will be making certain forward-looking statements. I will refer you to the safe harbor statement here on Slide 2. A description of potential risks and uncertainties can also be found in today's press release and on the company's latest SEC disclosure documents. The agenda for today's call is outlined here. Joe Oliveto, Milestone's President and CEO, will begin with opening remarks, including covering the basics of the product label. He will be followed by Dr. David Bharucha, the company's Chief Medical Officer, to discuss the clinician's perspective relative to the medical need. Lorenz Muller, Chief Commercial Officer, will then talk about the launch plans and Joe will conclude before we open the call up to questions. Also, Amit Hasija, the company's Chief Financial Officer, is with us today and will be available to answer questions during the Q&A session. So with that, I'll turn the call over to Joe to begin. Joe, go ahead.

Thank you, Michael. Good morning, everyone. And of course, thank you for joining us today. We're really excited to announce the FDA has approved CARDAMYST nasal spray for the treatment of PSVT. This approval means that for the first time the more than 2 million Americans who live with this unpredictable and very disruptive condition will now have access to a rapid-acting treatment they can use outside of the health care setting. Many of these patients we have interacted with over the years have expressed to us how having such an option provides them with the ability to better manage their condition, in turn, allowing greater control over their daily lives. CARDAMYST is, in fact, the first new therapeutic option for patients with PSVT in more than 30 years, and we couldn't be happier for those patients who have been waiting. Shown here is the approved indication statement. The full package insert can be accessed via this link through the Milestone website. We're very happy with the label we received from the FDA, which meets and, in some cases, exceeds our expectations. It reflects the strength of the clinical program with no major surprises to what we were expecting. I'll take a moment to show the primary presentation of clinical efficacy and safety. The primary efficacy presentation includes a Kaplan-Meier curve showing the conversion over 5 hours for the pivotal RAPID trial. The statistics, including the impressive p-value for the primary endpoint at 30 minutes are displayed with the graph. This presentation is highly supportive of portraying multiple aspects of the drug's efficacy data, including both the speed of conversion displayed at the beginning of the curve and the persistent effects of conversion over 5 hours. Presentation is also flexible in that it allows us to highlight any particular aspects of the display in our promotional materials. For example, this slide is a potential for trial of efficacy that focuses in more clearly on the primary end point the RAPID trial, the conversion period over the first 30 minutes, amplifying that section of the curve. From this view, it is easier to portray that CARDAMYST converts twice as many patients by 30 minutes and converts patients 3x faster as measured by median time to conversion. So the 5-hour curve provides excellent support for both messages, speed and durability as well as the flexibility to highlight messages with multiple different views. We're especially excited about how clean the label looks from a safety and tolerability perspective. For any investors who've been following the CARDAMYST story through its development, these data should look very familiar. There are no surprises in the label. Giving CARDAMYST as a calcium channel blocker, what is most important to health care providers regarding safety includes blood pressure reductions AV nodal blocks and syncope. What you see on the left-hand side of the slide is that the label conveys that only 0.4%, that's less than 0.5% of patients experienced hypotension and only 0.1% of patients experienced syncope with no patients experiencing AV nodal blocks of type 2 or greater. To the right is the presentation of the most common adverse events, those occurring greater than 5% in the CARDAMYST Group. There are only 5 AEs listed and those AEs are largely combined to the local site of administration and nose in face. The data is portrayed across the double-blind studies within the clinical development program. This characterization of tolerability is extremely consistent across the whole of the development program data, including other open-label studies that have been presented multiple presentations and publications. Precautions are portrayed in the label around the potential for a etripamil, again, as a calcium channel blocker to affect blood pressure and AV nodal conduction. Patients are instructed to be seated when they dose themselves and to not dose themselves more than 2 doses within a 24-hour period, all of which is very appropriate and expected and helpful in our view, for the ultimate protection of the patients. Transitioning to commercialization, our vision for the commercial success of CARDAMYST is very simple. Towards the bottom of the slide, make it easy for patients to use, make it easy for prescribers to write. And thirdly, and relatedly, price it and support it such that there is limited reason for payers to want to control it or to certainly overly control utilization. Regarding payers, before we get the payers, I will ask David, our CMO, who's also an electrophysiologist and manage these patients and continues to engage with his peers to provide thoughts on what CARDAMYST could offer to busy practitioners. So let me just say a word about payers and the patients. So regarding payers, we have spent significant time educating payers on PSVT on the already published CARDAMYST data, including both the clinical profile and the reduction in emergency department use that we observed in the clinical trials. We've provided them with modeling tools so that they can evaluate within their own populations in order to estimate cost offsets that CARDAMYST could potentially provide for their budgets. The payer feedback from these interactions provides us the confidence we have an offering that will allow plans to cover the product without significant managing the utilization of CARDAMYST. Lorenz will review our pricing and how it fits into our market access strategy. So now let me say a word about patients and the medical need from their view. We feel very strongly that PSVT is a patient-driven market. For patients, let's remember, CARDAMYST was prospectively designed from day 1, literally from the time it was envisioned on a whiteboard to be a patient-centric product. Patients will have CARDAMYST with them in their pocket, their brief case, purse, [indiscernible], et cetera, and patients themselves will decide when to use CARDAMYST. We believe and patients have expressed to us that having such an at-the-ready option provides them with the potential for living life with less reliance on the emergency department, which is currently their only approved option while experiencing an event. Less reliance on the emergency department means less disruption to their daily lives and in turn, alleviates the anxiousness that many patients often feel between events or episodes, and they often are thinking about when the next episode occurs and what they'll be doing. What if it happens while I'm driving the kids? What if it happens during an important day at work or I'm on a plane or I'm on vacation, right? What will I do? Can I get to resolve it? Will I have access to the emergency room? All of these questions and thoughts are going through their mind, not only in an event, but when they're making life choices. Very much like a migraine patient thinks about having their medication available to them during their next migraine or asthmatics think about having their rescue in available to them. We believe that with PSVT, many of these patients will be thinking about and have CARDAMYST top of mind as to having that available whenever or wherever they have their next event. It's clear to us that the ability to empower patients to take better control over their PSVT attacks is a highly attractive benefit that many patients have expressed to us and the feedback is especially encouraging when it's received relative to patients who experience CARDAMYST in the clinical trials, be it feedback directly from the patients or through their clinical investigators and study staff. With that, let me turn it over to David, who will provide views on the medical need and the benefits that CARDAMYST can offer to busy cardiology practitioners.

Thank you, Joe. I also want to say how happy I am by FDA approval of CARDAMYST and by this opportunity to make this self-directed treatment available to patients and health care professionals. Speaking as a cardiology arrhythmia specialist, I'll comment on the medical need after my having seen thousands of patients with PSVT, and I'll make several points. First, the patient experience has been problematic. Second, from a physician perspective, there's been an unmet need due to limited tools up until this point. Third, the basics of etripamil, now CARDAMYST, offer a simple and efficient solution to those previously unmet needs. First, PSVT or paroxysmal supraventricular tachycardia occurs suddenly, usually without warning and inevitably at a really bad time when a patient is in the middle of their everyday activities. It prevents them from engaging at a fear that they may have a symptomatic arrhythmia episode without the means to stop it and physicians up until now have not had an effective acute-acting drug to equip these patients with it. Second, shown in the lower part of the slide, PSVT commonly has disabling symptoms of palpitations, shortness of breath, lightheadedness, even chest pain and certainly marked anxiety. I use the word disabling deliberately. These are not nuisance symptoms. Although PSVT is not severely morbid, patients in the moment don't feel that way. Next point. For physicians as well, there's been truly an unmet need here. What's been available up until now? Well, limited treatments that are poorly effective, invasive or inconvenient. So moving from left to right on the current slide, options that have been available to physicians have been chronic oral medications such as calcium channel blockers or beta blockers. These, even when given at high doses are not very effective in preventing episodes. And it really doesn't make a whole lot of sense to take a medication every single day for an episodic condition. Patients are exposed to the side effects, the hassle of a daily drug. That would certainly give me pause before recommending this -- that type of approach. So since chronic oral dosing isn't very effective, quite simply, it's not worthwhile. Another preventative option is ablation, a catheter procedure performed by electrophysiologists. I performed many ablations myself and have guided many more patients as to whether they were good candidates. Ablations are generally safe and are often curative. However, they're invasive and carry some procedural risk, and they're not for everyone. In fact, research indicates that only 15% of eligible U.S. patients do end up having one. Bottom line, they're preventative. They can't get a patient out of an acute jam. For acute treatments, a pill-in-pocket approach is used by some prescribers, mostly because they simply have had nothing else to offer. A pill in pocket is when an HCP may prescribe taking a onetime dose of an oral calcium channel blocker or a beta blocker. However, the pharmacokinetics of oral therapies are simply not suited to the acute rapid conversion of PSVT. On the slide's right most panel, emergency visits. When each of these options fail, patients often end up in the emergency department and even hospitalized with all the inconvenience, time and costs that are associated. Now certainly, no physician wants their patient to end up in the emergency department, especially for something that could be handled at home. And so it really needs to be emphasized CARDAMYST as a patient-directed self-administered therapy is very much in line with what physicians have been seeking. To sum all this up, a cardiologist would much rather have a patient self-treat themselves at home with a proven therapy rather than having them end up in the emergency room. The other bottom line, patients continue to experience disruptive episodes despite the therapies that have been available to them. CARDAMYST, summarized on the next slide, directly addresses this burdensome need. It's a short-acting calcium channel blocker with clear activity as early as 5 minutes after self-administration. The CCB mechanism of action is well understood, time tested and already trusted by health care professionals. This familiarity, I believe, will lead to a low barrier of use and is strongly supported by our labeled safety data. This drug, also a new chemical entity and with patent protection extending to 2042, offers an important package. It's portable, can be administered on demand. It has a fast onset and is well tolerated. It has been extensively studied with self-administration in an outpatient setting, leading to our robust clinical data set, which led to this approval. As Joe has already summarized, CARDAMYST label supports its favorable safety profile, which I believe will give providers assurance in prescribing the treatment. This label provides Milestone with a really strong basis for communicating efficacy, safety and tolerability. So Lorenz, if you could update us all on how -- and all that Milestone is now doing to deliver this treatment to PSVT patients and to the health care professionals who care for them.

Thanks, David, and good morning, everyone, and thanks for taking the time this morning to learn about the exciting approval of CARDAMYST and our launch plans for bringing this to the patients that so desperately need a new therapeutic option for treating their PSVT. My mandate this morning is to give you a quick overview of the market opportunity as we see it and then talk a little more detail about some of our key launch strategies, tactics and success metrics. As I've shown you in the past, the PSVT market dynamics are quite stable. So while we continue to learn about the market, our go-to-market plans are largely the same as earlier this year. And as I will focus -- and as such, I will focus my comments today on a couple of quick reminders on the market opportunity, but then focus your attention on some new approval-enabled information like sales force targeting and pricing. So let me remind you that in the United States, there are about 2 million patients with the diagnosis of PSVT and that those patients are costing the health care system at least $5 billion a year, driven largely as is represented on this slide by emergency department visits, hospital admissions and ablations. Importantly, about half of the diagnosed patients in the U.S. are seeking treatment in the health care system each and every year because of the burden of their disease. What excites me about the commercial opportunity for CARDAMYST is represented on this slide. An ideal market for me is one where there's no anticipated branded competition, giving us both 100% share of voice and lower rebate pressure because we won't be negotiating against anyone for preferred formulary position. Physicians in market research have repeatedly told us that they're both very familiar with L-type calcium channel blockers and impressed with the robust data supporting CARDAMYST and as a result, express a low barrier to prescribing. And we believe all of this will result in strong demand generation and the ability to obtain quality coverage initially amongst the 50% of patients that are commercially insured. So let's dig in a little deeper into how we will get at this opportunity. This slide represents the 2 million patients that have a diagnosis of PSVT in the United States. Of those, as I mentioned earlier, about half are being annually treated, and those are being managed by around 40,000 health care providers. That actually would be a large sales force to be able to deploy against all those doctors. Fortunately, for us, this market is concentrated where roughly half of those patients or 500,000 patients are being managed by only 10,000 health care providers. The majority of those, no surprise, are cardiologists. So you can see here around 8,000 clinical and interventional cardiologists and 1,500 electrophysiologists are managing over 90% of those patients. Interestingly, there's around 500 primary care physicians that look and act a lot like cardiologists that are managing an incremental 40,000 patients. Together, these 10,000 health care providers represent the prescriber targets in our launch year, which can be engaged by about 60 sales representatives. This concentration of patients with PSVT is the reason we chose an initial sales force size of 60 reps. We believe this sales strategy will enable us to demonstrate robust demand in a launch year while also being good stewards of the company's resources. Next, I want to remind you of the vicious cycle of PSVT, define our target addressable market and show for which type of patients physicians tell us they'll prescribe CARDAMYST. You can see on the right side of this slide, the distribution of disease burden in PSVT in terms of episodes. The larger box in the middle represents our target addressable market of approximately 50% of patients with PSVT who experience multiple burdensome episodes per year and seek treatment for those episodes. On the left side of the slide, you can see the various use cases where physicians have reported wanting to use CARDAMYST. Of note, you can see that docs want to use CARDAMYST as either an add-on or switch therapy for patients on chronic prophylaxis, patients using off-label pill in pocket and patients receiving no treatment. Electrophysiologists report wanting to use CARDAMYST either as bridge therapy in patients they plan on ablating or as an alternative -- attractive alternative option for those patients whom they cannot convince to have an ablation. Let me now quantify for you the physician stated adoption for CARDAMYST. On the left side of this slide shows physician reported current treatment of patients with PSVT from market research with 250 cardiologists. As you can see, physicians report a desire to prescribe CARDAMYST to around 2/3 of their patients who are currently receiving pill-in-pocket therapy. A little less than half of their patients that are receiving chronic prophylaxis with calcium channel blockers and beta blockers and a little over half of their patients receiving no treatment, which results in an almost 50% stated adoption for CARDAMYST. Let me now switch gears to talk about our market access strategy, which is focused on product accessibility and affordability. Payers have repeatedly reported to us that they're not actively managing PSVT currently. And as long as we rationally price the product, they are open to putting it on a Tier 2 or Tier 3 formulary, especially for commercial books of business. And a lot of that motivation is driven by the potential for quantifiable cost offsets. As I reviewed a minute ago, coverage would result in physicians having an easier time prescribing because it would result in less onerous utilization management, meaning in many cases, just a prior authorization to label and potentially some quantity limits. And prior to achieving coverage, Milestone will offer reimbursement support in the form of health care provider assistance in pursuing medical and/or formulary exception and in select cases, even denial conversion for patients whose claims have been rejected. On the patient side, we have committed to retail distribution to make the drug broadly accessible without the limitations of having to go through specialty pharmacy, and we will offer robust co-pay mitigation in the form of a pay no more than $25 program for commercially insured patients. Also, Milestone will support patients with different nurse educator programs that will both help patients use CARDAMYST correctly and provide them with periodic refill reminders. Finally, I want to announce today that we've chosen a WACC or wholesale acquisition cost price for CARDAMYST of $1,649 per prescription, which aligns with net revenues to milestone of between $500 and $1,000 per prescription. We've chosen this price in part because of the value prop that CARDAMYST represents relative to the other treatment modalities, which insurance companies must reimburse, whether it's emergency department visits or hospitalizations or ablations. When we have presented this price to payers, it has been well received because they see it in the context of a budget impact model where we show a modest impact in terms of per member per month increase. And by modest, I mean a PMPM impact of pennies and not dollars associated with putting CARDAMYST on formulary for both commercial and Medicare books of business. Our strategic objectives for CARDAMYST in the launch here are relatively simple. We plan on focusing on driving provider awareness, trial and usage and establishing and maintaining broad and high-quality access and affordability. We're going to assess our performance by tracking and reporting weekly prescriptions and week-over-week prescription growth. On the access side, we'll be tracking and reporting on the percent of insured lives for which we have negotiated coverage over time as well as describing the quality of that coverage in terms of any utilization management that payers mandate. So in summary, our launch year goals are to get prescriptions written and filled. We're confident that we will achieve significant demand generation because our initial sales force deployment covers 50% of the annual potential because patients with PSVT are going to physician offices every week to receive treatment and because physicians are comfortable prescribing CARDAMYST for a broad array of patients because of their familiarity with our mechanism of action and the robust efficacy and safety data behind CARDAMYST. Of course, it's also very important to get prescriptions that are written filled. And so as I mentioned, we're committed to retail distribution, and we have invested in comprehensive provider and patient support programs that will facilitate compliant prescription fulfillment, both pre and post insurance coverage. And finally, we believe we can get relatively rapid formulary placement among target payers because we have no branded competition and therefore, not a lot of rebate pressure and an attractive health care resource utilization value proposition. Thanks very much for your time and attention. I'll now turn the call back over to Joe Oliveto for some concluding comments.

Thank you, Lorenz. I really do want to underscore the significance of our announcement today. The FDA approval of CARDAMYST is a very prideful day, represents an important inflection point in the evolution of milestone, marking our transition to a commercial organization. The FDA approval also represents a huge step forward towards achieving our mission of providing relief to patients suffering from PSVT by providing what we believe will become the new standard of care. Before I open for questions, the journey to develop CARDAMYST from a whiteboard idea to a drug and really the first new drug intervention in over 30 years for patients dealing with PSVT has taken the dedication of so many. I want to take a moment to thank all those people who have made the approval possible to my colleagues here at the company and our development partners responsible for the literally thousands of decisions, activities and for really portraying the grit needed to achieve and to succeed together as one team. I really want to thank the patients and their families who participated in our studies and provided their guidance and put their trust in us, who at the start, milestone was really an unknown company to them. I want to thank our clinical investigators and health care providers who worked on the program and generated really such impressive clinical data. And I want to thank our investors who have really supported us throughout this journey. We're grateful to all for your dedication, commitment and helping Milestone realize this important achievement. Cherry, I'd like to open the line for questions now.

[Operator Instructions] Our first question is from Ritu Baral with TD Cowen.

Just a couple on my front on -- more on the payer side. One, very briefly, if you could give us the Medicare commercial split as you see it right now. But the bigger questions are 2. In your payer conversations, what are your current expectations for prior auth before coverage? Is there any requirement for like documentation of events, documentation of a certain number of events that translates to severity? And then I have a quick follow-up.

Thank you, Ritu. And Lorenz, I think those are right down your fairway.

Thanks, Joe. Yes, Ritu. So the split between -- for patients with the diagnosis of PSVT is roughly 50-50 between commercially insured and Medicare. It's actually 45% commercial, 45% Medicare and then about 10% Medicaid and other. And that's important because that allows us to demonstrate demand in a large group of commercial patients that are just going to be easier to get coverage for in terms of a time standpoint and where we can co-pay mitigate to make the drug more affordable. To the second part of your question, so because we don't have coverage today at the approval date, we will have a program for pursuing medical exception, formulary exception. And we don't expect that process, by the way, to require documentation of rhythm strips for PSVT and attestation from a physician is more than likely sufficient. And then as we gain coverage, though obviously, medical exception, formulary exception will no longer be necessary. And as I mentioned on the call, we are expecting some mild prior auths to label to ensure CARDAMYST is being prescribed on label and also potentially some quantity limits to ensure that at least until payers have real data in their plans, that there is an overuse of the drug for patients that might have daily or weekly episodes.

Yes, if I can double down on that, you asked about severity. Even for interventions like ablations, there is no prior auth to severity or anything like that. You could literally have one event and go for an ablation. So we really don't have that anywhere in our thinking.

Very helpful. And a quick follow-up. What do you guys expect for time lines to formulary inclusion and sort of more standard coverage and uptake?

Yes. So while I'm sure Lorenz would love to boast what we think, we're going to keep that to ourselves for now and not give guidance on formulary acceptance and coverage. We really do believe -- we believe we'll get good coverage, right? As Ian mentioned, Tier 2, Tier 3, not specialty tier for the majority of plans. But we're going to hold the expectations of a little bit the when to ourselves and really start reporting and see how it goes.

Our next question is from Ted Tenthoff with Piper Sandler.

Sincere congratulations, a long winding road, but your persistence for these patients is notable and finally rewarded. So sincere congratulations. I wanted to get a little bit clearer -- a little clarity on 2 issues. One, I know you said that it would be available in retail pharmacies in the first quarter. Can you give us any more sense what that means? Is that early in the new year? Does it kind of depend regionally where you roll out? What outreach to physicians goes in hand with that in terms of making them aware of availability? And then secondly, on price, I appreciate the color both with the WACC and the price per patient, which has been very consistent. What are the factors that kind of go into that? I think the biggest being if they use 1 or 2 doses per episode, but how should we be thinking about that price revenue to you guys in a little bit more detail?

Okay. Thanks, Ted. And maybe I'll take the first one and ask Lorenz to take the second one. Really, the critical path to having access to drug for patients in our view, is primarily having sales representatives hired, trained and in the field. We're giving guidance as to really mid-Q1. We know that, that's a little bit wide. But given that we're right here at the end of the year in December and are essentially making offers this week, we have sales reps identified of the 60. We're very close to the full 60 identified. We will be making sales offers this week. And just the time it takes through the holidays to get them on before they can start being trained. There's a little bit of a variable that we're not exactly sure of yet. But certainly, mid-Q1, we should have sales representatives trained with materials in the field and the channel fill will also come in mid-Q1. So we feel strongly that we'll have it in mid-Q1. You probably won't see revenues probably until the end of the quarter, if not Q2, is our expectations. And then maybe I'll ask Lorenz to provide you some answers and a little bit more color around the price that you had asked about and the factors that go into how to think about net sales and the number of doses per episode.

Yes. Thanks, Joe. So there was 2 variables you were focusing in on, Ted. One was the number of doses that we might model per episode that a patient would use. And then secondarily, the number -- our estimates on the number of episodes per year that a patient would treat with. Is that correct?

No, I'm just more asking at a high level where -- what goes into the variability in that revenue differential between $500 to $1,000 for you guys.

All right. Sure. So if you think about net sales, when you launch a drug, you don't have coverage and you achieve coverage over time. And I mentioned during the formal remarks that we would have some level of denial conversion for patients and co-pay mitigation to help patients afford their drugs. Those are typically higher early in the launch than later. And so that would eat into our net revenues or net sales price because we're helping patients to get the drug. Once coverage is achieved, a, it's easier to get the product covered. There's less prior authorization. Ritu asked about what we did with medical exception and whatnot ahead of time. So those are the main factors that sort of lead to perhaps a lower gross to net earlier in launch in a launch year and even the entire year. And then as you get into a second and third year after launch, you get more to a steady state. But I do want to address the question on doses per episode and episodes per year because we also think a driver of net sales in aggregate in terms of demand is going to be how many times do patients refill a drug. We do expect at steady state in the second or third year on the market as patients are on drug and are rolling into each subsequent year that the average patient would use etripamil a handful of times. We model 4 to 6 times a year. But earlier in a launch, because of the dynamics of getting a prescription and then waiting for that episode to happen and then treating yourself and then getting another -- getting a refill, we actually model between 1 and 2. So at most 1 refill a year in a launch year on average. So I would just moderate expectations on how many refills. In terms of metrics, you heard me say earlier, we're looking at the new-to-brand, new patient starts as a key driver and that week-over-week script growth and not so much refills as a driver of net sales in the launch year.

Thanks, Ted. And let me just add one other comment just to the first part of the question Lorenz answered. These are full net revenues where when we say $500 to $1,000, these are not net sales to post payer. So it has the payer rebates and things like that, which are very mild to moderate rebates. It also includes distribution costs to the wholesalers, includes COGS. So those are full net revenues to the company when we give that $500 to $1,000. So full -- all those variables are in there.

Our next question is from Zhengxi Sun with Wells Fargo.

This is Zhengxi for Mohit Bansal. So congrats on the approval. I just have a couple of questions, if I may. So my first question is, of the 3 segments you guys mentioned in terms of cardiologists, electrophysiologists and primary care, is there any one of the segments that are prescribers where the heavy lifting will be relatively low and they can come on board faster than others?

Yes. I think I'll ask Lorenz to expand. But certainly, the ones who know most about the product right out of the gate is the electrophysiologists, right? They are the thought leaders. They're very heavily engaged in our program and have provided advice to us. They're very prominent on formulary decisions. They are a smaller group. So they've -- many of them are aware through our publications, which are highly oriented towards their publications that they read. So I would say the ones that know it best out of the gate are going to be the electrophysiologists. And as Lorenz had said, there are clear use cases for them to use it around their ablation procedures commonly. So we view the first year sales to come disproportionately, I would say, relative to peak year sales from electrophysiologists. But then over time, as cardiology learns about this from their electrophysiology colleagues as well as their peers that are close to the program, and there's just more of them, really, the lion's share of the scripts will come from cardiology, not electrophysiology.

I have a follow-up -- sorry.

Lorenz, do you need to add on that?

I was just going to add that we've done also early adopter analysis to know within cardiology, within electrophysiology, even within primary care, like who are likely going to be the earlier prescribers that basically adopt new branded products across all different use cases. And so we will obviously be targeting those when we first launch. And I'll remind you, our sales management team has been in the field now for 6 or 8 months. They were on board even back in March. And so they've been going out and engaging customers, profiling offices, disease state education. So they have a good sense within their regions, who are going to be the physicians and the health care practitioners that are more receptive to adopting early. And so that will also drive some of our early targeting activities.

And I have a follow-on question, if I may, that can you guys help us to understand the royalties to the RTW for the next few years? It seems like you guys have 7% until $500 million peak sales, but then there's a 2.5% additional number based on the sales target. I'm just wondering, could you guys help us to clarify that?

Sure. I'm really going to ask Amit, if he's on the line, to take you through the royalty with RTW.

Yes. And there's usually a slide in our deck that kind of go through this a little bit. You might need to go to the footnotes. But you're correct in the way that you described it. There's a 7% royalty at the kind of lowest sales threshold. Because of some of the delays, we will have that additional premium. So the way we model it is 7% plus the 2.5%. So 9.5% all-in royalty for the, I guess, foreseeable future, we're not really guiding on future revenues, but I would model that 9.5% in at least for the first year or 2.

Our next question is from Brandon Folkes with H.C. Wainwright.

Congratulations on the approval. Maybe just for me, can you elaborate on the refill process for patients? When prescribers write the initial script, can they write for a refill or a certain number of refills? How easy is it for a patient to get a refill? What is the process? Do they need to come in? Is this something once they have a documented diagnosis of PSVT, it's the telephone consult -- or just any color on that process would be helpful. And then just is that going to differ significantly initially when they potentially are processed as medical exceptions? Or could they get an exception for a number of refills versus maybe later on when you have broader coverage?

Lorenz, do you want to take that for Brandon?

Sure. Happy to. Brandon. So the refill process, and we will be promoting for this is a physician, if they're comfortable with the drug, can write a prescription and then indicate the number of refills because this is that kind of a therapy like a chronic oral in that way, where you would expect some refills, patients have ongoing episodes. And eventually, doctors have told us they want to have patients have access to the drug so they can treat themselves quickly. So ideally, they have one in the -- at home, in the office, in the car, that kind of thing. Having said that, you're correct, medical exception, formulary exception, every process is a little different. So in some cases, they may allow only one prescription and no refills. In other cases, depending upon the forms and everything and the actual approval that comes ahead of coverage, there may be the ability to get 1 or 2 refills. And some physicians are going to be comfortable writing refills right out of the gate because it is a calcium channel blocker. It's a mechanism they're very familiar with, early adopters typically are more like that. And then others are going to be more cautious and they'll write a script with no refill, ask the patient to call them back once they treated an episode, find out how they did and then they'll be comfortable writing refills. So we don't expect it to be a high bar, but there may be a little bit of slow ramp-up. And again, that's why I alluded to earlier, we're modeling between 1 and 2 doses per year per patient in the launch year.

Congrats again on the approval.

Our final question is from Dennis Ding with Jefferies.

This is Georgia on the line for Dennis. I wanted to understand a little bit more about the different like segments that you stated and which you expect to flip first or that might move faster than others between like the pill in pocket and the chronic meds and the bridge or alternative to ablation and just how your strategy may be different or the same as you move each?

Yes. Georgia, I'll start, but again, ask Lorenz based on the research he's seen to articulate that. And obviously, if David has an opinion based on his interactions. But I'll start with -- it's a great question because we have seen and heard from physicians that they see it useful in all cases. A reminder, 2/3 of our patients in our clinical trials were on background calcium channel blockers or beta blockers and still at events. So clearly, one of the things we're proud of is the drug can be used on top of existing therapies and would be a very natural add-on. But Lorenz, maybe you can provide a little bit of color on what you've heard from the physicians relative to your market research.

Yes. Joe, it's very consistent with what you just said. Physicians, once they understand the product profile, have a low bar of prescribing. They're essentially asking us who would I not use this in rather than who would I use it in. So they're really just looking for contraindications, which, as you've heard from the label, are relatively minimal. So pill in pocket to us is the absolute floor of the market because there's no reason you wouldn't write a script for CARDAMYST if you had offered pill in pocket to a patient given that the profiles of the 2, although we don't make direct comparisons is very obvious to clinicians. And I'll add, importantly, in terms of the type of target patient that we would deploy our sales force against when a physician asks, love the idea of the drug, who should I use it into one of our sales reps. Newly diagnosed patients that have more urgent need to find a therapy that they are comfortable with. Patients with a history of ED visits representing sort of a higher burden of disease. Those are -- and they might have a pill-in-pocket script. They might be on prophylaxis. They might be in queue for ablation. But in all cases, they represent a higher disease burden. And so those are the patients that we would ask physicians to get initial experience in. And then over time, like with many drugs, they'll broaden that experience to just about anyone who asked for it, just given the nature of this drug and the lack of therapeutic options once a patient is in an episode.

Yes. And David, can I ask you, David, to specifically provide a little color on when you're preparing for an ablation, this idea of a bridge to ablation and removing background meds, why do you -- why would -- explain what a bridge to an ablation is from the view of an electrophysiologist. That's something we hear over and over again.

Sure, Joe. A couple of quick points. The first is before an ablation is performed, the idea is a patient has to come off all of their background therapy that could theoretically or practically interfere with the ablation. And one of the goals of ablation is to measure the cardiac conduction system and to induce the arrhythmia itself, and that can be challenging to do if a patient still has some background therapy on board. So the basic idea is whether a patient is on background therapy with an AV nodal blocker or certainly on background therapy with an antiarrhythmic drug to wash those drugs out by stopping them, let's say, several days or perhaps a week in advance. That leaves the patient vulnerable to potential events right in the couple of days before their planned ablation. So for all those reasons, patients may need a bridge in order to make it to the ablation without having breakthrough symptoms. The other idea of a bridge is that patients often go for ablations when their background therapy isn't working. So the last thing an electrophysiologist wants to do is to recommend an ablation, describe that background therapy really isn't working because it often does not and then have patients have a couple of episodes in a couple of days or a couple of weeks while they're waiting for an ablation. The last point to make to you, Georgia, is that you asked about the type of patient that this might be prescribed for. I just want to underscore what Joe and Lorenz has already said. This is a simple calcium channel blocker. Cardiologists or even primary care doctors are very used to prescribing calcium channel blockers for all sorts of entities. Now in this particular entity, PSVT, background therapy doesn't work tremendously well, but physicians are very used to prescribing it. So they would be -- so the idea of having CARDAMYST, a readily available calcium channel blocker whose acute administration and rapid onset of action has been extensively studied already to prescribe that. It's just -- it's not going to be, I think, a complex decision in that person's mind, be relatively straightforward. This is a simple solution with a drug or a drug class, excuse me, that is -- physicians are very well accustomed to.

There are no further questions at this time. I would like to turn the floor back over to Joe for closing remarks.

Well, I'd like to just thank everyone for spending the time to listen in today to our update, and I'd like to wish everyone a great rest of the day and a happy holiday season. Take care, everyone.

Thank you. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.