Good morning, everybody. Thank you for joining us here today at the TD Cowen 46th Annual Healthcare Conference. My name is Athena Chin, as part of the biotech team, and I'm pleased to introduce Milestone Pharmaceuticals with Lorenz Muller and Amit Hasija doing a company presentation, followed by Q&A. Amit, please take it away.
Let me see. Thanks, Athena. And thank you to all your colleagues and our partners at Cowen for having us at this conference. I'm Amit Hasija, the CFO at Milestone, and I'm gonna take you through a little bit of the presentation, but also Lorenz Muller, our chief commercial officer, is here to also go through some of the commercialization efforts. We'll first talk a little bit about the product, a little bit about the company, and then take you through our commercialization, and then finally share some of what we're expecting on our next indication in atrial fibrillation. What I have up here now, you guys are probably used to, but you can look at this, our forward-looking statements on our website and review that at your leisure.
Start with CARDAMYST, which is the brand name for our drug etripamil. It was approved on December 12th of last year. We're just off to the races now. You can see a picture here of the drug itself, which is a carrying case and two nasal sprays. It's about this big, so you can get a sense of how large it is. Fits in your pocket, you can carry it with you. There are two sprays because the first spray is the initial dosage. Each of these has one dose, and the second one is in the event that your tachycardia has not broken, you can take a second dose. It's indicated for the use of conversion from acute symptomatic episodes of PSVT.
Let me take you through a little bit of the Milestone story here. We did launch CARDAMYST in PSVT. We had it in pharmacies as of January this year, and in February did our actual commercial launch. Field reps out there, a field force the size of about 60. We have a full commercial and marketing effort behind this product, and we're really focused on new patient starts this year, script growth, and broad commercial coverage. We are also looking, you'll see in the bottom left-hand corner here, at atrial fibrillation, which will be our second indication. We have done a Phase II study, and we're ready to start a Phase III study, a large addressable market which we'll talk about a little bit later. In the bottom right, a little snapshot of our finances.
A little bit stale now, they will get updated soon with our 10-K coming out in March. You can see that there is a reasonable cash balance as of September, which, to which we added $75 million more recently, a royalty payment from our partners at RTW, and so that is also on the balance sheet, and you expect to see that in the 10-K that comes out. As we move forward, I'm gonna give Lorenz the driver's wheel here, so he can take you through the commercialization.
Thanks, Amit. Good morning to everyone. Exciting times here at Milestone Pharmaceuticals, off to the races. You heard the approval December 12th of product in channel, reps detailing, you know, engaging thousands of customers a week, engaging copayors on coverage discussions. Everything is on track, and I'm very excited to give a little bit of an orientation of where we are, what our goals are for the year, then I'll turn it back over to Amit to talk about our pipeline and our financials. Let's first just remind everyone the problem we're trying to solve.
The disease is paroxysmal supraventricular tachycardia, which is a very rapid heart rate, often in excess of 200 beats a minute, that spontaneously occurs in patients that have the disease on and off for their entire lives, typically onset in early twenties. It is highly symptomatic in most patients. It is bad when you have it, and it is very anxiety-provoking in between episodes because it's unpredictable. You never know when it's gonna start, how long it's gonna last, how bad is it gonna be, when am I gonna have to go to the emergency department. It's more common in women than men, about 2/3, 1/3. About half of the patients are over 65, but that also means half the patients are commercially insured, and that has advantages from a commercial launch standpoint that I'll talk about in a minute.
Most of these patients are treated by cardiologists, so it gives us a focused call point. The treatments that are available once you're in an episode are essentially nonexistent in terms of evidence-based medicine. You can try a vagal maneuver, which is a bearing down. You can take an oral L-type calcium channel blocker or a beta blocker, which have exactly the wrong profile to stop an acute attack, slow onset and a long tail. What you want is an IV-like profile, something that goes up quickly, short-circuits the arrhythmia, and then is off-board, so you don't have any of the off-target effects, which is effectively what we have done. There has been nothing new in this marketplace from a treatment standpoint, from a therapeutic, since adenosine was introduced in the latter part of 1989, so over 30 years.
The opportunity is significant. This is not rare or orphan disease. There are over 2 million patients with a diagnosis of SVT in the United States and an incidence rate, newly diagnosed rate of between 200,000-300,000 per year. Many of these patients are going to the emergency department to seek treatment, which is costly, intrusive, and unpleasant. 25% of those patients end up going and getting admitted, which increases the cost dramatically, which is not lost on payers. Even though it's an episodic condition that self-terminates, it, and is rarely fatal, there's over 100,000 ablations performed a year.
People willing to undergo an invasive procedure to freeze or burn parts of their heart tissue in order to achieve a cure for this. Despite that, though, 85% of the market does not seek invasive procedures 'cause they're afraid about the consequences of that potentially. Importantly for our launch strategy, almost half this market, or up to half this market, 1 million patients a year, are seeking treatment for this condition independent of us motivating them to do so. They're going and getting scripts filled, visiting doctors, emergency department visits, hospital admissions, ablations, all of that captured in claims per year. There's an active market that is seeking treatment.
Our commercial strategy is to focus on physicians to make them aware and trialing to treat the patients that are already coming to them every week to seek treatment for SVT. Our solution, as Amit introduced, is CARDAMYST, which is a novel calcium channel blocker. It is not a reformulation of verapamil. It is a more potent L-type calcium channel blocker than either verapamil or diltiazem. As you heard and saw from Amit, it's portable and on-demand nasal spray. It is FDA-approved, and it has robust clinical data, which no other agent treating acute episodes can say. A very fast onset of action, Cmax in 7 minutes. It is extremely well-tolerated. I'm not showing any clinical data today, but you can see it on our corporate website in our larger corporate presentation.
The kinds of data you'd expect, a cardiologist would expect, Kaplan-Meier curves, hard outcomes measured on ECG, and objective evidence of safety. Shelf life is 36 months. It'll be a little shorter in the launch year 'cause we have, you know, clinical batches that we're using, but at least 18 months. Then at steady state, we'll have up to 3 years, which is more than enough time for those patients to get value, even if they're only treating an episode a year. As I mentioned, it's an NCE, so it has composition of matter, use patents, and formulation patents out through 2042. A lot of time to both develop the market and expand the market with indications like atrial fibrillation. Commercial success of CARDAMYST to us is really has 3 pillars.
We wanna make the product for patients easy to use, we wanna make it easy to prescribe for HCPs, and we wanna make sure that payers see the value and the novelty of it so that they have a limited need to manage, actively manage. We chose our pricing strategy commensurate with that and our distribution strategy. As a commercial officer spending my whole career commercializing cardiovascular therapeutics, I can tell you this is a very exciting opportunity. It's rare in this market where you can come into a large market and say, "I have no branded competition, not just now, but probably for the life cycle of the product." That means when I go out and send a sales force into doctors, I control the narrative. There's no one counter-detailing me.
On the payer side, there's no one negotiating against me for rebates to get into that rebate spiral like you see in the back in the day with lipids or novel oral anticoagulants or heart failure drugs. There is a relatively low barrier for prescribing in this market. What I mean by that is clinicians, cardiologists, even primary care, are used to using L-type calcium channel blockers, this class of agent, to treat arrhythmias for over 30 years.
They understand, and with hard evidence and robust data, it's not gonna be difficult, and this is based on all the market research we've done, not gonna be difficult to go in to convince a doctor to trial this on a patient when that patient comes to seek treatment because there really are no alternative treatments for the doctor to prescribe once a patient is in an acute episode. As I mentioned, there's lots of patients that are gonna be in the market without me having to spend tens of millions of dollars to activate them. Half the patients are commercially insured, which gives me leverage in a launch year when Medicare coverage tends to lag.
We'll achieve commercial coverage more rapidly than with Medicare coverage likely. About half the patients are commercially insured, so we can co-pay mitigate them down to pay no more than $25, so that it is not only accessible but also affordable for patients. A lot of that is in terms of contracting with payers will leverage the fact that we have demonstrated cost offsets. We saw a 40% reduction in ED visits in our pivotal trials. This is a complicated slide, but I wanna talk to you specifically about what part of the market we're targeting and the concentration of patients that makes deploying 60 reps in a launch year efficient but also feasible. The gray little stick figures in this chart across the entire chart represent the 2 million patients.
Each stick figure is 5,000 patients, 2 million patients that are diagnosed with the indication of PSVT. About 1 million on the right-hand side in the blue box of those are in the market every year seeking treatment because the burden of disease is sufficient that they want to have treatments to be able to prevent or treat the episodes. Of those, the lower half red box, half of those, 500,000 patients, are being actively managed by 10,000 HCPs. That allows us to deploy a sales force of 60 reps to call on primarily clinical and interventional cardiologists, about 8,000 of them, electrophysiologists, about 1,500 of those, and a small number of primary care physicians that are very high-volume treaters of cardiovascular disease, about 500, for a total of 10,000 targets for our sales force.
I will point out that that's where we can focus to demonstrate the market and be successful in the launch year. It gives us lots of opportunity as we achieve coverage to grow up into the remainder of those million patients by adding additional reps and to move to the left by doing patient activation exercises so that the patients on the left that are not in the market every year will end up coming in because they've learned about a new treatment to treat a disease that up until now they don't have any real feasible alternatives to treat while they're in an episode. Let me just pause for 1 minute and talk a little bit about our access strategy. As you heard me say earlier, we've focused on limiting the need for payers to wanna manage the disease.
First and foremost, we leverage the economic efficiencies of the cost offsets, which payers are very interested in. It doesn't mean we can charge a higher price. We've announced a WAC of $1,649, and we have plenty of room to negotiate down to rebates that will allow us to get tier-two and tier-three access even with Medicare. The expected use of the product is 3 to 5 times per year per patient, which does not scare payers at all.
What they want to avoid is patients using it 50 or 100 times a year, and we will likely allow some quantity limits in a launch year or negotiate for quantity limits to allow the typical patient to use it sufficiently enough to meet the disease burden, but not so much that the payers feel like they're not getting value out of it. This will enable tiered coverage, is our goal, tier 2, tier 3, branded, non-preferred brand, as well as with only modest rebates. As I mentioned earlier, we have a broad array of tactics that will allow us to have commercial patients pay no more than $25, as well as support systems for both HCPs and patients in terms of reimbursement and patient support in how to use the drug correctly.
That allows us to achieve our goals of making it accessible. As I mentioned, we're going through a full retail distribution, so it's available in 50,000 pharmacies across the United States, as well as easy to prescribe for the clinicians. Our key metrics in a launch year are gonna be fairly straightforward. It's all about driving physician or HCP awareness and adoption. We are a retail distribution model, so investors, analysts, people who are interested in our company and tracking our launch will see scripts every Friday or Monday, depending upon which service you buy, and we will report them obviously quarterly, as well as looking at week-over-week script growth. That's the primary focus of the launch year, is to demonstrate demand.
In order to enable that demand or accelerate it, we will also be actively contracting for, as I mentioned, for covered lives, primarily focused on commercial, and we will report quarterly on the % of target lives that are covered, and also the quality of that coverage, meaning what specific tier and utilization management have we allowed or negotiated for with each of these payers. In summary, we're focusing on generating scripts and getting them filled. We feel confident that we'll be able to exceed our forecasts and expectations because our initial sales force, we have 60 reps, covers more than half or roughly half of the potential patients that are gonna be in market in 2026.
Physicians are seeing these patients weekly in their offices, not daily like AFib, but weekly, and their familiarity with the class of drugs will make it much easier for them to prescribe. We're expecting, rather than the 6 to 7 details you typically need to generate a first script, we're optimistic that we'll see a more quick promotion response than that. On the filling script side, retail distribution makes it very easy for doctors to write it. They can send it to a Walgreens or a CVS and not a specialty pharmacy. We have active patient support programs in terms of nurse educators as well as reimbursement support, CoverMyMeds PA Plus, RelayHealth, eVouchers, co-pay cards, reimbursement call centers, everything you need to support a brand with what I would call hub-like services.
As I mentioned earlier, and it's very important, from a commercial standpoint, we have no branded competition in this market, and we're getting good traction from payers on the message of value driven by potential cost offsets. With that, I'll turn it back over to Amit to talk about our pipeline and our financials.
Thanks, Lorenz. On top of PSVT, that's now opened up the pathway for approval for an AFib program. We are planning to do an sNDA approval pathway and to have a Phase III, a single study Phase III, which I'll talk about a little bit later for atrial fibrillation. You can see here the numbers for the size of those markets. PSVT, about 2 million patients. Atrial fibrillation is significantly larger. Many of you may be familiar with atrial fibrillation, but what we are focused on is really those patients with rapid ventricular rates or episodes of rapid ventricular rate. You can see that leads to about 785,000 ED visits and hospital admissions each year for patients who have these kind of acute episodes.
What we have calculated with our own market research is that the AFib market's about 3-4 times larger than what we're targeting with PSVT, so opens up a whole new window and a large addressable market for us. We did run a Phase II trial already. Some of you may be familiar with this data, but we've condensed it here. What you see in the unshaded region was what we were really looking at, is the ventricular rate reduction over 60 minutes. What we had learned was that in this condition being a little different from PSVT, we're not breaking the tachycardia, we're trying to reduce the ventricular rate to make that patient more comfortable so they can take whatever other meds they might be on for their condition.
The idea here was to target a 30 to a 20 beat per minute reduction. We got to 30 to 35 mean beat reduction across that white or unshaded area. What was really surprising about this was these patients actually had not only a rapid reduction in ventricular rate, but also durable out to 180 minutes. We've extended the graph here just to show you that when those patients became more comfortable, it was a bit self-fulfilling. They were able to move on to their other meds very easily. Much fewer use of IV and oral meds in this Phase II study that we saw, we hope to replicate that in the Phase III.
Just turning our attention to what that Phase III might look like, it would be, as I said, following an sNDA pathway, a single Phase III study. It would have, it'd be a double blind randomized study with a primary endpoint being this reduction in ventricular rate, which we just showed you an example of in the earlier slide. A key secondary endpoint would be symptom relief, which we're prepared for and have seen early indicators that that could also win on a statistically significant level. We are gonna size it similar to what our experience has been with PSVT, so about 150-200 episodes that we'll try to record. It usually takes about 500 patients to be enrolled to get to that, and that's what we'll target to get the 90% power. We are ready to start this.
We had a little bit of a setback last year, as many people know, with the CRL. We stopped what we were doing, but we are prepared to start again this year, and there's more to come in terms of timing on that. We are planning for this to be about a 2-year study ultimately when we do launch it. The last slide that I'll end on here, again, these are September 30 numbers, we'll update them. As many of you look at our market cap and look at our total equity exposure, we have about 101.6, we call them units. That includes common shares and pre-funded warrants. On the right side, you'll see an inclusion of some of the raise that we did last year, which included some Series A and Series B warrants.
All of this is on our corporate website and our financials that you can look up, and we'd be happy to answer questions later. I conclude on that and see if, Athena, you have any questions for us.
Thank you for the presentation. Maybe to follow up, I'll start off, and then take audience questions. Can you review how the initial launch is going in terms of prescription volume and which areas in terms of settings you're seeing the most interest and uptake?
Great. Thanks for the question, Athena. I think maybe Lorenz's gonna be in best position to answer that.
Yeah. I mean, Look, we're a couple of weeks into the launch, and so I wouldn't suggest that we have any material trends or any important there, but, what I look at early in the launch is, A, are there scripts at all? You guys are seeing them weekly, and they are, and they're building, and that's really exciting. That gives us a lot of confidence. Most importantly, we're seeing that all of the systems we put in place that I just reviewed from a reimbursement support standpoint, patient support, pharmacies actually having the product, dispensing it to patients, all the medical exceptions that have to be, filled out because as of today, we don't have any contracted coverage, and we're obviously gonna change that.
That tells me everything that we planned on is working and it's actually generating volume. You know, I was thrilled that we had product availability within literally 1 month of the approval. We announced that in mid-January. You know, it's just past mid-February here. All the reps are out delivering literally thousands of calls every week and the reimbursement support is working. I feel like we're off to the races, and now it's a matter of every week watching the scripts grow and seeing how we do.
That's really exciting. When do you anticipate payer coverage to come mostly online?
We've been engaging with payers now for more than 2 years, and we've now transitioned from doing pie presentations and budget impact presentations to actual contracting discussions. Obviously focusing on commercial payers first, so the big three PBMs, Ascent, Emisar, Zinc , and that's gonna be the primary focus for 2026. That doesn't mean we won't be opportunistic about looking at Part D plans. They are required by law to review new products within 90 days, but they're not required to cover them, right? But we do think with our health economic story around cost offsets and ED visits that especially the MAPD plans will take an earlier interest than perhaps they normally would, which would be a 12- to 18-month cycle to get on next year's formularies.
Even IDNs, especially the ones that are also focused on medical risk as well as drug risk, we were in active discussions and anticipate. We're not guiding to any specific coverage, but we will announce quarterly at a minimum what we've achieved. As we get larger wins that we think are material, we'll also press release those.
You'll provide launch metrics such as prescriptions. What other kind of metrics should we expect?
Yeah. I mean, I don't have to provide weekly prescriptions 'cause everyone's gonna see them depending upon whether you buy Symphony or IQVIA data, you're gonna see it on a Friday or a Monday. What I'll be able to do on a quarterly basis is sum up that and give you a little more color in terms of how many doctors are writing and the breadth and depth of prescribing, those kinds of metrics, as well as then coverage.
Got it. Diving more into your launch strategy, how are you planning to scale with success? Can you walk us through what the rest of 2026 looks like and how that's going to inform your plans for the next 3 years?
Yeah. As you heard me say, we're focused on the roughly 10,000 doctors with 60 reps that are treating about 500,000 patients that are already in the healthcare system, and we're gonna drive awareness and trial amongst those physicians and amongst those patients. What we will also do. It's all about generating demand in a launch year and demonstrating that there's a real market there and that it's gonna exceed both our own expectations as well as the street's expectations. Having said that, we also have some dollars that we've started to invest in pilot programs around patient activation, different ways of non-personal promotion to physicians, all things that are, in this digital age, you can measure.
We wanna end the year, obviously, with having success with some of those, but also importantly, learning which ones gain traction, what's the ROI on those investments, whether it's activating patients or getting surround sound around physicians or even physicians in what we call gray space, which is we have large territories with 60 reps. You can imagine if a rep is focusing on one city in their territory, what kind of demand is being generated in the other side of that territory, and how can we resource that either through non-personal or other means?
From all of that, we'll learn this year, while exceeding expectation on the underlying script demand, we'll also learn, like, what kind of investments can we do in 2027 when we have broader coverage in terms of adding more reps or expanding our non-personal promotion or even engaging in patient activation to basically put gasoline on the fire.
On that patient activation, which types of PSVT patients do you think have been left on the sidelines, and how are you gonna try and recapture those?
I mean, in terms of sideline, the ones that are disappointed with treatment options, have probably had the disease for a number of years and are just. They've been to an emergency department once, twice, 3 times, not had a good experience. I'm not criticizing the emergency departments of the world, but just it's time-consuming, it's expensive, it's not pleasant to get adenosine, so they're in the sidelines. And they're sort of just sitting there and not engaging in the healthcare system. By introducing to them through various patient activation techniques, building a relationship with those patients, saying, "Hey, there's something new out there. Go talk to your doctor," we hope to drive a number of them into the office that normally wouldn't be going into the office in 27, in the next year. Even we'll test it this year.
That's how we'll pick up on some of that pent-up dissatisfaction that is not so dissatisfying that they're going into the healthcare system anyway. Those people will pick up in the launch year.
Got it. With that, I will open up the floor for any audience questions. Just let me know, and I'll pass the mic to you.
What's the biggest pushback from doctors?
It's a great question. What's the biggest pushback from HCPs? It's early days yet, but I'd say the biggest hesitancy we're seeing is just a lack of awareness of CARDAMYST and Just getting in front of the doctor, getting their time, cardiologists are busy people, and then actually spending the 5, 10 minutes to learn about CARDAMYST. I think that's probably the biggest obstacle is just apathy or a lack of awareness. It's important for me to note, I mean, this is a market that needs to be woken up, that takes time.
The good news is, when you have a great solution for a problem that is material to these doctors in terms of a burden on them and, of course, on the patients, once they hear about a solution and they believe in the clinical evidence, the Kaplan-Meier curves, the kind of evidence they're used to seeing to get confidence in the treatment, and the very broad safety profile and the tolerability of the drug, the likelihood is they're gonna write quickly to get experience. It's really just getting out there, getting in front of clinicians, and the time it takes to book an appointment, get in front of the clinician, have them hear your message, and then having a patient come in and actually that they can treat. I think all of that has to happen.
They're in the office weekly, the patients, but they're not in the office daily. It's just gonna take some time to build the momentum. Once a doctor is aware, and they start treating the first patient and the second patient, then it's gonna become more natural for them to, you know, treat half the patients that are coming in front of them.
The cardiologists are notoriously conservative. Do you see any pushback because I don't know this drug, and I don't know, how this works?
It's a great. Yeah. Cardiologists being conservative and just being hesitant and slower adopters, I think is the nature of your question. Look, I've been launching cardiovascular drugs for over 30 years, and I've launched a number of new classes, whether it's a NOAC or whether it's an ARB or whatever, and that is a behavior you often see. Those are new classes of drugs, many times an entirely new class of agent, and so they're naturally cautious, making sure it's safe and, you know, and the right kind of patient gets it. What I've been really excited about for etripamil, and the whole reason we developed etripamil is it's a known class of drug. Doctors know L-type calcium channel blockers. Been prescribing it for their entire career, even if they've been practicing for 30 years.
As long as we can prove it's safe, which we have, and as long as we can show robust evidence, and the fact that there's nothing else for them to offer these patients that actually is evidence-based, gives us a lot of confidence that they're going to have a much lower bar to prescribing, and then that will lead to a steeper promotional response curve than you typically see with a new chemical entity in cardiovascular medicine.
Can you talk a little bit about the patient journey?
Yeah. It's an onerous one. Actually, we've done an observational study that recruited 250 patients, which is the evidence I'll present to you, where basically they opt in, and for a year, they capture every episode that they have, how long did it last, how did they treat it, how bad was it, et cetera. It's the most robust data set ever been developed for SVT. From that, we've learned a number of things. The typical patient has 12-15 episodes a year. The onset of the disease is typically in their 20s or 30s. It is often just an acute onset of rapid heart rate. They often think they're having a heart attack. They rush to the hospital.
Sometimes it's captured on an ECG. They say, "Oh." On a single-lead ECG, a cardiologist can diagnose this disease. If they've converted spontaneously before they get seen and monitored, now they're like, "Oh, I don't know what this is. Mrs. Jones, you seem to be really worked up. Maybe it was an anxiety attack. Here, take a Xanax or a Klonopin and go see me, you know, see me next time." 50% of patients are misdiagnosed, especially women early on. It takes 2-3 years to get diagnosed, and then the treatment options aren't great unless they want an ablation, and the vast majority don't opt into that solution. It's an onerous one, driven primarily by the unpredictability of the disease, and then the severity of the symptoms when and if they actually have an episode.
Great. We have 30 seconds left. Okay, great. Yeah. Can you talk a little bit about your thoughts on launches ex-U.S.?
Yeah, I'll turn that one over to Amit, who's been doing a lot of that work.
Yeah. We're primarily focused on the U.S. as a company. Anything we would do ex-U.S. would be through partnership. We do have one partnership today in the Greater China area. They also ran a phase three. Are in the regulatory process right now. We're excited to see where that goes. The data was great. Looked very much like what we see in the U.S. We're hopeful that they will get approval soon. Other regions, we sort of are. Right now we're always in discussions with potential partners. It is also a complex time in terms of pricing and what the impact might be on the U.S. I think we're taking baby steps in that, in that regard. More to come as we learn more. Yeah.
Great. We're at time now, so thank you everybody for joining us today. Have a great rest of your days.
Thank you. Take care.