Milestone Pharmaceuticals Inc. (MIST) September 8, 2026 Conference Transcript

Thank you for joining us for the post lunch session and we have an exciting company so with us we have Milestone with us so we have Joe the CEO of the company and Laurence the head of commercial of the company with us. Thank you very much for joining us today.

Thank you Mahir. I appreciate all the colleagues at Wells Fargo for having us at this great conference. Thank you. so before we get started why don't you just like introduce the company and then those who are new to the story tell us the investment case in the company right now yeah no sure I'm happy to and Milestone Pharmaceuticals is a company that's focused on our lead drug which is called Cardamis the trade for the trade name a triple mill is the generic name and really designed prospectively from day one to be a treatment for patients living with types of tachycardias, and this drug itself is at a stage where it's been approved for its first indication in what we call SVT, supraventricular tachycardia. We'll talk a lot about the launch of that indication, but as I said from day one, it's It's a nasal spray calcium channel blocker, and the thought was to really, wherever an IV calcium channel blocker could be used, this could be used in the at-home setting rather than the emergency department. So the next indication is atrial fibrillation patients that have episodes of rapid ventricular rate, which we've started a phase three trial on. The company's founded in Canada and has U.S. headquarters in Charlotte, North Carolina. We're a team of about 150 people right now.

Got it. So again, exciting time. So you have launch and you have the development, both these things going on right now. So maybe let's just focus on launch and at least adoption a little bit here. So it has been a few months, like you started middle of February this year, right? So what have been the most positive surprises and the biggest challenges so far in this launch so far?

Yeah, so we have launched in mid-February, so going six to seven months into the launch year. We feel like it's a great time to take a step back, see what's worked really well and where we need to adjust. And I would say from two perspectives, the area that we're most excited about is the initial reaction to the actual compounds. When we get in front of health care providers, whether they be electrophysiologists, cardiologists, nurse practitioners, is a very important segment of this particular market they react very well to the actual drug itself it's a nasal spray calcium channel blocker it's designed to break these episodes of svt and the the profile in terms of efficacy and safety is really well responded to they get the concept they get the value prop the idea of keeping people out of the emergency department is a good win for them and it's a good win whether they're a health care provider the patient itself or the system in general so that reaction has been really strong uh it's very comforting and in particular the breadth of prescribers we're getting many people prescribing this after even as little as one or two details they become aware of it and they're ready to prescribe it so that reaction has been really positive um also payers are reacting quite well to the drug and the value proposition we've um so far achieved um coverage in i would say two of the main verticals out of the three main that we have on the commercial side of the business. And, you know, we just announced that at the last quarterly call that we just got the united sleeve of business, if you will. So the combination of the coverage and the reaction from the doctors and the breadth of prescribing are really the areas I think we're most excited about. I think when we think about what's to grow going forward, it's really breaking into, if you will, and I'll ask Lorentz to expand a little bit more relative to electrophysiology, breaking into the cardiologists, right? So electrophysiologists are the key opinion leader experts who are writing a disproportionate number of the scripts. That's a great thing for us because they are so influential across the board, but really our next challenge and opportunity is getting the word to the cardiologists, having them have it top of mind when they're in front of a patient.

And remember, they're not seeing SVT patients every day maybe a little bit more like a weekly two or three times a month so that remembering of it top of mind when they have a patient in front of them is really where we need to go and really where a lot of our programs are are based going forward and this you know six months into a launch we're seeing both EPs and cardiologists right for patients but it's more of a narrow subset of patients that are I would call the most engaged patients ones that have been newly diagnosed, ones that have recently been to the emergency department, where the patient is very animated about their episode, and they want to do something about it. And that works great with the electrophysiologist, because almost every patient that comes to them is considering an invasive procedure, and so they're already, by definition, engaged. With the clinical cardiologist, which is where most of the patients are for SVT, they're managed chronically, the ones that they're currently writing for just represents a small subsegment, and we want to work on making sure these doctors are aware that the patients, frankly, the majority of the patients in their practice that they're seeing every week, they may not be considering for Cardamist because they aren't as engaged, but they have just as much need. They're just not communicating it to the doctor in the way that they might if they just came out of the emergency department. So that's something we can manage in how we message and how we ask our reps to engage with doctors, talking about the variety of patients that they treat as opposed to just going in and talking about Cardamist.

Is there a low-hanging fruit when it comes to cardiologists that you, if you target X amount of cardiologists, you'll probably cover a lot of those patients as well? Is there a, is there a?

Yeah, so we did a lot of work, as you know, ahead of approval to try to figure out how patients are concentrated across the different specialties. Right. Because as you know, we had a stage launch. We didn't go out with 200 reps where we can just carpet bomb all of cardiology. And the results of that, actually, and we've, and we continue to refine it, and we're actually now using monthly claims data to look at this. And what it tells us is that there's a subset of cardiologists, which are within our 10,000 targets that we're going after, that disproportionately manage more patients, meaning that there are cardiologists out there that might see one or two patients a month, whereas others are seeing one every other day. It's much easier when you're trying to generate awareness and trial to get a doctor to write for multiple patients when they're seeing multiple patients a week. If you have a doctor that's seeing a patient every other week or every third week, by the time that second patient comes in, they may have forgotten if the rep hadn't gotten in there. So we're focusing very much, this will not be an issue later in the launch, but right now in terms of getting maximum efficiency, we're trying to make sure our reps are in front of the right doctors that see the most patients and doing it frequently enough where it becomes top of mind so that they start to write it pretty much for every patient they could write it for, not just for the one that they remember to write it for got it so it's more of an awareness thing and then once they start writing it they will probably and have it yeah trying to form a habit got it got it and then where does the where does the pair sit in this equation I mean I know you are doing a lot of work trying to get pairs on board so can you talk a little bit about the progress there with access and pair yeah so we feel like we're a little ahead of the

game relative to expectations. We announced as early as I think it was March or April, our first call, that we received coverage from Express Script, right? That's one of the big three or that sleeve of coverage. And that enabled us to report about 25% of commercially covered lives had Cardamus coverage, right? Remember, about half of this market is commercial, about half of this market is is medicare um and the learning there was that we the value prop resonated quite well with them they brought it on early and then at the second uh quarterly call which was in august we had just announced getting the united book of business plus other pull through from express grips and even from the third uh payer sleeve which cds care mark right so we announced being over 50% coverage. What we do see, though, what we did learn over Q1 is while we had 25% of commercially covered lives, it's not like a step change where it automatically converts to more scripts and better gross than that, if you will. It kind of trickles through as that comes down through the plans. And we'll expect that now, having seen it with the additional coverage that we'll expect from United and then through the rest of the year.

But at the end of the day, the value proposition is really resonating is what we're seeing we're a little ahead of plan and our expectation is that will continue as we continue to engage these payers both on the commercial side and then as we move into next year medicare got it completely makes sense so at this point i mean it's basically getting the access so like when you paint me a picture like when you get into next year i mean how should we think about this uh the launch uh here and we all are like hawkishly looking at the scripts as well so what should we learn from those scripts and what should we not over interpret from the scripts when when we see them

yeah it's it's uh scripts are double-edged short we see them every week we look at them as soon as we get them and obviously it is a big barometer and there's many other leading indicators but as we think of it in this market where you haven't had anything new really for decades quite honestly at least on the drug side and it is a little bit of a waking up of this market we don't see scripts as the ultimate indicator for the success of this market we see it as a combination of scripts a combination of influence the ability to get towards guidelines all these things will really ultimately drive what a Trippamil or Cardamus will be for PSVT. And then as we think forward, coverage will help Scripps, but also help those revenues come through. So we view this year as, you know, a big setup year. And with additional programs that we're putting in place, we'll see that inflection, expect that inflection of Scripps to happen later in the year and into next year. Got it. And then with Medicare, it is just the timing thing? Like when does the Medicare... Medicare starts as early as next year. We're in conversations with them now. Lorenz, maybe you could expand a little further. But we're expecting some coverage to come right out of the gate. The hardest coverage to get with Medicare is the first year you're trying to get in when budgets are not set yet. So we'll expect to have some next year. But then it's not a one and done. You get to continue to engage them and have coverage come on at, you know, reapply for Medicare and come through the rest of the year. So we'll expect some to happen early in the year and then continue through, like commercial in many ways. So it'll be a gradual build.

Yeah, I mean, we're actively engaging with them. We've made our initial offers. We're continuing to follow up on that. We would expect them to publish their coverage decisions in the fourth quarter because they then market that, as you know, to patients in the fourth quarter when they open up enrollment periods trying to grab Medicare patients and then in the new year coverage starts. So we should know where we've been successful or not. But it's not like a one bid and done. We're actively engaging, especially with the ones that have a Medicare advantage as the majority of their book of business, because that's the plan that has both a drug and a medical risk profile. And so the cost offset potential resonates better with them than, say, a PDP plan, which is just a drug benefit where they don't value the medical risk part of the equation.

Got it. Very helpful. and then so with the script like there's one more related question there uh at least early on there's a little bit of free drug program as well in the system uh you are trying to form habit for these prescribers at this point as well so how do you think about the revenue per script right now and the evolution of it over time like how should we think about that yes so another great question and you know we've made the conscious decision that the best way to build muscle memory here for a physician is to get the drug in their patient's hands right so we've by design

provided you know we do want them to write the script we want them to if we call it ping the system look for that coverage but we don't want any hurdles or hurdles to be too onerous because we find that those scripts get caught up in queues, and then that delays getting the drug in patients' hands. So we've been very aggressive with paying down those early scripts, and we'll continue to see that through the year. On the commercial side, it'll get better now that we're over 50%, but we expect that happening through the remainder of the year, let's say. Why? Because we want the drug as many patients' hands as possible, and we don't want to trade one set of problems for the physician which is their patients having angst over this condition at home with another set of not being able to get the drug. So we've made that choice. We would expect our average revenue from a script to be low this year. It'll get better as we get towards a little bit into Q4 but really better next year I would say and we'll continue to do that.

Now once we get to a critical mass of coverage, once we get that third payer on, whenever that are to happen and we get we get at least more confidence that it'll go through a little cleaner then i think we'll start to dial that down got it and we have got in the past to our expectations that steady state would be get to a 500 to a thousand dollar net price per prescription or per sku um when we get to steady state obviously in a launch year you don't get to steady state necessarily at least not the beginning of it but that's the range where we typically dollarize our model is at in terms of Scripps to dollars.

Got it. So the payer coverage so far, like at least from that basis, is somewhere in that range. Is that fair?

No, it's below that now because we're, and this is a double, requires some clarification. If it's covered, it's in that range. Got it.

That's what I'm saying.

But it's getting swamped out by the amount of free drug that we're going to.

Got it. My question, like the covered stuff is still in that range, basically. Yes. Got it. Very helpful. Now, when we look at the stock price, though, I mean, definitely, like, the market is significantly discounting the peak potential there. So can you talk a little bit about what you see in this market that investors are not able to see that?

And in next 12 months or so, like, what are we going to learn that will help probably change the perception? but the the perception yeah i would say that um investors uh really look at the scripts and the scripts are off to a reasonable start but it's a little bit linear right now we expect that to inflect up we have uh every reason to believe that based on our strategy of how we went out we went out to canvas this market we thought about this six to nine months as being that period where you really learn about this market, see how hard that muscle memory is to break, canvas it. And now we feel like we can dive in. We really are excited about the breadth of coverage. We like the idea that now we can start diving in with more frequency with those doctors we believe have the most patients. And as coverage comes on, we start to engage patients, right? The better one aspect we haven't spoken about is patients actually becoming aware of this drug, going in and asking for it with their doctors. That's just starting now. We were conscious to wait until we had at least a reasonable amount of coverage before we did that. So that's an exciting aspect of what lies ahead. And then I would say, lastly, especially as you think out 12 months, remember, foundationally, this product was really developed for two indications, right? Wherever a non-hydropyridine IV calcium channel blocker works, this theoretically should work, right? So we think of now I'll say a tripamil because it's cardamist for PSVT. We don't know what it'll be for AFib. It was really designed for both of these indications and now with the start of the AFib phase 3 trial, you know, 12 months from now we'll be well into that trial. We think greater awareness of a tripamil as a result of being out with a phase three trial will help the overall drug and I think we should start thinking about the value of the product being PSVT and beyond I would say and lastly just on the on the last piece I know you asked about it relative to the launch but we did just achieve the approval in China right right so we've always had the idea that this drug applies across the world the value prop is the same really no one wants to get treated in the emergency department for this condition that should apply to China it should apply to Europe should we get the approval again within that 12-month period so we think the drug

has a lot of legs ahead of it so to make patient ask for it is there a direct to consumer campaign you can run like I mean they cost a lot so you know like so like for a company your side like what can you do to create the awareness in the patient or consumer side of things yeah you want to yeah so we have to clarify so direct to consumer we define that as television ad networks you know 50 million plus a year that's not what we're talking about here yeah with the advent of digital media and streaming services and social media you can actually do direct to patient marketing where you advertise for patients develop a relationship with them by drawing them to a website or someplace we can get them to opt in offer services ask them to go see their rep copay cards that kind of stuff that's what we've built and we're now spending money so you build that and it's a fixed cost and then you invest in a collection of media that different vendors can help you with that actually identify where patients with PSVT disproportionately go, whether it's social media or endemic advertising on websites like WebMD or just search engines, a mix of investments in different markets that you can then measure. You know those patients are there, figuring out how many of them do you advertise to, how many click on an ad, how many go to your website, how many download things, And even ultimately, how many go see a doctor and fill a script? And that's what we've started now. So it takes three, six months, maybe more from the time you start advertising to the time you actually see a lot of scripts being filled in pharmacies as a direct result of that initiative. But we think it's like adding gasoline to a fire because if a doctor at that point is aware they're writing for all the patients that are appropriate in their practice, you're just driving more patients earlier into their practice. And that's really the goal here to get what you asked about before, which is sort of those determinants of acceleration.

Yeah, no one watches TV anymore. So, okay, this is very helpful. So let's just move on to the other indication for calcium CCB. But before we get there, there's one question we get a lot from investors is that, so why can't others do the same thing with calcium channel brokers? And then, like, what is your IP slash the drug device combo that gives you a moat against someone else trying to do the same thing?

I think a lot of investors think they hear calcium channel blockers, nasal spray. It's a 505B2. It is not. It's a new chemical entity. It's got composition of matter around the actual molecule. It's got IP that's been granted in the U.S. and other areas of the world around the formulation. And then we have additional patents around the unique dosing regimen that we have, which is a repeat dosing regimen. So that forms three sets of protective patents. We also have blocking patents around it, you know, as a result of the way we develop the drug. And, you know, that patent protection runs out to 2042, if you consider all three. And that's without any extensions from regulatory as a result of the development timeline. So we feel it's very well protected.

They would have to, if you will, get a new compound, really, to be able to deliver that in the way that we do. Very helpful. Thank you for clarifying that. So maybe, like, I mean, I think the first question I had you already answered, like, basically, why should it work in AFib? Because calcium channel blockers work in this indication.

Calcium channel blockers specifically impact the—it works, and you know exactly how it works. it impacts the AV node of the heart it slows the rhythm across that that AV node from the atria to the ventricles and for AFib the atria is going very fast they call it quivering at 300 400 beats per minute and that makes its way down to the ventricle for some patients and some events and really a calcium channel blocker just blocks that and slows it right and when you can slow the ventricles you bring the rate down and you bring down symptoms very helpful So can you just walk us through the data generated in Phase II Rivera trial?

Like, what can we learn from that trial that gives you greater confidence into the Phase III trial?

Yeah, so Rivera was done in Phase II in the emergency department. We always like to start there where there's a lot of measurables. We take patients that came in that were in atrial fibrillation at a rate above 100 beats per minute, and we gave them double-blind randomized drug, single dose, actually, of atripamil or placebo. We powered it to be able to see about a 20-beat-per-minute difference between drug and placebo. And we chose that because that's relatively what diltiazim, IV diltiazim of vratamil produced in the emergency department. So, again, if we can replicate the efficacy of an IV vratamil in the at-home setting, that's really what we want to do. And what we saw was actually a 35 beat per minute drop. The placebo had five. That was a 30 beat per minute difference. It was highly statistically significant. Patient's symptoms were also resolved, which is very important for the phase three study. And most interestingly, again, our drug is a fast-acting but relatively short-acting drug. You know, works and stays on board for about an hour or so. And the primary endpoint was over that hour. but we saw the effect last out to three hours again with a single dose of drug that was a unique learning for us and we think gives it an even greater potential in the at-home setting right if you can bring the heart rate down and have it last longer you know the idea of another drug being put on you can take your time to put other drugs on and have them convert the patient or continue rate reduction out with an oral drug for days if you want. So the fact that it came down quickly, stayed down, and stayed down for a long period of time was really what was most amazing about the drug in the Phase II trial. And now it's a matter of really doing that transition of Phase III as we did with the PSVT program. So in Phase III, did you plan to have the second dose as well? We will have the second dose. So that gives it. Now, what was interesting is we saw that average rate reduction of 35 beats per minute, but there were patients that didn't respond. So we think that second dose will bring it down for those patients. And the repeat dose works such that if you see the effect, you do not take the second dose. Right. If you don't see the effect, if you still have symptoms, then you take it. So we think we have a little bit more of a hedge to get even more patients to to resolve their symptoms. I'm just cutting you off every time. ticketing so very helpful so the one question I have is that you know from going from emergency department to an at-home setting like it kind of introduces another risk here so like how do you mitigate that like you know at home versus right now so that we've really wrapped ourselves around the axel on again in the PSVT program we had a convert or translate if you will from the phase two being in the electrophysiology lab, and that's, in that case, to the outpatient setting. We're going to use a lot of the same tried and true factors that work there. We'll go to the similar sites that performed well. We'll go and use similar cardiac monitoring systems that worked well and avoid the ones that didn't, because we had some that didn't. we got really good at understanding how safety events are measured relative to time so we're going to take all those learnings from the SVT study and really apply them to the AFib study in addition for the AFib study we have this you know requirement to show that patients not only reduce their rate but have symptomatic improvement as well that's a requirement in the FDA so it's a secondary endpoint of this trial but it is an important one to hit to get the approval and there what we're going to rely on again is patient reported outcomes that that performed well in our PSVT program and similar PROs that performed well in phase two to translate to this phase three study that we're going to do and need that endpoint so we feel we have a lot of confidence based on the experience is the bottom line. So the the heart rate decline after the drug is it also measured by patient like how is it like so it's it's it's measured on this cardiac monitor that the patient puts on so it's they don't see their heart rate and it's measured by a third party adjudication committee that'll see the rate reduction and confirm that it was a fib with RVR that's an important factor and then what the rate is and the primary endpoint is over the first 30 minutes got it yeah there are variables now so you can probably do this I'm They're wearable technologies now, so you can probably do them. Well, we don't put them in the trial. We don't preclude patients from having them, though, right? That's just the real world. And the reason we don't include it in the trial and require it is we feel that that could potentially bias the patient, right? If you see your heart rate either not reducing or reducing, you'll feel better or not when you throw out the patient for the outcome. So there's no way to blind the patient from their own wearable, but our cardiac monitor, that's why they do not see their heart rate got it got it very very helpful uh and then uh does FDA so FDA also cares about patient reported outcomes here that's a second that's yeah that's a require that's one thing we want to make sure our investors are aware of um we've powered it based on really the secondary endpoint if we powered it based on the primary of ventricular rate reduction be a very small trial on it so it's an 150 event trial um again we model it like we've modeled our PSVT trials, which are around the same size. We'll probably enroll somewhere in the range of 400 or 500 patients to get 150 events in about two years.

Got it. AFib is a much bigger market compared to PSVT. So do you think one trial is enough for identifying a patient?

Yeah. So there's two aspects, and I'll ask Lorenz to talk a little bit about the market there. But from a regulatory standpoint, it's not the size of the market that drives the trial. It's really the regulatory pathway. And here, since we're using the same dose and dosing regimen as the approved dose in SVT, you're able to follow what's called the supplemental NDA pathway or SMDA. And that's where you could rely on the safety data from the PSVT program and leverage it and really aim to prove efficacy in your single study. So it's modeled at a P.05 powering to be able to deliver a single study. But you are right, Mohit. This is a much bigger market than PSVT. Maybe you can mention a little bit about that.

Yeah, I mean, it's not only is it bigger, but it's growing much faster, too. So latest estimates are it's about five times as large as SVT, 10 million versus 2 million patients diagnosed prevalence. Of those, we've done some research long ago, so we'll have to revalidate this. But physicians tell us about 30 to 40 percent of their patients with a diagnosis of AFib have episodes of rapid rate that require treatment. So think of that as 30% to 40% of 10 million or 3% to 4 million patients would be our target addressable market. And then it's all about, you know, how frequently do they have these episodes? How many times would they use it a year? And we don't have a lot of good information on that, but it's no reason to believe it would be that dramatically different, although it might be a little lower than SVT, just in terms of a typical patient with SVT has 12 to 15 episodes a year from work we've done. I don't think the frequency of episodes in AFib is quite that large, but it's still, you know, significantly more than one or two. So I think on balance, yes, a bigger opportunity and one that we're really excited about, you know, getting, especially because it's the same dosing regimen and everything based on the commercially available product. And there's even some patients, about 20% of patients with a diagnosis of PSVT also have a diagnosis of AFib. So there's even some overlap between the two indications in the same patient.

And what is the overlap between the two prescribers? Is this the same prescriber base?

I mean, it's virtually 100%. It's the same docs managing both patients. They're just seeing where they see a handful of patients a month with SVT, one a week, one every two weeks. they're seeing multiple patients a day with AFib and treating them.

Got it. Very, very helpful. So to that extent, I mean, it seems like a very de-risk trial as well, right? Because you're already seeing the data, you have the phase two data, you have to basically execute on that.

It's a well-known mechanism of action. You know what it works, you know what to look for on the safety side. So yes, we think it's de-risked and we're very bullish on it hitting. and we'll execute on that.

Got it, so at this point, what are the timelines at this point?

Yeah, so again, based on our modeling off of the SVT program we're thinking about two years from the start and we did just start, we just announced that a couple weeks ago, so second half of 28 for data. And then we would look to quickly file that with the FDA and it would take a one year review. Got it, very helpful.

It's very, very helpful. So I think one last question I have, and I want both of you to answer this question, basically. So one year from now, Wells Fargo, 2027. I hope we all are sitting here. What would make you look back at the year and say it was a great year for us?

Yeah, I'm gonna let Lorenz answer his portion around the launch, which is a big focus, But let's not forget that we're going to be along the path on on an AFib phase three study. My full hope and expectation is that the launch in China is taking off. We're starting to see revenues from that. And it would be great to see it approved in Europe. And getting access to those patients. And we'll be on the search for a partner for Europe as well. So, you know, I would expect that to be a great year for us. But maybe you could talk a little bit more about the launch a year from now.

Yeah. Yeah. I mean, I'm looking back a year from now. I want to see broad commercial coverage. I want to see all three GPOs. I want to see, you know, well more than we have now and where it's really not an obstacle for physicians to write based on what the insurance that the patient has. I'd like to see a fair bit of Medicare coverage as well. And I think that's about achievable in 2027. as joe alluded to earlier i want to see an acceleration of prescription growth off of the current trends and i think that'll be enabled by coverage in part but also by physicians being more familiar more aware and writing it for you know 5 10 15 patients in their practice not just one or two and i think the patients that got a script in 2026 will start to refill those scripts in 27 and that adds a compounding effect as well so all those things to me gives us inflection upward and trajectory. And that's what I would, that's how I would measure our success next year.

Awesome. On that high note, all the best and thank you very much for joining us today. Thank you, Mel.

Appreciate it. Thanks everyone.