Good morning, everyone. My name is Brandon Folkes. I'm one of the equity research analysts here at H.C. Wainwright, and thank you very much for joining us at our Global Investment Conference. Next up, we have a fireside discussion with Milestone Pharmaceuticals. Joining me from Milestone are CEO Joseph Oliveto and Chief Commercial Officer Lorenz Muller. Thank you very much for joining me.
Thanks, Brandon. Appreciate all the colleagues at Wainwright for inviting us. It's always a great conference.
Always great to have you. Joe, we're just touching on this, but it's been a remarkable 12 months for the company. Can you just walk us through some of the success you've had over the last 12 months and where you see Milestone going over the next 12 months?
Yeah. Just appreciate the question. Realized we got a drug approved in the last 12 months. So, actually in December of last year, we got the approval after some hard work with the FDA. Very successful, very proud of getting Lorenz and his team getting the drug into the market, getting a field force stood up and promotional materials, by mid-February, which we thought was an aggressive launch, and in execution mode. I'm sure we'll talk about that launch. In addition to that, really bringing forward the second program. We've always thought of this product, etripamil, as a product for two indications, kind of following our nose where IV calcium channel blockers are used, and that is, for the second indication for us, atrial fibrillation with rapid ventricular rate. Really taking off from the phase II data and starting the phase III study.
We just announced last month our first patient in that study, so it's great to get that up and running. Really now moving into moving forward, it's really about execution on both fronts, getting the launch uplifted after being in the market about six months, which I'm sure we'll talk about, and then the AFib program, we've got it to about a two-year timeline to get to data with some pushes and pulls relative to our expectations and assumptions, but really moving into execution as we branch out into other territories and get that trial off the ground.
Fantastic.
Yeah.
A lot on your plate. As you mentioned, and no surprise we're going to start at CARDAMYST and sort of dig into the launch. If we just step back from the metrics that we're all so focused on, what have you learnt about prescribers' behavior as well as patient behavior in this being a new market, a self-administered PSVT treatment and has anything surprised you?
Yeah. I think the first thing we've learned is we've got a great drug, and that's something really uplifting as you go into the office every day. The reaction from healthcare providers, and that's really where most of our feedback has been so far, is really positive relative to the profile of the drug. They respond very positively to the rapidity, how quickly the drug works, the safety profile, the fact that we have a very low incidence of any off the important off-target effects, which are things like any syncopal or drops in blood pressure. So very positive reaction to the profile. They get it, and we're leaning into them wanting to have their patients managed at home rather than the emergency department. So from that perspective, really positive and foundationally important for the ultimate success of the product.
I think from a patient perspective, we're starting to see that flow through. We see that on social media a little bit. We see that through the doctor's offices, through our reps, and we believe that as patients feedback to their doctors, that's going to be a momentum builder for us. But early days on the patient side, I would say. With regard to surprises, I don't know if I would use the word surprise in as much as we always knew that the opportunity for this drug was really to wake up a market that hasn't had any new innovation, at least on the drug side, for many years. We knew that was going to be a challenge, and we're in the mix of that challenge right now.
We feel like we're on the right path, we have the right strategy, and Lorenz, I'm sure, will talk through as we get into launch, how we're going to uplift to get even more patients on this drug as we move forward.
Fantastic. And one of many things you've done really well is obviously the prescribing breadth to date, right? Can you just talk about or elaborate a bit more on what gets a prescriber to write that first script? And what are some of the frictions outside of, as you mentioned, just prescribing habits because there's been no innovation in this space that you've had to overcome?
Yeah. I will start, but really ask Lorenz to expand. He is at the forefront of this. Like most drugs, I think when you launch a drug, you think of the first patients being treated with that drug as being your most, quote-unquote, "severe patients," right? Sometimes you hear about the train wrecks are the first one. These are the ones that the doctors and their staffs have really no solutions for. Ours are maybe not in that severe category, but more the engaged category. These are the ones that are newly diagnosed. It is a natural time for them to want to learn about the condition and hear about all their options, and CARDAMYST is doing very well with that group. As well as those patients that may have had it for a while, but have had the unfortunate trip to the emergency department.
I am sure most of the people in this audience, if not have been to the emergency department, have had others that have been there. It is not a pleasant place to be, and it is not a pleasant place to be treated for this condition. They are very motivated to act, and CARDAMYST shows up really well there. The next opportunity for us is to expand that. There are new patients coming into this market every year, but then to get those patients that are maybe not showing up at the emergency department, have been diagnosed for a while, and get them in the mix here and there. It is just breaking a little bit of muscle memory, I would say. Lorenz, how would you expand on how we might do that?
Yeah, we are seeing a broad group of doctors write it for patients, sometimes with only one or two details. Actually, promotional response actually exceeded our expectations amongst some doctors. It obviously does accelerate as you get more engagement with the doctor.
What we have learned is what Joe focused on is most doctors, when they are giving us one or two patients, are giving us those, they are not what we used to call a train wreck patient, because you do not really have train wrecks like you do with heart failure or other heart attacks, et cetera. But you have got patients that are energized and want to change their treatment paradigm, or they are complaining to the doctor a lot. That is not the majority of the patients. Majority of the patients have been diagnosed a while ago, have tried beta blockers, have tried calcium blockers, have tried pill in pocket.
Have talked about their doctor ad nauseam about ablations and decided that it was not right for them. They are just sitting at home, and they might go to the doctor once a year, twice a year. PSVT may not even come up in that conversation because the doctor is asking about their cholesterol and their diabetes, all these other things. Since the patient does not know to ask about something new, because we have not gotten to them yet, and the doctor, it is not top of mind because the last time they saw our rep was three weeks ago, they are not thinking about prescribing it for a patient that could really benefit from it. That will come, but it comes with repeat detailing. It comes with awareness generation. It comes with activating patients to know to ask the question.
As we gain momentum on all those different initiatives, more frequency on target docs, more patient activation, et cetera, we will start to go from inertia, which is what this market is experiencing right now, to momentum. That's the shift that just takes a while to engender in a market where there's literally been no new therapeutic innovation in over 30 years.
How do we think about the timing of that conversion to really going deep into those prescribers? From changing them from one or two to making it standard of care. Is that just continuing to do what you do now, but that sort of repetitive core practice, patient feedback loop all sort of snowballs that prescribing habit? Or how do we think about that depth and moving those prescribers to front of mind in that conversation you mentioned?
Yeah, we haven't seen as much of it yet as perhaps we maybe thought we might, given that the product profile is so clean and everything else. But we are starting to see signs of it. So, what am I talking about there? Every week we see more doctors write their second patient or their third patient. Majority of physicians still have written one patient, but we see that metric weekly increase, not by 10%, but by low percentages kind of thing. Where we see, and you've noted on this in some of your coverage notes, that refills continue to trend up, and we're seeing, if you calculate from our earnings call, it's somewhere between 15% and 20% refill rates. That will go up. That won't just go up to 30% or 40% asymptotically.
That'll go to 200% or 300% as patients start to fill two and three and four scripts. Not in a launch year, but not in 10 years either. That's something that sort of a next year phenomenon, we would expect the patients that started this year, had a good experience, will start to go in, get on a cycle, get the refills, not have to go to the doctor, just electronically call it in. So I think those two, getting doctors to write more patients within their practice, not just the most obvious one, and refills, will really accelerate this launch. Optimistically later this year, but realistically for sure next year.
Fantastic. One area that has maybe surprised me is that electrophysiologists, they appear to just sort of be adopting it a bit faster than I thought. Why do you think electrophysiologists have liked the product? Again, it is still early days, but just sort of at this stage. How important are they to the overall positive experience? Is there impact on them having a positive experience to maybe cardiologists, just discussion within the community?
Yeah, I'll start, but then again, ask Lorenz expands. A lot of investors when they hear the initial pitch, they think, "Oh, electrophysiologists are going to be naysayers. You're going to challenge their business of ablations." We've just never thought that from day one. I think one of the reasons we're getting uptake quicker in the electrophysiologists is, number one, they're more aware of it. They're the thought leaders or they're at the forefront of any new innovation for rhythm disorders. We have a very clear message to them that this is supportive or supplemental of your ablation procedures. There's two very clear use cases there, and they've adopted this. They've adopted the idea that if they're going to ablate a patient and it is two weeks, two months away, they'd like to have them covered.
At some point, they're going to come off their background medications, and whether it's then or any point between the consult and the ablation, there's a chance that their patient could end up in the emergency room, and they don't want that. That natural bridge to ablation is a very clear use case. Of course, not every patient opts for the ablation. Whether it's, "I just want to think about it further, doctor," or, "It's not for me," in either case, the doctor wants to provide them something, ideally have them come back to them when they are ready for an ablation. Keeps them in their referral pattern. That messaging has played very well with the ablationist, I would say. Is part of the reason for the quick uptake, I would say. What does it mean for us in terms of going forward?
I've been thrilled with the EP adoption. We didn't think they would be what we call an assassin. That they wouldn't want to support this. I've been surprised at how receptive they have been and the amount of good promotional response. Our promotional response with EPs is significantly higher than it is with cardiologists, clinical cardiologists right now. Part of the reason for that, EPs, I see a few sitting here in the room today, EPs are techies. They love tools, right? Obviously, on the ablation side with all the new ways to be able to do very effective ablations, but even on the drug side, and we have a drug-device combination. It's something you can give a patient that they can have a good result with. They're going to embrace that because they're just technology-driven. That has panned out.
It is important because electrophysiologists are the rhythm experts. It is not like cardiologists do not understand calcium channel blockers, but SVT technically is an arrhythmia. In many practices, the cardiologist, the clinical cardiologist, is going to defer to the EP for new technology, obviously on the device side, but also on the drug side. Getting that early adoption, getting that impact on P&T committees that are governing coverage decisions and institutional adoption, guidelines, which we cannot directly influence, but let us face it, rhythm guidelines have not been updated since 2015, and they are written by electrophysiologists.
All of those things mean we are getting good traction, they are supporting us, they have a use case. They are not just going to be the Hair Club president, they actually can say they have used the drug. That is worth its weight in gold when they are a speaker at the podium or whatever the case may be. We are really, really pleased with how EPs have embraced this.
Fantastic. I think in terms of thinking about where Milestone is going, it is probably a good segue for me to just delve into the AFib program, if that is all right. I think you announced the trial, coming back online. Many of the same sites and kind of operational infrastructures, the PSVT trial. In your view, what does that do in terms of de-risking the trial, just de-risking a lot of maybe the initial learnings you had to go through for PSVT?
Yeah. I think even before that, Brandon, let us remember, this is a non-dihydropyridine calcium channel blocker that acts, looks like in many ways, when you look at a PK profile, like the IV, non-dihydropyridine calcium channel blockers that are effective and approved for these two indications. Right? Let us never forget that that is an aspect that really provides a risk reduction. But you are absolutely right. We learned a lot from the SVT program. We learned how to do studies in the outpatient setting. We got into the types of monitors to use, how to select patients, which sites did well at selecting patients, which ones did not, which ones produced quality data. We learned a lot through our review process of how the FDA thinks about side effects relative to time. Very specific items that are exactly translatable between the SVT program and the AFib program.
We have a lot of confidence in our success there that will be translatable into the AFib program. Let's not forget also that the drug performed very well in phase II, right? Remarkable P value off of the primary endpoint. We're taking a lot of confidence there as well.
Fantastic. This is an sNDA, right? If we think about the dialogue with the FDA during the PSVT program, a lot of that, correct me if I'm wrong here, should have been addressed through the original PSVT NDA, and thus, this is a true efficacy story. Am I correct?
Yeah. The beauty of sticking with the same dosing or lower, you're in the world of an sNDA by the regulation. You're there, you're not asking the FDA for anything unusual. You're within the guidelines. That's very comforting. Then to have them confirm that this would apply and you'd be able to leverage more or less the safety profile from the SVT program, means that you're doing a safety and efficacy study, of course. If there's some crazy outlier, the FDA is going to ask about it from the safety side. But by and large, we feel like we know this drug so well, we know the mechanism so well, it really should be a question of efficacy. Again, there, we feel like we're well powered to be able to deliver what we need to.
Fantastic. Just jumping ahead to the commercial opportunity in AFib, it's obviously substantially larger addressable population. Can you just talk about how you tackle that as a company? How much overlaps with your commercial infrastructure on PSVT?
Yeah. How would you like to describe it?
It's nirvana. It's 100% the exact same doctors that are treating SVT. They're seeing an SVT patient every other week, every week, maybe once a month. They're seeing AFib patients multiple times a day, and it's getting worse. Not good for patients, but if you're developing drugs and you want to help patients, it's a great thing because you can have a big impact. We estimate conservatively 3 million- 4 million patients today have AFib with rapid rate that requires treatment, and many of them, over 1 million a year, go to the emergency department to seek that treatment. These doctors don't want these patients in the emergency. If they're stable, hemodynamically stable, the last thing these doctors want is to have them clog an emergency department. What are they going to do? Run an IV, slow their rate, give them an oral, rate or rhythm control, discharge them.
Rinse and repeat multiple times a year. Wouldn't it be better if they could just do all of that, because they're going to have episodes of rapid rate, but treat it at home? That's for the vast majority of the market. So that is really attractive, both in terms of what we want to do as a company and there's a big patient benefit there, too.
Yeah, I think if I could add on to that, one of the things we have to do now with SVT in a market that hasn't had any new innovation is bring awareness. Foundationally, before you can get scripts written, they have to be aware of it, and that's part of our job, right? That's why we have a sales force and promotional materials, but in many ways, that is a process. This time between now and the AFib approval, that's building awareness of CARDAMYST, right?
The etripamil . You are coming to a market that is primed, and you already have awareness, then it is a matter of making sure that they can identify the right patient and then provide it for that patient. But this time period to almost set up for the AFib launch is really a bit of a blessing and would enable that launch, in our opinion, to go a lot faster because of the awareness that will have been built up between now and then on PSVT.
Coverage as well. Obviously, if you have a drug that has been covered for four or five years, you have gone through all that pain of getting it reviewed on formulary, when you drop a new indication with the same dose and the same SKU, it just facilitates that whole process as well.
Just given the overlapping core universe, as physicians know more about CARDAMYST, obviously you are not promoting to it, but are they already starting to ask questions about the potential in AFib?
Oh, yeah. All the time. That is why we have a field medical team to be able to address those questions compliantly. Yeah, we get those questions all the time. Remember, 20% of patients with SVT also have concomitant AFib, so there actually is a use case where a doctor could prescribe it for SVT, but patients might even end up using it in AFib, even though we do not promote for that. So there is going to be some use even before the trial reads out.
Fantastic. Then maybe just lastly, can you just talk about your cash runway, cash position, as CARDAMYST in PSVT ramps, and then we ramp up the AFib trial as well?
Yeah. So, as of the last quarter, we announced that we continued to reaffirm cash runway into the second half of next year. We're trying to be smart about doing two things at once, launch a drug and get a phase III program off the ground. But again, from the learnings from the SVT program, we're able to dial back some of those CRO costs and do more in-house. It is not a whole program, it is one study. We've gone to the sites we believe have performed well, so it'll be more efficient, and the combination of doing both allows us to get that runway into the second half.
Fantastic. Joe, Lorenz, thank you very much for joining me.
Thank you, Brandon.
Thanks, Brandon.
Thanks, everyone, for coming.
Thanks, everyone.