Great. So welcome, everyone. It's my pleasure to introduce the president and CEO, Marcio Sousa, and the CFO, Tim Kelly of Praxis Precision Medicines. My name is Kevin Strang. I'm one of the biotech analysts at Goldman Sachs. And, yeah, so welcome. So to start us off, maybe for those that are kind of newer to the story, would you mind giving a brief introduction and maybe what you view as your core competencies and philosophy as a company?
Yeah, absolutely. I appreciate it. I appreciate the invitation and being here today. I'm Mark Susan. Tim Kelly, our CFO, is here with us. I think what we're trying to do right now, right, and arguably done part of this and going to be hopefully finalizing the next part and then there's going to come the next and the next and so on, is to address like a fairly large number of markets in CNS. When you think about like a central framework, for example, which is our arguably largest part of this has really been nothing and maybe Tim can talk a little bit about the size of the market and I'll go back and talk a little bit about the science and so on. and everything else, I would say fades when you think about it, too.
So when we talk about essential tremor, it is one of the largest movement disorders, a prevalence of roughly 7 million patients in the U.S., about 2% to 3% of the population, and there's never been a drug designed for this population, which is staggering given the size of it. Another movement disorder much better known is Parkinson's, but that has a prevalence of about a million. If you get a sense of just how large the essential tremor opportunity is, while there's a prevalence of 7 million, our initially addressable market is about 2 million, and we get to that number from a longitudinal claims analysis that we did a few years ago that the conclusion out of that was there's about a million patients currently on treatment, and propanolol is the only approved drug. They're taking a number of other things off-label, and then an additional million patients who have tried treatment but come off of it. And so when we look at as we're launching, we're not going after the full 7 million. We think there's definitely opportunity down the road to bring market share to that group, but initially focused on those 2 million patients who are currently substandardly treated or have tried something and gone off. And then there's an additional about 200,000 patients who are diagnosed every year as well, particularly as this is an aging population and it is a disease that progresses with age So we talked about two to three percent of the broader population, it gets to be about six to eight percent of the 60 plus population also. There's quite a lot for us to focus on and target and what I think we'll go through in the next few minutes is the strength of our drug Elixacaltamide to address this market. We are in a phase right now where that's under NDA review with the agency and so a lot of what we're doing right now within the company is to prepare for the launch in the upcoming Pidufidate in late January of next year.
I think why I wanted to talk a little bit about the numbers, right, and get him to speak about that is we normally start with, like, the studies and, like, the STA process and things like that, but in a sense, the reality is there is no other market where you have, like, two, three million like, I think we've been putting this on the lower end of two or three million patients and with basically absolutely nothing for those patients and I think from a market opportunity perspective it is completely different than any other market what when you think about like competency as you said we proud ourselves for really thinking very deeply about like new markets as you probably I was just heard not only on the understanding on the next phase but before that where there are reasons why on a market that large no one but us at to this point succeeded and really on our relationships with the agency and making sure at moments like now, particularly in drug development, I think we have to be very thoughtful about how we engage with the FDA and with the other entities. On top of all the work Tim just mentioned about that we've done with physicians and understanding the markets and so on, a very deep understanding of the payer and how they view the drug and therefore what kind of process and particularly support for these patients you need to put in place. But there's no place we look into that does not result into a, like, very, very large, and I think sometimes when we put numbers like $10 billion peak revenue for this drug, it sounds, for some people, a little bit absurd because we just haven't had a lot of $10 billion drugs. But if you actually take the very simple mathematical way with, like, non-compactors, millions of patients, like a drug that is very clearly effective and safe for these patients actually become, in a sense, a conservative number, if I may.
So sort of to book on that, 2 million is somewhat of a conservative number in that they've already been diagnosed and treated and are either currently on therapy or have come off. And so I guess for elixircalzomide, you know, can you talk at a high level about how you can address sort of this unmet need for those patients the efficacy benefit that you're seeing I guess we can start there yeah absolutely so the there are
very few times I thinking in drug development particularly when you are looking for a new indication that you not only have like a large indication as you just talked about but what do you measure and what patients actually are asking for the same thing so when we talk and we can imagine talk to thousands of patients at this point in time, including a very recent survey we put a little bit in our corporate deck on really trying to understand what do you expect from a drug, number one, and how does this condition affect you. Because it's so common, I think one of the biggest features, unfortunately, I may say, of essential terms, is that people just try to hide. As you go through life, the vast majority of the patients start having symptoms at their teenage years, and that's one of the misconceptions like most people think about like an old people disease but it's actually very early in life that it starts 70% of them have family members so that's normal second or third or fourth person in the family has it but then it slowly progress on losing function and the reason why that's important is it's an increasing disability disease right where you're like feeling some internal tremor and then a lot more external and then like you can't quite write very well and it progressed to full-blown not being able to do anything like no dressing, no eating, no of course never leaving the house to socialize and things like that. So the FDA gave us a very strong advice a few years back that they had no interest in a sense on measuring the tremor itself and it was very wise and at the time uh we didn't think it was so wise but now we realize why it was uh because it varies a lot throughout the day but what it does not vary is the impact in life like uh it would be incredibly difficult for those patients to be like here and like drinking their coffee as we are or even having the breakfast as you just asked us if you had this morning that's not possible for them like compound that with age right and then you see like this really big problem with an aging population as we have in the US. The results of the essential three program we had anywhere between like I'll say the mean on about five functions on the ADL restored the way to zero like meaning the ADL goes to zero no function of access. We're looking to the American Academy of Neurology we had at the plenary meeting for like clinical research, over 20% of the patients have more than 12 functions restored. When you put that together if we're talking about the size of the market, this is not a small change. I would argue that even if it was small, it would be quite important to judge what's important for a patient. Those are very large chains on their lives every single day that gives independence, in a sense, to some of those patients.
Got it. And you've highlighted sort of the distinction between tolerability and safety, you know, when it comes to the profile of the drug. Can you characterize the tolerability profile that you're seeing?
So the drug acts on an incredibly important part of the brain, primarily, right, on the thalamus. And I think what we learned as well is there are certain patients, like about 70% of the patients, you can go very quickly to maximal efficacy. and they tolerate the drug really well. But for about 30% of the patients, it's a little bit too much to go that fast. Of course, we could just say, let's ignore this 30% or so because with a market with a multimillion number of patients in the U.S., from an overall financial perspective, it's irrelevant, but that's not how we think, right? Every single one of those patients is important to have the drug. So why would they then have any safety concerns and I think it's incredibly important to highlight this. When you're studying a population that the average age is on their 70s, in our study was 68, you're concerned about major safety issues, right, like hepatic, renal, like you name it, death. We didn't have any of that, but we did have a lot of dizziness that led to this continuation on about 30% of the patients. When you take a step back from that, our understanding very clearly now is that if you keep the patients for a few more days, they tend to basically stay, so it goes away, the dizziness. One of the conversations we had with the FDA, where they proposed for us that we kind of try to come up with a label that in analysis supporting the label, of course, that would allow for a lower number of patients to have this continuous dizziness. We did propose something for them based on the phase two, where this continuation was about 10% so we have that knowledge we're able to propose and it's actually incredibly simple at least a priority where you keep the patients for a longer period of time of 20 milligrams and they tend to resolve so we give them the opportunity one not to have like the dizziness that leads to discontinuation this I'm gonna call it small just because it's a minority of the patient small part of the patients and at the same time give the best possible benefits once they continue on the drug so again a great
outcome in general the way we see and sort of where would you say you are in terms of that strategy your confidence in being able to implement that and then you know with what flexibility doctors have in the real world and you're
holding yeah I'm going to start by the last part there Kevin that's okay the irony is that when we present this to a very large number of doctors they say oh this is just like every drug I have every single day in neurology and I'm just going to figure that out and I'm going to titrate them to effect when they need to so they were never the actual issue here and doctors are going to do what doctors do when the drugs available in the market I think it's important as well that we have as much data to inform in the label to inform those prescriptions and to inform the proper use and the combination of the phase two As I just mentioned, understanding that the tolerability is significantly better if you just slow down some of those patients with the FDA really, I would say, supporting at this point in time, including that in the label. Of course, it's going to be a matter of label review in the coming weeks as we're entering that phase with the agency.
One other thing I might layer in, when we talk to physicians as well, and the neurologist population in particular, they're very aware of the disease, but also that they have not been able to treat their patients sufficiently with the existing drugs, you know, propanolol being the only thing that's approved. But other things that they're using, it's not enough for what they want to do to provide their patients some relief. And so a lot of awareness about the disease and a lot of interest in olexicalcimide as a therapy for these patients as well.
And I want to talk about, you know, what you're assuming for sort of long-term persistence on the drug, you know, in the real-world setting. What are your assumptions going to that? What data points do you have in how long patients could actually stay on this drug? Is there sort of like a benefit threshold that they need? How do you think about that? Because I assume it's a factor going into your $10 billion.
It is. Take a step back here as well. I find it super interesting. When you go back to the studies, right, and the way we've done these studies was understanding that no one succeeded before what was the key features we needed here and we made it incredibly simple for patients to come in to the study which at the same time made it incredibly easy for them to lead the study so that that was one one factor here when you look into the number of patients right now like on drug and the study ended of course last year we reported the result it's pretty much everyone that completed like of course there's some life goes on it's a very very high number of patients that were on the drug at that point in time are still in the drug right now we have patients for years now receiving elixircaltamide hydrochlorides which is in our view incredible but maybe quite importantly as well we really haven't had like discontinuations that due to lack of efficacy directly to to your point right but by whether or not they were for lack of efficacy and then the patient and reports of course I cannot attest to that but in a lot of studies you see this right like lack of efficacy as one main reason so so the patients really see the effects in our rather limited but important open label extension from the previous study we see and increasing the response as they stay for three more months at the end. That's when we measure that, which is very encouraging. Of course, we're talking here about the progressive disease on their 70s. The fact that we are seeing multiple functions regain is nothing short of, like, fantastic, I would say. But the fact that they see that response, they tolerate the drug well after the discussion we just had about how to get to that point, and they stay for multiple years, it's fantastic. Are we counting for any of that on the forecast? No. Because I think the, like, again, I said simple math before, but if you actually go and do the simple math, this is not 10, right? It's probably like 20 billion dollars. So we are taking a conservative approach, and I know it sounds oxymoronic to say conservative and 10 billion on the same sentence but but it is so we're taking the clinical study discontinuation rates as one of the worst case that we've seen so far even knowing that we can do better than that that was without supports we're using the lower ends of what the pricing can be maybe even less than the lower end one could argue here and in a slower curve to get there in the recent work that Tim mentioned we did with a few thousand physicians in the US we haven't done a lot of work in the fields as you know in terms of like didn't have like a large MSL our group and going there and exchanging scientific information with these physicians it was incredible to see one the level of awareness and it is right things that we haven't really talked to them so how much they know but then the second that was the most fantastic for us was their day of launch intention to prescribe is about two and a half times our peak intention to prescribe expected so I think we're in very good territory one of the things about the forecast in general now your next question could be do you actually have supply for all of this right and that's something we're always being very careful on building the inventory to make sure we can on a one would call like a best case scenario not trying to inflate launch expectations quite the opposite I think I think we have to be responsible for what we are seeing but it is I'll say using all of this as you know very deeply this markets we're very happy with with how things are
shaping up got it I just want to do a quick question before we get to the the commercial aspect but you know just to bookend that the label and how you think about it where do you anticipate from now on the most discussion with the FDA and I guess just how should investors think about you know the titration language warnings contraindications like what should they be looking for in the label what are your expectations yeah yeah so think about
this like page one or section one there is no expectation for contraindications here so I'm going to be clear there the the warnings that you would expect is the things we just talked about, right? Yes, people can get dizzy. It's important that they discuss that with their healthcare professional, particularly in general. I think the bottom line here of this indication as well, of course, we'd never be able to speak for the FDA, but we've been multiple times now in multiple conversations with them throughout this program. In December last year, after reviewing the final results, they granted us breakthrough designation. I think that point is important because all the safety, tolerability, the efficacy were there. It is incredibly hard for someone to look into the clinical results of this study, particularly the level of detail the agent has, and say it's not bringing benefit for the patients. So then you turn to the other side and say, okay, is this harming patients in any possible way, like in normally the major organ systems and particularly liver cure? And the answer is no. So the benefit risk has been and will continue to be, in our view, quite positive. So the discussions now that we are entering, as you just said, pretty soon in terms of labeling, will likely focus on proper use. And we know because we asked for the advice from the agents, and they told us that they don't want to trade off efficacy for tolerability. So they think that we can figure it out both of them are together and the proposal at that point in time is for second iteration right the original iteration the titration the label is 20 40 60 one week apart milligrams per day and The alternative one is 20 milligrams like staying for a long time The the good news there is that it's not that you have zero efficacy at 20 milligrams So it's not something that you're just not having anything and and we switch to 40 you see basically the top of the efficacy there as well. So it's actually a pretty good benefit risk for the patients in general. We're very optimistic about it.
Great. And you talked about pricing briefly. I think you talked about maybe $50,000 as sort of an annual target price. Is that a target? Could that be a floor? And sort of what analogs are you putting into that?
So it is, I'm not going to be disingenuous here, just that there's a space there, right? It's more of a floor, the way we're looking. And the reason why is, like, we did a lot of analog work. Number one, if you look into the initial population, right, what you're going for, the kind of benefits the drug gives, but particularly what payers are telling us, because I think at the end of the day, that is going to be how they ramped it up. I think there's basically no resistance or elasticity, as we call it, like between, let's call it 50 and 100, or even maybe a little bit more than that. So then we have to ask ourselves, like, what is the best for the patients and what is the best for the company and our shareholders? And it probably is a number in between. And the kind of service that we believe we should be giving here, particularly like medical education in terms of proper use of the drug there's no expectation to have anything more complex than just the label so there's no rems expectation there's no mandatory medication guides or things like that but we do believe that we should be educating those things cost like money as well so we have to support and then the next development so i think to guide between 50 and 100 is probably the place to be get some analogs too we look at
the tartar dyskinesia market so a little bit smaller but it is a movement disorder there are a couple players in that space and the price is low six figures so it does give an analog and what we're talking about is a price that recognizes the value of the drugs we can support patients but also gives a floor
for great and you know on the commercial aspect and having filled with pricing You talked about, you know, potential step-through requirements for propranolol, which is the only FDA-approved drug. You know, can you talk about, you know, your expectations for how that will work? And then, you know, even though it is the only FDA-approved drug, not every patient is on it, you know, how does that dynamic work, you know, in terms of getting access to the drug?
Yeah, so I think when we're planning for uptake execution, it is more conservative for us to expect step through with propanolol and then you know work with that upside if there's not as much there so rather than be surprised by it with that we don't expect much friction there so one of the issues with propanolol it's a beta blocker given the age of this population about half of them are contraindicated from it from the beginning and then the other aspect of it is a number of them have already tried it so what we might expect is maybe there is some type of requirement for have they tried it in the last three years and I think a part of what we're looking at in terms of our commercial execution and rollout is how do we use data and systems as well to help support things like prior authorization and step through and accelerate that aspect of the process and it would also be part of what our medical communication and information is as well we can support the physicians as they're going through this with all that's required there so that if propanolol is required we do that but we get patients onto the drug that can really help them which is elixir, caltamide, hydrochlorate?
We'll give you like two data points there. So one, in our forecast, we assumed everyone would step through propanolol. So we'll think about how conservative we're being there. And then Tim just mentioned half of them cannot medically even do that. And the second is we went to the private payers, right? And we asked, like, what are you going to enforce? Any restrictions? And here's the population expecting for well that all of them are going to say yes that they want. And it was less than half that said yes to that. Understanding their population, right? We're talking about numbers. Like, think about the United Health Cares of Life. There's, like, a lot of those patients, for example, which was surprising, to be honest. And I think it's just looking into how much utilization of the system these patients end up having with conciliary support and then ultimately really needing a lot of care and what the drug can give, delaying the treatment is probably not wise on a drug that gives its maximum treatment starting around two weeks. So it's incredibly fast to get there as well and to help this patient. So it was another interesting potential upside here in general.
Sort of on the commercial readiness front, you've talked about maximizing your investment up front in terms of maximizing the commercial opportunity. So can you talk about that investment, what that entails in terms of field force and sort of education perspective? I know you started some awareness campaigns. Can you talk about where you are today versus where you want to be in January? So I would say we're more than halfway through it.
Our launch readiness expectation is in Q4. Like some place in Q4, I'm not going to give the exact numbers, so we're not trying to be ready by January, like the end of January as the PDUFA, but actually by relatively early in the fourth quarter. So we have to be pre-advanced right now in order to be there. One, things can always be accelerated with the agency. I know we normally think on the other direction, but we need to be ready for the both directions. And the second is just making sure we understand this market as much as possible. We start with a base of like over like 217,000 patients that were in our database. That's where we're starting from. And those all have like positions linked to them. And then as Tim just mentioned, we just refreshed the the claims data set which we were able to like really understand who in the last 12 months, 24 months, 36 months, actually seeing one of those patients was the largest concentrations. When you put all of that together it is about 13 to 15,000 targets in the U.S., or like accounts that we want to cover, when you back calculate all of those things, we are about 200 to 300 sales reps to cover that. I think most companies would start with 200, and I think we're making a decision that we start with 300 because then we can cover everything we just talked about, the potential upside. A middle of the country, particularly, There's a lot of large PCP practice covering the space for neurologists, and they need attention as well. And as we discussed, we want basically no patient left behind, in a sense, so we want to make sure the physicians prescribing understand the drug and can guide the patient. So the wave one of the launch is going to be neurologists and the top decile for PCPs on this disease.
I think we're fortunate with the balance sheet that we have right now. we can invest heavily up front into the commercial launch. The other thing I would say is Alexa in January is our second launch over the next three quarters. So we'll have a little bit of time maybe to get to Rolutra gene, but we have that coming at the end of September as well. So there's a lot of activity internally right now.
That was my next question, actually. So I know we can talk about that all day, but moving to Rolutra gene, this is actually potentially your first approved drug with the September PDUFA date. Can you talk about the opportunity and the initial genetic de-indication, and then how you're preparing commercially for that, and then we can move on to potentially the broader opportunity.
So the STN2A and 8A, which is intended to be like the first approval here coming up September, I think my guess is on the 25th, just because the 27th is the weekend, but you can tell me I'm wrong when we get there, and they actually do on Monday instead of on Friday. We'll see. We are preparing next month's launch readiness, a date for us. We want to be launch ready in a few weeks. It's progressing incredibly well with the FDA. I think the reason why we focus a lot on ET is really people not even grasp the surface on ET, and I think it's a little easier on Relitrogen to talk about that. But the first launch itself, and we should always think about the first indications, like, over, like, billions of dollars in potential revenue here for two reasons, right? So, one, 5,000 to 10,000 patients in the U.S., all of them need better drugs. Like, this is not a matter of, like, who is doing well, who is not doing well. No one's doing well on this condition. It's going to be the first approved drug for the indications ever, once again, just like. we're discussing before, and when you go back against your payers and so on, then we're talking about not really having an upper limit, and then we're just trying to understand what maximized access here in general. The choice we took was to actually cover a little bit more than the centers of excellence, I'm going to call, at time of launch. So we're going to hear us talking more and more about numbers, but you could easily cover this market with about like 30 or so like sales like reps or personnel in the field and maybe like about a third of that in MSL we're probably gonna go a little bit on the higher end as you can see this is a thematically how we're going through this we're not believers that every three or six months just say I'm gonna increase I'm gonna increase that you're chasing the demands is the appropriate way to launch drugs anymore but rather to get the best possible experience from the get-go maximize the launch and remember we have emeralds coming up in q4 right as a as a result which expands the the indication about 10 to 20 fold depending on how he wants to to see here our incredibly confidence about the the clinical profile and what we are seeing from a blinded view on that study and and what we're getting from the patients who already rolled out to the open label extension so when you consider should never launch for the second indication but I think we have to be ready for the fact that physicians are going to feel constant and I'm going to start wanting to have conversations with the MSLs and someone about that and we need to be there for them when they want to talk about it got it and can you share what
you're seeing in a blinded fashion that yeah I think there's a I'm gonna call a
shape of the distribution that gives you more or less confidence we always have to be incredibly careful about blinded review like what I think while being burned before I haven't I have for sure but there are certain like distributions I would call that they're just clinically impossible on a population they're so refractory so the more to like very high response rates I'll say in large number of patients in the study the more constant one should feel one particularly one that is associated with very good safety, as we are seeing on this study. We enrolled more than we were expecting initially on 160 patients here. I think we talked about it. We use very, very high quality pediatric sites. It's a pediatric condition. We wanted to make sure we have those patients there. And we wanted to make sure as well that there's no over-representation of some cohorts. particularly the ones we know that is efficacy already, like 2A and 8A, and we accomplished that. And I would say, having basically looked into this every day for many weeks, that I'm as confident as one can get about what we are seeing.
And is there anything in terms of the, like, how do you think about execution risk from going from that concentrated population to a more genetically diverse population?
So the good news here, twofold. So one, prescribers are the same, right? So when you're talking about promotionally about 2A and 8A, if they have a question, we can get that to our medical team to answer the questions about the broader. So we are right in front of them, which makes it incredibly easy. They are already coming to us and actually asking questions right now. And then on the second, of course, we're going to be pricing this, thinking about 2A and 8A. And what you're hearing from payers in general is that we probably have two to three years to make adjustments if we need to. So it allows for that very successful financial ramp on the following, like, two to three years without having to start considering price adjustments and things like that. So when you're looking for recent price on the rare disease space, on drugs actually, have competitors, which is not the case here, We're talking about anywhere between like $450,000 to $650,000 per patient per year. I think that's a good place to start here.
And I want to touch very briefly. You had a recent update for Matrogene in focal onset seizures. What can you say about that at this point in terms of the program and where you go from here?
Absolutely. So, we just had the results from the Power One study last week for rheumatoid gene. I think a couple of good news and a couple of bad news there, right? So, the bad news is that it's not the profile we wanted for that population. So, we did not meet the expectation from the tiered reduction that we wanted. There was positive on the responder rates on the 50%, so that's one of the good news. I think there's a lot of other good news here, right? So we see the drug at either 20 or 30 milligrams being really well-tolerated, like sub-10% discontinuation, really not idiosyncratic events, a good dose response between 20 and 30, which gives us what to go from here. And allow us to take a little bit of a step back right now and ask again, what is the drug for? And I think the more we look into this and the distribution of the patients, and what they're in, the closer it gets to the original profile of the drug, that it's really a great drug for the 60% or 70% of the patients, and that's probably where we should be focusing the development moving forward. And yes, it's going to be used on the hyperrefractory patients. That's what this study was, the highest seizure burden ever in a study. That was the power one, which is accomplishing the fact that we get a lot of very severe patients, but also talking about the limitations of getting there a severe patient so a few things to tighten up for the next studies and but we are quite optimistic
about how to move forward here great well Marcio Tim I didn't even get to Elsa nursing and the rest of your pipeline so I apologize for that but next time no thank you very much for being here thank you for having us appreciate it