Praxis Precision Medicines (PRAX) Q2 2026 earnings call transcript

I would now like to hand the conference over to our first speaker today, Daniel Ferry, Managing Director of LifeSci Advisors. Daniel, please go ahead. Good morning, and welcome to the PRAxis Precision Medicines second quarter, 2026 financial results and business update conference call. This call is being webcast live and can be accessed on the Investor section of PRAXIS' website at www. praxismedicines. com.

Please note that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.

These may include statements about the company's future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent PRAXIS views as of today, they should not be relied upon as representing the company's views in the future. PRAXIS may update these statements in the future, but is not taking on an obligation to do so. PRAXIS refer to PRAXIS's most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with the company's business. Joining us on today's call are Marcio Souza, President and Chief Executive Officer of PRAXIS, and Tim Kelly, our Chief Financial Officer.

After providing updates on our key programs, we'll move to a brief Q&A session where Marcio and Tim will be joined by Steve Petra, President of Research and Development, and Megan Shuninsky, Chief Operating Officer.

With that, it's my pleasure to turn the call over to Marcio. Marcio?

Thank you, Dan. Good morning, everyone. Thank you for joining PRAXIS' second quarter 2026 conference call. Three months ago, I told you this would be the year PRAXIS became a commercial company. This quarter is the one where that stopped being a plan and started materializing into the organization. We have two NDAs in late stage review with the FDA, with both approvals expected in about six months. It's extremely exciting to bring both elixacal mites to UT patients and relituragene to SCN2A and 8A patients. We have commercial leadership in place, a field force for the first launch hires and trains, and a distribution network established and inventory being built. I want to spend most of my time today on some key regulatory developments in what we have been building.

Let me start with Ulexacalc mite. Essential tremor affects over 7 million Americans, and there is still no FDA-approved therapy developed specifically to treat the condition. With the potential approval coming up by January next year, ULICS AccountMind is poised to change that.

Speaking about the NDA review, the FDA completed its mid-cycle communications with us and are very pleased with the progress and discussions with the agency. In that meeting, the agents identified no efficacy-related significant issues and stated that it does not plan to request an advisory committee meeting.

I would characterize the discussion as expected and very forward-looking. On the commercial build itself, leadership is in place and all core capabilities are where we expect it to be at this stage. We will be ready ahead of PDUFA to launch elixacalutamide for ET patients.

We're set up for a very successful launch and continue to think many years in the future, as we intend to continue to serve patients with ET and other neurological conditions. As part of that, you should expect updates from us in the near future about life cycle opportunities for T-type calcium channel inhibitors. One of those steps is the collaboration we just announced with Reimagine, which would extend the reach of Elixir further.

Their work is about expanding the value for patients and Praxis way beyond the initial launch year. Turning to reliturgyne.

SCN2A and SCN8A are among the most severe epilepsies we know of. Fisier onset in infancy, profound developmental delays, and no approved treatment. The addressable population is roughly 10,000 patients in the United States. As we disclosed last quarter, we submitted additional sensitivity analysis of existing clinical data, and the FDA deemed that submission a major amendment. And the review period was extended with a new PDUFA target now off December 27th this year. In the mid-cycle meeting for Rulutrogene, very similarly to Ulexacalpamide, as I just discussed, the agents also confirmed they do not intend to hold an advisory committee meeting. If approved, Rulutrogen would be the first therapy for SCM2A and 8AD and would be eligible for a pediatric review voucher.

Just like for ULIXA, launch preparation here is further along than the calendar might suggest. Commercial and medical teams are fully hired, the supply chains established, and have to build a comprehensive patient support program, program, all pointing to a very structured and successful launch. The broader opportunity keeps getting clearer. Enrollment in Emeralds, our studying broad DE's, exceeded its target with approximately 200 patients enrolled, spanning more than 50 distinct genetically defined etiology, amongst many others not genetically defined. There is a trial population that did not exist as a cohort even five years ago.

Assuming the study will be positive and the initial review for re-letrogen in 2A and 8A also positive, Emerald would serve as the base for a supplemental NDA approval in 2027.

It's also worth mentioning a quick regular update that spans both programs. During the quarter, the FDA conducted a BIMO inspection of PRAxis as a sponsor for both ulexacalcimide and relitrogena applications. The scope was very comprehensive, including corporate and clinical operations, safety, reporting, data integrity, statistical analysis, and the interim analysis for both programs, amongst other areas of the BIMO program. We are incredibly pleased that the inspections concluded without any findings, and therefore, no Form 483 was issued. Considering how complex both programs are with multiple studies and the first and its kind, the centralized study for ET, as well as the interim analysis, we're extremely pleased with the outcome of the inspections. One note on how it communicates from now on.

Given the stage of discussions on both applications, we do not intend to provide further regulatory updates until the expected action dates. I would ask you to read our silence between now and January as discipline, rather than a signal of any kind.

Let me turn to Vormatra Gene. In June, we reported top-line results from POWER1 in a highly refractory focal on set seizure population. As you know, the study did not meet its primary endpoints of reduction in monthly focal seizures frequency from baseline to week 12. It did meet a key secondary endpoint with a significantly greater proportion of patients on vermetrogen achieving at least 50% reduction in seizure frequency. That result tells you something specific, and you have spent the last several weeks making sure we took the right lessons from it, rather than the comfortable one.

The responder findings say the drug is doing something real in a population where very little works. The prime endpoint myths say our dose and a few elements of our design were not matched to the question we're asking. Those are design problems and therefore fixable. We are finalizing the plans to amend and revamp both Power 2 and Power 3, informed directly by what Power 1 taught us about the dose and entry criteria, and we intend to have both studies up and running by the fourth quarter of this year.

We will further describe the amendments and impact on the design once they are final in the very near future.

Switching gears to healthy nursing. In June, the FDA granted us BTD designation for our nursing for seizures associated with SCM2A DE caused by gain of function variant based on the results of the EMBRAVE Part A study. That's our third breakthrough designation since July next, last year. Three designations across three different assets on two different platforms. It's basically unheard of for a company like Praxis.

We're taking advantage of the access to the FTA that the designation give us and discussing a comprehensive plan with the agents in the near future.

Parallel to that, Embrave 3 continues to enroll well, with top-line results expected next year. We're incredibly pleased with all the progress made in all fronts this quarter, and we look forward for a successful rest of the year.

Let me now turn the call to our CFO, Tim Kelly. Tim?

Thank you, Marcio, and good morning, everybody. Thank you for joining today's call where you've heard about the good updates that we have going on. I'll provide a quick summary of our second quarter financials. In Q2, our operating expenses were $96.9 million, with $69.4 million of that for R&D, and the remaining $27.5 million for G&A, which compares to $76 million in operating expenses for the Q2 period in 2025. During the second quarter, PRAX has spent $78 million in operating cash, compared to $55 million in the second quarter of 2025, with the increase reflecting greater spend in both R&D and G&A.

We expect G&A will pick up more on the second half of this year to support our planned upcoming launches. This will be driven by adding two teams of commercial field-facing headcount, rolling out disease state awareness campaigns, building sufficient inventory, and ensuring solid business systems and infrastructure. We ended the second quarter with $1.4 billion in cash, cash equivalents, and marketable securities, compared to $926 million as of December 31, 2025. And we maintain that this is adequate to support our runway into 2028.

With that, I will hand the call back over to Marcio.

Thank you, Tim. Really appreciate the updates. Now I'm going to move into Q&A. Operator?

Thanks, Yazza. Absolutely share the sentiment that you just expressed there, right? Like incredibly complex programs, as we discussed on the remarks, to actually shackle the boxes. This collaboration with the FDA has been exceptional.

The real questions we got throughout have really been, I would say, very straightforward and really very similar to what we've been discussed before publicly, so we checked that box quite nicely as well. And of course, the cherry on top, it's always good to get the FDA in the house, checking everything, making sure that they agree. We always knew we were doing everything correctly, but that they agree with our assessments that data integrity, documentation, communications, procedures, safety of subjects, in these studies, everything was checked there. So we turn the page to talk about what we really like talking about, the millions and millions of Americans that are not served currently in the United States. We've been very diligent hiring a world-class sales, marketing, more tax, medical, of course, Tim, at Praxis.

And I can say this is probably an opportunity of a lifetime if you are in one of those positions to launch these drugs to transform patients' lives. But I'll hand over to Megan to discuss a little bit the phenotype and what we are seeing at this stage we are.

Thanks, Marcio. So, yeah, Marcio is sharing, right? Not unexpectedly, these are hot launches upcoming. They each represent the first targeted therapies for indications with huge unmet needs. So it's allowed us from a hiring perspective to be very selective, and we're incredibly pleased with the caliber of the talent. So certainly from the phenotype individuals with multiple launch experience, the rare noro space, the hunters that are going to go out there and really do a phenomenal job for us. And in the case of RelutraGene, now we've got the team hired and trained, so we have the next few months to really be active in doing the account profiling, which will set us up quite well from a launch readiness perspective.

And then the Alexa Field Force build is – build-outs well underway and also on track for where we'll be from a launch perspective.

Thanks, Megan. Thanks, Yael, for the question.

It was really meant to be what is looking to forward-looking here in the context of this application, right? So we are late stage now, approval, labeling, promotion, like making sure these patients have access. I think that that's what I meant by that in the conversation. I would say, Richard, the conversation itself in the room, it's a rare type of feeling when you are in a discussion with the FDA, At least in my view, where you actually feel very peaceful, and that's the way I would describe how I felt on that discussion, where they know for a fact that there will be incredibly transparent, like collaborations being incredibly high, and really all the elements that are necessary to make a decision have been on the table.

So on your sub-question about surprise, I would say not really. Maybe my surprise on the meeting is just how much of the discussion turns into proper use, I'm going to call, of the drug. And by proper use is when you discuss labeling and things like that normally later in the process, all you're really trying to do is proper use, right? So when you are actually marching towards proper use in conversations like this, I consider exceptionally positive the discussions, the level of collaboration and integration and the understanding of the application, the depth and breadth of the discussion, the number of people in the meeting, the presence of leadership and the support from leadership, all of that, what I meant is it is an application that matters for them as much as it matters for us.

And it was good to see that overall. The topic of titration did come up, to your point, as completely expected, right, is something we proposed to have. And once again, I was positively surprised by how much, like, further along our alignment is in that regard. While I cannot and should not predict what's going to end up saying on a label, I can tell you right now, unequivocally, that there is a very good understanding that when patients start to lexacalitomide, they will sometimes, in about 30% of the case, have some tolerability issues that does not transfer to true safety issues. But if they stay on that, that goes away, and they have this quite phenomenal, in my view, efficacy that is just not there for any other compounds.

And any reasonable person, and I think that's incredibly reasonable, and certainly we believe we are, We're looking to that as an opportunity to maximize the suffering on this incredibly difficult indication by figuring out a way for patients to get there. And I think we're really, really close to figuring that out. How this translates to commercial, and I'm going to hand back to Megan on this as well, right? You can imagine that 70% of the patients on 7 million or even 2 or 3 million at launch, anyone would say plenty for a very, but we want every patient to have the best possible experience, and you want to make sure every patient stay on drug if they desire to and if their physicians believe they should.

So maybe Megan can talk a little bit about what we are doing there.

Sure, thanks Marcio. So maybe just to recap again, the focus out of the gates for the launch will absolutely be on ensuring the high quality first experience so that we build the physician confidence and ensure that we have that durable patient persistence. I think in the context from the provider's perspective, and as we've been doing advisory boards and also engaging with the physicians, I think it starts with them setting up that first conversation with clear expectations. And what they're, as they see the Ulexic-Caltamide data, right, the ability to tell a patient there's going to be a rapid onset of effect, right, with a meaningful change, and that there might be some tolerability issues, which, as we hear from the neurologist, they're very comfortable with managing the patients through that.

In terms of some patient programs and services that we're building, Tim mentioned in his remarks, we're well underway in establishing the infrastructure we need to support this. We're basically building a hub of the future, which is fully integrated from the front end to receive the prescription all the way pulling through the channel to ensure that we have line of sight to where we are with fulfilling that first Rx. But then also having certain programs and services on the SP, the pharmacy side, with our integrated network to ensure that we're able to deliver the support to the patient to get them started on treatment as quick as possible and then tight-train through those early weeks. So it's absolutely a priority for us, Ritu, and we're feeling really good about where we are with that build.

And the excitement and enthusiasm from the physicians is there to get as many patients started on this therapy.

Yeah, thanks, Franklin, for that. I'll hand over to you to discuss a little bit.

Yes, I mean, you know, looking at the size of the trial, that spread of etiologies is precisely what you would think to get when you look at the distribution of prevalence in that group of patients, and the precise mix of people that we fully anticipate would be pharmacosensitive through a sodium channel mechanism is represented in that cohort.

Yeah, but with the caveat, right, I guess that's a true, like, multi, both genetically diverse, you know, genetically diverse, the study has not been run so far, but there are many that we can borrow from. And when you go through that analysis, I think what we know is, like, there are kind of three levels here. So the first, when you look into the overall response, and let's define whatever 50%, that benchmark is very clear. It's like very small for placebo.

Of course, these patients are so severe. I'll give you a number. The median baseline countable seizures in Emeralds is over 50 for 28 days. So imagine that kind of burden, and just how little it is, the possibility that these patients are going to naturally regress. The second is, as we move upwards the ladder, like 75% response, 90% response, those numbers become very, very ridiculously small for placebo. So as we are looking into the distribution, it was very simple, I would say, to model from a power perspective. And I would say very straightforward, the expectations, as you can imagine, as you heard from me before, as you hear from Steve now, we're very pleased not only with the a priori powering, but quite importantly, the a posteriori mix of patients that are pharmacosensitive to the mechanism.

So stay tuned soon to come up the results, but I think we should be as bullish as we are on what we're going to see on the other ends.

Yeah, absolutely. So we're going to reserve it, and I hope you don't see this as hedging because it's not. Like since we're going to be discussing this a little bit more in the future. But a couple of things that we, as we look into, like, in a very detail, and at the same time, keeping ourselves from seeing things that are not there, a really disciplined approach to what we're going to do next, right? Looking about the value right now, at least external value for the company, one could argue four-fifths of the value is on Alexa and Reliturgy. So, of course, there's a huge potential for upside and huge residual value for vermetrogen, but we really want to measure.

That's one of the reasons why we're not focused today on format. Dose clearly played a role. Duration at the dose clearly played a role. We sometimes say dose. It looks like it was only the 20 or the 30, but actually six weeks and six weeks play a role, I would say a pretty significant role on that. I think a few other things that you're going to be hearing further, including the number of failures that was extremely high to prior medications that could be tightened up, and a few things here and there. But every single parameter, maybe that's the matter I'm going to leave you with, that we look into are very easy to adjust and to fix.

And then once we do, without overstretching, without drinking the Kool-Aid, without seeing things that are not supposed to be seen, The effects on the other side for power 2 and of course, eventually power 3 are higher than what I would expect for this drug on those populations. So, great way to look into this. We're finalizing a few things internally and with our key advisors. I'm going to see an update, a full-time update about that in the near future and restarting up this study.

Yeah, absolutely. I'll start with, and then hand over to Steve here, Tiago. The first is, I find a little ironic, I'm going to say, to be the classical me in calls like this, that no one asks about how many serotonergic mutations are when this is being discussed as serotonergic one, but it's very easy to say sudden channels for us. So maybe one must revisit their own understanding of neurobiology. But having said that, I'll hand over to the person who really knows neurobiology here. That's not me. That's Steve.

So Steve, thanks, Marcio. I think when you look at the role of sodium channels in determining the behavior of neurons normally and in epilepsy, clearly they are the gatekeepers of excitability in a neuron. And because of that role, if the sodium channels themselves are altered in their behaviour as a result of mutations, as we saw in the Imbolve study, they are a clear target.

But beyond that, they are also the most downstream element in the etiology of other disorders that result in DEEs, whether it's other genetic mutations or acquired conditions. Because of that very unique role, they are also targets where a lot of the physiology converges. So we've got a lot of confidence that it doesn't really matter what the etiology is. Even in the cases of loss of function, and there's always a lot of chatter about that, clearly, even though we've lost sodium channel function as the primary mutation, we still have excitability issues. And the way to control excitability is through modulation of sodium channels. When these loss of function mutations occur, that can result in the upregulation of other elements in the neuron.

So we're confident that our preclinical data shows that. And this is all because sodium channels are concentrated in a very specific part of the neuron where the axon emerges called the axon initial segment. It's a pretty much crystalline structure of sodium channels and other elements. And that is the little part of the neuron that decides, from my experience, from everything that's upstream, what am I going to do? How am I going to respond to that input? And we know that that program is modulated a lot by sodium channel modulation. One other thing I want to say about sodium channels is the manner in which the sodium channel modulator interacts with the actual sodium channels themselves is very important.

And we know, we've talked about this a lot, that the mechanism of action and the profile of relutrogene distinguishes itself from any other agent in the market now. And that was the initial therapeutic hypothesis we started with, the religious gene, and we are following that through the trials right now.

No, thanks, Doug. Yeah, we do. That's maybe the short answer to that. There are steps between now and then to have conversations with the agency and to discuss exactly which label potentially that would result. But the bottom line is, both from a historical perspective and most importantly from a policy perspective, as it forms up right now, and even considering, like, the progressive nature of the division that all epilepsy falls within right now, as just restructured a couple weeks ago, I think we feel incredibly bullish about it. But it should be seen.

Meaning is there any kind of sort of subconscious enrichment perhaps ongoing in terms of picking a study in which they think a patient might be best to respond to Just given the different MOAs of the drugs Thank you No no I get it And I would say we always have to take without grain of salt anecdotal conversations we have with one or two physicians here and there But it is not unexpected, right, that you would say, oh, no, like, let's say we will start with serotonergics here. There are drugs approved. There are a lot of stuff that's being done on that space, hand-to-hand combat with multiple drugs for Dravet and LGS.

Yeah, if we're going to try another drug, let's try on the ones that I would humbly say that, yeah, that may be okay for a trial execution. It's a terrible strategy once you get to the markets, but I'll leave it there. I think likewise for us, the Emerald White, as we said, like about 200 patients, finished randomization like a while back.

And it is kind of obvious by what Steve just mentioned that when you look into the final mix, that either by chance or not, that this seems to be some of the most potentially active on this mechanism historically. So whether or not there was a conscious or unconscious kind of segmentation when there were sites that were enrolling both studies, it happens naturally.

You fast forward a few years from now, both mechanisms work, right? I think we know that. And on a market with, like, anywhere between 200,000 and 400,000 patients, the discussion is bringing on 10 other mechanisms, right? Like, this is a, number one, should be a dream for anyone on this space. It's an ability to help incredibly sick kids and young adults to control seizures. And any one of us that thinks that one mechanism is going to do this should be institutionalized. So I think it is more than reasonable to expect that multiple mechanisms are going to be not... I keep going back to the same thematic. You heard me saying this a thousand times, I'm going to do a thousand and one.

The zero-sum game idea in G is an epilepsy is purely serving to people who don't want patients to get drugs. It has nothing to do with either drug developments or market potential. So, if anything else, I'm going to say I'm going to be cheering every day for Loan Back to be incredibly successful, just like you're going to be, so we all can help patients with these conditions.

I appreciate it. So the next four more steps here are the quick late cycle discussion. I'll tell you that's in the books. That's label negotiations. That's in the books. So the reason why we mentioned my prepared remarks is that we're not going to be giving updates because you can imagine that this discussion as we move forward is very dynamic, right? There's a lot of back and forth. There's a lot of really cool discussions there.

We set the goal to be ready for launch way ahead of the Dufa. Promote for reasons. One, it's the right thing to do. Two, thanks to a lot of you listening to this call, we have the capital to do it. Three, I would challenge absolutely everyone in this call to name one market with millions of Americans that don't have a treatment right now that are getting every single day requests from physicians and patients to when is this drug going to be available. So it's just a responsible thing to do. So we'll be ready. We are basically ready, and we're going to continue to be ready to maximize in the case of the great fortune that the agents finished the review earlier, and we are blessed with that approval earlier than the PDUFM.

Yeah, absolutely. And so from a payer perspective, very, very active. So we did a lot of pre-work to shape like our general understanding. Of course, that is a lot of analytical work that can be done. We've done that benchmarking work. And we moved on the last several weeks to a different phase, right, where both proactively we want to talk to some of those plans as administrators, but I would say the latest wave is that they want to talk to us. And I would say there was a lot of those interactions.

Very, I would even argue I was positively surprised with one, their understanding that absolutely there's a need here and that they're not going to put a lot of stuff, not a lot of blocks in the way. The second is just like they want to be ready at day one, just like we want to be ready at day one. So that's good news. Our planning assumptions include step-added through propanolol. Not at all, by the way, what we're hearing across the board is going to happen. It's just a prudent thing to do or look into this. Now, we know, we did extensive work here from a medical perspective and claims and so on, that a lot of these patients, they're just super adecotic or something else, that it prevents them from ever going into a beta blocker.

So about half of the market cannot magically take propanolol. So one can call that low-hanging fruit, but I guess you call a median patient's low-hanging fruit delivered oxymoronic, so I'm not going to do that. So that is a very clear part of the markets. I think the other parts they just had exposed to that, I'll remind everyone on the stratified, predefined use of propetalol on the Essential 3 study, showing that on top of propanolol, elipsacal mites is incredibly efficacious.

And so there is really no restrictions here one way or another. And welcome. Do we believe that in the long run that's going to be needed to stay involved? No, but that's a belief. We welcome all the patients that they want to hear, And physicians are incredibly excited about hearing that, which is normally what payers actually want to hear.

So a lot of work has been done on the payer space. I know you asked about pricing. I think the more we talk to payers, the more we realize that our initial pricing assumptions are very well, I would say, grounded. We talked about a little bit over maybe $50,000 to $100,000 per year. However, there was a lot, as you know, from clients of yours and from people without you, a little bit of pushback and you actually go that high. I think right now, while we're not going to disclose the price specifically, I think we're actually very confident that that's the right range to operate in general.

Yeah, so thanks, Cambet. Good to hear from you. I would start with what is necessary and then what is possible, and I think those are two completely different things here, right? I mentioned earlier in the call on the background seizure burden for these patients, right? Like, it is absolutely insane. I cannot even imagine as a parent to have 2G or something like that.

These patients' strides and these parents' strides everything they could possibly imagine on those. So logically, no matter what he wants to believe, reducing consistently a part of those seizures, and therefore statistical significance, when you think about a study, that should be a bar, right? So the bar here is significance on the study. But of course we want to go about much, much higher than the bar, right? So bar for success, no doubts whatsoever. Physicians, patients are saying, help me control a little bit better. Let me give a little bit more hours without, like, being on top of these kids, nonstop, afraid of complications, you name it.

And that would be a big win. And biologically, though, by what Stephen just discussed, there are reasons to believe that it could be similar, if not better, than what you're seeing on in both. I think it's hard to imagine, right, being better than both. But we need to stay true to the science and to what we are seeing so far. We're going to discuss a lot more about this in the near future as well. But, again, we're going to have to stay true to what is possible. So, not necessary, but I would love nothing more than help these patients to an extreme.

Yeah, no, thank you very much. I think that's all those parameters you mentioned, right, this continuous of response, 50%, 70%, 75%, 90%, 95%, whatever you want, 100% are incredibly important. And we've been tracking and we've been, I would say, quite pleased about the entire distribution. I mentioned that maybe one point here that we haven't discussed as much. It is quite interesting as well to see what happens when they transition to the open label. And studies have been going on for a bit, and we enroll relatively fast. So there is a very large proportion of patients that have multiple months now in the open label. So when you put all of that together, I say initial response with the double blinds, the information we're able to get from the open label, I would say they depart a lot from what historical expectations would be.

And, hey, who here hasn't been burned by blinded data, right, from the first rock? So I'm not saying this is like completely proof of any possibilities of not being a misread, but it is just very hard to believe that we would read this incorrectly considering how severe this disease is and how high the seizure burden is. So, very happy across the boards, but we're going to stay vigilant until the end of this study.

Yeah, no, absolutely. I mean, so for this launch is going to likely have like several states. If you look into the, I believe we've been quite responsible defining the addressable population at time of launch around 2 million patients. And that is mostly, I'll say three-quarters or so of those patients would be the Medicare, Medicare Advantage, like arguably slightly older patients up there.

Maybe the phenomena that we are seeing more and more is the old family members, right, and the interests of those patients. And so I would say for the Phase II, very likely we're going to see is like a migration, continue to increase these patients on the 65 plus. There's also a lot of the 40 to 65 patients there. Of course, there's a different Bayer mix, there's a different dynamic on those patients.

Maybe the part we don't talk as much about, we kept this number static, but it's not static, right? The population demographics in the United States, and globally, but particularly in the United States, is shifting quite a lot. And when you're looking to the prevalence of essential tremor in the overall population, it's a little bit about like 2, 2.5%. When you get to 60s, that is about 2.5 times the overall prevalence. And then about every 10 years after that, it doubles. So we haven't discussed, but we're going to hear discussing a lot more, is actually the completely organic growth of these markets that is about double digits.

And we just don't have drug launch on multi-million patient markets growing organically as a market, double digits are moving forward. So that changed a little bit the mix. I know you had an Emerald question there as well The efficacy across the etiologists Oh the efficacy across the etiologists Thanks Tim Of course it's not going to be the same. Like I think it would be actually, I think my math teacher would tell me, would remove my diplomas if I say it's going to be the same on an etiologian population. But we do expect that it would be consistently positive. And I think that that's what we should be expecting at this point in time.

Yeah, so I would say those meetings are comprehensive, right? This is not exactly like, oh, they stayed quiet for several months and they come and end up a meeting on us. Quite the opposite, right? So it's been dialogue, and overall, it's an opportunity, as you might recall, when Senates, with heavy lobbying from the industry, requested a mid-cycle meeting to be implemented as part of a P2 for reauthorization, was to actually give us, as the applicants, an opportunity to have that discussion on how things are going. And I would say very, very little on areas that are of, I would say, interest for people that don't have an interest on this drug getting to the markets, like some of your clients.

A lot of the interest here was actually how to actually get this drug to help patients. All the errors were represented that you named there, as is normally the case. Of course, senior leadership was represented, since this is not only an important application, but as one with breakthrough designation, no drug approved mechanistically for essential tremor ever, only one approved. So you would imagine that that fits exactly the agenda for the FDA from a public health perspective in the United States.

And what I would say is, and as we said in the prepared remarks, which, by the way, were legally obliged to be complete, as you know, so I find some of the questions, to be honest, a little bit annoying, is that there was no major, like, comments here or there. So we see this as overall incredibly positive that we are. It's not over yet. It's never over. But one must take the stage we are, right? The questions before this call were what happens in the mid-cycle? Is the FTA going to have an advisory committee? Is this, this, and that? So maybe it's time to flip the page towards how large of an opportunity the central term is and burn the chips, as one say, in Carthagas, and start moving forwards, conquering new words.

I would say no. On the body language, I think we're all, that is, very collegial discussion throughout the group of the agents and ourselves, and it's amplified by the fact that we are really the only company that probably know every person in that room by name, and actually have a trust and rapport with each one of them because there are multiple INGs and multiple INGs. under review. Much, much larger, right? As you can imagine, the application for elixircals, my haliclorate, is so much larger, so there's a lot more people involved on that. But if anything, I'm a paranoid by nature person, so I never expect people to be very happy on meetings like this, but I will venture to say that I think it's very common, as I said, it's very peaceful, and body language, We're just incredibly positive across the board, and it reflects the collaboration throughout the review, as one would expect.

Sounds good. We start with the last part, and I'll hand over to Megan. The big sales here, I think we've been very conservative on when you look into the size of the opportunities. In general, from number of patients, from not really having anything else, the growth we just mentioned, there have not been adding, in general, feedback from physicians. You name it, we set that floor into around $10 billion. And I would say the more we move forward, I think the more we feel comfortable that that's really a fairly conservative number. Let me hand over to Megan to discuss the other topics.

Yes, absolutely. Thanks, David, for the question. So from a target perspective, you're right. Neurologists are our focus coming out for the launch with us targeting them primarily because of their strong ET influence and just the patient volume. So with sort of a call target sizing in the 13,000 to 15,000 range, that puts us in a place of having a field force around 300.

And as I shared earlier at the start of the Q&A, we're well underway with our hiring. And again, the context we're heading into with the first targeted therapy, you, John, met need, and just the opportunity to have the most successful launch here in neurology. We're definitely attracting top caliber talent that want to be a part of this. So, and again, the focus for the build out will allow us to be out in the field doing the account profiling, so we're very well prepared upon FIDUFA.

Yeah, I would say to call any patient with this condition non-severe is probably something I'm never going to be able to do it. So the population is the population here, right? We are, Steve represented us into the SCN 2A Family Foundation meeting last week, and we had several updates after that and discussions with them, And many clinicians gave us the feedback based on how they are waiting for this.

Some of these hospitals in American Centers of Excellence have, like, very largest, either the largest or second largest cohorts of GEs they have.

Why we should never be suffering is suffering, and we shouldn't compare. But when you look into other GEs that there are three or four companies going after, they are way, way, way less severe. And the majority of the patients are being treated there. So we don't see a segmentation per se here, but really careful use. I don't think we would want or like everyone should just start right away without doing the proper assessments of these patients, without making sure their background medications are optimized before getting into reliturgy.

So that is what's going to dictate the launch. I think our medical education exchange discussions are going to focus on proper use because proper use is what leads to maximum penetration and maximum retention. And, of course, maximum benefit for patients and the other parts that we're all interested is maximum revenues that can return to all of us and get more drugs to the market. So that is the strategy here, and I couldn't be more pleased to the feedback we're getting from physicians and patient groups.

Yeah. No, that is a fantastic question, and one that we spent a lot of time ourselves, and of course, discussing with the agency. That is why I can't possibly go through every line of evidence here.

One thing that is quite key that we haven't, and I'll take full responsibility for not actually discussing this properly publicly before, is if the patient's state, the odds of staying on drug and responding, if you just stay a day or two more after a rising intolerability, sorry, are disproportionate. So that evidence and the mathematical evidence is very, very clear. So imagine a study, when you conduct today's studies, we wanted to make sure we're not biasing these patients.

When a patient goes to an office to discuss with their physician, it's very different conversations like this is the possible benefit and this is the possible risks. But the benefit question is there. In a clinical study, the benefit question is not there. So that is a key driver. So we have a fair bit of data showing that if patients stay on the drug, and if they stay a little bit longer, not a lot longer, they're going to be able to tolerate and get fantastic, in my words, benefits on the other side of that. Our proposal in the label, not extending the fact that the label has to be approved by the agents and so on and so forth, is that physicians are instructed to, if they have concerns, because they know their patients, there are patients that chronically don't respond so well in terms of tolerability, they can keep the patients off for a little bit longer, right?

But it is important because they're going to see 70% of the patients doing really well. And then their desire is going to turn into, like, I want to get all my patients to do really well. And that's the bridge we want to. What Megan mentioned before about the hub of the future, right, it is really, and we're going to be talking about it on our commercial day coming up soon, I'm going to be announcing. It is really a state-of-the-art way to help the practice manage the patients and getting all the tools to maximize tolerability. We could be here saying, why do we care about those patients, right? It's completely irrelevant from a peak revenue perspective, but it's not because we know this drug works, and we want to make sure it's there with each one of those patients.

So I really appreciate it. It is something very close to our hearts. Our team worked incredibly hard to make sure every percent point is not only a percent point in revenue. It's a lot more patients that are being able to get benefits that they cannot get any other way.

Of course.

Yeah, so I think we've got a very representative distribution of what the background meds are here. Very happy. I will tell you discontinuation, for example, is a good surrogate. They are being extremely low on this study, tolerability being very good. We know, and unfortunately, like a lot of these patients, failed pretty much everything. So you name a drug, I'm going to tell you they failed or they are on it, but we're confident not only on the effects, which is important, but on the safety as well to get through a positive benefit-risk.

And then I'll leave the last question to Tim, who's been anxiously waiting for a financial question for the call. Thanks for the question about the runway, and I think part of what we talked about with the runway is it gives us this great flexibility and ability to launch into these launches, the way we're investing with Fieldforce and all the activities that Marcio and Megan have taken us through. With respect to the PRV, because we do anticipate approval for relutrogene for 2A and 8A, where we do have orphan designation and are eligible for a PRV, we would expect to receive that as well. It is not a meaningful impact to our runway, but it does ensure that we can continue to invest in these launches.

And you're right also about Elsinurson down the road because that also has orphan designation. We believe that would be our second product that could be eligible for a PRV. But thank you for the question.

Yeah, thank you so much. I appreciate it. I hope you've seen it try to be very comprehensive today, given updates on – it's just absolutely amazing, palpable energy that we get every single day here in the office with all the now sales team as well, And being there and talking to physicians, giving us a lot more information.

I would say as we move this page towards a commercial, a lot of you helped us along the way to make a successful clinical development for this drug. As I said, we're going to discuss less and less the clinical and regulatory. I just want to take a moment to thank all of you, who are certainly my biggest critics and my biggest supporters when we got into certain conversations. And I appreciate every feedback that's been given to the company made us to where we are right now.

Couldn't be prouder on behalf of patients. When we get these stories every single day, and trust me, we gather in every single day from the patients who transition on MRLs to the open label, or the ones who are involved, or the ones who are on emergency access of one of our medicines, or particularly these days for the ones wanting to be on lexacalthamides, That's what keeps us going. Thanks enormously for your support and really looking forward to the conversations later today and in the near future.