Amylyx Pharmaceuticals, Inc. (AMLX) Earnings Call Transcript & Summary

All right. Well, thanks, everyone, for joining us here on the last session of the day. We're really excited to have Amylyx here today with us. We've got Justin and Josh, Co-CEOs.

And maybe just to get started, could you provide a brief overview of the company, where it stands today and what you see as kind of key value drivers over the next 12 to 24 months?

Sure. Yes. Well, first, thanks so much for having us. Thanks for being with us between now in a cocktail hour. So good to see some familiar faces and hopefully get to meet some others. So as Corinne was saying, Justin, Josh, we're the Co-CEOs, Co-founders of Amylyx. So probably the biggest highlights for us are, one, you guys know well, we had our treatment for ALS approved by FDA this past September. So that's a trade name, brand name, RELYVRIO. That was after an approval in Canada with brand name ALBRIOZA. So we're -- we've announced 2 quarters of launch now. So our most recent first quarter sales of $71.4 million. In fact, we were profitable, which we're very excited about, but we think there's a lot more ahead. About 10% of the U.S. ALS population is now on treatment as of the end of the first quarter. That's about 3,000 people. But we have a lot more to do as well. We think this is an important treatment. And so we're excited not just at the prospects in the U.S., but I think there's a huge global unmet need in ALS. We estimate there's at least 200,000 people with ALS. And then we also are excited about getting back into research. The target of the drug and the mechanism is not specific to ALS. We think it has good scientific rationale in other diseases, too. So we recently announced plans to go into progressive supranuclear palsy. I'm sure we'll talk a little bit about that, which is another rare neurodegenerative disease, high unmet medical need, as well as we started developing our pipeline as well, so we can talk a little bit about that. So we're very excited with where we are today.

Great. You mentioned it, but maybe you could help us characterize the launch today, particularly with respect to where you're seeing the greatest initial uptake.

Yes, great question. So ALS is a disease where there's a concentrated set of prescribers as well as kind of a long tail of prescribers who see fewer ALS patients. As of the first quarter, 80 prescribers accounted for 50% of our prescriptions. So at the first quarter, we were still seeing a pretty concentrated prescribing pattern. I think that's a real opportunity for us. I mean, first, those centers are key. And so there's a real opportunity to keep getting deeper and keep educating with those centers, but there's also many, many additional centers that we're just starting to penetrate, just starting to reach. So that's going to be a focus as well as we keep going forward.

Yes. If you look at sort of the top 500 potential prescribers, about 65% prescribed at least once. So that's great. We're proud of that, and it's not surprising that's where we had our team's focus is in those areas where we thought there'd be really high demand, but that also means there's a lot of room to run. And that's just the top prescribers. There's the neuromuscular docs, the general neurologists as well. So I think -- right now, I think the focus is still staying on that sort of concentrated ALS specialist, but I think as we -- as the launch matures, focusing on that broader group will be important, too.

Yes. And how would you characterize the split between a prevalent population and a newly incident patient population? And also, what are the implications in terms of duration of treatment, et cetera?

Yes. I think we shared during the last quarter that we were seeing a broad group. We're seeing people who have just been diagnosed with ALS. We're seeing people who have had the disease for some time. And actually, I think somewhat surprisingly to us as well, we're seeing people who have had the disease for a long time. I do think as the launch matures, it's likely that we focus more and more on the incident population as we address more and more of the prevalent population. And I think ultimately for us, that's an opportunity and an advantage. I think, in an ideal world, we want people to get on RELYVRIO as quickly as possible and to be on it for as long as possible because we believe that's the way to have the best benefit. And I think it takes time to educate centers that speed to get on therapy and duration of therapy are so, so important and to keep on driving that message home to all of them.

In terms of reimbursement, I guess, what have you seen to date? And how do you expect that to improve over the course of the first launch year?

Yes. Thank you. And I think we've been very pleased with the coverage policy generally. I mean -- so just in terms of metrics as of the first quarter, about half, so 50% of total lives covered, we had a coverage policy for. But then, qualitatively, I think in rare disease, we always worry about, is it going to be closer to trial criteria? Or is it going to be closer to FDA label? In this case, label would be adults with ALS. And I think the vast majority has been much more towards label, which we're very pleased about. I think our hope is that -- I think, one, we have a very good team who is doing this. People are really experienced in sort of national accounts and talking with payers. But I think the other thing is we have strong data, unmet medical need, and I think we were pretty conservative on our pricing strategy. So I think our hope is that -- our hope was that payers will see that and say, this is a reasonable thing to reimburse. And I think that's what we're seeing. I think what's critically important for us is not just that it gets covered, but also that it gets covered efficiently. So now our teams have been very successful so far. About 80% of the prescriptions are going through on the first prior authorization, which is quite high. But the time to fill, we also want to go down, and time to fill, meaning drugs prescribed, when does it actually arrive at the person's door. And with ALS, time is just so precious. So we're excited to see in the fourth quarter, that was 45 days from time of prescription to fulfillment or to -- at the door, 30 days in the first quarter. Hopefully, with the criteria being good, that will continue to come down.

Yes, absolutely. What about compliance? What are you seeing in terms of discontinuation rate? And how does that compare to your expectations?

Yes. So I'd say, one, it's still a little early. We launched in the late part of the -- or I guess, mid part of the kind of first -- fourth quarter last year. So even if you think about it, especially about the first quarter of last year, patients had not been on drug that long. And so it's kind of early to draw discontinuation curve. But I'd say we're reporting our patients on therapy net. So at the end of the fourth quarter of last year, we had 1,300 patients on therapy. At the end of first quarter, we had 3,000 patients on therapy. Really can't have 3,000 patients on therapy actively if everybody is discontinuing. So -- again, I think what we are seeing is the ability to continue growing that net patients on therapy and that's what we expect going forward.

Yes, absolutely. So I guess it sounds like we're still in early stages. But as you think about the breadth versus the depth, what do you expect to drive the most growth over the next year? And then as you progress into the next 3 to 5 years?

Yes. That's a great question. I think it's -- and I think what we try to remind people often is that while ALS is a very well-characterized disease, it's a new market in many ways. We -- in the ALS community, we haven't had treatments. I mean, really, it's always been around for a long time, but it's generic. It was never really marketed, at least not in the way we tend to think of things. And then more recently, in Arizona. But so -- I think that the first thing is when you're in a new market like this, there's just a lot of new stuff. I mean doctors are not necessarily used to prescribing. They're not used to working with specialty pharmacies. They're not used to having to answer questions from insurance. They're not used to side effects. With our drug, we think the side effects are fairly benign: mild, moderate nausea, GI side effects, but those are new. When -- and so I think it's important, first, there's a lot of education. So we spent a lot of time on that before the approval, but I think now that we're in the market, that's really important. I think, too, that we -- as we get more into the launch, I think we have to constantly remember that we're changing the way people view ALS. I mean whether people are trained in medical school, at residency or fellowship, ALS is one of these diagnoses no one wants to give. And it's a really hard disease. And so in the U.S., the focus has mostly been on quality of life. As people progress, how can we help you do better? We're proposing something different. We're saying, we have a treatment. It's not a cure, but it can slow the progression and it can increase people's life span. That's a big change in mindset for people. So I think that's -- it's going to be a lot of education. And I think we also have to remember that while there is this concentrated prescriber base, the patient journey takes people from general practitioner to the general neurologist, to the neuromuscular doctor, to the ALS specialist. So I think we have to make sure we keep educating all along those different lines. But I think, early days, we're pretty pleased that it seems like those messages are getting through.

Yes. You've stated a target goal of 10,000 patients on therapy at steady state, 3,000 now. So I guess, how do you see the cadence to getting there? What's the path to normalization?

Yes. I mean, I think -- when we think of that number, it maybe starts from riluzole, which is the drug that's been out there for ALS for several decades. And riluzole, at any given time, depending on the data source you use, probably has about 9,000 people on therapy. Our view is there's no reason we shouldn't be able to get there. And so that's why we've set this target of 10,000 people on therapy. But I do think it takes a little time to transform a market. As Justin said, a lot of this is new. People aren't used to prescribing drugs. People aren't used to deal -- managing what, in our view, frankly, are relatively mild side effects, but still require that added management and everything like that. So it's going to take some time to get there. We haven't given a specific time line, but I think we've been going up pretty quick between the -- getting 1,300 at the end of Q4 and now 3,000 at the end of Q1. I think that's nice progress towards our goal already in just 2 quarters.

Yes, absolutely. What are you seeing with respect to the competitive landscape? Obviously, oral Radicava came to market around a similar time. So what are you seeing, in terms of patients, use of combination therapy or RELYVRIO first, second, how is that playing out?

Again, it's an area we've been pretty pleased. I mean, I think we've seen all of the above. We've seen people just on our treatment. We've seen our treatment plus riluzole. We've seen all 3 approved drugs, and I think from a payer criteria perspective, we really haven't seen pushback there either. I think that was one of the other questions. You have 3 drugs, are they going to have step therapy or something like that? We really haven't seen that. So I think we've been quite pleased. I think -- our opinion is that we think we've generated the strongest data to date in ALS. So I think we are very much trying to share that we think this should be a foundational treatment. Now that being said, this is not replacing riluzole. So I mean, I think in the future, we see this as we think you should prescribe it with or prescribe it first. But again, that's going to take time. But that being said, to Josh's point, we're considering that we're so early in the launch, and we're seeing these prescribing habits, we're pretty pleased.

I'd also say, too, this is a classically competitive market, if that makes sense. If you ask the person living with ALS in general, what do you want? They say I want to throw everything I can at this disease. So I think -- and you see that with a lot of physicians. The view is, sometimes you hear it called the 3Rs, Radicava, RELYVRIO and riluzole. And I think a lot of doctors try to get their patients on all 3 as quickly as they possible can.

Yes. One of the things you talked about before the launch was also competing with apathy in this patient population. I guess what have you seen with respect to that aspect of like choosing treatment?

Yes. It's -- I think it will continue to evolve. I think there are some doctors for whom it was approved and they said, "I needed to get every one of my patients on this instantly." And there are others who maybe sit and wait, and there are others who maybe aren't as educated on the data. But I would say, too, that, in talking with doctors, I mean, first, we have just the utmost admiration for these doctors and health care professionals. I mean giving an ALS diagnosis, caring for people with ALS, I mean it's just -- I don't quite know how they do what they do every day. But it brings up important points in how they communicate things with their patients. We were talking to a doctor recently, and we were saying, how do you explain the benefit on function and the benefit on survival? And they said to us, "I never talk about survival. I would never tell my patients that," because for them, talking about survival brings up the fact that this is a fatal disease, that their patient will pass away. Now that's not every doctor, but I think that's why it's very much individual by individual, center by center. I think if we want to transform how people think about ALS, we have to be very sensitive to those things because it is a really tough disease. And again, giving them so much credit, they've developed all sorts of ways of managing this really hard disease. So I think we have to adapt with that.

Yes.

Yes. I'm sorry to -- but maybe just to give a picture, too, ALS clinic is a really busy, busy place. People with ALS have every complication you can imagine. Think about a leg becoming paralyzed, an arm becoming paralyzed, no longer able to use your fingers, can't get around home, can't turn with torso and everything like that, unable to speak, unable to breathe, unable to talk. So these ALS clinics are focused on so many different areas of support for their patients. And I think the challenge and opportunity for a new drug is, where do you fit in that treatment paradigm? And I think what we're trying to educate is that treatment is really important and should be hopefully well up the priority list on that paradigm. But again, these sites are already dealing with so much for their patients. And so I think that's the real opportunity as you educate this market is to make treatment a big part of that algorithm.

Yes. I'll segue to PHOENIX in a second. But maybe first, I think one thing that patients have cited is the taste of the drug. I know that's something you guys are working on. So where do we stand in terms of new formulations?

Yes. Thank you for asking. I mean, I think -- so first -- I think we've had generally good compliance in our studies as well as on the market. And the drug has a bitter taste. And -- but I think probably many of us know taste is subjective. And so -- for example, we've heard that in Italy, where it's common people will have bitters or different bitter drinks, they like the taste...

We've got an e-mail that said...

We should have had that for cocktail...

Yes, exactly.

We got an e-mail from an Italian patient that said complements to the chef. So some people like it.

It's very subjective. Now that being said, we want this to be as -- especially from a taste side effect profile, we want this to be as easy as possible for people. And so we are working on a new formulation that would be tasteless. Things in drug development take a long time. If you change the formulation, there's all sorts of criteria probably primarily bioequivalents that you have to prove, but that is high on our mind. So we're working on that actively.

Okay. Safe to say it's not in PHOENIX, I assume?

Correct.

Not PHOENIX.

Can I just ask you about the insurance coverage process. You talked about the first pass approvals. What are the arguments when it doesn't happen on the first pass approval? Just kind of curious. And where do you expect that to [indiscernible] ultimately if these arguments have any bearing?

Yes, I'd say it varies. And I don't mean to say that in an invasive way, just that it varies in terms of -- it's everything from an administrative thing. You're supposed to check this box and you didn't check this box or you missed a form or you missed a document. That's certainly a big part of it. And then sometimes there is a true denial of everything was submitted correctly and there can still be a denial. Even in that case, you can still submit an appeal, which will lead to the doctor making their case for why this patient should be on therapy and everything like that. And we do see success frequently with appeals as well. I'll say if all else fails, we also do have a pretty robust, in our view, kind of safety net of a free drug program and everything. So our goal is that no patient gets left behind in this whole system. But the good news is, from the start, most of these are going through. And so I think that's a good spot to be in.

And painting a picture is something that I think we certainly learned as we were preparing to commercialize. In the U.S. right now, we have more than 6,500 health insurance plans. So you think of the number of outcomes that can happen and that there's a person at the end of every single one of those. And so I think that's why, as we were thinking about how can we support the community and our launch, it's one of the big reasons we brought the patient support services in-house. So our Amylyx care team, those are dedicated Amylyx employees, many of whom have personal connections to ALS. And it's because at the end of the day, we have the broad coverage criteria, but a lot of this also just comes down to one-by-one cases. And we felt like the best way we can support that is to have in-house people who really care and really care about the mission as opposed to working with an outside group.

Maybe shifting gears to PHOENIX. You obviously announced enrollment completion. We expect to see the data next year. Can you just remind us on some of the key aspects of that trial design?

Yes. So it's a large, randomized, placebo-controlled study. 664 participants, which is quite large for ALS. When you look at the literature, you'll often find recommendations for 300 to 400 to have Phase III level powering. This is 664 patients. So our view is this is powered even in a pretty conservative view of the world. The study is -- parallel group will follow people on active versus placebo for 48 weeks. Inclusion criteria are broadly pretty similar to CENTAUR. There are slight differences, but our general view is that those differences are slight and will lead to a generally similar population that will be enrolled. Primary endpoint is the same, ALSFRS-R. And we'll also be looking -- we'll get the ALSFRS-R quicker because functional progression kind of happens first, and that's expected to read out mid-2024. For survival, it's morbid to say but to get a survival outcome, you need enough survival events, deaths. And so for survival to accrue, we expect that to take at least a year longer than the primary outcome.

All right. Maybe we could just double-click on some of the differences between PHOENIX and CENTAUR. There's an inclusion criteria, we could start there.

Yes, we're happy to. So I mean I think, one, ALS, I think it's -- again, it's sad to say, but ALS is very predictable. So just to sort of give it for instance. In our -- just recently, at the American Academy Neurology meeting, Dr. Sabrina Paganoni, who is the principal investigator of the CENTAUR study, presented basically propensity score matched natural history compared to the CENTAUR study. In the propensity score matched natural history on our inclusion criteria, the predicted ALSFRS-R slope was 1.66 points per month. The slope in the CENTAUR study, 1.66 points per month. So I mean it is remarkably predictable. But again, it's sad. It's just the nature of the disease. But -- so the reason I start there is, as we think about the inclusion criteria for the PHOENIX study, we -- with feedback, particularly from EMA, they shared that they wanted a more inclusive population. So what we try to do is have a more inclusive population, but one that would still be very similar to the CENTAUR trial. Now that being said, we are still looking at people who exactly meet the CENTAUR criteria. But the key differences are: one, rather than -- in CENTAUR, we had less than 18 months from symptom onset. In PHOENIX, we have less than 24 months from symptom onset. There is something called the El Escorial criteria, which means basically how diffuse is ALS through the body. Originally, we said El Escorial definite, which means it must be in at least 3 body regions. Now it's clinically probable or definite, which means 2 or 3 body regions. And then SVC, vital capacity: in CENTAUR, it was greater than 60%. In PHOENIX, it's greater than 55%. So those are the key differences. Now that being said, with ALS being so reliably progressive and predictable, we expect the population to be fairly similar and behave fairly similar to CENTAUR.

Yes. And I'll just add, that all may sound like kind of a lot of -- well, those are differences and everything like that. We spent a lot of time modeling these out, and what we found when we've modeled them out is it enrolls a pretty similar population. And so again, that's what we expect to see in PHOENIX. And not to go off topic at all, but the other thing just kind of coming into PHOENIX, we're coming off of a randomized, placebo-controlled study that met its prespecified primary outcome and also showed a difference on overall survival. Coming off that, we're now running another randomized, placebo-controlled study, looking at similar endpoints, similar population -- sorry, the same endpoint, similar population. So I think that's -- those are all the reasons that coming into this, we have a lot of confidence in the design we've put forward, a lot of confidence in the execution of the study as well.

Yes. One of the differences is the length of the study is 48 weeks versus 24 weeks. Part of that is for Europe, I believe. So maybe you can expand on why you made that decision, and what you expect the time variable to do?

Yes. So I would say, if anything, the time variable should be helpful. I mean if you think if there's a difference at 24 weeks, there should also -- unless things suddenly go the opposite direction, there should also be a difference at 48 weeks. And if anything, that difference might get larger. So in most powering analysis, 48 weeks is actually an advantage when you look at the study. We also looked and presented at one of the AdComs on 48 weeks in CENTAUR, 48 weeks in CENTAUR looks good, too. So we don't expect -- we certainly don't expect any negative from the time variable. In fact, it might be a positive in terms of increasing power and overall difference between the groups.

And where does overall survival fit relative to how both physicians as well as regulators consider the asset?

So it's a critical endpoint. I mean I think, again, stepping back, ALS is a progressive fatal disease. So the things you want to measure are progression and mortality. So progression in ALS, we generally measure by the ALS functional rating scale. That's our primary outcome. Then you also want to measure survival, in this case, OS, and that's the secondary endpoint. So now in terms of time function, you can see a change in the shorter time period. And so that's why we expect that at the 48-week mark, at the end of the study, we expect that top line results mid next year. Survival, as Josh was saying, it just takes more time to accrue those events so that you can actually see the survival difference. So we expect to estimate that it's about a year after, so mid-2025, that I think is an estimate when we'll get those OS results.

Given you already have a full approval in the U.S., how do you think about the implications of PHOENIX from a perspective of regulators, from coverage in terms of reimbursement and in terms of how physicians will think about adoption or uptake?

Yes. I mean, I think, not to give a somewhat unhelpful answer, of course, it depends on the results, right?

Right.

But we're excited, kind of coming into PHOENIX and everything like that. I think a world in which we had 2 positive randomized, placebo-controlled studies, a world in which we had a 664-patient positive study is a really great, I think, opportunity for us and for the world of ALS broadly. In a case where the results are more gray, we're going to have to evaluate that. And I think we'd evaluate that together with the community, with patients, with physicians, with payers, with regulators, et cetera. But again, I think it all needs to be looked at in context. This is a horrible disease. People with this disease quickly lose the ability to hug a loved one, to speak. They end up essentially locked into their own bodies and then ultimately suffocating is the usual path to death. And so I think in that context, it's a question of -- if there's a benefit for patients, which is what we're seeing from CENTAUR, would you really want to take that away from patients? And so, again, it comes down to what the results are. And our North Star at the end is we want to do what's right for patients when we get these results.

Yes. One of the studies that's ongoing, it's an investigator-sponsored trial of TUDCA. I'm not even going to try to say it. And so I guess, what do you see as implications pending results from that trial? I think we could see it as soon as this year?

Yes. So first of all, we're not quite sure on time lines, and this is a primarily academic -- not primarily, this is an academic study. So they've made some statements that it could be this year, but anyone who's worked with academia knows that, that can sometimes have a long tail. But so, in any case, this is an investigator-initiated study, run during the peak of COVID. And you know how's kind of many of the trappings you might expect of an academic type study. At the end of the day, I think if this study reads out positive, I think it will be an interesting result. I think if anything, it's kind of validating towards us. I think if there's a less positive result from the TUDCA trial, I think we kind of come back to that being a primarily academic study that has a couple maybe challenges in how it was run and how it went over the course of COVID. And maybe the last thing I'll say is trial was originally intended to be 400 patients. They only ultimately recruited 300 patients. So again, just a lot of challenges with how that study has been designed and run.

Well, and going back mechanistically, too, I mean our preclinical data all shows that both of these agents in the combination are active, but the combination is superior, in fact, often synergistically better than either alone. And so I think as you then look clinically, it would not be surprising to us that this is an active drug, but we think the combination is better. So I mean, I think that's very much how we're thinking about the clinic as well.

Two quick follow-ups, if I could, on PHOENIX. Remind us what the geographic distribution of the enrolled patient population was? It was kind of concluding enrollment during the time when consideration of an approval in the U.S. was happening, and therefore, to avoid sort of the blurriness of that, you predominantly enrolled outside the U.S. And that threads over to the question of how you think, for instance, in a scenario that you do get a positive result from PHOENIX, the European regulatory narrative that you've had, the exchange, the dialogue has, as you've reported, not been optimistic. But in the event that you do have a PHOENIX trial, did that happen in any way behind closed doors? We didn't have a YouTube webcast of an ADCOM. It was kind of a different kind of dynamic, hence, no drama of unscripted comments from people named Billy, et cetera. But talk about the geographic distribution, talk about potential implications of PHOENIX outside the U.S.

Very happy to and very important points. So first, so as Chris was saying, so the PHOENIX study, we had recruitment in the U.S. and in Europe. But of course, in the U.S., originally, the PDUFA date was June. And then, of course, it was extended to September. But so we chose to stop enrollment of the study in early 2022 so that we wouldn't have truncated data on people. The last thing you would want is you enroll someone in the study, you have 1 data point, you can't do a slope. And of course, if they don't have sufficient time on treatment, they're just not going to have the benefit. So the vast majority of recruitment has been in Europe. Now that being said, that was always the design of the study as well for a number of reasons. But so it didn't interrupt the conduct of the study whatsoever. And in fact, with the PDUFA extension, we ended up getting sufficient data on pretty much everyone in the U.S. anyway. As far as the European consideration, so for those who maybe are newer to the story, so we issued a press release a couple of weeks ago sharing that the CHMP was trending towards a negative opinion. And that's a little confusing, what in the world does that mean? But as Chris was talking about, we had what's called an oral explanation meeting, that's a meeting where the CHMP meets about the application. They invite us for a very short window where we're allowed to present or answer questions and then the rest happens without us. And so afterwards, they give us a sense of what's going on, and that's where they said it's trending towards a negative opinion, but they won't actually vote and adopt that opinion until later this month. But I think in terms of the broad picture, in Europe, we said in our press release and publicly that we strongly disagree with the conclusions. We think that if ever there were a case for conditional marketing authorization, it's this. We have a progressive fatal disease, we hit on the endpoints that one would want to see and we have the ongoing confirmatory study. So I mean I think it's a textbook case for conditional marketing authorization. Fortunately, EMA has a very tried and true re-examination process, whereby you are assigned 2 new rapporteurs, and that kicks off about a 4-month process where they re-review the application guided by those 2 new rapporteurs, and then they can come to a different opinion. And I think the really important part is that, in all of these approval cases, especially in a case like this where you have a single study, it's a judgment call. And I think that while we can say these things, these messages are so much more meaningful coming from the community. We've been under review with the EMA for 18 months. And this whole time, it's been confidential. So I can say from talking with people in Europe, I think the community thought, yes, of course, this is going to be approved. It's FDA approved, it's approved by Canada, we're next. So this is the first they heard of that. So I think since the time we issued the press release, virtually every major patient organization in Europe has been in an uproar saying, what the heck? We're dying. We need new treatments. The last approved treatment in Europe was riluzole in 1996. It's been over 25 years. So I think -- but I think it's so much more important and powerful. Those messages come from the community, not from us. So I think in a big picture, having this out in the open, I hope, is a good thing.

Yes. Maybe I'll wrap up with 2 quick ones. You just started -- or you're planning to start a 600-patient trial in PSP all time together. First, explain the rationale for that? And second, with the investment in the business, how should we expect profitability would you hit this quarter to continue?

Yes. So maybe first starting with PSP, it will be hard to do in 30 seconds but I'm going to do my best. So first of all, maybe to take back to the past a little bit, we started this company and made this drug, originally AMX0035, now RELYVRIO, based on the idea of targeting cell death. We've showed in all of our preclinical models an ability to rescue cell death and a whole variety of different systems, and we ultimately selected ALS as our first indication because it is the disease of profound cell death. But there's nothing ALSO-specific about the drugs. There's no reason ALS had to be our kind of first disease that we chose. And we've always thought and we've always communicated that we believe this drug could work in additional neurodegenerative indications. So over the last few years, we've gone through a process to look at various other neurodegenerative diseases and try to align the constellation of the clinical data, the preclinical data, the scientific rationale. And through that process, PSP, we selected as our most promising indication to go into next with the compounds. Some of those elements include that we ran an Alzheimer's study, randomized placebo-controlled, that showed a highly significant reduction in total tau protein and phospho tau protein. Various elements of preclinical evidence that I've gotten us excited here, and the fact that PSP is just very measurable. You look at the PSP rating scale over time. You have a very measurable type disease. And I'll also say that it's a nice position to be in. We have an approved drug. We've already done all of the CMC. We've done all of the talks. We have all the manufacturing ready to go. The idea of going into an additional indication is just a very logical and I think sensical investment. I'll tie that into the other question. In terms of profitability, maybe one thing first to clarify, I think -- coming out of our earnings call, I think there was maybe some confusion about what we said about R&D spend. And just to be very clear, what we said is that spend will settle into the $30 million to $40 million range on the R&D side. I think some people thought we said it will increase by $30 million to $40 million every quarter, which would have been a much different scenario. But yes, I guess, in terms of profitability, we haven't given formal guidance. I'll give the equivocal answer, that it depends how fast your spend grows and it depends how fast your revenue grows. But I think if our spend grows, it will be to make investments in things that we think are really going to matter for the business and really going to matter for patients. So if our spend grows faster than our revenue, it will hopefully be because we're making smart investments.

And I'll just maybe add one thing as we're concluding. I think it's part of why we're so excited to be at the point we're at right now. I mean we have a sustainable company. This is what we've been waiting for, for 10 years. While it wasn't our target to be profitable, it wasn't an accident. We try to run an efficient shop so that we can make those smart investments like Josh was talking about. We have an important treatment for ALS. We think we need to get people around the world. We have a sustainable business and we can reinvest in smart research. So we're super excited with where we are.

Okay. Well, thanks, everyone, for joining us here.

Thanks.

Thank you, guys.