Compass Pathways Plc - ADR Aktie

Okay. All right. Let's get started. Good morning, everyone. I'm David Huang. I'm the senior U.S. biotech analyst here at Deutsche Bank. So I'd like to welcome everyone to the second day of our second Annual DB Healthcare Summit. With us here, we have COMPASS Pathways for a fireside chat. So COMPASS is a pioneer in the field of psychedelic medicine with its psilocybin therapy, COMP360, on track to becoming the first classic psychedelic to potentially reach the market in 2027. I'm joined by Lori Englebert, Chief Commercial Officer; Teri Loxam, Chief Financial Officer; and Dr. Steve Levine, Chief Patient Officer. So thanks to you all for joining us. I'll pass it over to the COMPASS team for some introductory remarks to help level set everyone and for those in the audience who may be less familiar with the COMPASS story before we dive into Q&A.

You want me to start? We're going to be passing it back and forth throughout today. So thanks for having us, first of all. I really appreciate being here. We'll likely be providing some forward-looking remarks. So because our lawyers are always interested, check our risk factors. But we are, as David mentioned, in the lead in terms of psychedelics potentially getting to market. We're in really, really good shape. We've completed 2 Phase III trials, both being highly statistically significant, really great results and really incredible profile that Lori can talk more about as to why we feel like COMP360 is so differentiated.

First indication is for treatment-resistant depression. We are also underway with a late-stage trial in PTSD, which will be a follow-on to TRD. We are in a rolling submission and review right now with the FDA for our TRD product. We anticipate completing that submission in the fourth quarter, and we have guidance out there that we expect to launch within the first half of next year. So we are really on the doorstep here of bringing our synthetic psilocybin product to market and really excited by the progress. We have made tremendous progress not only from a clinical development perspective, but also on the commercial side.

And the only product right now that's out there approved for TRD is Spravato, which is a J&J product. And we are able to leverage a lot, if not all, of the work that they have done in launching their product for COMP360. And so both Lori and Steve can talk more about that. We're in really, really good shape, really excited to bring this product to market.

Great. Well, thank you for that. So maybe to begin, could you walk us through the sequence of events going from the completion of the NDA filing for COMP360, which I believe is expected to occur in Q4 from there to potential commercial launch in the first half of '27, as you have talked about. And really, what are your estimates, I guess, at this time in terms of FDA review, DEA rescheduling and state rescheduling?

I'll take that.

Do you want to take that?

Yes, I'll take that one. We spend a lot of time together. So probably going to be figuring out who wants to answer which question each time. So right now, as we've previously stated, we intend to complete our NDA filing in Q4. And just to level set, we -- in 2018, we received breakthrough therapy designation. But most recently, in April of this year, we received the commissioner's priority review voucher, and we also will potentially benefit from the executive order on DEA. We also had an agreement with the FDA prior to receiving the voucher to undergo a rolling submission and rolling review. This is something that the psychiatry division, to our knowledge, has not done at least in the recent history. And so we would have been the first product to benefit from a rolling review.

Then we received a priority review voucher, which did 2 things. What that did is it increased the frequency of conversation with the FDA and then it also allowed the FDA to have a target review time of 1 to 2 months. So once we complete the NDA filing in Q4 of this year, what we anticipate is a little bit of uncertainty in terms of timing of approval because the FDA does clearly state a target of 1 to 2 months. We do not know if they will take the 60 days to do an acceptance period and then the target 1 to 2 months. But certainly, we are prepared even if they don't. Once we receive an approval at some point in a very short proximity after filing that completing that NDA in Q4, the DEA then needs to reschedule because this is a scheduled product.

And right now, the DEA is by statute supposed to reschedule a product with an approved medical use within 90 days. And so the executive order back in February asked the DEA to work in a timely fashion for psychedelics. And so there could be a potential to shorten that time frame from 90 days after approval. Then the states need to reschedule, which we've done a lot of work to prepare the states to reschedule within 30 days after DEA. And so all of this to say is we don't have a real good answer of when a potential launch will happen, but we feel very certain that it will happen in the first half of 2027.

And how should we think about the label language that you're likely to receive for COMP360? And I'm just thinking of how the product was studied in clinical trials. So for example, would you expect the label to discuss things such as induction dosing, whether it's 1 or 2 doses and how frequency -- how frequent can you redose in terms of maintenance?

Steve, do you want to take that?

Yes, I'll take that one. We expect a fairly broad label to essentially say for the treatment of treatment-resistant depression. As far as the dosing, we have studied up to 4 doses in a year in our COMP006 trial. There were up to 3 in the COMP005 trial. And we looked at an initial dose in 2 different ways. One was a single initial administration in COMP005. That was our placebo-controlled trial. In our 3-dose low, medium, high COMP006 study, we looked at 2 initial administrations 3 weeks apart.

What we have seen from that study with the 2 initial doses 3 weeks apart as well as from the Part B data, the blinded Part B data from the first study where that second dose was given a bit later, typically between weeks 10 and 14, is that for many participants, there was a significant additional benefit of having a second dose. Ultimately, we think that, that will translate into a label that may talk about initiation of treatment as 2 doses no sooner than 3 weeks apart with additional treatment at clinician discretion or as clinically indicated. And that will likely be a clinical decision truly because this is a heterogeneous population.

One thing we showed in the Part B section of both studies was a breakout of cohorts by initial level of response. And you can see the trajectories of those patients where some just 24 hours after that first administration are in remission and then may not need another administration for quite some time, whereas others have received up to 3 or 4 doses over the course of 52 weeks. And so ultimately, we would expect in the real-world patients to have treatment on a frequency of 2x to 4x per year.

One thing that's important to point out with that is that currently, the only pharmaceutical product that is approved in this population, Treatment-Resistant Depression, which is a very different population than MDD, for which there are 50-plus approved products. is that, that only approved product is Spravato, which unfortunately does not have significant durability. And so it is administered typically on the order of 25 to 50 times per year, which places tremendous burden on both patients and their caregivers that need to drive them to this treatment. And so regardless of the final nuances of that label language, it will indicate that this is a treatment administered on a scale quite different from what is currently available to these patients today.

Do you have any expectations for how the REMS program might read? And given how we know what Spravato's REMS program looks like, do you think there would be a similar patient monitoring requirement?

Yes, I'll keep going here. We -- first of all, and going back to some things already mentioned about the cadence that we've had the opportunity to engage with FDA, starting with our breakthrough therapy designation back in 2018, certainly more recently after they aligned to a rolling submission and review and now with our priority review voucher, we've really had the opportunity to have a very engaged dialogue with the agency, and it has been very productive and constructive.

As part of that, they have guided us in terms of their expectations for REMS to look at the existing Spravato REMS as well as what they prepared in their briefing materials for the Lykos AdCom a few years ago, which is very consistent with the Spravato REMS. And so with that, we do expect a REMS that is very comparable to Spravato, which fortunately has not been onerous to these sites. We believe that those who are delivering Spravato today will deliver COMP360 when approved because it is exactly the same infrastructure, same rooms, same staff. So they are already used to working with the REMS that we expect to have for our product. The key difference just being the length of monitoring time required for Spravato, it's 2 hours. For us, we expect 6.

Okay. Great. Well, I'd like to pivot a little bit now to the commercial launch picture. So can you talk a little bit about what you've been doing with interventional psychiatry clinics to prepare them for the launch of COMP360? I believe there's about 8,000 or so clinics of this nature out there, which of these clinics would you be targeting at launch? And how do these clinics think about integrating COMP360 alongside their current offerings, whether that be Spravato or TMS or something like that?

Steve and I will probably tag team this answer a little bit. So you're correct. There are about 8,000 sites right now that are currently capable and certified to administer Spravato. What that effectively means is that they are certifying that they can administer multi-hour treatments with Spravato being a multi-hour treatment. They are growing. These sites are growing at about 500 sites a quarter. So whereas there are about 8,000 now by the time we launch, if that trajectory continues, there will be quite a few additional clinics that will be prepared to administer multi-hour treatments by the time we launch.

This has been pretty remarkable growth. And these sites are growing because they are growing in anticipation of additional multi-hour treatments coming to market. And Steve can certainly talk to how that is good for business for these sites. Right now, given where we're at with the sites that do prescribe Spravato, we're already thinking about what our sales force would look like. We've already started our sales force hiring to make their offers contingent upon approval to which they will cover all of these 8,000 sites.

But most importantly, they will also cover referring physicians. So those physicians that are surrounding outside of these interventional psychiatry treatment centers to make sure that physicians who have treatment-resistant depression patients in their practice understand what the opportunities are for new products coming to market. And in terms of what we've already been doing with these sites, I'll hand it over to Steve to talk about some of the work we've done there.

Thanks, Lori. I mean, first, we know these sites intimately and the space intimately. And I don't say intimately like in a weird way. Yes, you do. I say it from First, a few words about my background prior to COMPASS. I've been here 6 years. But prior to that, between 2010 and 2020, I was leading a national network of mental health care delivery sites that operated coast-to-coast in 10 states that were the first examples of this type of infrastructure. That -- bringing that into COMPASS, not only understanding that business, but also many of the other sites that have opened in the period of time since then, we have done extensive work through a network of strategic collaborations, which is something that we put together.

It's a bit unique. These are live sites of care currently taking care of people living with treatment-resistant depression that span the gamut of where they receive their care from community behavioral health to hospital systems, integrated models. decentralized models and others, but also including the top examples in the country of interventional psychiatry as in the highest volume prescribers of Spravato today. And through information exchange over the past few years, it's really given us a very valuable opportunity at a very granular level to understand the challenges and opportunities of implementing new treatments within these sites, but also to realize, which is probably fairly obvious in the first place that they did not build their sites to be Spravato clinics.

They built them to be platforms to deliver all of the approved available options that can serve this population because, number one, they recognize that there are unmet needs and they need new options for their patients. Number two, it's healthy for their business. And so one of the reasons why we see that there is a lot of capacity in these sites now already is because they understand that COMP360 will be coming and other treatments behind us, and they've been building that capacity ahead to be ready. Additionally, one other thing maybe to mention is that apart from understanding them through our strategic collaborations work, we've also had a medical science liaison team out in the field for the past few years, meeting with all of these sites as well, having scientific exchange, answering their questions about our data.

Great. Well, thank you for that. I want to get even a little bit more granular here in terms of how the practice economics may play out, and I'm specifically thinking about billing and reimbursement and things like CPT codes. Do you expect that this will be a buy-and-bill product? And are the codes in place essentially to help ensure favorable practice economics?

Guess that's me. Yes. I mean, first, although it's not typical for a biotech or pharma company to be thinking about provider side economics and ultimately, it's not our role. It is important here because we are aiming towards broad and equitable access. And we know if this treatment isn't viable economically for these sites, they won't write these prescriptions. And we did have a front row seat to some of the early launch challenges for Spravato, largely -- I mean it's multifactorial, but largely because of the lack of a reimbursement framework in place for these providers to get adequate reimbursement for the multi-hour monitoring in office.

Specifically, J&J did not apply for new codes. And therefore, it started off in a very confusing situation where various codes were being used and in many cases, not reimbursed. It's been somewhat ironed out over time, but ultimately, they are not using codes that are specific to their product and therefore, reimbursement really isn't optimized. We were able to take a note from that a few years ago, we applied for new CPT codes that are specific to the administration of psychedelic treatments in office. Those codes were approved. They are live in their Category 3 form and ready to be progressed to Category 1 with the approval of these new products.

Additionally, you mentioned the buy-and-bill model. Buy-and-bill was brand new to psychiatry with Spravato. It has taken some time to penetrate probably about 35% to 40% buy-and-bill at this point for Spravato. It is a big revenue opportunity for the sites, frankly. And we also believe the coding strategy that we are taking with our intention to apply for a J-code after approval will also optimize the buy-and-bill revenue for these sites.

I wanted to touch on the payer side of the equation. Could you just speak to any interactions with payers, the feedback you're getting there? And then maybe if Spravato makes sense in terms of a pricing comp?

Yes. So we have already started our exchanges and dialogue with payers. We did that after the COMP005 26-week data. So we really could go to payers and start talking about them what the product profile looks like and what the value proposition looks like. And so we've been doing that for the past several months. Feedback has been overwhelmingly positive. And the reason it's been overwhelmingly positive is because they have only one product that they are covering right now in treatment-resistant depression.

And what that means is that there's only one product that has proven clinical efficacy in a patient population that does unfortunately cause tremendous disproportionate economic burden versus MDD to the health care system. And so when you can prove efficacy in a patient population like this, payers tend to react very favorably. Payers, in particular, have been reacting to the fact that this product works in this patient population specifically. This product works within 24 hours for those who respond. And if you take a look at some of the data that we've generated and that dramatic drop within 24 hours, this is a patient population that we studied that had been in their current depressive episode, their current episode for 3 to 4 years.

That is a very long time to be depressed. And then you take one dose of COMP360 in the very next day, you feel better. and way overgeneralizing. But that is effectively what is happening to these patients and payers are responding well to that on top of physicians, on top of patients. All that is great. The other thing that payers are starting to respond to is the durability of the products, not having to come back into the office to get treated again only a handful of times over the course of 50 -- or over the course of a year is also highly interesting to these payers.

Bigger picture, how should we think about overall market opportunity here in TRD? And again, for reference, I have some numbers here with Spravato annualizing currently, I believe, north of $2 billion, something like $2.3 billion. And J&J, I believe, has guided to something like $3.5 billion in 2028. So how should -- how should we think about that overall market opportunity for COMP360? And maybe a follow-on there. Do you expect that the majority of COMP360 patients would be sort of new interventional starts? Or would there be any major switching over, let's say, from Spravato?

Okay, David, we're on day 3 of conferences. So you're going to have to maybe remind me of some of these questions. My brain is right. I will start with one question I didn't answer and the last one, which is pricing because that does help articulate what the opportunity could be. And so right now, currently, on average, Spravato is in the range of anywhere from $50,000 to $65,000 annually. And so we have -- based on our discussions with payers, but also given the product profile and the value proposition that we're bringing, you can expect pricing on an annualized basis to be around that.

We will be pricing on a per dose basis. So part of the reason why the 52-week data that we just released last week, which showed the benefit of having an additional dose after 26 weeks, really helped us to narrow in on what our average dosing on an annualized basis is likely going to look like. And we believe that will be somewhere in the 2 to 4 range, which means an average of 3. And so -- but the reason I say 2 to 4 is not to be silly, but it is to articulate that there will be definitely patients that probably only need 2, and there will be patients that probably need 4.

But the average will be somewhere in the 3 range. In terms of the opportunity, you are correct. J&J themselves are guiding to a $3.5 billion run rate for Spravato by 2028. Guys, we're sitting at the end of 2026. And there is no reason to believe that they can't hit that $3.5 billion. that would be -- that would mean that they would slow down their trajectory as to what they've been doing over the past couple of years. So we fully believe they will hit that. They also will likely get some uplift based on all the things that Steve mentioned when additional products come to market, more awareness of treatment-resistant depression will help them.

So we fully believe they're getting to $3.5 billion. In terms of what that means for us, they're only treating 2% of the available TRD patient population. They're treating 100,000 patients out of 4 million. So there is not a shortage of potential patients who deserve adequate treatments that have been studied and proven clinical efficacy in treatment-resistant depression. So we feel very good about the potential patient population. It's probably important to note that we do not anticipate switches from Spravato. Will we get them? Absolutely. As Steve mentioned, the burden to patients is quite profound for this treatment, but we're not going after Spravato patients.

These are treatment-resistant depression patients. If they're stable and they're doing well on Spravato, I don't want them changing to COMP360. Again, that is something that will happen, and we know that will happen, but it's not who we're going after. We have an entire market, an untapped market of treatment-resistant depression patients that are coming in and that will come in. And we also have many who can't commit to the Spravato burden. That is 52 -- 25 to 50 days off of work on an annual basis that you and your caregiver have to take off to go and get treated with Spravato versus the 2 to 4 that you may have to do for COMP360.

And just to expand on that one more step. The other benefit that we see with us -- with our profile and only really having the patients come in 2 to 4 times a year means that they're likely more willing to drive longer distances to get to a site. Now with the expansion of sites, they're probably not going to have to drive that far. But if you're on Spravato and you're needing to commit 25 to 50 times a year, you want to be pretty close to that site because of how -- the strong profile that we're seeing and how highly differentiated we are, we'll likely be able to expand the radius around each site in order to bring new patients in. And so that is one of the reasons, in addition to everything Lori said as to why we are so confident in the potential for this product.

And then one more thing. on top of all that, but wait, there's more. This is specifically the opportunity in TRD, but also worth mentioning that we have a late-stage program in PTSD, which is potentially even a larger opportunity. There are 13 million patients living with PTSD. There's been a lot of focus on our veterans as there should be, but they ultimately represent a minority of people with PTSD, about 15%. The vast majority are women survivors to sexual violence.

This is a terribly underserved population. There are only 2 approved products for PTSD, both of which are old generic SSRIs. They're modestly affected at best, and there hasn't been an approval in more than 25 years. We are in a late-stage trial now, a Phase IIb/III that is subject to review by FDA, designed to be a single trial for registration. So we are -- especially based upon the data we've generated in a Phase II study we published last year, really excited about the potential there. And as I mentioned, really a very large opportunity to follow.

I appreciate the very thorough responses to my multipart analyst. Okay. So getting into the first year of the launch here, 2027, we know Spravato was a little bit slow out of the gate but granted the infrastructure back in 2019 had not been built. I think we've discussed that. How should we just think about the shape of the launch curve here in 2027 for COMP360 as this product makes its way to the market?

Yes. So we will be the first classic psychedelic to market. And that -- yes, the infrastructure is there. And yes, they do understand how to get billing through. They understand how to get PAs. The staff is already established. There's nothing incremental that the sites will need to do to get prepared for COMP360. But we're going to take extreme care to make sure that patients and the sites have a good experience. That includes having a field reimbursement team out in the field. We know the #1 reason that physicians won't prescribe and Steve alluded to it previously, if you don't get reimbursed or it's not easy to get reimbursed, they likely won't prescribe the product.

The patient has a bad experience because they're not well prepared or they don't understand what is happening or they themselves can't get the product reimbursed then they likely -- the sites will likely not prescribe. So we're trying to remove all those barriers. And because of that, it will take some handholding along the way to make sure that sites are well trained, well educated and fully prepared and can hopefully get the reimbursement codes through easily. Due to that, we anticipate the launch to be somewhat slow coming out of the gate just because this is a new product and sites are going to want to get a little bit of clinical experience before they start doing additional ramp. But we do expect, if we do it well, that, that ramp will be quite dramatic and most likely be a pretty dramatic increase in a fast fashion. slow to go fast.

Yes. And we're seeing a tremendous amount of anticipation for this product, both from providers and from patients. So we're not seeing anything on the demand side for this not to take off. It's to Lori's point, we are purposely trying to help providers go a little bit slower at the beginning just to make sure everything is ironed out so that we can get to that full access that we anticipate, one wants this product and two, has access to it.

Great. So I thought maybe we could pivot a little bit now to discuss the competitive landscape and how this might play out over the next few years. So there is a competitor with an LSD-based therapy that is looking to come to market for both GAD and MDD. How do you think the profile of COMP360 and psilocybin here would stack up against an LSD-based product? And for instance, are there qualitative aspects of the overall experience with psilocybin that may appeal to patients?

Yes. So first, I want to clarify that we don't view them as competitors. They are in MDD, we are in TRD, 2 different patient populations. Their study was in a completely different patient population than what we studied in. Again, they're entering into a market with many MDD products available. We are entering into a market where there's only one product available. However, that being said, we want them to get to market.

The more products that actually get to market, the better the economics are for these sites, the more awareness is around psychedelics and the potential for psychedelics for patients, the more patients that come into these clinics. I'm going to hand it over to my psychiatrist friend down here to talk about what his feelings are about the difference between the 2 molecules.

Yes. Well, just first, just to pick up exactly where Lori left off, I think. And just to give a little bit more detail on the difference in the populations that we studied in the recent MindMed LSD data set, the average duration of an episode was about 9 months. Whereas in our trials in a TRD population, that average duration, the chronicity of the current episode was 3 to 4 years. And it's well established that the longer someone has gone without successful treatment, the more difficult they are to treat. And so it stands to reason that you can move upstream. And if you've proved efficacy in the most difficult population, then your product will work well in a less chronic population.

The opposite has not been borne out over time. There are many products that are labeled and indicated for MDD that have tried to prove efficacy in TRD and not been able to do so. And so just to further drive home the point that these really are different populations. But then to come back to some of the other points around the difference in the nature of the experience or at the patient level or what the implications might be for these sites, Number one, LSD is known to be a longer experience compound -- and the challenge may be the delivery of their product within the typical operating day of a clinic.

Beyond that, truly, as Lori is saying, this isn't a competitive landscape in the sense of the sites will be making these trade-off decisions. First of all, at the time that we launch, the only real competitor, so to speak, will be Spravato because it will be the only approved product in TRD. And as I mentioned before, these sites have capacity. So any treatments they're delivering will be incremental. They won't be making trade-off decisions here. But beyond that, not any given patient will necessarily respond to any one treatment, and that's why it's important that there will be multiple options at these centers.

And ultimately, no matter what treatment someone receives there, they may be receiving multiple of these treatments over time. That's good for patients to have those options. It's good for the sites for their practice economics. It's healthy for their businesses. And to the point already made, it's healthy for the sector because ultimately, this is good for the field of psychedelics. It will grow the pie over time, increase awareness and it just creates a very healthy system all around.

And it may be worth, Lori, double-clicking into a little bit more why we are so well positioned being in TRD from a payer perspective because I think it does get missed a lot in terms of seeing the number of patients in MDD, there's an automatic assumption that means more revenue. That's not necessarily the case. And I think it's important not only from a revenue side of things, but also just from a patient throughput. The point that Steve made around us having established data in this patient population is really important. So I do think it's worth maybe just expanding on that a little bit, Lori.

Yes, happy to. So earlier, you asked a question about how things are going with payers. Again, the value of this data set in payers is they only have one other product that has proven through clinical trials, efficacy in this patient population. So typically, what payers will do when they have limited options and again, a patient subset that is disproportionately impacting the health care system they respond very favorably to that data set.

And typically, it is a different economic situation in terms of negotiating with payers in terms of formulary access than it would be versus a product that has MDD efficacy along with 5 other branded products that they're covering on top of 50 different generics, but they're also trying to figure out how to make company step-throughs. And so MDD products, although very valuable, we need more options, typically have different dynamics with payers in terms of negotiating to get to formulary access.

Another angle that's been looked at is the idea of a shorter-acting psychedelic experience with some products looking to replicate an in-office profile that's more similar to Spravato. And obviously, those will be a few years from the market, if successful. But how would you think about the landscape evolving if shorter-acting psychedelic products come to market? And in your view, is the duration of the experience a differentiating factor?

The short answer is no. The expansion on that is, first of all, even before we think about the differentiated economics of short versus long or the fact that there isn't a differentiation in those economics in an appreciable sense, it also ignores the idea of these molecules will not only be indication-specific, but they will have differentiated experiences, both for the patients receiving them, the providers delivering them. And there may be some considerations with some of the shorter-acting products and what it's actually like to implement those.

But just the very notion that a shorter-acting compound that lots into the delivery window of Spravato being more favorable doesn't hold up when you dig into the economics of that. First of all, if you have a shorter treatment delivery, you still need to fill that room for the day because you're going to be paid for the time that you're seeing those patients and you need to fill -- keep that room full. And that means you need to turn that room over multiple times during the day, which adds operational complexity. It also means that no matter how efficient you are, there will be downtime between patients when you're turning that room over that you're not paid for.

Additionally, as it exists with Spravato right now, because they don't have dedicated codes, the reimbursement is adequate. Clearly, it's on a $2 billion run rate, but it really isn't optimized. And what it means in terms of pure dollars for them is about $250 to $300 per visit, and they're blocking that room out for at least 3 hours. So it's less than $100 per hour. With the new codes under any scenario that you model because it's a formula that gets to the valuation of the codes and the fact that they're reportable on an hour-by-hour basis, that hourly reimbursement should be more favorable actually.

And it is a very good thing for the site to know that they can have somebody in the room for a longer period of time. It's going to be reimbursed at full time. And by the way, while they're in that room, that patient is going to look like this. see this a look on my face right now. These sessions are largely silent. This is generally a very uneventful monitoring period. And so there's very little the sites have to do. And that makes this very easy for them, particularly when the broader proposition is generally safe and well tolerated, you will likely know almost immediately whether this is benefiting your patient. And if it does, then it will have a durable effect such that they may only need a total of 2 to 4 treatments in a year.

Okay. Well, thanks for walking us through that. All right. So I want to ask just about the, let's say, SSRI usage in this patient population with TRD patients, I would expect that they have probably been exposed at some point, if not multiple points with very limited effect. But -- how do you think that SSRIs might be used once COMP360 is on the market? Do you see this as -- is there a potential to use them as adjunctive therapy? Is it even possible that they may be added on and used to extend responses and remissions in patients treated with COMP360?

Yes. And there's -- it's been written a lot about lately that many people have difficulty withdrawing from serotonergic antidepressants. Within our trials, both of our Phase III studies were monotherapy studies and patients on SSRIs were withdrawn from them over a period of about 4 weeks. It actually went pretty smoothly. Most patients were able to tolerate a withdrawal within that period of time. That said, choice is always good, and there will be many reasons why patients or their prescribers may want them to continue on their antidepressants.

Fortunately, we will have generated data through our trials that supports the safety of that co-administration and the fact that those who are on antidepressants have not had a diminution of the efficacy. And I say that because in Phase II, we had a 19 participant open-label study where patients could continue on their antidepressants. And in our 2 Phase III studies that run a full 52 weeks, within Part B, where it's still blinded, participants are given an option of a retreatment or to go back on an antidepressant. If they opted for the antidepressant in Part B, they were still eligible for open-label treatment in Part C.

And this is how we have been generating data with co-administration as well. And so we fully expect the label that is agnostic. You won't say monotherapy or adjunctive. It will just say for the treatment of TRD, and there will be choice on the part of patients and their caregivers.

Okay. Great. So I know we touched on it in passing before, but I would be remiss not to mention the PTSD opportunity here. So perhaps you could just recap for us the data that you have generated to date for COMP360 in PTSD. And then just talk about what are the next steps there in development.

Yes. The data that exists is the Phase II study that I'll describe more. as well as some academic studies, all of which have been really positive in terms of generating a signal of efficacy for psilocybin or COMP360 psilocybin in this population. Our Phase II study was open label, 22 participants. It was largely designed as a safety and feasibility study because there hadn't been much data generated in this population prior, it wasn't yet known how people with PTSD would tolerate psilocybin specifically and how to best monitor and support them within this clinical trial context.

To that end, this study was extremely reassuring in the sense that we supported patients with PTSD in the same way that we supported patients and monitor them in our TRD trials. which is very different than what had been looked at by Lykos in their MDMA psychotherapy-assisted program, where these are very active sessions. They were really actively discussing their trauma, very onerous sessions, both for the patient as well as the people in the room with them.

In the case of our study and going back to it, I was saying about the typical experience in our TRD trials of somebody having COMP360, this was very well tolerated. In fact, in about half of cases, participants weren't even thinking about their trauma during these sessions. So very well tolerated. It showed that this model was very feasible. But on top of that, we did have an efficacy outcome measure, the CAPS-5, which was a very exciting signal with 80-plus percent of patients responding. And so with that, we've been moving full steam ahead with this late-phase trial, and we really think this will be a highly differentiated new option for patients.

And for clarity, it's probably worth noting there is no psychotherapy as part of our trials in PTSD or in TRD, which has been misunderstood in the past. But to Steve's point, very inward journey, no interaction, no psychotherapy. And Lori, you might want to touch on just the synergistic potential for this.

Yes. Thank you. I'd like to add 2 points actually. I think Steve said this. But if not, I just want to reemphasize, this is a late-stage trial, and we have designed it as a single registrational trial. So that's important to note in terms of timing of potential PTSD coming to market. In terms of synergies, this is highly synergistic with the exact infrastructure that is currently existing for Treatment-Resistant Depression.

So along with all the data that we'll be generating in terms of safety and understanding of comorbidities with treatment-resistant depression, which we'll be able to use with the PTSD filing, it is because of the synergies. These patients are treated in the centers that COMP360 will be treated for TRD.

Now we're coming up on time. So I'll see if there's any questions from the audience. Otherwise, I can ask one to close this out.

I'm not expecting switches from Spravato, but 25x to 50x a year versus potentially 2 or 3 -- is that not very likely to happen?

I think there's a nuance, and I'll let Steve also answer. There's a difference between expecting versus targeting. So we're not targeting Spravato patients, but we do absolutely know that many of them will want to switch. So maybe you want to think about it from a clinician standpoint?

Well, I was going to say exactly the same thing, surprisingly. We share brains up here. But yes, but on top of that, you're right. And this is something we are hearing from many clinicians now that either their patients are having difficulty continuing on Spravato because of the frequency of treatment. In fact, most do give up after 6 or 7 months or they've had some benefit from Spravato, but really aren't where they want to be. And so they are thinking that there will be many switches. But as Lori said, we won't be targeting.

Maybe just a follow-up on the pricing dynamics. right? Some might only need 2 per year, but per dosing. So are you actually getting penalized for being more effective? Is that right or wrong?

Part of the -- it's part of obviously the complexity behind how we end up pricing and to make the complexity even worse, Spravato has 2 different doses in which they're priced at and a dosing paradigm for their treatment that makes the annualized number quite broad. And so we're taking all that into account when we think through pricing. And that's really why we narrow in on 3, so our average number, and so we will price on that annualized divided. Yes.

Maybe I'll just fire off my final question since we have a second. Do you see opportunities for COMP360? We talked about TRD. We talked about PTSD, but do you see broader opportunities in the neuropsychiatric landscape?

Yes, definitely, do you want to talk AUD maybe next?

Yes. It does seem that classic psychedelics like COMP360 may have somewhat transdiagnostic potential. It may work across many indications, which gives a lot of choice. We certainly do see a lot of potential and a lot of need in substance use disorders and particularly in alcohol use disorder. We've also generated some data in some other indications through IISs that look very promising as well. And so we will be taking all of that into account and thinking about both the life cycle of COMP360 as well as potential future assets.

Yes. And just to add to that, and I know we're up on time, but I think it's important right now, we've got COMP360. We have early-stage development work. We have a very large library of compounds that we just haven't been focusing on because we are trying to get COMP360 over the finish line. We have a library of over 1,000 compounds, many of which have preclinical data. And we are also looking more extensively from a BD perspective to add to the pipeline, given we now have commercial infrastructure built and a late-stage development engine. We are a natural filter and natural consolidator going forward to build on our pipeline.

Okay. Great. Well, with that, we're out of time. COMPASS team, thanks so much.

Thank you for having us.

-- this session of the Morgan Stanley Global Healthcare Conference. I'm Judah Frommer, one of the SMID biotech analysts here. We're very excited to have Kabir and Lori representing COMPASS Pathways. Let me just get through a quick disclosure and then we'll jump in. For important disclosures: please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have questions, contact your Morgan Stanley sales representative.

All right, so with that, welcome again. You're at a pivotal time in the company's history. NDA filing in process with rolling review underway. FDA actively working through module submissions, PDUFA timeline guidance with priority review, and launch guided for 1st half of '27.

So with that, kind of, as the background, maybe for those less familiar with the company and the broader development landscape, I thought we could spend a couple of minutes just on the history of COMPASS, how you've differentiated your approach versus competitors and maybe how the team has more broadly progressed psychedelic drug development efforts. I know that's a lot, but...

Thanks, Judah, and thanks. It's great to be here and just our own disclosures. I will be making forward-looking statements. We will be, kind of -- please refer to our various risk factors. Yes. So COMPASS was really founded to make psilocybin available through the medical model with broad and equitable access, and that's exactly the purpose we've been engaged on now for the last nearly a decade. One of the things that I think is key, and perhaps investors still don't fully appreciate, is the decision to go into treatment-resistant depression. So we are working in a patient population with chronic recurring depression, a population that's really very different from an MDD population, where many other things have been approved. And that's a key point of differentiation and Lori will talk more about that in a moment.

As you said, we're in a great place right now. We are going to complete the submission in Q4. We have a National Priority Voucher. I'm sure we'll talk more about it, but really the agency is extremely engaged with us. One thing we have to acknowledge as the 1st likely psychedelic to be approved: we're doing a lot of the heavy lifting. So where we are going, others will come behind us. So when we talk about not only the way we've designed our trials, you'll actually see imitation is a great source of flattery. I mean, lots of other people have designed similar trials. Indeed, the FDA's own guidance for psychedelic trials really described our Phase III program.

So we believe in many ways we have been pioneers of set the standard in this field. We're just very excited now to be within sight of the next huge milestone of potential approval and launch.

Okay, great. So maybe just a little bit more on the, kind of, that TRD versus the MDD landscape. Maybe just a little bit on the unmet need in TRD, how the opportunity differs from MDD, and really underscore, what's the standard of care for these patients.

Yes, happy to. Right now there are currently 55 MDD-approved products being used on an annual basis. 5 of those are branded and they're all pricing at innovator pricing. TRD has 1, and that is Spravato, which is currently being used. And the reason that this is such an important difference to make is there are 4 million patients who actually are TRD. TRD is traditionally defined as the failure of 2 antidepressants. And so 4 million patients out of the 13 million MDD patients that are currently being drug treated is a very, very large patient pool of patients who only have 1 option currently indicated for.

The difference between MDD and MDD in terms of being able to have this efficacy set that we have proven in this patient population is and comes down to payers. And so payers will -- because this product is the only other 1 that will be approved at the time, will most likely cover us PA to label, that is how Spravato is used today, and again, Spravato made $1.7 billion last year and only treated 100,000 patients.

So there is tremendous pricing power potentially with payers and having efficacy in this patient population specifically.

Okay, great. And you mentioned the Phase III trial could be, or maybe, it says briefly here, but maybe just describe the Phase III trial design, right? There were 2 trials here. There are differences in design between both of them. So COMP006 versus 005, maybe the various subcomponents and what you were hoping to learn from each of those, and then we'll we'll get into the data.

Absolutely. So COMP005 was 2 arms, single dose of 25 milligrams against true placebo. And that was really designed as a safety study, and the dialogue with the agency was around truly establishing a safety baseline. And again, remember, we were the 1st psychedelic to enter Phase III, so that was part of that dialogue. COMP006 is the same 3 arms that we used in the Phase IIb. So the 25 milligram, which we believe was the active dose, 1 milligram replacing the placebo, so not an inert placebo, but something that would have some potential subjective effect, and then 10 milligrams chosen as an intermediate dose, which 1st in a fully naive population, would actually help from a blinding and confounding perspective, but also, we know the agency likes to see a clear dose dose response to show that this truly is a drug effect, so that was the other part. And that is 2 fixed doses 3 weeks apart. Primary endpoint in both 6 weeks. Also both running fully blinded to 26 weeks, which is I think unprecedented in depression trials, but certainly pretty unusual.

So we really knew even though we designed these trials before the FDA issued their draft guidance, the durability was going to be key, not only from a regulatory perspective, but as we'll come on to discuss absolutely from a commercial perspective as well.

Okay. Okay, great. So with that in mind, maybe we can walk through, kind of, key learnings on both safety and efficacy from the Phase III program. I thought we could touch on MADRS reductions, responder remitter rates, and safety specifically, but help us with what has resonated most with practitioners as well.

Yes. So I'll briefly touch on the data and then hand to Lori to talk about how we see that translating into real clinical and commercial practice. So in both studies on the primary endpoint, highly statistically significant results, we saw a separation of just under 4 points in the change from baseline on MADRS. Again in this population, and again just to perhaps belabor the point of this treatment-resistant depression population, the typical, the average duration of the current episode of depression was 3 to 4 years in our trial. So this is truly a population that, while to enter the trial had to have failed at least 2 antidepressants in the current episode, typically over the course of disease had tried multiple medicines and really nothing else is working, so very much a chronic refractory population.

That just under 4-point MADRS difference, 4-point MADRS difference is highly comparable to Spravato in a similar population. What's really important, though, is we saw rapid onset. So if this drug is going to work, you will know within 24 hours. We saw with 1 administration roughly a quarter and with the 2, 3 weeks apart, 40% having a clinically meaningful response and then what we see is with an additional dose, either 3 weeks apart in 006 or at a more variable time point in 005, we actually see durability all the way extended out to 26 weeks.

So what you're seeing is a combination of very rapid onset, durability from 1 or 2 doses, now supplemented by the 52-week data from 005, where we actually see that a potential 3rd dose also has the same efficacy as a 1st or 2nd dose and extends durability out to a full year. So that combination of rapid onset, durability, limited dosing is remarkable from an efficacy perspective and it's generally safe and well tolerated. I mean, the vast majority of adverse events are transitory and resolve on the day.

They are day-of-dosing nausea, headache, some fatigue. Not surprising, this is a fairly intense experience on the day for a patient. But overwhelmingly resolved within the 1st day or 2. And moreover, we see on repeat doses and so on, we actually see some potential trend towards lessening your symptoms.

So I'll now hand to Lori to translate that into what that means. Sorry, that was a lot.

There are team members in here of mine who can attest to this, but when I 1st saw our data represented in a graph form, I almost cried. And I mean that literally. These are a very, very sick patient population. These are treatment-resistant depression. By the sheer definition, they have not had efficacy on other products, and they are in a severe state of depression. What our trials showed in both 005 as well as 006 is that these patients saw a dramatic drop in their MADRS within 24 hours of their day of dosing, 24 hours. And as Kabir said, the average duration of depressive episode for the patients that went into this trial was 3 to 4 years.

Can you imagine living your life 3 to 4 years depressed and then you have this 1 treatment and the very next day you feel better? That's why I almost cried. What made me have even more tears was the fact that we were able to see -- what we were able to see achieved with actually in a 006 with an additional dose or a 005 with Part B.

That durability lasted out to 6 months. This is contrasted against the -- again the only other product approved for treatment-resistant depression where these patients have to go in at least every other week to maintain their efficacy.

And this has become a very highly burdensome paradigm -- treatment paradigm for patients and their caregivers because Spravato patients have to be driven home by a caregiver. We will have to be driven -- our patients will have to be driven home too, but that is contrasted versus 1 or 2, maybe 3 times in a year, versus 52 times a year.

Maybe just spend a minute. We hear from time to time that MADRS is great for a clinical trial setting, but it's not the most relevant endpoint for a practitioner. So responder remitter rates, I guess, have those stood out more for clinical practitioners and maybe just frame those for us.

Yes, so I mean, I think you're absolutely right, and physicians aren't typically taking a MADRS score. Response and remission is important, but typically a psychiatrist takes a more holistic view of quality of life and so on. Yes, so what we saw in 005 was remission rates were around just under 10%. Full response rates were around 20%. We saw that improved in 006. What I think is really exciting is what we've just seen in the 52-week data from 005, which is now clearly open label but therefore much more representative of the real world. And there we saw across both placebo patients who were getting a 1st dose, or those on the 25 milligram arm getting typically a 3rd dose, you're seeing actually remission up in the 30s and 50% response up in the 40s.

And to us, that's much more analogous with what you're likely to see in the real world where people know what they're getting.

Okay. Helpful. And then maybe just back to dosing frequency, right? Like you said, patients have gotten 1, 2, or 3 doses. Just, I guess, better contrast that to Spravato, whether it's in the 1st year or if patients are continuing?

Yes, so let me start by saying what we believe our label will say. And so what we believe the label and the dosing administration will say is 2 initial doses, minimum of 3 weeks apart, so analogous to what our 006 trial was. And that's very important because there are 2 things to think about, what we saw in 005 versus 006. If a patient responds after the 1st one, does not preclude, there's no reason why they need to take the 2nd one, the physician will make that decision. But we believe that the 2 initial doses does give a patient a much more dramatic and longer durability.

And so the maintenance period, we won't say maintenance, but in effect what is contrasted to the Spravato label maintenance period, we'll say redosing upon physician discretion. And the commercial team will help educate sites and physicians on what to look for, what to expect from their patients. They'll get clinical experience. They'll understand at the time of redosing.

We do expect the minimum to be somewhere between 2 and 4 annually, and I know that's 3 on an average. I I can't do math occasionally, but we do expect there to be somewhat of a range. And that is how we will price. So we can come back to that later, but that is what we're looking at. For Spravato, by label, their initiation phase is twice times a week for the 1st month, once time a week in the 2nd month, and then every week or every other week for a maintenance period forever. There is no end point. And so you have to compare and contrast what that burden is for a patient of either 2 to 4 days off of work to their caregiver days off of work, versus potentially 25 to 52 times in a year having to go in for Spravato.

And what you also had to recognize is because of that patient burden, in practice, few patients get beyond 7 or 8 months since Spravato. And, of course, they are then not necessarily better. So that's a suboptimal treatment, both from a patient, clinicians, and importantly a payer's perspective as well.

The frequency of treatment also with Spravato does limit the radius at which patients can feasibly go into a center and get treated on that frequency of the basis. When you're going in 2 to 4 times a year, that definitely opens up our radius of patient population.

Okay. And so maybe just on that point, maybe just walk us through the current Spravato infrastructure set up today why, it could represent sort of a running start for COMP360? And maybe at the same time, what are some of the areas of confusion for investors in assessing whether Spravato and COMP360 are both attractive from a provider perspective?

Yes, so I can answer both of those without directly answering both of those. Right now, there are 8,500 sites that are currently available to administer Spravato. And what that means is effectively that they are prepared to administer multi-hour treatments, Spravato being the only psychiatry pharmacologic product out there that is multi-hour.

And it also is very important for me to note that a Spravato -- REMS-certified Spravato center is ready for COMP360. The rooms are the same. The staffing requirements will be the same. The getting a PA through REMS requirements outside of the hours needed for monitoring should be highly similar. And so there's nothing that the sites that are currently existing for Spravato needs to do to get ready for a COMP360, they're already ready.

And so that I think is the fundamental miss from investors. On top of that, they have capacity. Spravato sites are growing at about 500 sites a quarter. And that's impressive. Spravato is a very good drug, but these sites are growing because they understand that psychiatry, particularly depression, has multi-hour products coming behind it. And so these sites are getting prepared to have multiple options. Again, the current sites are not at capacity and they have a very -- they're only treating 100,000 patients out of 4 million in TRD.

Okay, great. And then maybe just touching on the regulatory side, just remind us of your FDA interactions and designations thus far, your Breakthrough Therapy designation. I think it's called a National Priority Voucher at this point. So how have those factored into from level of communication with the agency and frequency?

Yes, so you're absolutely right. We've had Breakthrough Therapy designation since 2018, and now we received the National Priority Voucher in April. So I think the 1st thing to say is throughout the development of COMP360, we've had a really good relationship with the Psychiatry division. We were not the earliest to move forward, but there have been other companies in parallel as well. And I would say that the division truly has an appreciation of the potential of psychedelics. I mean, they have said publicly that between a 1/3 and a 1/2 of everything under review is now psychedelic. So, putting it in context, we already had a high level of engagement. They were already putting out draft guidance and so on.

With the National Priority Voucher, that really means 2 things. 1st, at the back end, there is the target of approving it once the submission is complete within 60 days, and that will be very nice to have at the back end. But I think much more importantly, it's led to a fundamental difference in the way the day-to-day interaction goes. We have got a rolling submission underway, and we also genuinely have a rolling review underway, because sometimes you had 1 without the other. But we are getting information requests. We're turning them around. We actually have a draft label already under review. The REMS framework is under review.

We've already submitted the 8-factor analysis for rescheduling, and there are inspections happening as early as this week. So I would say that the level of engagement, interactivity, the lack of the formal bureaucracy and timelines they have used to govern FDA interactions has been incredibly refreshing. At the same time, the division has been very clear with us that there is no change to the standards. Yes, they are going to hold us to exactly the same standards, they would ever have held any other psychiatry drug to, and we think that's exactly right.

So we're very happy with where we're at. We will complete the submission in Q4. We honestly don't know if there'll be the typical 60-day acceptance. There could be, even though we've done a rolling submission and rolling review, and then we expect the clock to start with a potential 60-day. We do think they may still issue a 6-month PDUFA and beat it, but again, there are so few precedents to any of this at the moment, it's not quite clear.

Yes, great. So that could set you up for a launch, I think you said as early as 1st half of '27. So maybe just give us an idea of how investors should think about adoption. What are key factors to pay attention to following potential approval? And I think you have said recently there could be a slow ramp out of the gate, but there could be some snowball effect as, kind of, experiences gain. So I guess what metrics should folks be paying attention to and what timelines should we be thinking about?

Yes, so let me just reorient people to the timing of launch and what that might take, because I think that's very important to understand. As Kabir just alluded to, the timing of approval will be a little bit fluid. Hopefully that's understandable. And then the DEA needs to reschedule, because this is a Schedule I product, they will need to federally reschedule it. And given the executive order, that could be anywhere from 1 day to 90 days after approval.

Again, we're doing everything we possibly can as a company to make sure that that's done in an expedited fashion, but it really is out of our control. What is in our control, though, is to making sure and helping states reschedule as well, because after federal reschedules, the states need to reschedule. And so once the states come online and reschedule, we can then legally ship as well as physicians can legally prescribe the product in their states.

We've done a tremendous amount of work over the past 2 years to make sure that as many states as possible are intending to reschedule within 30 days after federal.

And right now, 93% of the population lives in a state that will reschedule within 30 days, and we're continuing to do work. So by the time we launch, that number will inevitably be higher. And the reason we're thinking about a slower launch is not because of demand. We have almost unheard of demand from not only excitement from physicians but also patients and patients that we're speaking to. We're not concerned about demand at all. What we are concerned about is making sure that sites get reimbursed and they have no reason not to prescribe and that they are well prepared to administer the product and we are very focused on making sure patients have a good experience.

We know that fundamentally if those 2 things go wrong, our launch will derail pretty quickly. Not only that, we will derail it for the entire class. So we're taking that very seriously. And so we're going to spend a lot of time making sure that sites can get reimbursed appropriately. So a little bit of hand-holding, white-gloving it, if you will, more rare disease type, making sure that sites are adequately prepared and that reimbursement is not a hurdle for them, as well as making sure that patients are well-educated and prepared.

So that inevitably may mute the launch a little bit, but once these sites get clinical experience, they know they can get reimbursed for the time that they're spending, as well as the product can get reimbursed for the patient, that should should skyrocket pretty quickly.

Okay.

Exactly. And we also think that word of mouth, peer-to-peer, both at provider and patient level is going to be critical here, which is why those early experiences need to be positive.

And how are you thinking about REMS, I guess, relative to Spravato? Presumably monitoring time would be different, but anything else you'd highlight?

No, we don't expect anything outside of what the REMS requirements are right now. In fact, we've had early discussions with the FDA to guide us towards that. Where this lands, we'll see, but there's no reason to believe that it would be anything outside of Spravato requirements, basically, other than the time required.

Okay. And maybe just coming back to the addressable population a bit, do you have a sense for proportion of TRD patients that are receiving any interventional treatment, whether maybe it's Spravato, ECT, TMS, beyond pharmacological even? And of these, do you get the sense that there could be a switching dynamic when COMP360 potentially potentially comes to market or are de novo TRD patients more of the initial target?

Yes, it's a great question. Right now, Spravato treats about 2% of the TRD patient population. ECT and TMS treat about another 2%. So less than 5% are actually receiving any treatment-resistant depression-indicated products. And so, again, that's out of a patient population of about 4 million. And so the capacity to grow the market is sitting ripe for another TRD-indicated product to come to market and really start to make sure that physicians are well-educated on treating with appropriate medicines.

I do, the switching one is an interesting one. Will there be switching? Absolutely, and it has to do with the fact that we -- of what we just talked about, the burden of Spravato is high, but is that who we're going after? Absolutely not.

These are treatment-resistant depression patients. If they're stable on Spravato, please stay stable. We're not -- we don't want to risk that, but there will be some switching. We know that. We know that from patients we've had engaged with.

The patients we will be going for are patients who either are coming in de novo, and we know that that demand is there. The sites are already telling us that they have a waiting list of patients, but there's plenty other ways of attracting patients, not only from us doing marketing and making it aware, but also the sites are attracting patients.

And the real patient need here is to move psychiatrists and so on to recognize TRD much sooner than they do today. And that's why we've already started to do that and so on around that because while the technical definition as I say, maybe 2 failures being failed by 2 drugs in the current episode. In practice, so many of these patients have been cycled through multiple drugs, but haven't worked. And so that's the real opportunity. So there is a huge pool of patients for us to go after without needing to target Spravato or anything else.

That's right, and we just launched our "Change the Tune in TRD" project disease state education website, and we're premiering it at Psych Congress today. And so we are very, very excited about increasing disease education, mostly this is a pharma world. There's a lot of interest in uses of MDD products because that's all that's really been available to psychiatrists. Now we actually are proving efficacy in this patient population, and the more people out there talking about efficacious treatments for this patient population, the more that pie will grow.

Okay. Maybe just coming to reimbursement, right? I think there are maybe questions around reimbursement for clinicians in these centers. You've said you'll have a field reimbursement team fully deployed at launch, so clearly you're on top of it. CPT codes we have to touch on, as always. So where are we currently? Where are they headed? You've done a lot of work to lay the groundwork here, so what's the process and timeline for getting these to Category 1?

Yes, so there are a couple of things I want to make sure we highlight. And 1 is no site should be disadvantaged versus providing Spravato. Right now, Spravato uses general evaluation and management codes. They will be the exact same codes that they will use for COMP360 reimbursement until our Category 3 codes get moved to Category 1. So there is no possibility of there being a disadvantage here. So I want to make that very clear. The reason the field reimbursement team becomes very important is 1, to make sure that the sites understand this, but also so that they can attach the CPT-3 codes to the reimbursement.

The more pings to payers, the more proof that these are actually being used, the faster it will move up to Category 1, and they can get -- the category -- the codes can get assessed at the value that the sites are actually administering which we believe should be higher currently than what the general evaluation and management codes are today. Then the faster it will move up. But there will be some time, and we have to be honest about that, there will be time, naturally, until we prove usage in this.

Okay, great. And you touched on it briefly, but I guess, just on pricing and you talked about dosing being in that 2 to 4 annually, I guess, what have conversations with payers sounded like? How receptive are they to the unmet need in TRD?

Yes, I've been doing this for a very long time at this point. I've never had payers as interested in talking to us. Now, that I will fully admit. That doesn't mean anything, but it is a very good starting point. Usually, companies have to go out to payers and beg them to spend time with them to show them the data. We are having quite the opposite effect. We are having great interactions with payers.

Payers truly understand the burden that treatment-resistant depression is adding to the payer system, and they are very excited not only about the dramatic reduction on day 1, within 24 hours, but how long this actually lasts with only 1 dose, maybe 2 doses. So we're very, very encouraged with where we're at.

Okay, great. And maybe just a little bit on competition within the broader space, which is probably a good thing to see, kind of, more psychedelic drugs moving through the clinic. But for those utilizing shorter duration psychedelics in the treatment landscape, we've seen some acquisitions. I guess, do you get the sense that clinicians and patients are excited to have multiple options and these are subjective experiences potentially?

Yes, I mean, I think the important thing to stress here is that the 1st, we do welcome more psychedelics coming through. I mean, the growth of these clinics, as we said earlier, is not being driven by Spravato. It's being driven by the expectation that there will be multiple coming. And another dynamic we haven't even touched on is the buy-and-bill now accounts for 35% to 40% of Spravato. As you see more products coming through, you'll see more and more psychiatrists seeing that there's a business opportunity here across multiple products. But in terms of actual products themselves, a couple of points here. 1st, we've talked about the unmet need.

There are vast numbers of patients across TRD, MDD, GAD, PTSD, and so on. So in the same way as there were multiple SSRIs or antipsychotics that received which is multiple billions, I think you'll see the same. The 2nd though is duration is only 1 element and truly only 1 element of the differentiation between these products. So psilocybin is a relatively gentle experience. Yes, it comes with some inner-directed work that can sometimes be challenging to work through. But physically, it's actually a very stress-free experience. Yes? Somebody's got eye shades, listening to music and so on. Some of the shorter acting are physically challenging experiences both for the patient and the provider.

So again, 1st, they are several years behind us, so until we've actually seen Phase III data around the profile, we don't know. But I do think the nature of the subjective experience and how different they are is also going to be an important element of provider and patient choice.

I agree, and as Kabir alluded to, these sites are growing because more options is better for business. And also, there is a tremendous unmet need for patients. And this is the psychedelic sort of future. I stand behind that.

Great. And I want to make sure we touch on the PTSD program. So what should investors be looking for in terms of updates from the ongoing Phase IIb/III in PTSD? And maybe just spend a minute on how that opportunity differs from TRD. Sure, why don't you start with the unmet need and the demographics, yes?

The unmet need is potentially larger than the treatment-resistant depression opportunity right now. This is why we're so excited about PTSD. So PTSD is about 13 million patients. The last product was approved 25 years ago. And so there's not been any innovation in the space in a very long time.

We do hear a lot about veterans and PTSD. Obviously, that is an important area of concern for us. They actually only represent about 15% of PTSD patients.

So it's important to note that it is far reaching beyond just the VA and veterans. It is 60% women. And there are plenty of opportunities. The most important thing to note is the synergies are incredible here because PTSD patients will be treated in the exact same centers as the current infrastructure for depression.

And from a design perspective, essentially we've mimicked 006 in this single late stage [ registrational ] space. We decided -- even though we'd done the open-label study a single dose based on what we saw from 006 that suggested a 2nd dose can deepen the impact. So this is a 2-fixed-dose study. 25 milligrams, again, we believe will be the effective dose here. Again, we have the same intermediate dose from a blinding perspective and so on. And the primary endpoint is at 8 weeks just because CAPS-5 is a 4-week look back, so it has to be at 8 weeks. So primary endpoint at 8 weeks, blinded to 12 weeks, open label thereafter for a year.

We've designed it in a way that we believe it can be registrational. The agency has already agreed that from a safety perspective, much of what they already know translates across. We hope and believe with, kind of, the emerging flexibility within the agency that this single, very large, robust study should actually be sufficient. Over time, the study is now up and running as we get more into recruitment and so on, we'll be able to update on timelines right now. We can't have any guidance for that.

Okay, great. I think with that, maybe we'll move in the last couple of minutes to a mini survey we're giving all the biotech management teams and some of these may be less relevant, but curious to hear your responses. So the 1st topic is just on China's rise in biotech innovation. Any thoughts on competitive positioning, whether it could affect business development and strategy?

So what I will tell you is that 1 of the best known analysts from another bank went on a trip to China and his report, what he wrote was, "The only sector I cover that doesn't need to worry is psychedelics because none of them even knew what the word meant." So no, honestly, I mean having worked in China myself, albeit a long time ago, it's been 3 years, the treatment of serious mental illness is still in a very different place even now.

And I don't think China specifically is somewhere that we regard as an area of potential. That said, we are very interested in NCE development, new things that are coming through in the broader psychedelic pipeline. And if some of that innovation came from China, we will clearly be open to that.

Okay. And the next topic is AI. I guess, can you talk about how COMPASS is leveraging AI or thinking about potential disruptions from AI?

Yes, so we are leveraging it, as you would expect, as a productivity tool, essentially widespread across the whole business and a mix of using 3rd-party resources, plus some really interesting ones inside. So I'll give you a good example. Obviously, our dossier is huge and massively cross-referenced and so on.

So our internal team developed a very powerful tool that is actually dealing with all of those cross-references, getting out duplications and so on and so forth. So, yeah, we're using it as a tool broadly. We don't do drug discovery, so that's not relevant to us for a discovery place. And on the commercial side, we will again be making extensive use as we roll out tools.

Yes, productivity is incredibly enhanced by AI and we are putting in place right now. And really, we are also highly regulated too. So, it does help from that standpoint, but there are lots of programs available right now that can help increase the productivity of sales reps in particular.

Okay, great. And last one, just on regulatory. I guess, which aspect of your regulatory interactions or strategies are most impactful? FDA, pricing, tariffs, anything else?

Yes, from our perspective, it really is the FDA, clearly with the NPV and so on. And as I just hinted at as well, I think it's not just what we've been able to do with our core Phase III program in TRD. We're excited about the opportunity for future flexibility, for instance, a single PTSD study being potentially registrational. And the other area, which I think is going to be really important, is real-world evidence. So historically, psychiatry has not been open to label expansion, indication expansion through RWE. I think we see a potential open door there because we will be collecting a lot of real-world evidence as we roll out.

Great, right. We'll leave it there. Thank you again, guys.

Thank you. Thanks for having us.

Thank you. Thanks for having us.

Good day, ladies and gentlemen, and welcome to the COMPASS Pathways Second Quarter 2026 Conference Call.

[Operator Instructions]

As a reminder, this call is being recorded. I would now like to introduce your host for today's call, Stephen Schultz. You may begin.

Thank you, operator. Welcome all of you, and thank you for joining us today for this conference call. Again, my name is Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways. And today, I'm joined by [indiscernible] and Lori Englebert, our Chief Commercial Officer. Teri Loxam, our Chief Financial Officer, will also be available for the Q&A.

The call is being recorded and will be available on the COMPASS Pathways Investor Relations website shortly after the conclusion of the call and will be available for a period of 30 days. Before we begin, let me remind everyone that during the call today, we will be making statements about our future plans and prospects that constitute forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. Including those risks and uncertainties described under the heading Risk Factors in our most recent filings with the U.S. Securities and Exchange Commission.

These forward-looking statements represent our views only as of today. and we specifically disclaim any obligation to update or revise any forward-looking statements, even if our estimates or assumptions change.

I'll now hand the call to Kabir Nath.

Thank you, Steve, and thanks all for joining us today. The first half of this year has been an exciting time for COMPASS. Now that we have highly statistically significant positive Phase III primary endpoint readout as well as demonstrated durability through 6 months from both our trials. We believe we have largely derisked the clinical and regulatory profile of COMP360.

In addition to confirming its rapid onset and durability, the totality of different the program so far shows it has a generally well tolerated and safe profile. Taken together, these data reinforce our belief the COMP360 has the potential to fundamentally change our mental health [indiscernible]. With these data sets in hand, we continue to make significant progress towards our NDA filing for the treatment of TRD. Our rolling submission and review process allows us to submit data in waves to the FDA, and they have started to review some modules that we've already submitted. We continue to expect to complete the NDA filing in the fourth quarter.

With the potential for an accelerated approval following our final submission, we are advancing our commercial readiness. We built a fantastic commercial team with incredible experience and we're executing on all fronts to be prepared to get COMP360 for millions of patients living with TRD who urgently need new treatment options. We're also well positioned with our strong balance sheet with $433 million of cash on hand as of June 30, which carries us well through launch and into 2028.

Let me now hand the call to Lori to talk through in more detail how we're preparing to transform treatment options for these patients.

Thanks, Kabir. Hi, everyone. Thank you for joining. As Kabir outlined, we have achieved significant milestones in the first half of the year. Notably, advanced important commercial readiness initiatives across organizational capabilities, strategic collaboration, healthy and payer engagement and distribution, all significant steps towards being launch ready.

Earlier this year, we rounded out hiring of the commercial leadership team, attracting highly experienced energized leaders who immediately to build out the functions. My direct reports, come from companies like J&J, Gilead, [ Okko ] and Axon, and between them have led over 70 product launches. The prospect of launching the first psychedelic in history with a medicine that has the potential to fundamentally change the way mental health is treated is a very powerful attractor of talent. And we are bringing in outstanding professionals from across the pharma industry.

I am incredibly proud of the team we are building at COMPASS. In the first half of this year, we also announced additional strategic collaborations with Radial and Osmind, taking the total to 8, each with their own distinct capabilities. These collaborations played a critical role in helping to inform our priority focus at launch of ensuring optimal and patient experience.

With the final submission of our NDA expected in the fourth quarter, our focus in the second half of this year is on operationalizing launch plans and ensuring launch readiness. This includes advancing everything from training, education, access and reimbursement, and patient support mechanism. Importantly, we have also already initiated recruiting for the sales force.

Our time line for launch remain fluid given the national priority review voucher and executive order in April and the need for DEA, federal DEA and state rescheduling. We remain focused on being ready to launch which we anticipate being in the first half of 2027. At launch, we will leverage the well-established existing interventional psychiatry treatment center infrastructure. These treatment sites are specifically designed to support in-office treatments for products that require multi-hour monitors such as Spravato, TMS and ECT.

The established infrastructure has existing capacity and importantly, is already equipped with the staff and operational know-how needed to support additional multi-hour treatments like COMP360. Seven years ago, when Spravato launched, this infrastructure did not exist. Today, there are more than 8,000 established sites across the U.S., and this continues to grow rapidly.

COMP360 is poised to lead a profound shift in mental health care, moving beyond daily or frequent dosing toward an option potentially evolving just a few treatments a year, which could be life-changing for patients. Across 2 highly statistically significant and positive Phase III trials, COMP360 demonstrated, extremely rapid onset of action, with deep and clinically meaningful reduction in depressive symptoms as quickly as 1 day, unprecedented durability sustained through at least 6 months and notably, reproducibility of effect in a chronic treatment resistant patient population, one of the most difficult psychiatric conditions in which [indiscernible].

The data are strong, and both patients and prescribers are excited about the potential for a new treatment option. In recent prescriber focused market research, approximately 90% of interventional psychiatrist stated that they would prescribe Comp within the first year being available. In my experience, this is the highest willingness to prescribe percentage I have ever seen in prelaunch market research. With the COMP360 emerging profile and continued interest and excitement around the class, we are eager to bring a new treatment option to the 4 million patients living with TRD today who have limited treatment options. And we are confident in the blockbuster opportunity.

COMP360 has the potential to fundamentally change the way that patients living with depression are care for and COMPASS is committed to helping as many patients as possible. We are making significant progress towards being launch ready, and I look forward to discussing more with you throughout the rest of this very exciting year.

Thank you, and let me hand the call back to Kabir.

Thank you, Lori. Our progress in the first half of the year has meaningfully derisked the path towards potential approval and launch and reinforces our confidence in the strength, consistency and robustness of the COMP360 data package that we are submitting to the FDA. With the regulatory process underway, our focus is on disciplined execution, completing our filing activities and preparing for a first pass approval and ensuring we are poised to deliver COMP360 to patients with TRD as quickly as possible following approval. And as you just heard from Lori, we will be ready.

With that, let me pass the call to the operator for Q&A. Thank you.

[Operator Instructions]

Your first question is from the line of Paul Matteis with Stifel.

Specifically, I was wondering if the team could offer some perspective on the recently issued FDA guidelines around psychedelics. And more specifically, how did you interpret the discussion of those guidelines as it relates to 12-month blinded [ durability ]. What do you think that really means or what the FDA is asking for? And how do we think about that in the context of the COMP360 program?

Thanks, Paul. I'm just checking, you can hear me clearly, yes.

Yes.

All right. Thanks. Yes. So look, I think as you're aware, this is a finalization of a set of draft guidelines. And the original draft impact came out even after we had fully designed our Phase III aligned with the agency on that and so on. So our perspective is we have had very robust continuing dialogue with the agency throughout this program. And while the guidance is certainly interesting and we do have those on the 12 months blinded and that would seem like a pretty tall order in any psychiatry drug. We actually don't think it's going to impact the process of our regulatory approval at this stage.

I think the other parts of that, that I draw your attention to is the design of Phase III studies in a complementary pair continues to be effectively exactly in line with the design of our studies. So while I think the guidance is interesting, and obviously, in terms of future endeavors, we will be carefully looking at that. We honestly do not think that these guidelines are going to impact the regulatory process that's already underway for us.

Your next question is from the line of François Brisebois with LifeSci Capital.

I was just wondering, in terms of launch, can you help us understand this always happens, but especially in your situation, just the reimbursement challenges, what are we going to have to go through just to get a better feel for the cadence here with the launch expected next year?

Francois, as you mentioned, launches are traditionally hard coming out of the gate with the reimbursement just because you need time. What we are doing now is our market [indiscernible] team is already engaging with payers, and they have been now for some time. We're getting very positive feedback from the payers, especially in this TRD patient population, where proving efficacy has almost been impossible to do in the past. So it is playing very well with a key stakeholder who really truly understands the economic burden that patients with TRD can have on a payer system.

So at launch, what we expect is we are intending to have a field reimbursement team fully deployed at the time of launch. Who will be out helping these sites ensure that they can code and get the reimbursement that they need to code for and make sure that they're well educated in the process.

In terms of the drug reimbursement and the conversations we're having with payers right now, we are working through that. We are still ingesting the data that we just got and released a couple of weeks ago into the value proposition that COMP360 can bring, and then we'll make decisions as we get closer to launch on what that might look like in terms of rebating and paying negotiations for formulary access.

Your next question is from the line of Gavin Clark-Gartner with Evercore.

Maybe you could just characterize how any ongoing regulatory discussions are progressing? And separately, what are your expectations for DEA scheduling timelines at this point?

Thanks, Gavin. So on the first part, I would just say they're going well. I mean the rolling submission is underway. As I noted in the remarks, some of what has been sent is under review. We're getting questions on it. Clearly, given the acceleration, given the NPV, the onus is also on us to respond very quickly, and we're doing that. So the team is doing an amazing job of being responsive to that. So nothing out of the ordinary that I would say we remain on track. And as you know, one kind of in the later stages that things like label and REMS really come into play. Those are typically negotiated fairly late in the day. So nothing -- really nothing untoward to report except we're very happy with progress.

On rescheduling. I'll hand to Lori.

Yes. Gavin, we are accelerating our 8-factor analysis getting that to the CSS, FDA division of controlled substance as quickly as possible. And in hopes of that enabling a faster FDA and DEA coordination along the way. We're also heavily engaging with the DEA or attempting to engage with the DEA to help see if we can get any further clarity on what that looks like.

As I've mentioned in the past, the DEA is pretty consistent in hitting their 90 days, so we feel very confident that they will reschedule within the 90 days, but it's still a little bit fluid in terms of when that actually will happen. But given the exit order in April, we are confident in the ability to potentially pull that forward.

Your next question is from the line of Ritu Baral with Cowen. Please go ahead.

Another question for you, Lori. Specifically around the term training that you used in the prepared remarks, it sounds like in response to some of the prior questions, some of that training for the interventional psychiatry sites will revolve around coding. But I wanted to ask what other aspects of training does the team plan on offering interventional psychiatry sites. Especially given that you have a good -- a very solid precedent REMS to sort of train against and anticipate. How do you anticipate offering sort of readiness services to those sites?

And how does that impact, I think, how all of us may model 2027 rollout. We've -- here at TD Cowen, we've had experience with sponsors really wanting to manage the early experience with the drug at [indiscernible] with clinicians on early rollout. So anything you can tell us about sort of the general shape of 2027 as you see it now with the training offered.

Yes. Ritu, thanks for the question. I'm going to try and collect it all into one cohesive [indiscernible]. So the way I think about training -- you're brilliant at this. I -- we think about training in 2 parts. So there's going to be training are going to be education. So I will address both, but in terms of training, it's typically training. We announced a little while ago that we are participating in grants for third-party companies to help with the training of the site. Both on psychedelics and as soon as COMPASS gets the final label on anything that's required for the monitoring time that the patient will be in the room. We want to make sure that, that patient experience is a very good one.

And so we will -- we're still doing that. So the sites will need to be trained because in the REMS, they will need to attest to being trained and part of that will be based on the training that these third-party providers are enabling.

Already, there are well over 1,000 people who are already trained on the psychedelic portion of that training. And so there is a broad group of people already ready to go with that training.

The other training, again, the COMP360 piece of that particular training on how to best support the patient and helps enable a very good patient experience that will come after we see the final label and we get that finalized. We are also -- we'll need to do training on REMS to make sure that they are compliant with REMS certification and all the things that they need to do with REMS. So in terms of rollout, in some cases, the fact that there will likely be a little bit of time between when we get approval and when the DEA will reschedule and then the states will reschedule, Obviously, we're trying to do this as fast as possible. We are going to leverage that time to the best of our ability. And so we will have teams out immediately upon approval, helping these sites to make sure they know the requirements that will be under the REMS.

And as we learn a little bit more and get closer, we'll be able to start communicating what we expect in terms of site readiness. This will be obviously a key KPI that we will want to communicate on. And then obviously, when it comes time to prescribing as we are thinking through this, obviously, and you mentioned before, which you've listened to me in the past and the importance of making sure that the sites and the patients have a very good experience. We are very acutely aware that we are leading the way here, and it is important for us to maintain that leadership.

And so the other piece that I do want to quickly touch on is there were all limations. This is our field force, educating the prescribers, the referring physicians. This is our medical science liaison who are have been out in the field for 2.5 years now continuing to educate there. And we're going to continue to do additional support things like our education and enabling that in an outsized way just to make sure that we are covering all the bases and everyone is very much aware of the potential of COMP360.

Your next question is from the line of Andrew Tsai with Jefferies.

Thanks for the update. So I think you guys are in a very unique position be the leader in the psychedelic space. So to maintain that leadership over the next year, what is your appetite like to do even more studies with COMP360 outside of PTSD and so forth? And any new indications or other new psychedelics we can hear about? Or is the expectation for us to be focused on the launch itself.

For the question, Andrew. So yes, the expectation should be to be focused on the launch of lease for now. Clearly, as a new company with our first asset, we have a team that's incredibly working incredibly hard on the submission. But more than that, as I said in the prepared remarks, on a first pass approval because submitting is something that this needs to be a really robust dossier. We are the leaders, you can imagine from a quality perspective, from inspections and so on. All of this is brand new to the agency. So we really are very, very focused on not only a real robust submission, but also doing our best to get that first part approval.

You've heard a lot from Lori and we'll continue to hear a lot more out the preparations and so on on that side. the PTSD study is now underway. I think the way we think about this is, as we move through what we hope is an expected approval and launch, absolutely, we will continue to look of other opportunities for COMP360. There are clearly some very interesting areas. There is a lot of interest, obviously, in substance use disorder with AUD in particular, at the forefront at given the size of that as a public health issue. And potentially more broadly, what other assets that may be out there as well. But in the short term, you should take us to be very, very focused on this submission approval and launch process for TRD.

And Andrew, if you don't mind on mind, I'll just add a couple of things there to help add a little more color. So consistent with what Kabir has mentioned, we have and supply study drug to an enormous amount of IIS studies. And so we will be looking through those to understand where the potentials may lie if that becomes an option for us with COMP360. And at the same time, we're also going to be collecting a lot of real-world evidence to really understand more about patient populations that may be responding to COMP360. We will be attacking this on all fronts in terms of understanding what would be the next viable indication.

And just -- sorry, I should have said that, Lori, to build on that. We had taken a pause for a couple of years on our IIS. As we said, we have supplied a lot of drug for a number of indications. We are now ramping that up again. So we actually have a number of IIS starting in areas such as OCD, which I think is potentially very interesting area. So that now as we're getting closer to the regulatory finish line for TRD, we're actually restarting our IIS programs.

Your next question is from the line of Madison El-Saadi with B. Riley.

Maybe I'll ask on REMS certification. If you can just kind of help us understand that process if this is something that's molecule-specific. And can sites proactively progress that process before DEA rescheduling takes place? Or is that something that happened sequentially?

And then secondly, if I may. Are you continuing to collect safety data or safety follow-up data? Or has the full safety data package been submitted?

So I'll take the second part first and hand back to Lori. So both studies run to 52 weeks. So we will ultimately be providing the full 52-week safety data to the agency. Right now, obviously, with the 26-week data from 006 in hand, our core focus now in terms of preparing the submission is really integrating the safety from the 26 weeks blinded. of both studies into an integrated summer, and that's clearly a key area of focus for us. But ultimately, the agency in the process of review, we'll see the 52 weeks of data as well.

Madison, I'll take your first question around REMS. So as you know, the REMS will not be finalized until we receive approval. And so -- because of that, we will only be able to go out and start ensuring that sites are aware of any REMS requirements and going through the process for certification once we receive the approval. And as I mentioned earlier, as it stands now, we're going to do everything we possibly can in between the time of approval and DEA rescheduling to make sure that these sites are well prepared to administer the product [indiscernible] it becomes available.

Your next question is from the line of Judah Frommer with MS.

Just wanted to ask on the post hoc analysis you mentioned in the release on the 8% of administration sessions for the [ 2b ] and PTSD being in [indiscernible]. Any thoughts on how that could impact monitoring whether it's for TRD or PTSD and potentially staffing requirements going forward.

Yes, let me start, and then Lori will build on that. So Yes. I mean I think to us it's very interesting data and really very much validates the point we've been making for a fair amount of time now that are still a side in experience specifically truly is in a directed one where the patient is largely [ lean ] experience and the role of anyone who is sitting with a patient is just for monitoring and for safety in case of need. And we see that very clearly revealed. As we said, with 80% of that being silent.

And yes, to your point that clearly to our mind, does introduce a broader range of possibilities but who could sit in the room. If indeed, ultimately, you need somebody in the room at all.

Agree. And Judah, the only thing I'll add there is in the near term in terms of when we receive the REMS, there will be a requirement for stack-out minimum 6 hours. That is consistent with our clinical trials. And the label or the REMS requirement for who sits in the room will and should be -- or we expect to be fairly broad in terms of a health care provider. And that is because the [indiscernible] Spravato is now. And as you probably already know, Spravato has found ways to become very efficient with their rooms and how they monitor. Of course, our most important requirement is going to be safety for the patient during this experience. And so we will not lose sight of that. But site after getting clinical experience, we'll learn how and who to put into the room to help these patients.

Your next question is from the line of Patrick Trio with HC Wainwright.

It's [indiscernible] on for Patrick. I guess, for the PTSD trial, do you have any updates on site activation enrollment cadence target size expected readout timing or VA implement that you can share?

So other than the slide is underway, nothing in terms of enrollment and so on. The trial is 300 patients in total across 3 arms. There are going to be a number of VA sites enrolled in that. I can't give the specifics on that. What we are doing though is in line with the overall percentage of PTSD patients within the population where shall we say, VA or military related are not more than 15%. We're capping patient numbers again at that out of the 300. But yes, it is underway. And yes, it's a 300-day trial.

Your next question is from the line of Leonid Timashev with RBC CM.

Josh on for Leo here. So with the physician discretion coming after the 1 to 2 recommended doses for COMP360. Given that you've been doing these surveys of psychiatrists, what kind of feedback might you have been hearing from docs on expected dosing schedules? And how widely might that feedback have varied.

Josh, thanks for the question. The surveys that we're doing are based on a product profile of COMP360 and what we've seen through our Phase III clinical trials. And as I mentioned in my remarks, what we're seeing is an overwhelming response to willingness to prescribe. And not only am I seeing numbers I've never seen before in my career. But even the facilitators of the market research are saying the exact same thing. They've never seen numbers that's high in terms of willingness to prescribe.

These -- the reason that this is so exciting for physicians right now is truly because of the TRD patient population. CRD patient population, again, just 1 product or 1 drug products available to patients right now in that drug product, although it does work for some patients can be highly [indiscernible] for patients. And so the dosing frequency becomes a no driver for these physicians and why they're so excited about it.

What we -- we have not heard any hesitancy around that. And to be honest with you, it's going to be incumbent upon the sales team and our field teams to really educate based on all the additional data that we will have available on what the frequency of dosing may look like.

Your next question is from the line of Sumant Kulkarni with Canaccord Genuity.

It's a part of from a value proposition perspective, what's the best way one could place COMP360 time and clinic in context versus products that might promise a 2-hour or less station in the clinic. And from a competitive perspective, what are your assumptions on whether there might be another FDA approved psilocybin molecule within the first year of approval of COMP360.

Thanks for the question, Sumant. So I think as we have often said duration in clinic is only one element of a product profile, yes. And I think from the perspective of the patient and the provider experience, it's not necessarily going to be the primary driver. Clearly, there's an efficacy and safety bar that's got to be clear for any asset. But we actually do believe that the nature of the psilocybin experience is something that is inherently attractive to patients and providers.

Also, as we've discussed in the past, even on an economic basis as long as there remains capacity in the system, there is actually not a good economic argument for why shorter is better in terms of the ability to generate revenue [indiscernible].

Your next question is from the line of Rudy Li with Wolfe Research.

Just a quick follow-up to the market dynamics. So probably, there are a lot of discussion on short duration versus long duration psychedelic following the leading deal. So maybe in 5 years, we have a couple of options, different compounds, different duration, maybe different indications. So a very exciting time, but maybe talk about your understanding of the market dynamic with multiple psychedelic options and the positioning of COMP360 in the broader psychiatry space, depression and anxiety.

Rudy, so the good news is that psychedelics continue to produce very robust, very exciting data. And hard reason why you were seeing these clinics, the Spravato certified clinics who are enabled to support these multi-hour treatments is because the -- this is a very exciting time for the sale of mineral health. And so they are growing very fast and they're growing in anticipation of additional options being available.

These products don't work for everyone. And there are 4 million -- at least 4 million patients who are underserved today and not being treated with an interventional treatment like a Spravato or an ACP or a TMS that is indicated and has shown improving efficacy in this patient population. And so these centers, regardless of duration. And because we have repeatedly talked about, the economics not being a driver, it is really going to come down to patient preference in terms of what a patient starts, provider experience in terms of what that patient has to go through or what that site has to deal with when a patient is having their experience.

And let's not forget that we're going to be on market potentially be a market first and that we will have continued time to establish the leadership position that we are in, and we'll get some proving clinical efficacy while we're out there.

In terms of economics for the site, and I'll just double down on what Kabir said earlier, we have our strategic collaboration partners as well as outside of that through our medical science liaisons. We are not finding anyone bringing up the fact that this is a longer treatment than the shorter acting as being a prohibiting factor to prescribing.

Next question is from the line of Jay Olson with Oppenheimer.

Congrats on all progress. maybe a big picture question, recognizing that the company is acutely focused in the near term on the approval and successful launch of COMP360. Looking ahead to after you've accomplished that objective in the next year or 2, what will become the next major strategic priority for the company.

Thank you. So PTSD clearly is a strategic priority for us. So that study is underway, and we see that as a very important second indication. As we mentioned to earlier answers, we will -- we clearly have very interesting signals in a wide range of psychiatric conditions, and we will prioritize some of those to move forward. We will, at [indiscernible] have always been clear from an ex U.S. perspective, we will probably likely need to partner, but that's something that we will address once we have U.S. approval in mind. And then I think more broadly, this is a space where you continue to see a lot of innovation now with psychedelic assets and so on. We would see ourselves as a leader with hopefully a successful launch under our belt essentially being in a position to play a role in that and seeing what other assets may be available.

Your next question is from the line of Ben Burnett with Wells Fargo.

I also want to ask about your efforts just to prepare to train site ahead of commercial adoption Specifically, can you talk about what are your target sites? It's our understanding that the interventional psychiatry footprint sort of offerings Spravato today is expansive with some sites associated with the University Hospital, others may be more suburban. So I guess can you just talk to your strategy here and which centers do you plan to target initially and offer training too, initially?

Ben, thanks for that question. So as I mentioned in the remarks and it's pretty widely known, there are about 8,000 sites right now. This number has grown dramatically quarter-over-quarter, where it looks about adding about 500 per quarter at least. And again, that goes to just the excitement of potential additional options coming to market.

The easiest way to answer you is we're going to have a field team that is out calling on all of these sites. They will be making sure that they cover all 8,000 sites to make sure that these sites if they have a willingness to prescribe COMP360 they are well educated and well trained and prepared to prescribe this product. We are also going to call on physicians that may be in the system with a high number of TRD patients who are serving as -- refers to these sites that can administer these products as well.

So our target list will be quite expensive at launch and comprehensive. The other thing I think we're finding as we do some of our work is that the dosing profile of COMP360 and the potential dosing profile of COMP360 lends itself to a wider radius. So to your point earlier, if some of these are quite suburban coming in for a once a week or every other week treatment like those that are currently available, becomes quite difficult for someone within a certain radius of a treatment center. Even though these centers are growing very rapidly, there are still some patients who need to drive quite a way to access one of these treatment centers.

With an infrequent dosing like come proposes this does open up that ability quite a bit.

We have reached the end of the Q&A session. I will now turn the call back to management for closing remarks. Please go ahead.

Thank you very much all for attending. As you heard, the first 6 months or I guess the first 6 months or 1 week of this year have been a very exciting and very productive time for COMPASS. With the Phase III data now, both the primary endpoints, very statistically significant positive primary endpoints from both studies and now the 26-week data from both studies confirming the profile of COMP360 as a compelling differentiated profile that truly can serve to meet huge unmet needs in treatment-resistant depression. So we're focused on execution.

We're very happy with the process of the rolling review. As I said, we're preparing not just to finalize that to fulfill that with that expected to complete in the fourth quarter. But really ensuring it's a really high-quality dossier so we get a first-pass approval. And as you've heard from Lori, there's activity across an extraordinary range of fronts on the commercial side to be ready for launch.

So we look forward to keeping you updated on our progress on both of these major work streams through the end of this year. So thank you again. It is a very exciting time for patients with TRD. Thank you.

This concludes today's call. Thank you for attending. You may now disconnect.

Good day, ladies and gentlemen, and welcome to the COMPASS Pathways Update webinar. [Operator Instructions] As a reminder, this call is being recorded. I would now like to introduce your host for today's call, Teri Loxam, Chief Financial Officer at COMPASS Pathways. You may begin.

Thanks. Welcome, and thank you for joining us today for this webcast. Before we begin, let me remind everyone that during the call today, we will be making statements about our future plans and prospects that constitute forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement, including those risks and uncertainties described under the heading Risk Factors in our most recent filings with the U.S. Securities and Exchange Commission.

These forward-looking statements represent our views only as of today, and we specifically disclaim any obligation to update or revise any forward-looking statements even if our estimates or assumptions change. The call is being recorded and will be available on the COMPASS Pathways Investor Relations website for a period of 30 days following the conclusion of the call.

With that, I will turn the call over to Kabir Nath, who I'm joined with as well as -- who's COMPASS Chief Executive Officer; Dr. Guy Goodwin, Chief Medical Officer; and Lori Englebert, Chief Commercial Officer. Myself and Steve Levine, Chief Patient Officer, will also be available for Q&A portion of the call. I'll now hand the call over to Kabir.

Thank you, Teri, and thank you all for joining us. COMPASS Pathways is at the forefront of one of the most promising innovations in mental health in decades, and we are proud to be leading the way to unlocking the potential of psychedelics. With significant unmet need in both treatment-resistant depression and PTSD, we believe COMP360 has the potential to transform outcomes for patients who have not benefited from existing treatment options.

And while we advance COMP360 towards an anticipated launch in TRD, we're also progressing our late-stage trial in PTSD, where there's an even larger population of about 13 million patients in the U.S. who urgently need new treatment options. Given our Phase II data in PTSD and the overlap in patient populations and prescribers with TRD, we're well positioned with COMP360 to address both these large underserved markets. With today's data announcement from the 26-week Part B of the COMP006 trial, I am thrilled to confirm that COMPASS continues to make significant progress towards the potential approval of COMP360 in TRD with launch anticipated in the first half of 2027, a much needed and welcomed highly differentiated treatment option for patients living with TRD.

The data further validate the previously reported COMP360 durability profile. These 006 results are remarkably consistent with what we previously shared from the 005 trial in February. We've now demonstrated that COMP360 can be both a very rapid acting and a durable treatment for individuals who suffer from depression. Spravato is the only marketed drug product approved today in TRD, and it takes 10 administrations to achieve an equivalent treatment effect at week 6 compared with 1 or 2 administrations with COMP360. Similar to the previously announced 005 data, Part B data from 006 demonstrates durability out to at least 6 months for those participants who had a clinically meaningful reduction in MADRS.

The safety data for COMP360 is also encouraging with a generally well-tolerated and safe profile. The majority of adverse events are transient and predominantly occur on the day of dosing. We're convinced COMP360 will lead to a profound shift in mental health care, moving beyond daily or frequent administration towards an option potentially involving just a few treatments in a year that could be life-changing for patients. And we are accelerating our momentum to drive this change.

We have demonstrated consistent and robust data across 3 positive late-stage trials in over 1,000 participants. We have differentiated the COMP360 profile with ultra-rapid onset of clinical effect and durability data out to 26 weeks from our Phase III trials. We have a clear and accelerated regulatory path with rolling submission and initial review underway, where our active interactions with the FDA are collaborative and positive. We have a multi-blockbuster opportunity with programs in 2 very large underserved patient populations, TRD and PTSD, where there's an urgent need for new and effective options. And we have a commercial team that's made up of the best in the business who will be ready to launch when COMP360 is approved and rescheduled.

These achievements, along with our first-to-market positioning, reinforce our leadership in the field of psychiatry. We can't wait to provide COMP360 as an important option for patients. Let me now hand the call to Guy.

Thank you, Kabir. I'm very pleased to present these important results from the COMPASS COMP360 Phase III 006 pivotal trial in more detail. Before I do, let me take a moment to describe how I feel personally about the successful delivery of these trials. I was a psychiatrist in practice for nearly 40 years. I mostly treated patients with mood disorders, and I knew how to do that. However, 6 of these patients I knew well died by suicide. A beloved aunt of mine killed herself too. Many more patients I saw lived with depressive symptoms that were chronic and unremitting despite me knowing what to do as there just weren't effective options available.

COMPASS has made a real advance for exactly these people. Our trials promise something that can transform lives. They deserve it, and I count myself fortunate beyond words to have been able to contribute to making it happen. Let me begin by reminding you of the design of our Phase III program, which consists of 2 trials; COMP005 with a single administration of either inert placebo or 25 milligrams COMP360 psilocybin in Part A; and COMP006 with 3 active arms of 2 fixed doses, 3 weeks apart of 1, 10 and 25-milligram COMP360 psilocybin in its Part A. Both trials had a Part B, which was blinded through 26 weeks and where there was a readministration option of a single additional dose based on specified criteria.

Both trials also have a Part C from 26 weeks to 52 weeks, where a single 25-milligram dose of COMP360 is available for all participants open label. Today, we are presenting initial 26-week Part B data from COMP006. This data is remarkably consistent with the equivalent 26-week data from 005 that we showed in February. But of course, 006 is in a much larger patient sample and with the intermediate dose was better blinded to the treatment allocation. It confirms the validity, consistency and durability of the efficacy signal evident over the full 26 weeks of follow-up. Therefore, if we look at the results for the 25-milligram and 1 milligram arms of COMP006 out to 26 weeks overlaid with the 005 trial in the accompanying slide, we noticed 3 things.

First, there is convincing separation between the 25-milligram arms and the control conditions maintained over the whole double-blind follow-up in both studies. Second, the durability of effect is confirmed as a feature of treatment with COMP360. Finally, we can see the benefit of a second dose, whether as a fixed dose after 3 weeks as in the 006 trial or later in the 10- to 14-week time frame as in 005. These extraordinarily consistent and meaningful trial results make the emerging profile of COMP360 a clear option if FDA approved for the tremendous unmet need in treatment-resistant depression.

We will go more into the results in a moment, but first, let me further highlight the difference between MDD and TRD patients and just how difficult to treat the patient population in our trials have been. As we've discussed before, we set a high bar for inclusion in both of our Phase III studies relating to prior treatments. While to mandate at least 2 treatment failures in the current episodes is conventional, we also required the duration of these prior treatments to be properly documented to have lasted at least 8 weeks at adequate dose and with proven medical records.

In ordinary practice, it is common for treatment trials to be shorter and therefore, not often to meet this criteria. Therefore, we selected for persistence with treatment as well as treatment failure. Moreover, as shown in the top part of the table on the left of the slide, almost 40% of the participants in the 25-milligram arm of 006 had failed 3 or more such treatments in the current episode. Participants on the highly severe and chronic end of the depressed population who are very difficult to treat. In fact, as the table on the right shows, the length of the current depressive episode was on average more than 3 years and with an average of more than 6 lifetime episodes.

This is truly representative of very chronic late-stage treatment-resistant depression. As you can see from the publication on this slide, in multiple real-world cohorts of depressed patients, the length of episode chronicity is the strongest single predictor of subsequent nonresponse to antidepressant treatment as shown in the accompanying figure. It is because TRD is too often a chronic condition that individuals with TRD are impacted disproportionately compared to those with MDD, including both longer depressive episodes and more significant impact on quality of life, work performance and the risk of suicide. Together with significant medical comorbidities, these features of TRD cause much greater financial stress in health care systems and constitute a very different patient population from those treated successfully early in a depressive episode.

Baseline demographics are shown in this table. Baseline severity estimated with the MADRS in the 006 trial averaged about 32 across all arms and over 60% of the participants met criteria for a severe level of depressive symptoms. Only 6% to 7% of participants had prior experience with any psychedelic and 3% to 4% had prior experience with psilocybin specifically. This was largely a naive patient population, which will have helped with the blinding of the study. Turning to the 26-week efficacy data from 006, which includes Part A and B, we see a rapid effect from COMP360 25 milligrams evident from the day after drug administration, which is apparent after both the first and second fixed doses in Part A. We can also see that compared with the 25-milligram arm, the 10-milligram arm shows numerically reduced effects at all time points from soon after the second administration of drug.

This consistent efficacy, dose response and durability supports the validity of our trial design and our recommendation of the 25-milligram dose as the basis for approval. It is remarkable to see the persistence of the treatment effect of 25 milligrams COMP360 over the full 26 weeks of a double-blinded study in treatment-resistant depression. I have seen nothing comparable before in my psychiatric career. Recall that after Part A of the trial, eligible participants had the option for a third administration of COMP360. Just under 60% of the participants in the 25-milligram arm received a retreatment in Part B. Most of these treatments occurred between weeks 9 and 14. This data gives us further confidence in the profile of COMP360 that the 25-milligram dose is effective quickly and is remarkably durable.

If we dive further into the 25-milligram arm, as we did in February for the 005 trial and look at the patterns across remitters, responders and nonresponders, we get some further insights. This chart shows a breakdown of the patients receiving 25-milligram COMP360 into 3 groups, defined by MADRS change from baseline at week 6. Remitters, shown in green, showed a very rapid reduction of symptoms to levels below 12 on the MADRS. Responders and partial responses shown in blue achieved a MADRS reduction of at least 25%, but excludes the remitters. We regard this group along remitters as demonstrating a clinically meaningful response. The nonresponders are shown by the gray line. An independent peer-reviewed Delphi study published in molecular psychiatry recommended a less than 25% change in MADRS to define nonresponse in TRD.

As we discussed in February, even modest reductions in depressive symptoms over 25% can provide significant benefit to TRD patients and lessen the risks associated with being chronically depressed. This is why we are including all participants who achieved a reduction in MADRS of 25% or more in the group having a clinically meaningful response. It is notable that a second fixed dose in Part A drove a higher proportion of patients into response by 6 weeks. In the 005 trial, where there was a single dose in Part A, we had 25% of participants achieved a clinically meaningful response.

In 006, this jumped to about 40% with the addition of a second fixed dose in Part A. Remember, for this chronic patient population who, on average, had not been responding to treatment for over 3 years, having roughly 40% with a meaningful response and durable benefit from COMP360 is very gratifying. Additionally, we saw that almost 30% of those who had a clinically meaningful response, but were not remitters at week 6 became remitters after the Part B redosing, a similar finding to what we saw in 005. These data across both Phase III trials, while showing important consistency, also demonstrate patient level heterogeneity.

Some patients may benefit from a single dose, while others may benefit from 2 to 4 doses. We will be diving into this in more detail when patient level data becomes available and as we work through final labeling with the FDA. But what it is starting to look like is 1 or 2 doses initially, a minimum 3 weeks apart with additional doses at physician discretion based on responder status. Overall, to see patients respond so quickly and have responses that are so durable is extraordinary in this very chronic TRD patient population and bodes well for when COMP360 could be used if approved in the broader 4 million TRD patients.

Moving on to safety. The data in 006 through 26 weeks further shows COMP360 as having a generally well-tolerated profile. Regarding specific treatment adverse events, we saw the usual headache, nausea, hallucination, et cetera, most of which were transient occurred on the day of dosing. Differences in incidences of events between 25 milligrams and 10-milligram arms were limited. The 1-milligram dose was associated with fewer reports of nausea, hallucinations, illusion, dizziness and tearfulness as would be expected. Looking at the top serious adverse events shown as percentages in brackets, you can see the relatively low number of events. Importantly, we are not seeing any imbalance in suicidal ideation and no other drug-related events of concern have emerged.

There is one suspected suicide in the 25-milligram arm, which has been determined by the investigator based on the specific circumstances and timing as not related to the treatment as well as an event of suicidal behavior and one suicide attempt in the 1-milligram arm. Overall, we see a low number of suicidality events that are generally evenly distributed across the treatment arms. In summary, we're pleased to see the emerging safety profile of COMP360 from over 1,000 patients to be generally benign and well tolerated. Given this and the ultra-rapid and observably durable efficacy profile, I believe COMP360, if approved, will be a logical option to prescribe for the depressed patients I struggle to treat as a prescribing psychiatrists and its approval will be a landmark in medical science.

Thank you, and let me hand the call to Lori.

Thank you, Guy. I am excited to speak to you today about the potential opportunity we see for COMP360 based on the emerging clinical profile from the data sets presented today and update you on our commercial preparations. Data from our 2 positive Phase III trials clearly demonstrate that COMP360, if approved, will be highly differentiated from currently available treatment options and is strongly positioned to be the leading treatment for the millions of TRD patients who are underserved today.

Let me start by quickly illustrating just how many MDD patients are considered treatment-resistant. In 2025, approximately 12 million diagnosed and treated MDD patients were prescribed over 50 different antidepressants. However, despite having a multitude of options, approximately 1/3 of those patients were failed by at least 2 prior antidepressants while in their current episode and are considered treatment-resistant. This equates to a patient population of approximately 4 million TRD patients in the U.S. Once an MDD patient is considered treatment-resistant, data show that the chance of achieving meaningful clinical outcomes from additional antidepressants is significantly diminished and the patient and economic burden of disease becomes dramatically higher.

Proving consistent efficacy in this patient population in clinical trials has historically been almost impossible to achieve. It is so difficult that there is only one FDA-approved and marketed drug product available today for TRD, Spravato. In fact, it took Spravato 5 trials to achieve the 2 statistically significant results needed for FDA approval. COMP360 has now demonstrated clinical meaningfulness and statistical significance across 3 robust late-stage trials. This is why the consistency of the COMP360 results is so impressive and is bringing hope and excitement for a potential new treatment option to patients, their loved ones and their providers.

Taking a holistic view of the top line data that has been presented through 26 weeks for both Phase III trials. From a commercial perspective, the most important takeaways are: First and foremost, COMP360 has demonstrated through multiple robust clinical trials and in over 1,000 participants, consistent clinically meaningful efficacy in a patient population that has historically had limited treatment options. Second, in both 005 and 006, COMP360 demonstrated extremely rapid onset of action with deep and dramatic reduction in depressive symptoms as quickly as the day following the first administration. In 006, we saw those results improve even more after the second initial dose 3 weeks later. These are impressive results, especially in this particular patient population, where other available antidepressants have provided limited to no relief.

Effects that quick can be life-changing for patients, and this is highly differentiated when compared against other products that can take weeks to months to determine if the treatment is working. Third and perhaps most significant, in both 005 and now with Part B of 006, after rapid onset, COMP360 then demonstrated unprecedented and truly remarkable durability that is sustained through at least 6 months with only 1 or 2 additional doses after the first administration. This dosing profile is distinctly different from the only other TRD marketed medicine, Spravato, where per label, Spravato would need to be dosed 20 to 28 times over a comparable 6-month period.

If approved, COMP360 could offer significantly reduced patient and caregiver burden without sacrificing clinical outcomes for TRD patients. Finally, and importantly, COMP360 demonstrated a generally well-tolerated and safe profile, potentially making it easy for patients and clinicians to try. COMP360 is redefining rapidity and durability that can be achieved in a TRD patient population and providing hope and excitement for a potential new treatment option. The data presented today only adds to the emerging clinical profile of this promising new drug. COMP360 has the potential to revolutionize how mental health conditions are treated, and we are confident that if approved, COMP360 can provide a highly differentiated and compelling treatment option for a patient population that currently has minimal options. With the rolling NDA submission and initial review underway, the commercial team is actively preparing for launch with many critical work streams ongoing.

Time lines are fluid for approval and DEA rescheduling given the national priority review voucher and the executive order in April. However, we do expect the FDA review to happen in a faster time line than traditional reviews. And as such, we continue to focus on being launch-ready by the end of the year with an anticipated launch in the first half of 2027. COMPASS has been very active with pre-commercial work over the past several years. Now with the clinical profile of COMP360 more fully emerging, we have begun the more advanced launch preparation work. This includes detailed discussions with payers, preparing effective marketing materials, enabling product distribution, setting up patient support mechanisms and preparing for field force execution.

All of this is complementary to the ongoing scientific exchange with KOLs and educational efforts with advocacy organizations, sites of care and federal and state policymakers. At launch, we will leverage the well-established existing interventional psychiatry infrastructure. These treatment sites are specifically designed to support in-office treatments for products that require multi-hour support and monitoring, such as Spravato, TMS or ECT. With approximately 7,500 sites across the U.S. and growing rapidly, these centers are already equipped with the staff, operational know-how and infrastructure needed to support additional multi-hour treatments like COMP360, with many of these sites already scaling in anticipation of a COMP360 launch.

At approval, our focus will be on site preparedness. This includes everything from training and educating, REMS certification, assistance with reimbursement and patient support. We are heavily focused on removing barriers to prescribing and making the patient and site experience our top priority. We anticipate that COMP360 will be the first psychedelic approved in this highly anticipated new class, and we feel a responsibility to patients to enable a successful launch. As a company, the work we are doing now is leading the way for all psychedelic products coming behind us. And with our firmly established leadership, we intend to not only be first-in-class but best-in-class.

If COMP360 is approved, it will undoubtedly bring a welcomed and meaningful new treatment option to TRD patients and their providers as effective new treatment options are desperately needed. COMP360 has the potential to fundamentally change the way that patients living with depression are cared for, and Compass is committed to helping as many patients as possible. We are making great progress towards being launch ready, and I look forward to discussing more with you throughout the rest of this very exciting year.

Let me hand the call back to Kabir.

Thank you, Lori. Let me first thank all the participants, sites, clinicians and caregivers involved in our COMP360 clinical program. With your incredible support, COMP360 will potentially be the first classic psychedelic to be approved by the FDA in a condition with significant unmet need and where patients today have few options. As I said earlier, the FDA is actively engaged on our rolling submission and initial review. We've shared today's data with the FDA, and we'll continue to submit each wave of data to them as they come in, facilitating as rapid a review process as possible. As Lori discussed, commercial preparations are well underway, and we will be ready to launch whenever FDA approval and DEA rescheduling are complete.

Based on everything we know today, we expect to launch COMP360 in the first half of 2027, and we will keep you updated as things progress. We're confident that COMP360 can be effectively integrated into a rapidly growing infrastructure and offer a differentiated and compelling treatment option for patients and providers. We believe that COMP360 has the potential to transform the standard of care for the millions of patients living with treatment-resistant depression. Importantly, the capabilities, infrastructure and expertise we're building in TRD are expected to translate directly to PTSD, our potential second indication where we see significant commercial synergies.

We have created tremendous momentum with a clear path forward in TRD, an exciting next chapter in PTSD, a robust commercial foundation and a world-class team, we're operating from a position of strength and look forward to delivering for patients and delivering the transformative potential of COMP360. Thank you again for your attention. And I'll now turn the call back to Tara for Q&A. Thank you.

[Operator Instructions] So our first question comes from Andrew Tsai at Jefferies.

Thanks for sharing the detailed data and congratulations on being close to the goal line. So my question is about the commercial aspect of COMP360 actually now that you have 005 and 006 fulsome data sets on hand. So as we think about how you will be leveraging strategically Spravato's infrastructure, can you talk about what you envision the REMS requirement could look like for COMP360 and then maybe compare and contrast how the monitoring staffing language might read compared to Spravato's REMS.

Thanks, Andrew. It's Kabir. Just to check, you can hear us clearly.

Yes.

Great. I'll hand that question to Steve, if I may.

Thanks, Kabir, and thanks, Andrew, for the question. With the breakthrough therapy designation that we've had since 2018, we've had ongoing robust dialogue with FDA. And certainly, more recently, with the agreement with them on a rolling submission of our NDA and their rolling review, we've had the opportunity to have some preliminary discussions about the REMS that we'll propose. Naturally, as you know, that's something that will need to be negotiated with them and will be determined later in the process. But within those initial discussions, we've been guided to look at the existing Spravato REMS as well as what FDA prepared themselves for Lykos AdCom a couple of summers ago.

And with that, what we would expect is fairly typical language within REMS that specifies a prescriber on site that talks about a licensed health care provider being available. The main differences that we might see from Spravato to COMP360 would primarily relate to the observation time. Spravato requires 2 hours of observation after it takes 20 to 30 minutes for patients to self-administer the nasal spray. Based on the design of our trials, we would anticipate a 6-hour observation period after a patient takes the single capsule.

Our next question comes from Frank Brisebois from LifeSci Capital.

Congrats on the update. I was just wondering if you could talk a little bit more about the severity of these patients. You mentioned, on average, 3 years of an episode and 6 lifetime episodes. Is there a duration here with these episodes where it's just -- it's not considered an episode anymore. Just talk a little bit more of how severe these patients and why they might have been so difficult to treat.

Thanks, Frank, and I'll ask Guy to take that.

Yes. I don't think we can say there's a threshold. There's not a sort of particular time over which people cease to be classifiable as having an episode and maybe having as it were a long-term personality problem. But it's certainly true that when you talk to some of the PIs who have treated the patients in our studies, it's clear that patients have spokes may have spent much of their adult life depressed. But we were fairly insistent that they do recruit people who have been well at some point. So we're not recruiting patients who, in a sense, can never tell you they've been well.

So they have episodes, these episodes, as you can see, are very long. And the main reason they're so well represented in our studies is that our criteria clearly selected for people who have been consistent in taking medication and not all patients are, and they had sufficient medical records to validate that they have continued in care. And I think both those factors result in getting patients who are highly valid as treatment-resistant, but of course, particularly difficult to treat. And I think they're well recognized by clinicians as being a major part of the population who are described as having treatment-resistant depression.

Our next question comes from Paul Matteis at Stifel.

Congrats on all the progress and thanks for taking a couple of questions. We appreciate it. One, just on the suicide event. Can you give a little bit more context on why that was deemed to be not drug-related? And maybe just curious how proximal that event was to the actual treatment itself? And then second, I was wondering if you could clarify in the longer-term follow-up data after patients get the additional dose, were any other treatment options offered were patients allowed to go on to SSRIs?

And maybe just like in the real world, do you think that maybe SSRIs might be used to extend the dosing interval and help maintain patients given that SSRIs are maybe not the best acute therapies, but good maintenance therapies?

Thanks, Paul, and I'll turn to Guy for those as well.

Yes. I think we won't make detailed comments about the particular circumstances of the suicide because actually, we believe they're still under some sort of legal review in Spain. But I can say that it occurred over 80 days following treatment. So it was not within the time frame that was related to the treatment. And that was the fact that the clinician was in close contact with the patient throughout follow-up gave him confidence about his conclusion. I think we can say that much. Your second question is about the use of antidepressants. There was within the protocol, the option for patients in Part B to opt to go on to antidepressants instead of receiving a repeat treatment, and this is true in both 005 and 006.

And we know that a significant fraction of patients took advantage of that. In addition, there will be patients who effectively violated the protocol by going on to antidepressants. And we will obviously have data on that because we were continuing to follow those patients through the duration of the trial. I think it is quite likely that we will see in real practice, as you suggest, that patients are treated with both modalities, and it's a very interesting possibility that patients become more treatable with SSRIs as a result of receiving psilocybin.

It will be very interesting to see that. And then finally, there is the issue of co-administration, which we think will also be an issue, and we will have data on that from Part C of the study because patients who remain protocol compliant, who went on to an SSRI into Part C were then eligible for a 25-milligram dose co-administered with their ongoing SSRI treatment. So I think there's several aspects of the interplay between SSRI use and psilocybin use. We'll get information on that from further analysis of patient level data in 006. But obviously, it's highly relevant to clinical practice when the drug is finally approved.

Our next question comes from Ritu Baral at Cowen.

Congratulations on this data. If we are doing the math right over here, for 006, we're backing into about a 25% remission rate at week 26 or month 6. And for 005 with retreatment, we're backing in for Part B into about 10%, which suggests to us that there's a pretty strong dose response here, especially on measures of remission. How do you guys see that evolving into the label? Can you guys address how this is being or will be presented as part of the rolling NDA?

And then what sort of indication or administration language is possible as far as determining which patient should get what, which -- and is tolerability also a consideration in that final dosing recommendation that could be?

Thanks, Ritu. So I think I'll ask Guy first -- yes, just to address the kind of the remission number and then Lori to address the labeling side. What I will say as a preamble is clearly that is still more data that we need to actually really understand that and determine what final label we'll be putting forward. But Guy, first on the remission side and the impact of the second dose.

Yes. I think -- thank you, Ritu, for the question. I mean it's highly pertinent obviously, to how the drug will eventually be used. I think really 006 is probably the most instructive because it brings the second treatment rather earlier. And so the issue of whether you would get 1 or 2 is a little better addressed by the data from 006. You remember in 005, people have to wait for quite a long time. I mean the way we're thinking about it is that because of this very immediate clinical response, which is detectable and obvious in those patients who remit or respond literally a day and certainly a week after the administration of the drug that we think clinicians will be able to judge dosing on the basis of clinical response.

And so therefore, we think it will be boiled down to if people have a spectacular response to the first treatment, which many patients do, then that may be a reason not to give a second if they don't want it. But at the same time, if there's any question of the first treatment not having given a full effect, then it's very likely a second would be recommendable and would probably be the way the clinical treatment would evolve. So we're tending to see 2 treatments as the likely preferred approach. But clearly, in individual cases, you'll get variability because clinical practice is inherently variable.

Lori, anything you want to add?

No, I'll just add, too. I think, obviously, Guy said it well, and I'll echo Kabir's comment around we need additional data to really make sure we're determining what we go in with dosing recommendation for the label. But right now, as it stands and as Guy alluded to, the label language that we're thinking about is 1 or 2 initial doses followed by physician discretion for redosing. And I know that we will use the patient level data that continues to come in to help guide the clinical decision-making and really help payers understand what to expect from payer response levels.

If I could squeeze one last question in. Any updates on the CPT codes or determination of RV use?

Steve?

Thanks, Ritu. I always appreciate a good CPT question. So as a reminder, the CPT codes are still currently in their category III form, which is prior to receiving evaluation through the rough process and giving the recommendation to CMS. The criterion primarily for progressing that to Category 1 would either reporting of the code with the use of services that apply to the code. The bulk of that will likely happen post approval once COMP360 is being prescribed. We will have a team. We've already started building a team that will focus specifically on billing and reimbursement and ensuring that sites appropriately know how to code for delivering COMP360 when approved to ensure that we can progress that process moving from Category 3 to 1 as quickly as possible.

Our next question comes from Judah Frommer at Morgan Stanley.

Congrats on the progress. I guess just within the regulatory and commercial time lines that you've cited, any new insights into how quickly COMP360 could be rescheduled post approval? And then just, I guess, more high level, maybe just given prior experience in the space, can you qualify interactions with the agency given the priority voucher granting and how those interactions have maybe been more [indiscernible].

Yes. Thanks, Judah. So I'll start and then see if Lori wants to add on the -- So as you know, the executive order did include the suggestion that the FDA and DEA work, shall we say, more closely and that there'd be a way to accelerate federal DEA scheduling post a potential approval. We are still kind of working to learn the mechanics of that and how likely that is. So right now, the base case continues to be that they have 90 days, but there is some optimism that it could happen quicker, but we can't give you a definite guidance on that. In terms of interactions, yes, I mean, I think with the priority voucher, important to say that the FDA's target is to complete a review in 60 days. It's not actually a commitment.

So again, we're cognizant of that and the potential still to need to accept the filing. What I would say from an interaction perspective is absolutely, there is a, shall we say, a fluidity and a to and fro that you would not normally get through this and that that's actually been very positive. Now it goes both ways. We also need to address questions quickly and so on, and we're committed to that side from our perspective. Lori, anything to add on rescheduling?

Yes, I'll just add quickly on rescheduling. And hi, Judah. You know, we there's a reason why we continue to say we'll be launch ready by the end of the year. And the reason we continue to say we'll be launch ready by the end of the year is because if everything works the way that in the most optimal fashion, we need to be launch ready by the end of the year. And that includes rescheduling in a very timely fashion. And as you've heard me speak about before, we've had a very strong government affairs approach and presence on the Hill over the past 2 years where we have been educating on the importance of making sure that rescheduling happens in a timely fashion.

So the executive order only adds credence to the work that we've been doing to try and expedite that. And like I said, and as we've all said, if it happens sooner, we will be ready to launch.

Our next question comes from Madison El-Saadi at B. Riley.

Curious, what was the longest time remission lasted? Just curious how this may inform the dosing interval range in the real world? And then secondly, if I may, does anything in this readout refine the language you're seeking in the label? And then have you had a chance to collect any kind of unblinding or unblinding data?

Yes. Thank you very much for the question about durability. We certainly had patients in 005 who remitted to the single treatment and remain remitted throughout the 26-week follow-up. Obviously, the numbers that we will see in any subsequent or real-world population is going to depend upon individual resistance to treatment, which I think will turn out to be a continuum.

But we have certainly seen patients who have received a single treatment have gone the full 26 weeks. So that will be something that clinicians will see in real life, so to speak. Obviously, in 006, we have more patients, but they had 2 treatments and a significant fraction of them in the group who are illustrated in green in our study went through in remission through to 26 weeks as well.

So it's certainly a clear cut phenomenon that occurs. Its frequency will depend upon how you select your populations for treatment.

Yes. Lori, I don't know if you want to take the second part. I mean I think we already addressed that in talking really about how we're thinking about dosing and labeling at the moment. And clearly, that is informed by this cut of data. Lori, anything you want to add on that?

I'll just add a couple more comments. So at the risk of restating earlier comments, the way we're thinking about the label right now based on this data, which reconfirmed a lot of what we saw in the 005, 26-week data is 1 or 2 initial dosing doses, minimum of 3 weeks apart. And that is obviously informed by the 006 data. And then redosing upon clinician discretion, obviously, informed by the 26-week 006 data.

What we expect to see or what we expect to happen in the real world and more specifically to answer your question is probably on average, a 2 to 4 per year per patient, somewhere around there. And we will continue to look at the patient level data to help inform clinicians and again, payers as well what the expectations for that might look like based on -- potentially based on patient response level.

Our next question comes from Leo Timashev at RBC.

I know when you guys were discussing TRD, you mentioned that there's a high level of comorbidities. You mentioned pain, anxiety, migraine. I guess as you look at your data, does anything suggest that COMP360 treatment is helping lift patients out of those? I mean, even anecdotally, that you're really sort of breaking the TRD cycle on any of these other comorbidities as well?

Yes, not yet. We've obviously got a hierarchy of data cuts, and we're looking at the top line and moving down, so to speak. And we'll get to addressing that kind of subgroup question in due course. But at the moment, not really. And in speaking to individual PIs, they have not spontaneously reported anything like, oh, well, yes, the migraine cleared up as well.

So that would be highly anecdotal in any case, but we will get to some of this as we go through data that we've collected, particularly on patient experience, which we're just starting to look at now, which will be relevant to the question you just posed. But we don't yet have the granularity that you would interest you, I think. But if with patients, we'll get there.

Yes. Leo, I just want to add, I think your question is a really good one. And once we get the additional data, especially some of the secondary endpoints, we will be taking a look at things not necessarily specific to comorbidities, although we will address some of that and can address some of that through IIS studies that we are currently running.

We are -- we'll use the secondary data for quality of life measures, which is becoming increasingly more important, not only to obviously the patient and understanding how patients feel and what those improvements look like, but it also is becoming a critical decision-maker for physicians and also interestingly enough, becoming very important for payers. So as we get that information and additional data, we'll be taking a look at how that increases the value proposition for the whole product.

Our next question comes from Sumant Kulkarni at Canaccord.

Thanks for moving the product that much closer to potential use by patients and taking our question. From a commercial targeting perspective, what did you learn about any common characteristics of patients in your trials that were responders to COMP360 versus nonresponders? And do you expect a specific label limit on the number of discretionary COMP360 retreatments after the initial 1 or 2 doses per year for a patient?

Thanks, Sumant. So I mean, I think we don't have anything that really drives us towards being able to identify a priority responders or nonresponders. But as we've said, clearly, the response to the first dose does clearly seem to signal the likelihood of a subsequent response.

I suppose -- by the same token, nonresponse seems to predict nonresponse, but we're going to take the data down to a finer grade level in due course just to try and answer that very question actually.

Yes. And if I could, Sumant, I'll just quickly add. You probably have often heard me reference the patient level data that we'll use to help guide the clinical decision-making. A lot of that will come once we get the patient level data, we'll be able to understand and be able to use through our field force execution standpoint, additional data that helps physicians understand potentially what type of patients to look for in terms of their response level and when and how to retreat.

I also just want to call out that in our trials, the maximum number of doses that we have dosed in an annualized basis is 4. So I don't expect the label to limit the number of doses, but there could be potential payer limitations. These are things that we'll have to look through, especially in the first year of launch. But obviously, as we collect real-world data, we'll continue to evaluate what the appropriate dosing on an annualized basis looks like.

Yes. And specifically from a safety perspective, we did run tox studies and so on after work with the FDA that would support many more doses to Lori's point. So from that perspective, it's unlikely to be a late limitation.

Our next question comes from Jay Olson at Oppenheimer.

Congrats on all the progress and appreciate all the work you're doing for patients in need. Did you observe any characteristics or particular symptoms that might help predict which patients could maintain durable remission from those who ultimately require retreatment? And then did you find any learning effects with retreatment that could shorten the time to discharge for patients who receive subsequent doses?

Just to take the last question first. We observed actually that the post-hoc ratings of the experience by patients were remarkably consistent from one treatment to the next, which was something that really hadn't been documented well before. So it didn't -- it's not like you see any adaptation or desensitization to repeated treatment. So people are getting the full effect according to the dose that they've given.

We have looked a little bit in our Phase II data for predictors of response without success. There remain things that one can do, and we are digging into aspects of the information that we have, both around baseline symptoms and also some of the interactions that we recorded in the preparation of patients, which might answer this question, and there are various obviously, methodologies that would allow us to dig a little deeper into things.

At the moment, we can't comment on what that's going to show because at the moment, we're still too much into the designing the necessary studies rather than having completed them. But you asked a great question, and we hope to provide better answers than we currently have. But at the moment, we're still rather top line as you've heard.

Steve, do you have a comment on discharge.

Yes. Just a couple of additional words on the issue of time to discharge. Important to point out that we intentionally in our trial design did not include multiple early assessments of readiness for discharge. We weren't trying to rush participants out of these study sites. So in practice, what happened in the protocol was that the first assessment of readiness was not until 6 hours post administration. And when you factor in some additional administrative work, the checking of vital signs, a couple of scales, et cetera, what we saw was that most patients were ready to leave at that point.

Post approval in a real-world environment, what we would expect is because of our trial design that our REMS would stay a minimum of 6 hours of observation. But we think that given the typically 3 to 4 hours that is the more typical duration of this experience that sites may leverage common areas, lounge spaces, et cetera, within their sites for the efficient movement of patients through. And that with the gathering of some real-world data, there may be an opportunity over time to reduce the observation time.

Our next question comes from Tom Shrader of BTIG.

Congratulations. This was asked, but I don't think you got to it. Is there an update on how much blinding you think you're really getting from the 1 mg dose -- and are you collecting any data? And do you consider the 10 mg to 25 mg? Would you consider that fully blinded? I know it's an old question, but I think it will be discussed. So just any updated thoughts you have?

So Tom, yes, we are collecting the data, but we're not yet in a position to share that. But Guy, I don't know if you just want to comment on design overall.

Yes. I mean we -- if you look at other people's published data, it's fairly clear that disguising a nonevent if it were, is really very difficult. I mean people tend to pick the 1 milligram or lower doses. There are sometimes they're much less confident about picking intermediate and higher doses, and that was why we chose the design we chose.

So our prediction was and remains that 10 and 25 will be very confusable. And we think overall, the different expectations that surround 3 options rather than a very binary inert versus active will be resolved. I think what will be more interesting is to subdivide patients on the basis of their certainty about what they received and to see if that actually affects the treatment response because much of this criticism is around whether or not there is unblinding on the assumption it makes a difference. It remains to be proved that it really does.

And in the little data that we have, for example, in TRD from the EPISODE trial published by a German group earlier this year, it's pretty clear in table they published that actually whether or not people knew that they were on the high dose actually didn't seem to make a difference to whether they responded or not.

So we -- I would predict that that's what we will also find, but we haven't yet got that data in a form that we can share with you in a meaningful way. But great question, great problem to have and one I think we can solve.

Just to reiterate, so you've agreed with the FDA how you're going to ask people what they think they got?

Yes, we indeed did. Yes. We asked them exactly what the FDA asked us to ask them, yes.

Our next question comes from Rudy Lee at Wolfe Research.

Congrats on the progress. As you highlight the difference of TRD versus MDD, now you have data in the most difficult-to-treat patients. I mean, how do you plan to use the data for payer discussion and physician education, especially given the competition from other psychedelic programs for MDD?

Lori?

Yes, happy to take that. Yes. So for payer, I'll start with payers first. And as I mentioned in the call, there is only one product right now that is indicated for and marketed for TRD, and that is SPRAVATO. And payers, because of the strength of the data and in that particular patient population, payers understand the economic burden that come with treatment-resistant patients. They see it in their claims database. They see the impact. They feel the impact of all the comorbidities of TRD patients.

So they cover SPRAVATO pretty broadly PA to label. And that is very, very encouraging from a TRD negotiating standpoint for COMP 360. MDD with payers, as I mentioned, there are over 50 indicated MDD products right now being used on an annual basis. And payers routinely will require new MDD products to step through several products before they can actually move to an expensive new innovative product.

And that is because the MDD trials by nature, MDD is less difficult to prove efficacy in. And so the fact that we are coming in with very strong 3 consistent trials that proved very strong efficacy in this patient population, I feel very good about our opportunity with payer negotiations and where we'll end up from a formulary access standpoint and potential gross to net.

Our next question comes from Chiara Montironi at Kempen.

I think my question was already partly addressed. I was wondering if you could provide a bit more color on the DEA scheduling. How does the process look like? Which are the expected time lines? Any nuggets will be helpful.

Thanks, Chiara. I'll ask Lori to take that.

Sure. Absolutely. Hi Chiara, the DEA rescheduling process right now as it stands is when an FDA product becomes approved and it is currently Schedule 1, which means there's no medical use approved for it. Once it becomes approved, it then automatically becomes approved for -- and the DEA then needs to reschedule it at a federal level.

And right now, they -- by statute, they have 90 days to do that. And historically, over the past 10 years, they have routinely taken about 90 days to reschedule the product. After the federal DEA reschedules, then the states need to reschedule so that physicians and prescribers in that state -- those states can prescribe the product legally within their state.

We have been doing a lot of work, again, with the government affairs team to make sure that, that is done in a timely manner on a state-by-state basis. And right now, we're sitting with approximately 90% of the U.S. population living in a state that will intend to reschedule within 30 days, after the federal DEA.

So the time lines from a federal DEA standpoint, as we mentioned earlier in the call, could be shorter than the 90 days based on the executive order. But once it gets federally rescheduled, then the states will reschedule and the majority of them will do so within 30 days after that.

Our final question comes from Michael Okunewitch at Maxim.

Congrats on the data. I just wanted to ask something, I guess, a little bit more broadly about the market and how it's evolved. In particular, there's been -- there have been a lot of headlines around psychedelic medicine. There's been a lot of new high-quality data coming out. So have you seen any increased acceptance towards this particular modality at the patient and the provider level?

Thanks, Michael. The easy answer is yes, but I'll turn to Lori and Steve to provide some more color behind that.

Do you want to start by what you're hearing from the provider level, and I can add in some patients. And I think it's also probably important to add in some payer receptivity as well.

Yes. Thanks Michael. As Lori said, we can kind of divide these stakeholder groups that we talked about, patients, providers, payers, certainly at the provider level from multiple sources, including the ongoing work that we've been doing over several years with our network of strategic collaborations, which are sites that are today caring for patients living with TRD, in many cases, delivering the most analogous treatments SPRAVATO, in all cases, very much looking for additional tools to be able to bring to bear to this very, very difficult to treat condition.

They have been excited. I think they've only -- that excitement has only grown as they've seen high-quality data and as they see that we are really on the cusp of the potential approval and then really having this option in their hands. That's also been supplemented by the work we've been doing with our medical science liaisons who've been out in the field now for multiple years, engaging with health care providers. And similarly, as data has been released both on COMP360 as well as for other development programs, health care providers only continue to have more excitement and they really do see the potential for this to shift the paradigm of how these patients receive their care.

At the patient level, we've been working for many years with advocacy organizations, and they've been highly supportive. They increasingly are putting out educational content to their membership to prepare them for the potential approval of psychedelic treatments. But to further build on that point as well as talk about payers, I'll hand to Lori.

Yes. Thanks, Steve and Hi Michael, this is a great question to be our last question of the day because I can say with a lot of certainty, what we're seeing and hearing not only from, as Steve mentioned, through the strategic collaborations and the work with the advocacy organizations, but through market research, through conversations that we're having with the market, both payers, providers, patients is unlike anything I've seen in my 25-plus year career.

The -- even the market research companies that we are working with sometimes state that they've never seen such receptivity or interest in a product in all the market research that they have done. Payers will come to us versus us proactively going to them to seek out information. There is truly an excitement and an interest level that I don't think psychiatry has felt in many, many years.

And so we're obviously extremely excited about the opportunity. We're doing everything we possibly can to make sure that this launch is successful. And I mean what I said in the prepared remarks, and that is we will be potentially first-in-class, but we fully intend on being best-in-class. And that's because we're going to maintain this leadership that we have established and worked very hard to establish over the past several years.

Great. Thank you for the question, Michael. So this concludes our Q&A session for today. I will now turn the call back over to COMPASS Pathways management for closing remarks.

Thank you very much, Tara. So again, thank you all for your participation on the call. As you've heard, we're very excited by the way that today's data really confirms in a remarkably consistent way the extraordinary compelling differentiated profile for COMP360 in its unique combination of extremely rapid onset and durability out to 6 months from just a handful of doses. So with this data in hand, we're reconfirming our intention to complete our submission in Q4 of this year. We will be launch ready. We have very good dialogue with the FDA. We're excited about the path forward, and we're looking forward to bringing COMP360 to the 4 million TRD patients in need as soon as we can. Thank you again, and we will keep you updated on our progress towards that over the remainder of this very exciting year. Thank you.

Good day, ladies and gentlemen, and welcome to the COMPASS Pathways First Quarter Results Conference Call.

[Operator Instructions] As a reminder, this call is being recorded. I would now like to turn -- to introduce to you your host for today's call, Stephen Schultz. You may begin.

Welcome, all of you, and thank you for joining us today for this conference call. I'm Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways. And today, I'm joined by Kabir Nath, our Chief Executive Officer; and Lori Englebert, our Chief Commercial Officer. Teri Loxam, our Chief Financial Officer; and Dr. Steve Levine, our Chief Patient Officer, will be available for the Q&A. The call is being recorded and will be available on the COMPASS Pathways Investor Relations website shortly after the conclusion of the call and will be available for a period of 30 days.

Before we begin, let me remind everyone that during the call today, we will be making statements about our future plans and prospects that constitute forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement, including those risks and uncertainties described under the heading Risk Factors in our most recent filings with the U.S. Securities and Exchange Commission. These forward-looking statements represent our views only as of today, and we specifically disclaim any obligation to update or revise any forward-looking statement even if our estimates or assumptions change.

I'll now hand the call to Kabir Nath.

Thank you, Steve, and thank you all for joining us today. It has been a very exciting and productive quarter for COMPASS. The company continues to lead the way in psychedelic science, validated by the confirmation of a rolling NDA submission and review and the award of a Commissioner's National Priority Voucher or CNPV. With our 005 and 006 data announcement in February, we have delivered positive data from both our Phase III studies. COMP360 has therefore demonstrated what no approved drug for TRD offers, clinically meaningful efficacy with both rapid onset and extended durability.

In fact, these extraordinary results redefine rapidity and durability for TRD patients. With only one drug approved and actually used for TRD today, we are confident that COMP360 with its differentiated and compelling profile will be an important option for the millions of patients that have been failed by the many approved treatments for MDD. After we announced results of our first positive Phase III trial last year and based on discussions with the FDA, we began preparing for a potential accelerated launch. As we've said before, we will be launch ready by the end of this year.

We've aligned with the FDA on our rolling submission and review plan and have begun submitting modules for the COMP360 NDA. We will continue to submit additional modules on a rolling basis over the coming months. Part B data from 006, which we continue to expect in early Q3, will be the final data set to complete the submission. Given the award of the CNPV, we are already working closely with the FDA to enable as much efficiency and acceleration as possible. In addition, based on the executive order, we are accelerating our engagement with the DEA since there is the potential for federal rescheduling to be completed sooner than the current statutory 90 days post FDA approval.

Our 2 large Phase III trials blinded to an unprecedented 26 weeks for psychiatry trials, supported by our large Phase IIb trial has resulted in over 1,000 patients in the program. With comprehensive and strong preclinical toxicology, safety and CMC data, we are confident that we will have a robust NDA submission that supports a COMP360 approval. We've also continued to make great progress in our commercial preparedness, which Lori will cover in detail. Our strategic collaborations across diverse settings of care, including the interventional psychiatry infrastructure have provided significant learnings.

Together with our foresight in establishing CPT 3 codes specifically for providers to get fully reimbursed for psychedelic monitoring, this has set us up well for a potential near-term launch. We are ramping up rapidly, building out the commercial team with outstanding, highly motivated talent and initiating all activities in anticipation of approval. In addition to TRD, we are also progressing our program in PTSD, which affects 13 million Americans. PTSD is another significant area of unmet need and an opportunity to expand COMP360 to individuals that have few medical options.

We believe COMP360 can be an important new treatment for PTSD, and it is a very logical next target indication for COMPASS. Our work with the CRO and sites for our late-stage PTSD trial is underway, and we look forward to updating you as it progresses. With both the successful financing and warrant exercises in the first quarter, we have a strong balance sheet with cash that carries us well beyond launch and into 2028.

Let me now hand the call to Lori for more on our commercial preparations.

Thank you, Kabir. Hi, everyone, and thank you for joining. Today, there are 4 million patients with MDD who are considered treatment-resistant. Spravato, the only drug indicated and used for TRD is expected to reach $3 billion in revenue by 2027 and as of 2025 was treating less than 2% of the TRD patient population. We believe that if approved, COMP360 will reach blockbuster potential by offering a transformative new treatment for the millions of patients who deserve more options.

As Kabir noted, we are pleased to have been selected for the Commissioner's Priority Review Voucher. One benefit of being selected for the voucher includes the potential for an ultra accelerated review time line of 1 to 2 months after final NDA submission. This provides helpful clarity on timing expectations and allows for more thoughtful and focused planning efforts. Based on the current time lines for data and submission, we remain focused on being launch ready by the end of the year.

Last month, the White House also issued an executive order, recognizing the profound urgency of the mental health crisis facing millions of Americans and the potential impact FDA-approved psychedelics could have. In that executive order, timely rescheduling of approved treatments was stated as a priority. As a Schedule I product, COMP360 will need to be rescheduled at both the federal and state level after approval in order to be prescribed. We are accelerating work with the DEA to ensure rescheduling at the federal level goes as rapidly and smoothly as possible. We have also been working at the state level for the past 2 years to ensure that the states follow the federal rescheduling decision in a timely manner.

Over the past 2 years, we have made significant progress. And today, almost 90% of the U.S. population live in a state that intends to reschedule COMP360 within 30 days after FDA approval and DEA rescheduling. Through this work, we have markedly reduced the time line to launch and for patients to access COMP360 after approval. Enabling broad and equitable access includes ensuring that both COMP360 and provider monitoring time are adequately reimbursed. Kabir mentioned earlier the work we did a few years ago on securing psychedelic-specific CPT 3 codes, which will ensure that sites are reimbursed fully for the time required for psychedelic treatment monitoring.

These codes are billable by the hour and were designed to cover clinical work and practice expenses incurred with multi-hour psychedelic treatments. We are also accelerating reimbursement and formulary discussions for COMP360 with payers. TRD has a significantly greater impact on individual's lives and accounts for a disproportionate share of health care costs versus MDD. TRD patients accrue 62% more mental health care costs and experience 41% higher work-related costs than MDD patients.

COMP360 has consistently demonstrated through 3 late-stage trials, clinical effects and a well-tolerated safety profile in a TRD patient population, and we expect payers to respond favorably to the emerging clinical profile and potential value that COMP360 can bring to the health care system. Along with enabling access to COMP360, we want to ensure that the clinical experience for the patient and the site of care is positive. This requires thoughtful consideration of how we deploy the field force and how we educate, train and prepare patients and the sites that will be administering COMP360.

Through the insights generated through our growing medical science liaison team, through market research and through continued close work with our strategic collaborations, we have a deep understanding of what is required to enable a well-prepared and well-supported COMP360 experience. Lastly, but notably, we have been rapidly building the commercial organization in preparation for launch. This includes bringing in an extremely experienced commercial leadership team that has collectively launched over 50 products. This level of experience is remarkable, and we are privileged to have such an impressive team leading launch preparation for COMP360.

COMP360 has the potential to fundamentally change the way that patients living with depression are cared for, and COMPASS is committed to helping as many patients as possible. With COMP360 expected to be first to market in a highly anticipated new class for mental health, COMPASS is at the forefront of shaping the future of psychiatric patient care. We are strongly positioned to successfully launch COMP360, and I look forward to updating you more on our progress.

Thank you. And let me hand the call back to Kabir for closing remarks.

Thank you, Lori. This is an incredibly exciting and defining time for patients and COMPASS. We are confident in the rigor and robustness of our development program to demonstrate the benefit of COMP360. We have conducted our program to the highest standards, which we believe must be paramount in this new field of psychedelic science. We now have data from 3 robust, well-controlled clinical trials that enrolled over 1,000 participants, including over 800 from 2 successful pivotal Phase III trials.

I do want to underscore the difficulty of establishing efficacy in TRD with only 2 medicines ever having been approved despite multiple efforts that COMP360 has consistently demonstrated a clinically meaningful, rapid and durable effect and a generally safe and well-tolerated profile is a remarkable achievement and one that promises to be a transformative new offering for those living with TRD. I want to sincerely thank our investigators, trial site teams and most importantly, the participants whose commitment and trust has made this progress possible.

Thank you. And let me now pass the call to the operator for Q&A.

[Operator Instructions] Your first question comes from the line of Andrew Tsai of Jefferies.

Congrats on the great progress and the great news. I had 2 questions. The first one is based on your guys' ongoing FDA discussions, has the FDA given you any inclination whether there will be an AdCom or not for COMP360 because on one hand, the review time lines could be really accelerated and FDA does -- but then FDA does seem to be doing away AdComs. And then I can't help but think that Lykos got one and maybe it could be prudent for the FDA to hold one. So I'd be curious to know what you guys -- where you guys lean here.

Thank you, Andrew. It's Kabir. I'm just checking that you can hear us clearly?

I can hear you, yes.

Great. So thank you. Yes. So it is the FDA's decision and the FDA's only decision around whether or not to hold an Advisory Committee. They will only make that determination once they see the totality of the data we've submitted. We will be prepared for one, and that is in our planning, if necessary. But at the moment, we do not have an indication of whether or not that's likely to happen.

Got it. And then secondly, when you share the 26-week Part B data from COMP006 study, the second one in early Q3, would you consider sharing a cut of the additional 26-week long Part C portion of the 005 study, your first study in conjunction with that top line release? If not in early Q3, then can we expect maybe a cut before you're possibly approved? I figure it's open label and then sharing additional long-term data could be helpful or important for pricing or labeling discussions.

So thanks, Andrew. Yes. So I mean, from a timing perspective, you're right that the 52 weeks of 005 clearly run in parallel with that. We haven't made a final determination of what we'll share at what point, but I hear you loud and clear in terms of the value potentially for payers and for commercial purposes. So that's a decision we will come to in due course.

Your next question comes from the line of Francois Brisebois of LifeSci Capital, LLC.

Very well said on the Francois. Yes, that's great. So just quickly here, in terms of the third quarter data for implications, can you just help us understand maybe what the expectations are? And why -- is it still a gating factor to complete the filing based on the developments that have happened recently? I just want to kind of better understand what that data is and how important it is for launch here?

Thanks. And Francois, may I call you, Frank, please?

Frank is totally fine.

Thanks for the question, Frank. So yes, clearly, and just for complete clarity, we had already aligned on our rolling submission plan with the FDA before the executive order and the award of the CNPV. So we had already fully aligned with the psychiatry division on what we were going to do and the time frames in which we were going to do it. That hasn't changed. And I think it's really important to note that the CNPV potentially accelerates the end part of this process, the final review, but it's been very clear in our discussions with the agency that in no way does it change the evidentiary basis that's needed for an approval. So from our perspective, we remain on track with the filing strategy we've laid out with a rolling submission, and that does indeed include the 26 weeks of 006, which we see as significant in terms of really finalizing the profile, and again, for commercial purposes.

Okay. Great. And then can you give us a little more color on the reimbursement and maybe the CPT code where maybe the evolution of it? Is there anything else that we need from the CPT angle between now and approval and after? And then just a little more color on -- there's a lot of discussions about the support, the psychological support and kind of the prep and then maybe the amount of people that you would expect to be in a room and their qualifications just on the commercial side, thoughts around those ideas.

I'll hand that question to Steve.

Thanks, Kabir. Frank, on the CPT portion of the question, in terms of the work remaining for the CPT 3 codes, they are in a Category III form at the moment, which is their tracking form as those codes are reported more and they have started to be reported in a limited number of cases. It really will require our approval and launch for them to be reported in greater quantity. But as they reported, that will enable the American Medical Association with their RUC Committee, which is an acronym for the RVU Update Committee, with representation from APA to do their work to understand the work involved in delivering this treatment in the practice expenses in order for them to make a recommendation to CMS on the valuation for the code.

This is not entirely a black box. It's formulaic. There are analogous treatments to look at in terms of having some expectations coming in for where this valuation may land. But again, ultimately, the codes will need to be reported so the codes can be progressed to the Category I valued form. Ahead of that, there will be the opportunities for negotiations directly with payers by providers for reimbursement of treatment.

On the staffing-related question with how patients will be prepared and what delivery will look like as far as treatment models. Ultimately, those treatment models will be up to sites of care as part of the practice of medicine. Staffing ratios, descriptions of the roles of people involved, the language that will ultimately end up in our REMS will be a result of discussion with FDA in due course during the review period. We have been guided to expect to this point that the REMS will be consistent with the one that exists for Spravato today as well as what FDA have prepared in the briefing materials for Lykos' AdCom with use language to the effect of a prescriber available, a licensed health care provider on site. And these, of course, are the important elements in terms of having the sufficient experience and training of providers necessary to ensure safeguarding patients.

Your next question comes from the line of Paul Matteis of Stifel.

This is Julian on for Paul. Congrats on all the great progress. Just 2 from us. I guess what are your expectations for retreatment after 2 initial doses versus 1 initial dose, thinking about the 006 26-week data coming out and how you think that will be assessed by FDA with respect to implications for labeling?

And then our second question is, from your commercial work, have you been able to identify what proportion of patients being prescribed for Spravato are at large academic medical centers versus private practice clinics? And curious how that may or may not influence your commercial strategy.

Thanks, Julian. So yes, on the first question, as you know, from what we've already shown, we saw that there was a 25% of patients had a clinically meaningful response in 005 from that single administration of COMP360, and we saw that, that was 40% in 006 with the addition of the second fixed dose. So clearly, we are expecting that higher level of response to be sustained through 26 weeks, but we really do need to see the data to understand what the potential impact of a third dose for those who had it may be and indeed what the second dose after week 3 does for sustained response without necessarily a third dose.

So turning to what that means, and I'll start, but Lori and Steve may want to jump on here. I mean we are seeking a label that essentially says from 1 or 2 doses and then with further episodic dosing at provider discretion. So that gives discretion because clearly, if somebody responds very well to a first dose, there may not be a need for something within 3 weeks or a short-term period. But equally, we clearly saw so far that there are patients who do benefit from having that second dose 3 weeks apart. So that's how we're thinking about label.

And then I'll hand to Lori and Steve to talk about first that and then the percentage of patients.

Yes. I agree with Kabir. Julian, by the way, this is Lori. I agree with Kabir's assessment on what we're seeking for the label, the 26-week data that we're getting from 006, combined with the 005 data is really going to be used to help guide clinical decision-making from the field force as we're out educating providers. So Steve, anything you want to add on that?

No, that covers...

In terms of the Spravato patients being treated in academic centers versus the more -- what everyone calls the interventional psychiatry treatment centers, the academic centers are treating a very, very small portion. It is, I think, less than 5% of patients are actually being treated at academic centers. And so the primary focus of ours will be at launch on the interventional psychiatry treatment centers that are currently prescribing Spravato, which is at about 7,500 already.

And I'll just add to that, that we do engage with many academic centers. We hear a lot of excitement for them about the potential of implementing COMP360. So we do expect academic sites to deliver COMP360. The nuance is that they are typically not built to have high-volume operations. They tend not to treat high volumes of patients. They don't have the kind of throughput that the interventional clinics have. So they will deliver the treatment, but the -- reflective of the breakdowns that we see with Spravato prescriptions, we expect that to be similar with those centers having a higher capacity to treat more patients.

Your next question comes from the line of Joshua Schimmer of Cantor.

How are you thinking about the incremental capacity for COMP360 administration at the 7,300 or so interventional pathways? And is there any way to quantify that? And then what percent of the centers do you expect will be adopting the buy-and-bill model for COMP360 early on? And how do you expect that to evolve over time?

Thanks, Josh. I'll pass both of those to Steve.

Josh, good to hear from you. Thanks for the question. So on the capacity side, we know that these centers have existing capacity today. And it's an important consideration when we often get questions about how these sites will make decisions about which treatment to deliver and whether they're making trade-offs based upon reimbursement that they may receive for delivering various treatments. First of all, these sites know that there are huge unmet needs for the treatment-resistant depression population. They are excited to have more tools available and to have the opportunity to make decisions of which treatment to deliver.

But in the meantime, given especially that a Spravato room and the Spravato staffing model are the same as what we anticipate to be required to deliver COMP360, they don't need to make any adjustments in their centers today in order to have capacity to deliver the new treatment. They'll be able to use the rooms interchangeably. It is likely that within the same day, they may treat a patient with COMP360 and one with Spravato later in the day or that over the course of the week, these rooms may be used for either treatment. So there's plenty of existing capacity that they will first fill prior to adding additional space, should they have the good problem from their perspective of treating lots of patients and running out of capacity, the economics are very favorable for them to add space or add new locations.

On the buy-and-bill part of the question, what we've seen with Spravato is that the penetration of buy-and-bill relative to specialty pharmacy reimbursement has increased over time. We don't know the exact numbers. We believe it's somewhere between 35% to 45% of Spravato prescriptions at this point are buy-and-bill. This is something that the psychiatry model has not been used to prior to the advent of Spravato, but they are beginning to recognize the economic value of processing claims in this way. So we would -- and I'll hand to Lori to augment this, but I think we would expect that in the earliest days of launch, more sites may as they get used to delivering our treatment, initially work with the specialty pharmacy channels, but we would quickly expect them to adopt buy-and-bill and for that to increase over time.

Yes. The only thing I'll add there, Josh, is that we will enable both at launch. And so that is just an important nuance to add is that it will be enabled, but we do, from a realistic expectation standpoint, expect there to be a little bit of a ramp to heavier buy-and-bill.

Your next question comes from the line of Judah Frommer of MS.

Congrats on all the progress. Maybe just a follow-up on kind of how providers are thinking about potential administration. I think there's a little bit of discussion about whether psychedelic treatments should fit into that Spravato dosing window versus maybe something longer that COMP360 would take. Can you just remind us from the provider's perspective, the economics of turning over a room maybe 2 or 3x for multiple Spravato applications versus maybe a single administration of COMP360 and what the economics look like relative to each other?

Thanks, Judah. This is Steve's favorite question.

Yes. Thank you for the opportunity to talk about this, Judah. So yes, exactly as you said, there are inefficiencies with shorter treatments and needing to turn a room over multiple times in a day because this is, I guess, self-evident, but when you have time in between patients where you need to turn the room over to clean it, the administrative work of an additional patient, et cetera, that is a gap that is unreimbursed time. Therefore, if you are able to fill that room with one patient and you are reimbursed for the entire time that the patient is in that room, then that is much more efficient for these sites.

To put some numbers to it, if you consider that a site operating at full capacity, which, as I've just said earlier, doesn't exist, these sites have plenty of capacity. But to be conservative, let's say they're at full capacity. And then let's say they're maximally efficient, which most sites also are not. That would mean they could get 3 Spravato patients in a room in a day. With average reimbursement for Spravato session somewhere south of $300, but using $300 as round numbers, then that means they're potentially being reimbursed for the room at $900 per day. That works for these sites. That is not ideal necessarily in their minds.

And so that's really kind of the target that would be the minimum that they would need if they were just purely making these trade-offs. That makes us very confident that this will make sense for them. But in addition, if we consider that the observation time for COMP360 will probably be about 6 hours within a typical operating day for these sites, it means they could also most likely get a Spravato patient in that room, too. And since most of these sites aren't having more than one Spravato patient in that room in a day anyway, this is all upside. This is all additive for them.

Your next question comes from the line of Ritu Baral of TD Cowen.

Steve, you mentioned the RUC Committee of the AMA. So our understanding is that this committee meets once a year and unfortunately, has only one psychiatry rep and it's very sort of surgeon dominated. Is there anything that you guys can do -- first of all, do you know when this RUC Committee is scheduled for the year? And second, is there anything you can do as far as prep for this committee to sort of optimally communicate the value proposition of COMP360?

And then I've got a follow-up on the DEA discussions. Have you been in communication with the DEA proper? And do you have an idea at this point if communications and review of the FDA will start even before the NDA is complete? Or would you expect that this would still be sort of expedited review on the tail end of approval? And then if I can just ask a quick follow-up after that. What are your expectations for the REMS insofar as the requirements for administration as well as either preparation and consolidation afterwards? Like what will actually be required by the REMS because we've heard from doctors that, that will be absolutely the most important thing.

Thanks, Ritu. So I'll ask Steve to comment on the RUC. I'll take the DEA question with Lori, and then Steve will take the REMS question.

It will be a sandwich. Okay. So starting with the RUC portion. You asked about the date of the next RUC meeting. I don't have the schedule on the top of my head. We can follow up on that. But to the rest of it, you're correct that historically, there has been the overrepresentation, let's say, on the RUC of surgeons and other procedurally focused committee members. That has been shifting, fortunately. I don't know exactly how many psychiatrists are currently sitting on the committee, but there has been an effort to correct the historical imbalance in the representation on the committee.

When we did the initial work on the Category III code a few years ago, we took advice from a number of people, including those who had served on the RUC in the past. So we were very well informed heading into the initial application for the Category III code. We will continue to work with experienced consultants as the code progresses to Category I and make sure that this goes in a direction that is very favorable to ensuring that there is adequate reimbursement to ensure patient access.

I will hand over for the second part of the question and be back with you on REMS.

Yes. So Ritu, on the DEA, I mean, as you know, the executive order mentions the fact that the analysis could potentially start as soon as Phase III is completed. After further conversation with those who are responsible for that, it's clear that the intent is that the DEA and the FDA can arrive at their conclusion simultaneously. However, it would still be a sequential process. So essentially, we will provide an 8-factor analysis. The controlled substance staff within the FDA will then review that. Historically, they have submitted their findings at the end of the review period because that's just the way the FDA has worked. That could potentially be accelerated with the DEA then doing their sequential review, with all of this coming together in time on the same day or a day apart at the end of it. That's the intent. Where we will actually get to in practice, we will have to see.

The only thing I'll add is that we are working with DEA consultants as well as accelerating our time lines to what you would traditionally communicate with the DEA so that we can reach a further understanding. But to -- for planning purposes, as of right now, we are not planning for -- we will be ready if there's anything that happens before, but we see no indication that these time lines have shifted forward.

And then back to me for REMS, Steve again. So you're referencing in our clinical trials that we had spent time preparing patients ahead of administration, supported them on the day of administration and then followed them up for safety after. Within a clinical trial context, it was important that everyone had the same conditions, the same experience that everything was highly standardized. And so in that context, we specified a number of preparatory sessions as an example, as well as a standardized length of those visits. As this translates into real-world care delivery and how this will be guided by the REMS, what becomes most important is not a certain number of sessions or a length of those sessions, just that patients are adequately prepared and they are properly followed up for safety.

And so anything that would be in a REMS would be very typical of REMS language and not get down to the granular level of detail of dictating the practice of medicine. The reality is that with any treatment, there is some preparation and safety follow-up anyway, so much as any necessary language that just gives a little bit of guidance on what activities are important in terms of preparing patients. And that would include being enrolled in the REMS, having informed consent and so on and then ensuring that patients are followed up afterwards as a safety check.

Your next question comes from the line of Madison El-Saadi of B. Riley Securities.

A couple from us. Maybe what have you learned about the CNPV mechanics since receiving the award a couple of weeks ago? Should we think of this 1- to 2-month CNPV review clock as not really starting until that final module is submitted? Or has it, I guess, to some degree, already started, which would imply the FDA response closer to 1 month versus 2 months? And then afterwards, an unrelated follow-up.

Yes. So thank you for the question. So our understanding is certainly that, that formal 1- to 2-month goal is following the completion of the NDA submission. However, what it also does imply clearly is an even more flexible and responsive way of working with the agency. As we've said before, we already have an excellent relationship with the psychiatry division. It's collaborative. It's constructive. It's focused on solving problems. And what we've already seen in the last couple of weeks is that, that is even more so. And in particular, some of the standard time lines of 30 days to request a meeting and x days for a response and so on, those have gone away entirely. So this really is about, first, a much more flexible day-to-day interaction with the agency. But no, the actual formal clock about 1 to 2 months as we understand it, will only start with the submission. And again, to be clear, that's a goal. Yes, it's a goal that they can complete it within a couple of months.

Understood. That's great to hear. And then secondly, so many of these sites offer TMS. Based on what we know or what we believe we know about how psilocybin works, how TMS works, do you think there may be an additive or even a synergistic effect from combining these treatments?

That's definitely a Steve question [indiscernible] on the call.

Thanks, Madison. Yes, that's an intriguing one. It's something that has been raised to date. It's really a matter of speculation. You can concoct theoretical reasons why there may be synergies. It would be good to see some data. I know that there's at least one small academic study already looking at the concurrent use of these 2 modalities. I'm sure that the sites that deliver both treatments, both TMS and COMP360 may be interested in that question. And if they do, I hope they track outcomes and we gather data and have some guidance on whether that may be an effective approach. Ultimately, these sites are ecosystems of care.

They offer multiple treatments. They're trying to offer as many tools as possible for these patients to maximize their outcomes. Treatment-resistant depression is, for many patients, a chronic condition, and they will receive many treatments over a lifetime. And so whether these treatments are combined in some way or whether over time, they wind up having multiple of them, we would expect that somebody receiving their care in one of these sites may have more than one of these treatments over the course of their care.

And Madison, if you don't mind, I'll chime in as well. Part of the benefit of us producing the data in treatment-resistant depression is that we believe that there's a huge unmet need. Spravato is the only indicated product -- drug product being used right now in this patient population. And given the frequency of treatment that Spravato requires, it is often patient prohibitive. And so in order for patients to want to receive these type of treatments, it has to fit into their schedule. And we believe COMP360 brings a very complementary patient profile -- patient-friendly profile to these patients. So we expect COMP360 to be earlier line than where TMS is currently being used right now, which is traditionally one of your later to last lines of treatment.

Your next question comes from the line of Patrick Trucchio of H.C. Wainwright.

A few questions. The first is regarding the Phase III trial, the COMP006 for the Part B 26-week data that's expected in the third quarter. Can you tell us, first, just which measures will be released at that time? Is it sort of maintenance of greater than 25% MADRS reduction, remission durability, time to relapse, treatment frequency, patient-reported outcomes and as well as safety? And which parts of those data matter most for the NDA as well as the label and payer discussions?

Yes. So Patrick, we haven't yet determined what we would release publicly. From a simple perspective, all of that data will be necessary from an NDA perspective. So clearly, everything, all those endpoints, primary, secondary, all the safety data will clearly go to the FDA. And I'll hand to Lori to talk about the commercial piece.

All of that data will also be important for payer and clinical decision-making, which we will all have in due course to help inform all of those decisions. But in immediate discussions with payers, it will be the redosing and the durability piece that we will -- that we are really looking for so that we can inform payers on how many doses to expect per patient. And Steve?

And just one -- sorry, Patrick, just one thing to add to that, which is similar to what we guided prior to the release of Part B of 005, just to be clear, there isn't a particular bar. There isn't some number that's a measure of success there. It is important data, but it's data to really round out the profile of the drug. And as Lori said, to have discussions with payers to guide expectations clinically with providers. So there's nothing that we're rooting for necessarily. We just need to understand the longer-term trajectories of these patients.

Great. And then just on the commercial side, more specifically, I'm just wondering if you can talk more about just your launch readiness and being ready by the end of the year. And to what extent you've begun that process of hiring a field force and building out a REMS infrastructure and sort of discussed the sort of the structure with payers and distribution contracts and as well related to that, of the 7,300 centers that could offer the treatment or greater than 7,300 centers, how many have you actively engaged with? And what proportion do you think are ready or will be ready to administer COMP360 within the first 3 to 6 months after approval?

So given the work of the strategic collaborations that we've been doing for several years now, which really sets us up for success and also enable us largely to be able to be -- to say that we will be launch ready under such short time lines. I'm going to let Steve answer that last question, and then I'll answer your original question at the end.

We're flipping it around in reverse order. Okay. Yes. So in terms of the sites that we've engaged with and we'll be ready, as Lori said, we've been working with sites like this for quite some time now, whether it's formally within our strategic collaborations, whether it's engagement by our field medical team as they've been out for the past couple of years, meeting with health care providers around the country or other relationships we already have with the leadership of these organizations, I think it's fair to say that we've engaged with the vast majority, and we know really quite -- many of them quite well. It is that level of engagement and knowing them that well that gives me a lot of confidence to say we don't need to encourage these sites to get ready. They're almost more excited than we are.

This is really why they've built the infrastructure in the first place. It wasn't to deliver one treatment. It wasn't to deliver Spravato. It was in anticipation of having more treatments, particularly ones with the profile like COMP360. The feedback we've been getting since the last data release is that they are just so excited for their patients to have a treatment that has this rapidity of effect, this durability of effect, which is on a scale far different from anything they've had available to them to this point.

The ability to recruit patients from a much larger radius to the point that Lori made earlier about the burden on patients of the frequency of treatment with Spravato, but particularly with TMS needing to come every day. It's really hyperlocal patient recruitment with COMP360 with just 1 or 2 treatments, they're able to have patients travel for much further area. So they are excited. They are really bombarding us every day with questions of when are you going to be approved? What do we need to know? So they will be ready.

Yes. And Patrick, so will we. And so hopefully, you can hear through my and Steve's excitement -- collective excitement here about this particular topic, just how confident we are in the fact that we are not only building out a pretty remarkable team, this team, this leadership team, getting them on board first was very important so that they could start to build out their teams. And all of that is underway right now. So every single aspect and function within a commercial organization has a remarkable leader at the helm, and they are currently in the process of building out and have already expanded the team. The team has already doubled in the past 2 months.

And so we are well on our way of making sure that we are adequately prepared. All that -- everything you mentioned is underway. So compliant payer discussions are beginning right now. The negotiating piece, I just want to set expectations on the negotiating piece with payers. We won't start negotiations until we understand the clinical profile better of COMP360, as we mentioned before, but we certainly are engaging with payers to start those initial discussions right now. Trade distribution is well on its way. We are working there to understand what our distribution strategy is. And again, with some really remarkable leaders and very, very experienced at the helm.

Your next question comes from the line of Leonid Timashev of RBC Capital Markets.

I wanted to ask on PTSD. Obviously, another part of the executive order was significant underlying excitement for treating PTSD. So I guess I'm curious how you're thinking about your program specifically, whether there's any changes you're envisioning to the trial, whether you think the evidentiary standards may be lower and you can move ahead with just one Phase III registrationally, and given the focus on veterans from the administration, whether there's plans to explore that subpopulation more deeply?

Thanks, Leo, and I'll start on that. So first, yes, we agree PTSD is a very significant unmet need. As we have said, we are planning that as a single late-stage trial. Obviously, we will have to see what the data says and so on because ultimately, it will be an FDA decision around that. Within that trial, we will have VA sites. More broadly, though, we are already heavily engaged with the VA, and I'm going to hand to Steve to talk a little bit about what that is. Just before I do, we should also note that it is now, but we are supporting a study within the VA, which is a very robust clinical study, which is a TRD population with heavy PTSD comorbidity. So that study, we're also supporting. But I'll hand to Steve to talk more broadly about the work we're doing with the VA.

Thanks, Kabir. Yes, PTSD is an area where we are really excited. This is 13 million U.S. adults who currently have very few options, terribly underserved. So really excited to be moving this program forward. As a reminder, the design of this study was from the beginning, intended to support registration with a single trial. And so that still remains the aim. As Kabir said, we already are engaged with the VA in various ways. He mentioned the study that we are supporting. We are supplying the drug as well as the training of the initial cohort of trainers for a large multisite VA study, looking at people living with both treatment-resistant depression and PTSD in addition to a second study as well within the VA.

Beyond that, we have had active engagement for quite some time now with VA's integrated project team, which has been working for multiple years now on their preparations to be able to implement psychedelic treatments as they're approved. So that engagement is robust and ongoing, and it certainly is a priority for us to ensure that as we bring new treatments to market that these are available for veterans.

Your next question comes from the line of Sumant Kulkarni of Canaccord Genuity.

I have a few here. First, how do you expect competitive and legal dynamics on psilocybin to play out given the Usona Institute also has a national priority voucher for its product and could already have its Phase III data in-house for major depressive disorder?

So I can only comment on the fact that we, Sumant, at COMPASS have 2 very large Phase III trials where we've already declared the primary endpoint, and we've agreed on a rolling submission and review plan, and that's what we're focused on right now.

And do you expect a label limit on the number of treatments per year for COMP360? And how soon after a patient needs retreatment would they be able to get it in the real world?

So no, but I'll hand from a kind of commercial payer perspective to either Lori or Steve. Lori?

I'll speak to it from a payer standpoint. Steve can speak to it from a clinician standpoint. So I agree with Kabir completely, we expect no limit in the label. We will through negotiations, be discussing with payers what that looks like and if there would be limits from a prior authorization reapproval process that is not only standard practice, especially with these type of treatments, but also should be expected. But it is, again, not going to be overly onerous for the sites nor again, is outside of the norm of what happens in clinical practice right now.

Well, to answer the last part of your question, Sumant, about the treatment frequency or the intervals. What we've seen so far is that some patients have some benefit from a second administration, whether it's on the fixed interval 3 weeks after the first or on a more variable basis as we saw in Part B of 005. Because the minimum interval we studied is 3 weeks, I would expect that there likely would not be dosing closer than 3 weeks apart. There really clinically would likely not be a reason to. Otherwise, I think the upcoming data from Part B of the longer-term progress in 006 put together with Part B of 005 will help give some guidance to clinicians on how they would think about retreatment. And then otherwise, as Lori said, that will be further guided by payer policy.

Got it. And then last one on PTSD. Other than less frequent dosing, what are the key reasons that would make patients want to take COMP360 versus Otsuka, Transcend's TSND-201, or methylone?

So they are likely to be first. We need to see data in terms of efficacy and safety on both of them, clearly. They are likely to be very different experiences from a patient perspective. These are very different medicines with different MOAs. To your point, certainly, the Transcend protocol hitherto has been more burdensome from a patient perspective as well. But I think we will need to see how those are fully characterized through the clinical trials, we believe, both in terms of patient experience, provider experience and infrequency of administration, there's clear differentiation between them.

And to be clear, there hasn't been an approved drug in PTSD this century. There are only 2 approved options right now. Both are all generic SSRIs that are only modestly efficacious, more options, more options, right? There's 13 million people with PTSD. It is not one or the other. There's not going to be one winner here. We are excited for any new option that is safe and efficacious in this population. The patients living with PTSD deserve to have more treatment options.

Your next question comes from the line of Tom Shrader of BTIG.

This is Jinnie Kim on for Tom Shrader. Congrats on all the progress. A couple of PTSD questions. What's the primary endpoint for the PTSD Phase IIb/III trial? And has the FDA aligned on that endpoint in a special protocol assessment? And in the TRD program, the 2 doses of COMP006 were administered 3 weeks apart, but in COMP202 for PTSD, you landed on a 4-week interval. Could you walk us through the clinical rationale for that difference?

Sure. So the primary endpoint is the CAPS-5, which is very well validated as the normal primary endpoint in PTSD. So we are using the standard primary endpoint. And because the CAPS-5 requires a 4-week look back, practically speaking, the second dose has to be at 4 weeks. It can't be at 3 weeks, and that's the reason for that. So it's tied to that endpoint. But as I say, this is the standard endpoint that has been used in PTSD trials. And no, there is no SPA on this. That doesn't need to be.

Your next question comes from the line of Jay Olson of Oppenheimer.

Congrats on the progress. Maybe we'll just follow up on PTSD. Could you talk about any synergies that you expect to capture from the infrastructure that you're building for TRD? And also, what are some of the differentiating benefits to psilocybin versus other compounds being used or studied for PTSD? And then maybe just any other indications you're planning to pursue for psilocybin beyond TRD and PTSD.

Yes. So we'll go backwards through these. So -- and I'll leave Steve and Lori to talk both about synergies and some of the reasons to believe. So we're clearly very focused on some of these broader neuropsychiatric conditions that do indeed share synergies in terms of patterns of prescribing, locations of treatment and so on. And while we haven't made any determination on other areas, you can imagine there are some such as bipolar II, OCD, in all of which we have seen signals based on IISs and studies we've supported, but we don't -- not yet in a position to lay out formally where else we might go.

So let me hand to Lori to talk about kind of the commercial synergies and then maybe Steve to touch on reasons to believe.

Yes. Given the high overlap in comorbidities between TRD and PTSD, the infrastructure that currently treats will be the same infrastructure that treats for TRD patients. So the synergies are exceptionally high. Steve mentioned earlier the work we're doing at the VA. Obviously, there's a large focus on PTSD patients at the VA. So we fully anticipate that the VA will be well equipped and ready to treat patients once it becomes available. And from a sales force standpoint, there would be very minimal change to the sales force to add on PTSD.

And then the last part, nice to talk to you, Jay. One of the things that we saw in our Phase II study in PTSD, one of the reasons along with the opportunity to meet the unmet needs for these patients was the experience that our patients had in that study. We were able to do qualitative interviews with the participants. And we heard some really important feedback that seems highly differentiated from other options that are available for patients living with PTSD or are currently being investigated. And that is that one of the reasons why people often avoid PTSD care is that they're forced to confront exactly the source of their trauma, which is a very frightening prospect.

It can make treatment itself very distressing. It's something that we're aware comes up with some of the empathogenic treatments like MDMA, where these are very intensive sessions. It's the reason why in many cases, these are studied with psychotherapy with trained psychotherapists actively engaging with them as traumatic material comes up. What we saw in our Phase II study, which was largely focused on safety, feasibility, acceptability was that this was a very acceptable treatment, one that was very pleasant for patients, where the trauma itself didn't even necessarily come up during the experience.

And that was something that surprised and was gratifying to them afterwards that despite the fact that they weren't forced to go through such a traumatic experience in getting treatment that they had profound shifts in the emotional relationship to that trauma. And so we think that bodes really well for this -- the further development of this as a potential treatment because of that really positive patient experience.

With no further questions, that concludes our Q&A session. I will now turn the conference back over to management for closing remarks.

Thanks, everyone, for your participation today. As you've heard, we are excited by the fact that we are aligned on a rolling submission and review with the FDA. We were already aligned on that before the award of the CNPV, but that clearly validates and is a recognition of the really great work we've done, the robust data that we have generated. So as you've heard, we are working with the FDA and DEA to see if there are other further opportunities for acceleration.

Most importantly, though, you've heard how excited we are about the opportunity to be to launch a first-in-class psychedelic. As we talk to providers, patients, current employees, prospective employees, everyone truly sees this as the opportunity of a lifetime, and we are delighted to be in the forefront of that and leading the way in establishing psychedelics as a transformative new option for patients in need of new treatments. So thanks for your attention, and we look forward to updating you on our continued progress during the remainder of the year. Thank you.

This concludes today's conference call. You may now disconnect.

Good day, ladies and gentlemen, and welcome to this COMPASS Pathways update webinar. [Operator Instructions] As a reminder, this call is being recorded. I would now like to introduce your host for today's call, Stephen Schultz, you may begin.

Welcome, all of you, and thank you for joining us today for this webcast. Again, my name is Steve Schultz, Senior Vice President of Investor Relations for COMPASS Pathways.

Before we begin, let me remind everyone that during the call today, we will be making statements about our future plans and prospects that constitute forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement, including those risks and uncertainties described under the heading Risk Factors in our most recent filings with the U.S. Securities and Exchange Commission.

These forward-looking statements represent our views only as of today, and we specifically disclaim any obligation to update or revise any forward-looking statements even if our estimates or assumptions change.

The call is being recorded and will be available on the COMPASS Pathways' Investor Relations website shortly after the conclusion of the call and will be available for a period of 30 days.

Today, I'm joined by Kabir Nath, COMPASS' Chief Executive Officer; Dr. Guy Goodwin, Chief Medical Officer; and Lori Engelbert, our Chief Commercial Officer; Dr. Steve Levine, Chief Patient Officer; and Teri Loxam, our Chief Financial Officer, will also be available for the Q&A portion of the call. I'll now hand the call to Kabir Nath.

Thank you, Steve, and thank you all for joining us. I'm very pleased today for us to be presenting these important results from the COMP360 Phase III 005 and 006 pivotal trials. I hope you've all had the opportunity to review our press release issued earlier today with these positive results.

Let me start by setting the stage. There is tremendous unmet need in treatment-resistant depression or TRD. It's estimated that over 4 million adults in the U.S. live with TRD each year. This is a chronic condition. With a significantly greater burden of disease than MDD. Over the years, many products that have tried to demonstrate efficacy in a TRD patient population have failed so much so that currently there is only one marketed medicine approved for use.

In comparison, COMPASS has now met its primary endpoint with high statistical significance in three consecutive trials. We believe that the safety and efficacy profile that's emerging for COMP360 through our Phase III trials is highly differentiated and the COMP360 can be an important novel first-in-class treatment option for patients with TRD.

These positive results we're sharing today mean that with two Phase III trials in our large Phase IIb trial together in over 1,000 participants, we are three for three in achieving the primary endpoints with high statistical significance.

The key takeaways are the COMP360 is safe to try and that if you respond on average, you do so on day 1. And if you have a clinically meaningful reduction in MADRS, the treatment effect is durable. In 005, 25% of patients achieved a clinically meaningful reduction in symptoms by week 6, and that response was sustained through 26 weeks. In 006, that figure increased to 39% of patients.

Taking all these results together, the emerging profile for COMP360 is redefining rapidity and durability for TRD patients. To see patients respond so quickly and to have responses that are so durable is remarkable in this condition that's chronic, extremely refractory with very few options. The only drug that's currently indicated for TRD and actually used is Spravato which is now nearing $2 billion in annual revenue.

Importantly, patients need 10 Spravato treatments by week 6 to achieve a similar effect to what we're seeing with COMP360 at week 6 with one or two treatments. There are no approved drugs for depression, including Spravato that offer rapid onset, clinically meaningful effect and durable outcomes from just one or two treatments. This supports a compelling novel paradigm for patients and providers where effectiveness can be determined almost immediately after a single treatment. This is incredibly exciting news for those living with TRD.

We've submitted this data to the FDA and have requested a meeting with them to further discuss our NDA filing strategy and the potential for a rolling submission and review. With breakthrough designation, we will also request an expedited review, which we believe is likely to be granted. With these accelerated regulatory options, we will be prepared to launch by the end of this year. Lori will discuss our commercial strategy and the work we've already been doing to be prepared for launch.

First, let me hand the call to Guy, who will take you through the data in detail.

Thank you, Kabir. Let me begin by saying simply that the COMP360 clinical program, I believe, sets the international standard for psychedelic medicine. It is robust, it's creative, and it cuts no corners. The program has generated the most robust and consistent evidence to demonstrate the pharmacological efficacy of psilocybin for treatment-resistant depression. I want to thank the team that made this happen. They brought their experience and commitment to the single goal of developing a drug to change the course of treatment for patients with intractable depression. The team, which includes patients, caregivers, clinicians and the COMPASS team have our sincere gratitude.

First, let me review the design of the COMP360 Phase III clinical program in treatment-resistant depression. In our trials, TRD was defined as having failed two to four previous treatments in the current episode. The MADRS total score was required to be greater than 20 at both screening and at baseline so moderate to severe current symptoms. Participants were also required to come off any existing antidepressant medication that they were taking.

All 005 patients were from the U.S. about half of the patients entering 006 were from Europe and the other half were from the U.S. and Canada. COMP005 compares a single treatment with 25 milligrams of COMP360 to placebo, and primary endpoint at 6 weeks is the change in MADRS total score from baseline. The MADRS was administered remotely by blinded raters throughout our clinical program.

After the 6-week point in Part B, patients were eligible for retreatment, if their symptoms had failed to remit. Patients had the option between blinded retreatment with the original dose of COMP360 or placebo or they could elect to go on to one of the predefined list of antidepressants.

Today's data goes up to the end of Part B for 005. This was a blinded portion of the trial, which continues to 26 weeks and is now complete. Part C continues out to week 52. The second trial, COMP006 compared three doses of COMP360, 25 milligrams, 10 milligrams and 1 milligram delivered twice at a 3-week interval. Today, we are presenting data up to the 6 week primary end point and beyond to 9 weeks, which is the end of Part A in this trial. It is an ongoing study so patients are continuing in Part B, which remains blinded. The criteria for retreatment are as in 005.

Approximately 80% of patients have now completed Part B in 006. Note that in 006, the comparator is 1 milligram COMP360 delivered twice. It is an active, not an inert placebo. The advantage of this are that it reduces unblinding leaving patients uncertain of which dose they're likely to have received. Therefore, it adds validity to any claim about a pharmacological effect at 25 milligrams and also effectively parallels the design of our Phase II study, COMP001.

The primary endpoint for 006, like 005 was changing the MADRS total score from baseline at week 6 comparing 25 milligrams and 1 milligram and there were additional secondary end points, which are not all available at this time.

Looking now at the demographics 005 and 006, the blinded randomized allocation of the patients between the arms successfully generated very similar treatment groups. Over 800 patients entered the two studies, there were 171 randomized to receive 25 milligrams of COMP360 and 87 to receive placebo in 005 and 296 to 25 milligrams, 142 to 10 milligrams and 143 to the 1-milligram group in 006.

Study discontinuation rates were low and well within the assumptions that we made in creating the power calculations and the model for analyzing this data.

Prior psychedelic use was again well below the 15% threshold set for the studies so an overwhelmingly psychedelic-naive population.

Next slide shows the treatment history of the current episode. This and the MADRS baseline of 32 confirms that this was a highly symptomatic treatment-resistant population. Bear in mind that these treatments were required to have lasted 8 to 10 weeks at adequate dose and with proven medical records, which was a very exacting criterion for study entry.

The number of patients required to withdraw from antidepressants in the trials was about 70%. Everything, again, was very consistent across study arms in both trials.

Finally, in both trials, we see a consistent depression history. The mean length of the current episode was over 3 years and the number of lifetime episodes again, relatively high in all groups, illustrating the persistent and recurrent nature of the disorder.

So to summarize, this represents a patient population who had recurrent depressive illness and a current episode that was well documented, chronic and proved very difficult to treat, a very different population from MDD trials, which we are much more used to seeing in the literature. We have successful recruitment, even patient distribution successful randomization to the different treatments and the high patient numbers required for a high-quality, well-powered clinical study.

Let us now look at the results of the 005 trial, starting with Part A. Last year, we announced just the primary endpoint of this study at 6 weeks, the difference between 25 milligrams and placebo. Here, you can see that the 25-milligram dose produced or a bigger effect than placebo at every time point with high statistical significance. Moreover, the effect of the treatment is immediate and so observed, in fact, the day following drug administration, an extremely rapid onset of action.

Next slide, please. The data from Part B provide the key finding from COMP005 that we present today for the first time. It is a remarkable graph because it demonstrates the persistence of a treatment effect of one or two 25-milligram doses of COMP360 psilocybin over the full 26 weeks of a double-blinded study in treatment-resistant depression. You can see numerical separation at all time points up to 26 weeks.

Recall that after 6 weeks or Part A, eligible patients have the option for a second administration of COMP360. About 70% of the patients in the 25-milligram arm and 50% of the patients in the placebo arm received a second administration in Part B. So our second dose of 25 milligrams for the 25-milligram randomized patients and a second placebo for the placebo allocated patients. Most of these treatments occurred between 10 and 14 weeks. Some will alternatively have started antidepressants, but we do not have these numbers at this time. There are also patients who withdrew from the study in both treatment groups at approximately equal rates. Accordingly, further analysis is needed for a complete understanding of this data.

Nevertheless, viewed as an intention to treat, it's very striking that the treatment difference is maintained over such a long double-blind follow-up. Furthermore, the relative nonresponse in the placebo group is prospected evidence to suggest that this patient population was indeed difficult to treat and further demonstrates the robust execution of this trial.

We have also looked further as planned at the 25-milligram arm to clarify just how the average effect you see here can be understood as composed of patients showing good effects of treatment and those who are effectively nonresponders, something we had tentatively explored recently -- previously pardon me in our Phase II trial.

This chart shows a breakdown of the patients receiving 25 milligrams COMP360 in 005 into three groups. The first group were defined as remitters and are shown in green. These were patients who showed a very rapid reduction of symptoms to levels below 12 on the MADRS. And you can see that the effect is well sustained out to 26 weeks. Only three of these 11 patients receive retreatment and only after week 12. So a sustained remission is possible out to 26 weeks after a single administration of drug. It represents a smaller group in this trial than we saw in our Phase II study. However, if you look at the portion of participants that achieved a clinically meaningful reduction in MADRS of more than 25% in the 005 trial at 6 weeks, which was 25%. Interestingly, this figure in the 006 trial increases to 39% with the second fixed dose.

Responders and partial responders are shown in blue. The justification for taking an interest in partial responders or patients who had a reduction in symptoms of between 25% and 50% is that in TRD, even marginal changes in the intensity of severe symptoms is a significant benefit, both subjectively to patients and objectively in terms of the cost of their illness and the risks that are associated with being chronically depressed. The dotted red line on this graph provides a guide to what a 25% reduction of the average baseline score of 32 would look like.

A 6-point change in the MADRS has been recommended previously as clinically meaningful in TRD after an in-depth analysis of data from the esketamine trials. This obviously corresponds to a less than 20% change from the mean of 32 in 005.

Some of this group will have received a second treatment between 10 and 14 weeks but as a group, they show sustained benefits out to 26 weeks. Of those who did receive a second dose in this period, over 40% achieved remission after that second dose. And then finally, for comparison that there are the nonresponders, the gray line. This is a group who do not particularly benefit from COMP360 as a dose of 25 milligrams, and one knows that very quickly because they never show a sustained benefit.

So to summarize, 25% of participants in the 25-milligram arm achieved a clinically meaningful reduction in MADRS at week 6, and that effect was maintained at least through week 26 with the majority of retreatment between 10 and 14 weeks. The magnitude of the MADRS improvement among responders is cost, consistent, it's durable and it's clinically meaningful, and Lori will talk more about how commercially meaningful it is as well.

Now I will review the Phase III COMP006 trial data. The results of the primary endpoint from 006 at week 6, as shown on this slide. In orange, you can see the response has change in blinded MADRS ratings from baseline to 1 milligram repeated dose of 3 weeks. In green, the response to 10 milligrams repeated at 3 weeks. And finally, in blue, the 25-milligram dose repeated at 3 weeks. There is a statistically significant difference from the 1 milligram dose for 25 milligrams at every time point beyond baseline. In addition, you can see that at 1 week, 3 weeks and 6 weeks, there is a numerical dose response effect with 25 milligrams showing a bigger effect than 10 milligrams and a more markedly different effect from 1 milligram.

The 10-milligram effect is bigger than we saw previously in our 001 study, which did not find 10 milligrams to be an effective dose. It is notable that the effect size at 6 weeks of minus 2.5 while statistically significant is below the level of 3 on the MADRS, which is often regarded as a threshold for clinical significance.

In summary, we have a successful clinical trial demonstrating clinically meaningful and highly statistically significant effects of 25 milligrams COMP360 repeated after 3 weeks in patients with severe treatment-resistant depression. This is a remarkable finding given that we now have as Kabir has already said, three positive results in three similar trials for our preferred dose of 25 milligrams.

For completeness, this slide shows the same data up to 9 weeks, the end of Part A. We do not see this data as fully interpretable without the longer-term 6-week data we will see later this year.

To further understand the relationship between the two studies, 005 and 006, this slide compares the primary endpoint results from 005 overlaid with the results from 006 for 25 milligrams and their comparator. What you can see is the remarkable reducibility reproducibility of the treatment effect at day 2 and week 1 for the solid line 25-milligram dose and the secondary response to treatment with 25 milligrams at weeks 3, giving a deeper response at week 6 in blue than we saw in 005.

Turning to the dotted lines, 1 milligram also shows a numerically greater response than inert placebo at all times from 1 week, suggesting that it is acting as planned as a low dose of active drug different from inert placebo. Obviously, the difference from this comparator is less than might have been seen had there been an inert placebo in 006.

This, again, is a validation of our trial design a validation of what we thought was important in terms of providing an active comparator and clearly, validation of the idea that retreatment with this drug produces a significant reduction in symptoms.

Moving now to safety. We will consider the two trials, 005 and 006 together. Just to give a high-level summary, we believe COMP360 has been demonstrated in both trials to be generally well tolerated with a safe profile and the majority of adverse events resolving on the day of treatment.

Overall, the safety we have observed is consistent with the known profile of COMP360, and we had no new safety signals identified in this large database of now over 1,000 patients. For the data available to date across both trials, the rate for SAEs, Serious Adverse Events of suicidal ideation was less than 1%. There was only 1 SAE of suicidal behavior which occurred in the 1 milligram arm in COMP3 -- 006. The DSMB noted that there is the data monitoring board noticed that there is no evidence of a clinically meaningful imbalance between treatment arms in suicidality in either study.

For both 005 and 006, most treatment-emergent adverse events occurred on the day of study drug administration and the majority resolved within a day. There were 11 treatment-emergent serious adverse events in 005, which includes both Part A and Part B and six in 006. I'll show the tables with greater detail on the next slide.

Looking at the top treatment-emergent adverse events shown as percentages in brackets for Part A of both trials, you can see the relatively low number of serious adverse events and the rapid resolution of most of the nonserious adverse events within a day seen in both studies. The somewhat higher rate of treatment-emergent adverse events in 006 would be expected because it includes two administrations of drug.

Next slide, please. Regarding treatment adverse events in Part A of both trials, we see the usual items, headache, nausea, hallucination, anxiety, albeit in a slightly different order between studies. The more common events clearly also show dose response, as one would expect in study with studies with different doses of COMP360. The high number of COMP360 related events is, of course, expected given the change in conscious experience it produces. Accordingly, it is important that the reported events tend to resolve so rapidly.

Looking at the serious adverse events, the SAEs in Part A, you can see that across 005 and 006. The evidence assessed by the DSMB is revealing no evident clinically meaningful imbalances of serious adverse events between arms, particularly those relating to suicidality. We see a low number of suicidality events that are evenly distributed across the treatment arms and perhaps an unsurprising phenomenon in a TRD population.

Next slide. Finally, considering the TAEs and the SAEs through 26 weeks through Part B in 005, there are no important additional treatment-emergent serious adverse events. Of the five instances of suicidal ideation or depression, suicidal in the 25-milligram arm, three of these events occurred in Part A, one on the day of dosing, which resolved within 24 hours and two in nonresponders also both resolved. The two additional cases in Part B also occurred on a day of drug administration and resolved in 24 hours. These events on the day of dosing appear to be transient and inconsequential. It may be important to distinguish such phenomena from the suicidality that is the usual part of depressive illness. Once our safety database is complete, we will be able to give clear guidance on this regard. There have been no attempted or completed suicides to date in these studies.

In summary, we are pleased to see the emerging safety profile of COMP360 from over 1,000 patients being generally well tolerated with a safe profile. Thank you, and let me hand to Lori.

Thanks, Guy. I am thrilled to be able to speak today about the potential commercial opportunity for COMP360 based on the emerging clinical profile from the data sets presented today and update you on our commercial progress. Given we now have two positive Phase III trials, and as you heard from Kabir, our plans are to be launch ready by the end of the year.

Data from these trials demonstrate that COMP360, if approved, will be highly differentiated from currently available treatment options and is well positioned to become the leading treatment for the millions of TRD patients who are underserved today.

Let me start by highlighting the tremendous unmet need for patients with treatment-resistant depression. Approximately 1/3 of drug-treated MDD patients are considered treatment resistant and prevalence is high with an estimated 4 million patients in the U.S. alone. Once an MDD patient is considered treatment resistant, which is only after being failed by two currently available to antidepressants, the chance of achieving meaningful clinical outcomes from additional antidepressants is significantly diminished and the patient and economic burden of disease becomes dramatically higher.

TRD has a significantly greater impact on individuals' lives compared to MDD, and those impacts start as quickly as the second treatment failure. The famous STAR D trial showed that due to ineffective treatment options, chances of achieving remission from MDD are cut in half when a patient needs to start a third-line antidepressant, the point at which they are considered to have TRD.

Treatment-resistant depression is a chronic condition. These patients experience 3x longer depressive episodes, increased comorbidities, for quality of life, greater work time loss and a greater than 50% increased risk of suicide compared to MDD.

Medication treated MDD represents a staggering economic burden estimated at close to $100 billion annually. Approximately 1/3 of MDD drug-treated patients are considered treatment resistant. But given the drop-off in clinical outcomes and increased health care costs after being failed by two antidepressants, TRD patients disproportionately account for almost 50% of the overall cost. This suggests that if effective treatment options were to become available, it could potentially lead to large economic and societal gains.

Historically, it has been incredibly difficult to establish efficacy in a TRD patient population and clinical trials. Several MDD indicated products have tried and whereas they did prove efficacy in a broader, less severe MDD patient population, they were unable to prove efficacy in TRD. Currently, there is only one approved and used TRD indicated medicine available, Spravato, and even they failed to demonstrate efficacy in some of their TRD trials on the path to approval.

Difficulty in establishing efficacy in a TRD patient population has led to extremely limited treatment options and a huge unmet need given that even when including nondrug neuromodulation treatments of ECT and TMS, less than 4% of TRD patients are receiving TRD indicated care.

We released a lot of meaningful data today. From a commercial perspective, the most important takeaways are: First and foremost, COMP360 demonstrated through multiple robust clinical trials, consistent, clinically meaningful efficacy in a patient population that has limited options. With only one other medicine FDA approved being used for this patient population, the potential approval of COMP360 will bring hope to millions of patients and their providers.

Second, in both 005 and 006, COMP360 demonstrated extremely rapid onset of action, with deep and dramatic reduction in depressive symptoms as quickly as the day following administration. These are impressive and meaningful results, especially in this particular patient population where nothing else has worked. Effects that quick can be life-changing for patients and may give clinicians the ability to determine as quickly as the day after dosing, if COMP360 is the right treatment for their patients. This is highly differentiated against other products that can take weeks to months to determine if the treatment is working for their patients.

Third, and perhaps most impressive, in 005, COMP360 demonstrated durability that lasts at least through 6 months after only one or two administrations. This is highly differentiated versus Spravato, where per label Spravato needs to be dosed every 1 to 2 weeks to maintain durability following the high burden of 12 initial treatments. If approved, COMP360 could offer significantly reduced patient burden without sacrificing clinical outcomes.

And finally, but importantly, COMP360 demonstrated a generally well-tolerated and safe profile, potentially making it easy for clinicians to try COMP360.

COMP360 is redefining rapidity and durability that can be achieved in TRD. Given the data presented today, we are confident that if approved, COMP360 can provide a highly differentiated and compelling clinical profile for a patient population that has previously been difficult to treat.

Given the limited treatment options available and the only other medicine being prescribed for TRD is treating less than 2% of the TRD patient population and still generating close to $2 billion in revenue. We believe COMP360 is well positioned to bring a welcomed new treatment option to patients and realize blockbuster potential.

If approved, COMP360 will be the first to market in a highly anticipated new class. Given the data shown today, COMP360 could be the first and only option that demonstrates extremely rapid onset of action, with durability out to at least 6 months after only one or two doses.

As we work with the FDA to seek approval for this important new treatment, the commercial team is actively preparing for launch. COMPASS has been very active with pre-commercial work over the past several years. Now with the clinical profile of COMP360 emerging, we can begin some of the more advanced commercial prep work. This includes more detailed discussions with payers, preparing effective marketing campaigns, enabling distribution and preparing the field force. All of this will be complementary to the ongoing educational efforts with patients, HCPs, sites of cater and federal and state policymakers.

At launch, we are prepared to leverage the well-established existing interventional psychiatry infrastructure. These treatment sites are specifically designed to support products that require a multi-hour support and monitoring such as Spravato with over 7,000 sites across the U.S. and growing rapidly. These centers are already equipped with the staff, operational know-how, and infrastructure needed to support additional multi-hour treatments like COMP360, with many of these sites already scaling in anticipation of a COMP360 launch.

If COMP360 is approved, it will undoubtedly bring a welcome and meaningful new treatment option to TRD patients and their providers as effective new treatment options are desperately needed. Our launch planning efforts remain focused on ensuring sites are prepared to administer COMP360 and that TRD patients can access COMP360 upon approval. COMP360 has the potential to fundamentally change the way that patients living with depression are cared for and COMPASS is committed to helping as many patients as possible. The launch of COMP360 is poised to be one of the most highly anticipated launches in recent history, and I look forward to discussing our launch readiness with you over the coming year. Let me hand the call back to Kabir.

Thank you, Lori. Let me first thank all of the participants and clinicians involved in our COMP360 clinical program. Your support has been remarkable and has helped position COMP360 to be the first classic psychedelic to be approved by the FDA and a condition of significant unmet need where patients today have so few options.

As I said earlier, we've requested a meeting with the FDA to discuss our NDA filing strategy. The agency has shown strong interest in an aggressive filing strategy, including the potential for a rolling submission and rolling review.

That would enable them to review the clinical module as data comes in and not require all clinical data in the package prior to commencing review, which makes the 26-week 006 data due in early Q3, the last gating item to complete our NDA package.

Practically speaking, this could shorten the review cycle and result in an acceleration of the approval time line. And as Lori said, we expect to be ready to launch commercially by the end of this year. As she mentioned also the continued increase in the interventional psychiatry clinic infrastructure driven both by Spravato and the eager interest around the potential promise for psychedelic treatments such as COMP360 is exciting for patients.

We're confident that COMP360, if approved, can be effectively integrated into this growing infrastructure and offer a differentiated and compelling treatment option for patients and providers. COMP360 has the potential to transform the landscape for those living with TRD through a rapid, safe and durable treatment option. We're looking forward to meeting with the FDA to see how expeditiously we can move this forward through a potential regulatory approval process.

And with that, thank you all for joining. Thank you for your attention. I will now turn the call back to the operator for Q&A. Thank you.

[Operator Instructions] The first question comes from Francois Brisebois from LifeSci Capital.

Congrats on the data and the update here. I just had a question in terms of the -- on the 006 front, the dose dependence there, I think you mentioned that the 10 mg arm seem to have worked a little better than it had in the past. And so is there a possibility here with the two doses that there's some sort of a ceiling effect may be where the 10 mg arm worked better just because there was another 10 mg, 3 weeks later? Or just any color on that dose dependency between the 10 and the 25 here that we saw.

Thanks, Frank. Just to check, you can hear us clearly?

Yes. Yes. Absolutely.

I will hand that to Guy in a second, but I think just the first thing to say, well, acknowledging that there was a modest significant effect for 10 milligrams here, we didn't see that in 001. So from our perspective, we're really focused on the 25 as the active dose that we want to take forward. But let me hand to Guy to comment on your question around the two 10s.

Yes. I mean thanks, Frank. I mean we're going to be very interested in looking at this data in detail once we have, for example, individual distributions to look at the different time points, which may give us some understanding together with a look at the intensity of the psychedelic experience, which previously was very informative and understanding who responded and who didn't. So I think I'm afraid we simply have to say at the moment, we don't really know the answer to your very good question. But we do think we have the data to approach the answer subsequently, and we'll obviously put that forward and publish it in due course.

Okay. Great. And then I'll sneak in a quick one here. There's a lot of data. Just can you help us understand, you mentioned maybe the difference that you're seeing between a true placebo and the 1 mg arm and the implications of that?

And then lastly, was safety here, how happy are we with the data, the safety seems very, very clean off two doses within 3 weeks. Is that something that is almost surprising or we're just happy and we're moving forward here.

Well, we're certainly happy about the second of the points you make, and particularly that in fact, if anything, the side effect profile reduces a little bit with the second administration, so in a sense, it becomes more tolerable.

On the first issue, I'm not sure that we have a really clear answer to that. So we're going to have to see how we go. It's most important really that the 1 milligram gives validity to the trial. The usual criticism, of course, is that inert placebo is fully unblinding and any comparison with that and an active drug is invalid or at least really is just a safety study. We designed both 001 and 006 to overcome that by having a low dose, which was the main -- so the low expectancy response arm of the study was actually active drug and then patients when they were consented would be told truthfully that they would definitely receive the drug. It's just they would get different doses.

So we think that the validity from the point of view of this interpreting efficacy is very good. The difficulty, of course, is it means the comparison with -- if it's an active treatment, then, of course, in a sense, diminishes the difference that you see between it and the 25-milligram dose. So yes, it's a very -- it's going to be a very interesting debate that we have subsequently. And there are further data that will weigh on, particularly relating to expectancy that we'll be able to clarify in due course.

The next question comes from Paul Matteis at Stifel.

Can you hear me okay? Excellent. Great. Congrats on the data. A couple of questions for me, if you don't mind. So on the durability data, I appreciate the transparency there. How do you expect FDA to evaluate and do sensitivity analyses on the durability data? And I know it's premature to talk about what a label looks like, but even just generally, what do you see as the likely directive that's going to be provided to physicians on when and how to redose?

And then second, I appreciate that a second dose in the 006 study is showing some evidence of additive efficacy, is it your perception that most patients will get these two doses for induction? And is that how you think might be the best way to position this commercially? And then I have one follow-up.

All right. Thanks, Paul. So I'll ask Guy initially to comment just on how the FDA might view some of this from a durability and then come to Lori to talk about the label and the commercial implications. So Guy?

Yes. I mean it's certainly the case that in their guidance, the FDA have emphasized that they want to see evidence for durability. We're providing that in spades. I mean, they're, in fact, only requesting 12 weeks. We're going to provide 26 weeks. I think it would be a little bit presumptuous for me to suggest how they should analyze it and I'm reluctant to. We have a very good relationship with the staff at the FDA, and we think we should leave them to make their own decisions about how they analyze the data.

Paul. So from what we expect from the label, I mean just based on what we're seeing from the data now, it will likely be more of a one or two induction-ish type phase to start a patient and then less directive on winter retreat and likely will be more on an episodic base, well so that would translate like the -- based on the data that we're seeing, obviously, we'll be up to physician discretion and patient discretion, but I don't expect the label to be restricted to or directive to dosing. I also would love for Steve Levine to chime in here from a physician standpoint on what he thinks from based on the data in terms of dosing, what might look like in the real world.

Thanks, Lori. Yes. So as Lori said, likely some language related to one or two initial administrations. I think that in clinicians' hands and in discussion with their patients, given that we're able to see the impact of that first treatment almost immediately, that will give them very quick and useful information to make a determination about whether a second dose initially may be indicated and then following them clinically over time when it may be appropriate to retreat.

One thing that I'll point out is that one of the things we saw very clearly in Part B of 005 related to a second dose is that group that had at least a 25% reduction in their MADRS, which is clinically meaningful. These are partial info responders. Those that received a second dose 40% of them went into remission. I'll repeat that because it bears repeating. Of the 25-milligram arm, those that had at least a 25% meaningful reduction in their MADRS who got a second dose, 40% went into remission, which tells us that not only can this group have a very meaningful initial response, but a second dose might deepen that.

This is a group that's very heterogeneous and so this will be a matter of discussions between patients and their doctors over time. But the sum total of this data suggests to us that one or two treatments with either on a fixed interval or over a longer period of time can have significant durability at least out to 6 months.

The next question comes from Judah Frommer of Morgan Stanley.

Congrats on the update. Maybe just to follow up on Steve's comments there. Could you help us parse out kind of MADRS reduction versus responder remitter rates and how those can be viewed or will be viewed by both regulators and clinicians. I think investors are kind of laser-focused on that MADRS separation. But how should we be thinking about remission rates and how will docs think about those?

And then just on the safety profile with the suicidal ideation, it sounds like it's largely transient and kind of goes away on day of dosing. How could that factor into monitoring time lines and potentially monitoring profile that you'll be able to tie into the CPT codes you've talked about.

Thanks, Judah. So I'll hand to Steve to talk about that.

So first, on the question about the MADRS separation, the meaningfulness of the different categorizations of response. Certainly, initial remission is wonderful. This, as a reminder, is a very different population than MDD though, patients living with treatment-resistant depression have a severe and chronic refractory course of care.

And anyone who's cared for patients living with TRD know that even small reductions in MADRS can have outsized impacts on their clinical course, on the quality of life, on the resources that they consume and receiving their care, et cetera. That can be even minimal change can have an outsized impact, but a robust reduction of 25% of their MADRS will frequently result in significant improvements in quality of life and level of function. And so that's why it's important, I think, for us to consider not just the typical categories of remission or full response as a reduction of 50% in symptoms. But the way the clinicians will look at this is what can I expect in terms of the impact on the course of my patient's illness. And today, they really have very, very few options that will make that meaningful impact.

In terms of the second part of your question about monitoring and how that relates to the CPT codes, yes, we'll be -- as we dive deeper into this data, we will learn more about the total time that patients were monitored and supported on this administration day ultimately with the new CPT codes because they're reported on an hour-by-hour basis regardless of the needed length of monitoring, all of that time will be fully reimbursed for providers.

And Judah, if I may, I'm actually going to ask Guy, just to comment on your question around the transient nature of the suicidal ideation and perhaps give some actual concrete examples of what we saw in the study. Guy?

Yes. I mean it's very striking that we see these very brief transient effects in the 25-milligram arm in 005. We haven't actually yet seen them in 006, but obviously, we're still collecting data there.

Looking at the detail, they're somewhat unusual in that -- to give an example, one of the cases with someone who had the full day of 25 milligrams, they went home and in a somewhat altered state was struck by the surroundings being extremely messy in the house being in a tip. And out of that grew the conviction that if this woman could sit there and will herself to die, that she might be able to do it and that she should do it. And that lasted -- that state lasted for another about an hour or 2 hours, and then finally passed in the next morning, she was completely without these symptoms.

Now that seems to me potentially something that one needs to understand as a manifestation of the -- some of the unusual features of having exposure to high-dose psilocybin. On another occasion, a lady was the next day, had a very strong flashback to the face of a friend who she pictured during the dreamlike state of the 25-milligram experience. And this had a very big impact on her transiently that she became very tearful and felt suicidal for about, again, a couple of hours.

Now these phenomenon being described during a very intense supervision by medical staff. So we don't know whether they would occur naturally in the course of illness. But I don't think I've heard patients really describe that very frequently. And so I think it's something we may have to factor in as a feature of the management of these patients that we have to maybe warn them about and think about incorporate into clinical management. But they're not very common, and they don't seem to carry the same kind of threat as if depression -- the impulse to kill oneself arises in the course of a depression where the other symptoms are present. And therefore -- and it may last quite a long time.

So some of the other instances we see not related to dosing are of that kind. So these are nonresponders. They have a lot of depressive symptoms. Their suicidality goes up that's a very kind of well understood and common phenomenon of severe depression, in particularly TRD. And that just as a clinician feels different from this kind of rather transient effect we observed with the dosing. Rare though it nevertheless also is. But it's going to be part of the risk benefit as we understand it, and we're clearly going to be transparent about anything that we see in this area.

And Judah, just one final point to reiterate something Guy said, we are not sharing remission and response data from 006 at this point because that study is ongoing, and there are still some ratings to be done for patients remaining in Part B and that would run the risk of effectively unblinding the final part of Part B if we were to share the arms for now. So I just wanted to reiterate something that Guy mentioned.

The next question comes from Josh Schimmer at Cantor.

The Part B component of the 005 study, what percent of patients were redosed and what do you expect the real-world redosing spectrum to look like? You talked a little bit about how you expect kind of the initial one or two doses to evolve. But how do you see it occurring for the rest of the treatment phase?

Yes. So what we know, Josh, is that on the 25-milligram arm, 70% elected or retreatment and on the placebo arm that was just over 50% that elected a retreatment. In terms of how we think that's going to translate into practice, let me turn to Steve.

Thanks, Kabir. Josh. In part, I think we're going to want to see the 26-week Part B data for 006 to inform that as well. Because what we're seeing in Part B for 005 is the rates of retreatment after a single initial treatment, which might look somewhat different than after two initial treatments. Nonetheless, and repeating some of what I had said earlier, this is a heterogeneous population. Ultimately, it's going to be a conversation between patients and their clinicians evaluating their initial response to one or two doses to make that determination. But given what we've seen now, we have the two fixed doses in Part A of 006 as well as the effect of a second treatment in Part B from 005. It certainly is a very exciting finding that one or two treatments can have such a durable response after 6 months and potentially longer.

Can I just quickly ask Guy the suicidal ideation cases and it sounded a little bit like reactivations that are characterized through some of the other psychedelics, is that a reasonable comparison in terms of what these patients are experiencing?

Reactivations as in the sort of HPPD diagnosis. I'm not -- I don't think that we really picked up all the phenomena that are associated there. There was some visual imagery for one of the examples that we gave. Maybe that's a little bit related. But you'll appreciate our understanding of even that phenomenon is something that is developing as we see greater use of these drugs in controlled settings.

I mean, clearly, many of the more florid consequences of taking these drugs have been described in recreational settings with uncertain doses and co-administration of other drugs.

So I think we have to watch this space. We're developing the biggest database that you could over 1,000 patients and many exposures. And I think when we get to summarizing that, we'll be a lot clearer about whether there is a relationship or not to the sort of phenomenon that you just mentioned.

The next question comes from Gavin Clark-Gartner at Evercore.

So I just had one set of questions for COMP005 on Part B. What were the percent discontinuation for any reason on both of those arms. When did those happen over the course of the 26 weeks?

Also, what percent of patients in either arm received any rescue treatment, not retreatment, but rescue. And then finally, can you just remind us if any data gets imputed during this period and how it's done.

Yes. Guy, do you want to take those?

Yes, yes. The discontinuation rate in both arms of the study was about 28%. And most of the discontinuations in Part B, and that isn't all of them because, of course, people also discontinued in Part A. Most of them -- all of the distribution has taken place by the -- by 10 weeks. So by 10 weeks, almost all the patients who are going to drop out or dropped out, and the numbers were about 28%.

Bear in mind that one of the features of the design was access to open-label treatment in Part C of the study. And so we had hoped that we would retain patients very well. Overall, that was true. So that dropout rate is very low compared to standard antidepressant trials, for example, in MDD or indeed TRD.

Sorry, what was your other -- the other question was the number of rescue treatments. We don't have that data yet. Much of this was -- is fairly detailed in 005. It's not the full data set, and we don't have that yet.

And Gavin, just to add the dropouts to Part A, were well within our planning assumptions from our power calculations and actually somewhat lower than you would typically see in a depression trial even to week 6.

And by the way, just on the stats, we had not -- there's no imputation at all for the data given beyond 6 weeks. There is an invitation for missing values, missing at random model in up to 6 weeks, obviously.

The next question comes from Ritu Baral at TD Cowen.

Two for Guy and Steve and forgive my voice this morning. And then a follow-up for Lori. One, just given that intriguing 40% remission rate, what in 005. Guy and Steve, can you disclose at this point what the criteria, the prespecified criteria for that second dose was that possibly drove that week 10 to 14 change in the 005 MADRS line? And two, can you talk to any details around the time -- average time to discharge readiness? And as part of that question, could you just address any cardiovascular heart rate or blood pressure excursions that you might see? There didn't seem to be a lot of detail in the safety event, and I just wanted to make sure that, that was because there were no events. And then I have a follow-up for Lori, please.

Thank you. So I think guy, if you could take the criteria for redosing in Part B, please, if you start there?

Yes. We have actually that public in the current summaries of the data in public. So I'm not sure that we want to give that as a help to our competitors. But suffice it to say, there is a criteria in which was carefully exercised.

I think we can add though that high level, it was those who have not yet achieved remission at the end of Part A or those who had subsequently relapsed.

Got it. And time to discharge?

On the day of administration, you mean?

Yes, including any CV parameters or CV excursions you saw?

I don't know that we have time to discharge data. I'm not aware of that. That's something that may come in due course, but we don't have that at the moment. And then Guy, if you could just comment, I mean, on the blood pressure side, specifically.

Yes. I mean, certainly, we see blood pressure -- there is a blood pressure signal, and this is already well known with COMP360. And similar drugs. As you can see, we have -- we will be describing that in full detail in due course, but there was nothing that was concerning and there was certainly no subsequent consequences of elevations of blood pressure. Most of them were -- virtually all of them were within the sort of excursions you would see during moderate exercise.

Got it. And then the follow-up for Lori. Lori, you mentioned on your slide that some of the activities would be enabling distribution activities at this point as you have the data in hand. What sort of activities will you be embarking upon for, I guess, helping set up distribution sites for later in the year and next. What can you help sites with?

So it's -- I think of distribution as more of this product being shipped through a distributor to specialty pharmacy or to sites of care for buy-and-bill situation. So there are a couple of things to that enable distribution, and that is one working with the FDA -- I mean, the DEA after FDA approval to get the product rescheduled so that it can be successfully distributed as well as states to make sure that state-level rescheduling is also done so that physicians can prescribe and the product can be distributed to two sites of care during immediate as quickly following approval as possible.

The next question comes from Patrick Trucchio at HC Wainwright.

Congratulations on the data. A couple of questions from us. First, I'm wondering if you could further elaborate on how the Phase III program design, particularly the use of the 1-milligram active comparator in 006 and blinded remote MADRS raters helps to mitigate any questions around functional unblinding and expectancy effects.

And then secondly, can you walk us through the regulatory path forward from here? And specifically, I'm wondering if there have been any meaningful shifts in FDA feedback, personnel or perspective as the program has progressed over the last year that could impact the rolling submission. And as you look toward a potential 2026 launch, what would be those key gating items we should look for between now and year-end, including 26-week durability data from COMP006, is that required for approval? Likelihood of an advisory committee and anticipated timing and mechanics of DEA rescheduling.

Okay. Thank you. So I'll ask Guy to comment first on the question around the 1 milligram dose and the central raters and how we do believe that, that should deal with the functional unblinding question. Guy?

Yes. I mean we believe it will have fixed it. But in addition, we built into this design additional to what we did in 001 pretreatment measures of expectation and post-treatment measures of unblinding. So we'll have some idea of both what patients expect to happen, whether that in any way predicts response, which in some other studies, it hasn't with psilocybin and also whether post hoc, we see differences in conviction and accuracy in guessing what dose was delivered. So we will be able to deliver an assessment of whether our design has achieved what we believe it is likely to have achieved.

And from the regulatory perspective, Patrick, let me -- last year when we had the primary endpoint from 005, we said we'd met with the agency. They were intrigued and we're clearly open to discussing a rolling submission and review. But clearly, they needed a reason to believe. And that's one of the reasons why we put all this data together in a simultaneous release today.

This data is now with the agency. We believe that this does give a strong reason to believe and a confidence in potential approvability. We have requested a meeting at which we would hope to align on that potential for a rolling submission and review.

In parallel, we've obviously been doing work at risk so that we would be in a position to put in modules effectively very quickly, such as on a preclinical and CMC side. And as we said, if in fact, they are open to that review, for instance, this pretty significant amount of data at this stage, than the 006 26-week data, which we expect in early Q3. Our ability to integrate that into the submission becomes the final gating item for the submission. And that's how we're thinking about it.

As I also mentioned, we do have breakthrough designation. While that does not guarantee priority review. It's historically been pretty highly correlated with priority view. We would expect to get that -- and again, with an NDA being completed in Q4, and obviously, we would target sooner in Q4 if we could. But with an NDA be completed, that gives you some sense of the potential approval time line.

On the DEA side, the formal process is that while the FDA makes their own recommendation on rescheduling based on analysis and so, the DEA independent, but subsequently, does it as well. But I'll ask Lori to comment a little more on that because clearly, we have had some engagement around that.

Yes, Patrick. So the DEA has 90 days after an FDA approval to reschedule the products right now currently. We are obviously doing some work. It's been pretty well publicized. The work that we're doing, especially with this class being Schedule 1 products, almost all psychedelics have breakthrough therapy, doing some work with the FDA and DEA to help tighten up those time lines. So that is work that is in progress. We're trying to educate as much as possible and push there. And then after DEA from a federal side reschedules, then the states need to reschedule before any prescribing and distribution is allowed in the states. And so that -- we are actively working there to make sure that, that is done as quickly as possible after federal DEA reschedules.

That's helpful. And just lastly, as you think about the emerging product profile, how would you expect payers, clinicians and patients to position COMP360 relative to Spravato when making treatment and coverage decisions, particularly given this rapid onset we've seen a potential for durability with one or two administrations.

Yes, thank you for picking up on how impressive that is because it's a very -- I can sit here and scream from the rooftops, how incredible it is to see this dramatic decrease, especially for the patients that are responding on day 1, this is a patient population that has never had efficacy or most generally never had efficacy. This is truly unlike anything we've ever seen before and it gives you -- the durability data is really quite impressive.

I think you've heard Steve and Guy so you've got two in-house physicians who can comment on that, and I'll pass to Steve in a minute to add a little more commentary. But from a payer standpoint, remember, there is only one product that payers are covering right now in this patient population, and that is Spravato and even though we believe that the efficacy and durability that we're seeing and economic benefit potentially for patients on COMP360 exceeds that of Spravato. Spravato is already pretty broadly covered after two failed treatments, which would be a prior authorization to label. And so we expect payers to react pretty positively to this, especially given the patient population that we are studying. But I'll hand it to Steve to see if we must add anything from an HCP receptivity of this.

Thanks, Lori. Patrick, from a psychiatrist and patient perspective and particularly from as a psychiatrist who has treated thousands of patients with TRD, this emerging profile that we're seeing, the possibility that with one treatment, a product that is generally safe and well tolerated, then you will know almost immediately, if your patient is going to benefit from this treatment. And then with that one treatment or maybe a second could have durability out to 6 months relative to the couple of other options that are available today, and I'm glad they exist, but they do require patients and their caregivers to have multiple treatments, especially initially, really a high burden of initial treatment with those other options, and it still takes weeks or even longer to know if you're going to benefit from those treatments. So with an option that you know almost immediately with one safe treatment that could be so durable. This is what I've been waiting my whole career for.

The next question comes from Leonid Timashev from RBC.

I had maybe two related to baseline characteristics and the correlates of response. I guess, first, is now that you have two trials under the belt, two Phase IIIs, anything you're seeing with what's correlating between deeper responses, those that remit and sort of the patient baseline characteristics that you can use to steer physicians towards who they might want to treat first?

And then the second question is, obviously, across these trials, we've been very careful about selecting patients that are actually treatment-resistant, you had international sites as well. But I guess how do those patients compare to what you might expect in a real world U.S. treatment setting? And would they be more or less likely to respond and remit, I guess how should we think about how the real-world data might evolve once this is actually in physician hands.

Thanks, Leo. So I will hand the second question to Guy and Steve sequentially. Just in terms of your first one, that is analysis we don't yet have. I mean, clearly, it is a very interesting question. But right now, we have none of that looking at the baseline epi, looking at pretreatment, looking at psychedelic naive and so on. So there are a bunch of interesting questions there, but we don't yet have that analysis. But clearly, we will be doing that, and we'll be reporting that as and when. But let me then hand first to Guy and then to Steve to talk about how this population, frankly, differs from what a real-world TRD population we look like.

Yes. I think just to add, I mean, we will also be looking at the characteristics and intensity of the experience, which we think may be somewhat predictive, not a baseline characteristic admittedly, but nevertheless, something that we think may be mediating. I think when it comes to what these patients how they're mapped onto the real world. We are looking at that in pragmatically within COMPASS, and we'll have something to say about that systematically.

Just anecdotally, it seems to me that by setting the bar as high as using the questionnaire that we required to screen patients for failure to respond to antidepressants, the Massachusetts General Hospital test that we used is extremely exacting and requires patients who have been treated for longer than is common in ordinary practice. So I think we will have selected patients who were more chronic and therefore, probably more difficult to treat. But I'm not a U.S. clinician. So I hand to Steve at this point, and he can comment further.

Thanks, Guy. No, you may not be a U.S. clinician, but I fully agree with you. And I'll just add that, yes, these likely these participants in our trials likely map pretty well on to patients living with treatment-resistant depression in U.S. clinics. But it is also the continuing reality that if we look at the treatments available today for people with TRD, they tend to get them too late. Spravato is widely covered PA-to-label. And so patients will be eligible for that treatment after they've been failed by two treatments. Yet what we see in claims is that it's often five to seven treatments before they're getting Spravato.

And that means that there is ongoing work to do to educate clinicians, those that provide these treatments as well as those that refer to them on the importance of early referral once patients meet the criteria of TRD and think earlier about treatments that have proven efficacy in this population.

And so this is work that our field medical team has been doing. They've been out educating for the past couple of years that we will continue to do and expand. And certainly, as we build more of our commercial infrastructure.

And so to directly answer your question, I think they're representatives, but it also points out to us really the larger opportunity to make sure that our treatment can get to more of the patients that are waiting.

The next question comes from Thomas Shrader of BTIG.

Congratulations just remarkably reproducibility, amazing data. I have just a couple of patient level questions and I'm worried you won't have answers for, but how clear are the repeat effects? If a patient gets nothing on the first dose, do you ever see one get something significant on the second dose? And then the slide went by quickly, but it looks like you have about a 10%, I would say, miracle response group, people who get a MADRS below 12, is that a real group? Did they start with high MADRS? And do you ever see that kind of effect in the placebo group?

Thank you, Tom, and I'll ask Guy to comment on that, please?

Yes. I mean just on the -- this very small group who do really well, we have not really looked in yet had the chance to look in detail at them for their particular characteristics. I mean they're certainly within this sample, they're relatively small, but they're so striking in terms of how completely they remit that it's most impressive to me as a clinician. There is the odd -- I mean we have not looked in detail yet at the placebo group to be fair. We know at least 1 patient who showed that kind of response in the placebo group. But we need to absorb this fully to make sense of it.

Only the question of whether or not you kind of get a different response depending on the first or the second administration, that's a great question that we will be looking at in detail, but we don't -- we haven't yet had the bandwidth to do that at this point. We haven't had the data for that long.

The next question comes from Sumant Kulkarni at Canaccord Genuity.

Nice to see you advancing the field with data and thanks for taking our questions. I have three. First, other than staying responders or remitters, what were the key reasons for patients not opting for retreatment.

We don't yet know that. We don't actually -- I think as Guy said in answer to an earlier question, we actually don't have the analysis of antidepressant use and so on. So we don't have -- we will get some more insight on that. Obviously, secondary scales, including PROs and so on could be interesting to that, but we don't have any of that at the moment.

Got it. And then given the 6 weeks primary endpoint in Part A of COMP005 is somewhat arbitrary in the first place, how soon do you think patients could opt for retreatment or physicians might like to retreat in the real world?

Steve?

That's a great question. I think while we have a clearer picture of the profile with this data, we don't yet have the full picture of that, and it will really take the Part B of 006 to have more of that information.

I think given what we're seeing so far, that one or two treatments, whether it's at that fixed interval 3 weeks later in Part A of 006 or the retreatment in Part B of 005, seeing the initial durability of this treatment, I think it's less likely that commissions will jump to retreat in the very, very near term, although that will be individual clinical decision-making. And rather I think people are going to be really encouraged that this appears to be quite a durable treatment for those who benefit. But again, I think we're going to want to see the really large data set of Part B of 006 to really further guide our expectations of the frequency of retreatment.

And my last one, I think, is perhaps my most important question. A real world again, how important do you think a more active level of psychological support as part of the dosing experience might be for eventual clinical outcomes for COMP360?

So I'll start and then hand again back to the rest of the team. So I think as part of the dosing experience, we would absolutely say that is not relevant. We are clear that the psychedelic experience with psilocybin itself does not require or justify therapeutic intervention in the dosing. The container for the patient is a different question, so I'll hand to Guy and Steve to take that. Maybe we'll do the Steve, Guy order this time.

Yes, so as Kabir started with, let's exclude that administration day where there isn't a role for any more active support than what we're providing in order to safeguard patients receiving COMP360. There is a question of whether some more active psychotherapy and evidence-based psychotherapy might enhance outcomes in the period following administration. That will be an open set of questions. Of course, it's not what we studied. We are really excited what we've been able to demonstrate purely with the effects of one or two administrations of COMP360, I think there are a lot of people who assume intuitively that some ongoing therapeutic process after this treatment might be beneficial. But that will be an interesting set of questions that will maybe have the opportunity to explore hopefully prior -- excuse me, subsequent to an approval, okay?

I think just to say that I think post approval, when this drug actually becomes more available and less restricted by current scheduling, we expect to see innovation around the container that Kabir has described. And I think it's going to be a very exciting time to be some people working in this field and treating patients with these conditions and with these drugs.

The next question comes from Jay Olson at OpCo.

Congratulations on these landmark results and thank you for hosting this event. We have a few questions. Do you anticipate any learning effects on the average time to discharge for patients who receive a second dose? We're curious if you expect monitoring requirements to decline after a second dose as patients and their caregivers gain experience and maybe require less monitoring. And then how will you guide the treatment of Spravato experienced patients in terms of when and how those patients could or should be switched from Spravato to COMP360? And finally, is there any read across from today's results that inform your thinking about PTSD or other indications that you plan to study?

Thanks, Jay. So I'll ask Steve to take the first two in terms of how we're thinking about the monitoring and then Spravato experience in the relationship to treatment.

Yes. That's a really interesting question about a learning effect and whether there could be a reduced requirement for monitoring with a subsequent or potentially multiple subsequent treatments. I think we'll need to spend more time with this data and dive into the time and other aspects of readiness for discharge within our clinical trial setting.

I think you're thinking along the right lines, and that's certainly a possibility. We'll just need some more information to better understand that. As far as potential considerations of switching from Spravato to COMP360. I think if we are approved and at the time of launch, there will be at least two buckets of patients, those who have not yet tried Spravato and maybe making a decision between the two possible treatments and those who already are on Spravato and might think about switching. And in that second group that you're asking about, I think there's a number of considerations.

There likely are a number of patients who maybe have had some benefit from Spravato, don't have other options. And so continuing maintenance even if they don't feel that they've had the full benefit that they would have hoped for. And also those who continue to have the burden of the frequency of maintenance treatment with Spravato and it's a burden that falls both on them as the patient as well as their caregiver who needs to drive them. And as a reminder, after the 12 initial treatments with Spravato, eight in the first month, four in the second, maintenance is typically weekly or every other week, which really can be a challenge logistically in terms of time, but also when patients are better and may be able to return to work that can be inconsistent with working a full-time job. So I think those may be some of the switching considerations.

And then as we were saying earlier, in terms of initial decisions, the possibility with a generally safe and well-tolerated treatment knowing almost immediately as of the next day, whether you've benefited and that having the potential, maybe with one more treatment to be durable out to 6 months, we think is really compelling as far as stacking that up against your other options.

Thanks, Steve. And in handling the final part around other indications to Guy, I'll also just repeat something Guy mentioned, which is we saw a trend that we wouldn't yet say it's a conclusion that the side effect profile from the second administration may be slightly lesser from the first, which would also kind of support your first question. Guy, if you want to comment on cross indication learning space?

Yes. I think we're impressed by the second administration, frankly. And that's a reason to think about that in relation to PTSD. Ditto the 10-milligram dose. I mean, clearly, we probably have to know a little more about that. But it's a little premature to pontificate on that. We're still in the process of finalizing the protocol for our first -- our second study in PTSD, and rest assured we'll be thinking this through in the next few days around exactly these questions.

I'd say certainly, this -- I think the safety may read across, and this very large safety database at this point is very encouraging as we look to new indications like PTSD.

I think the last question will come from Michael Okunewitch from Maxim.

Congratulations on what looks like great data so far. I guess to start, I'd like to see if you're planning any qualitative analysis into the nonresponder population to see if there are any identifiable factors going into the session or in the reaction or even external factors that might contribute to the lack of response and may be able to inform that container that you're discussing once you get into a real-world use.

Yes. So I think, as Guy mentioned earlier, we don't yet have, in particular, the measure of the subjective experience, the dimension or the state of consciousness, which in the IIb turned out to be a potentially useful diagnostic tool. So again, when we have that, other PROs, other secondaries. I think we'll be in a better position to answer that question. It's clearly a question we would like to be able to contribute towards answering given the level we saw of nonresponse. But right now I'm not sure we have any, Guy, anything you want to add on that?

Yes, I think we do -- we will have something to add because although we didn't put qualitative interviewing into the main body of the protocol because it might have been unblinding, it might have interfered with various kinds of nicety around the design of the trial. We have put in a sort of free text questionnaire at the end of the study where patients will get asked about the experience, about their preferences, about the experience with the person who's the support provider or a kind of stuff that you're intimating may become important.

And so we may very well get something from that, which is quite useful given that we're having quite so many patients going all the way through the protocol and staying with us. But this will be kind of at the end. So we don't know yet how complete the coverage will be and how useful it will be. But we've certainly thought about that, and we hope that we'll have something interesting to share in due course.

I do appreciate that. And then one last follow-up for me, and I'll jump back off the call. I'd just like to see if you could clarify what you mean specifically by launch ready by year-end '26, given the submission is expected to complete in the fourth quarter. Is that just getting everything lined up ahead of approval? Or is there an expectation that the rolling review could enable approval actually within 2026.

So I'll answer the second part and then hand back to Lori for how -- so no clearly, we are not saying that we are expecting -- we're not giving any guidance for an approval time line but we're conscious of the fact that there is a lot of interest behind this is the first-in-class psychedelic. We appear to have a motivated agency. And I think with this data, we are optimistic that continued dialogue will be very positive and actually even accelerate. But we're not giving specific guidance on approval, Lori?

Yes. And when you think about getting prepared for commercialization, commercial has to back up to the best possible scenario to be ready because the worst thing that could happen is we receive an approval and we're not ready. And there's a lot of lead time required to make sure that we are prepared to successfully launch that includes preparing the market earlier in terms of disease state education, like Steve mentioned, our MSLs out and the field force will be doing other efforts around that, including thinking about how we ensure training of the sites so that when an approval comes, they can very easily adopt COMP360 in a fast and early adoption fashion. So our goal is to just make sure that if something were to move quickly or quicker than normal time lines, we are ready to go.

This concludes today's Q&A session. I'll now turn the call back to Kabir for concluding remarks.

Thanks very much. So thank you all for your time and attention this morning. Again, let me thank the participants and the clinicians and the COMPASS team who have worked so hard to get us to this point. As you've heard, we're incredibly excited about these results. We believe that with COMP360 with the emerging profile, we have the ability to redefine rapidity, durability for patients with TRD who today only have one possible available treatment option. So with this data showing the rapidity of onset, that consistent separation from day 2, showing significant numbers of responders, partial responders who with one or two doses are able to sustain response out to 26 weeks. We truly believe this is the start of a novel compelling paradigm for patients and providers.

We're excited. We've already sent the data down to the FDA. We've requested a meeting and we look forward to working expeditiously with them to see whether we can move this towards regulatory approval and provide another treatment option for 4 million patients who desperately needed. So again, thank you for your time and attention, and have a great day, everyone.

Good day, ladies and gentlemen, and welcome to this COMPASS Pathways update webinar. [Operator Instructions] As a reminder, this call is being recorded.

I would now like to introduce your host for today's call, Stephen Schultz. You may begin.

Welcome all of you, and thank you for joining us today for this webinar. My name is Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways. The call is being recorded and will be available for 30 days -- I'm sorry, the call is being recorded and will be available on the COMPASS Pathways Investor Relations website shortly after the conclusion of the call and will be available for a period of 30 days.

Before we begin, let me remind everyone that during the call today, the team will be making statements about future plans and prospects that constitute forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement, including those risks and uncertainties described under the heading Risk Factors in our most recent filings with the U.S. Securities and Exchange Commission. These forward-looking statements represent our views only as of today, and we specifically disclaim any obligation to update or revise any forward-looking statement even if our estimates or assumptions change.

I'll now hand the call to Kabir Nath, Chief Executive Officer of COMPASS Pathways.

Thank you, Steve, and thank you all for joining us. During today's program, we'll be updating you on both our COMP360 programs for post-traumatic stress disorder or PTSD, and for treatment-resistant depression, which we'll refer to as TRD hereafter. Today, we announced our pivotal Phase IIb/III PTSD trial design. PTSD is an even larger patient population than TRD with an estimated 13 million individuals that suffer with this condition in the U.S. Like TRD, there are very limited therapeutic options with no new medicines approved in PTSD in decades, and we believe COMP360 has great potential in this population. Guy will provide a physician's view on the unmet need in PTSD, and Mike will walk you through the trial design.

We'll then turn to our commercial preparedness for potential TRD approval. TRD is a difficult condition to treat. Any treatment that demonstrates clinically meaningful efficacy and is well tolerated has the potential to address the estimated 4 million patients in the U.S. alone. We're pleased today to have Dr. Gary Small, Director of Behavioral Health Breakthrough Therapies at Hackensack Meridian Health join us. Dr. Small will provide his thoughts on this condition and what a new treatment option like COMP360, if approved, would mean for patients.

Of course, our network of treatment centers ready, willing, and able to deliver COMP360 if approved, is essential. Steve will discuss how COMP360 compares to the only medicine that's indicated and actually used today in TRD, esketamine, under the brand name Spravato. As part of this discussion, Steve will host a roundtable with three of our strategic collaboration partners about how they anticipate seamlessly integrating COMP360 into their offerings.

We have made excellent progress in our TRD program. We've completed a roll out ahead of schedule in our 006 trial, our second Phase III trial, and we've seen openness by the FDA to a rolling submission and review. Based on these developments, COMPASS has significantly accelerated our launch time lines. We will be launch ready by the end of this year. And Lori will give us an update on our commercial readiness.

So with that, let me begin by handing to Guy to discuss PTSD.

Thank you, Kabir. In the next few minutes, I'll outline the critical unmet needs in treating PTSD and the compelling clinical rationale for advancing a new development program for COMP360 psilocybin. Let's dive in with the first slide. First, what is PTSD? It's a debilitating mental health condition triggered by experiencing or witnessing a traumatic event, which could be combat, assault, disaster. Symptoms include intrusive memories often as vivid unsettling flashbacks, hypervigilance and irritability, avoidance and emotional numbness or negativity. Their persistence can profoundly disrupt daily life, relationships, and work.

According to recent data, PTSD affects over 6% of the U.S. adult population in their lifetime with higher rates among women translating to millions grappling with this condition in the U.S. and around the world. The human cost of PTSD is immense. It appears to lead to higher rates of substance abuse, depression, and suicide, 4x to 6x the general population risk. Overall, the U.S. economic burden from lost productivity and healthcare has been estimated at $230 billion. That's $0.25 trillion per annum or the equivalent of the annual GDP of a middle-sized national economy. 82% of these costs are attributable to civilians and 18% to military personnel and veterans, but the annual cost of PTSD per person is proportionally higher for military and personnel veterans.

Compounding this burden of disease, current treatments fall short. The gold standard of an evidence-based psychotherapy can help but requires intensive sessions over weeks or months. Access to such treatments is often limited. In addition, for trauma-focused therapy, dropout rates often due to the emotional toll of reliving trauma can exceed 30%. It's also important to notice that on the pharmacological side, despite significant efforts, only two FDA-approved medications exist, sertraline and paroxetine. Both SSRIs and both approved for PTSD over 25 years ago. These antidepressants can reduce symptoms, but full durable remission is unusual. In addition, they are not necessarily well tolerated. Side effects like sexual dysfunction, weight gain, and sedation may be distressing in their own right and lead to poor adherence to treatment.

PTSD appears to involve dysregulation in brain circuits involving the amygdala, hippocampus, and prefrontal cortex, which can be read over to the observations of impaired fear extinction and hyperarousal. The comorbidity and the potential underlying biology suggest a close association with major depression. Thus, the efficacy of the SSRIs, which primarily modulates serotonin in both PTSD and major depression provides an additional pharmacological link. Therefore, the positive effects of serotonergic agonists like COMP360 psilocybin in treatment-resistant depression could also translate to PTSD.

Psilocybin offers a novel potential mechanism with the possibility of durable changes in emotional processing that can underpin more complete clinical responses. Our preliminary work with COMP360 psilocybin indeed demonstrated both the -- pardon me, possibly a durable change in emotional processes. Our preliminary work with COMP360 psilocybin indeed demonstrated both the necessary tolerability and a rapid resolution of the core symptoms of PTSD after a single dose with sustained responses lasting for up to 12 weeks.

The unmet needs in PTSD, limited treatment options, insufficient efficacy with incomplete symptom relief and the long absence of innovation demand bold action. The clinical rationale is clear to leverage advantages in the clinical understanding of psilocybin and create a more beneficial treatment option, providing faster and more durable symptom relief without the undesirable side effects seen in currently utilized medications. We at COMPASS Pathways are prioritizing a PTSD program that will bring hope to millions of patients and their families.

Thank you. Let me now hand over to Mike Gold, our Chief R&D Officer, to go through the details of our PTSD program. Mike?

Great. Thank you, Guy, and thank you all for the opportunity to talk about our PTSD study for your time and for your attention. The COMPASS Pathway team has created a very strong and well-designed study. And today, I want to give you a brief background on our PTSD program, where we are, how we got here, our study design and next steps. As Guy referenced, and you can see on the screen, COMPASS completed and reported an open-label safety and tolerability Phase II study in 22 patients with PTSD, which was conducted across multiple sites in the U.S. and the U.K. It tested a single dose of 25 milligrams of COMP360, which is our proprietary synthetic formulation of psilocybin in patients with PTSD, obviously.

The study detected a large benefit in the CAPS-5 score, a benefit that was sustained through week 12, which was the end of the study. And you can see on the graph on the slide, the change from baseline in the -- from the study. On the basis of the efficacy signal that we saw in this study, the overall clean safety profile of the study with no serious adverse events observed and supported by the data that we were accumulating from our own treatment-resistant depression studies, we felt there was a very good potential to address the huge unmet medical need in PTSD that Guy just described.

We aimed to come up with a study design that would allow us to maximize the chances of getting an approval with a single trial, and to stay within the rigorous scientific approach that we've developed with our TRD program. So where are we now? We've agreed on the design after meeting with FDA and taking into consideration their feedback. And as you heard earlier today, our IND has been accepted by the FDA. So let's wait.

Let's see the next slide come up. So there we go. As you can now see on the slide, this is the finalized design. It's a 3-arm Phase IIb/III study, which will test two doses of 25 milligrams as a target dose compared to 1 milligram as the active control. We're using a smaller population of patients at 10 milligrams to help address the questions of functional unblinding, similar to what was done in our Phase IIb and our Phase III COMP006 TRD studies.

Similar to our Phase III COMP006 study in TRD, we will use a two-dose paradigm for PTSD. Our belief based on prior studies of COMP360 is that more than one dose of a classical psychedelic is likely to be the best approach to maximize benefit. The primary endpoint for this PTSD study is the CAPS-5 at week 8. CAPS-5 is the standard instrument used in PTSD studies and measures a range of different aspects of the condition. A key secondary outcome is the PCL-5, which is another PTSD checklist to measure other elements of the PTSD syndromic picture. We're also collecting other secondary measurements to understand depressive symptomatology and anxiety and to get a broader and more holistic view of the drug's benefit. Obviously, we're also evaluating safety.

Part A is a controlled double-blind randomized 12-week portion and will include the two doses of COMP360, 4 weeks apart. Part B is an open-label portion and will run 40 weeks, so for a total of 52 weeks in the study. Similar to our TRD studies, participants who are nonresponders or those who are remitters and then later relapse will have an opportunity for another dose in Part B. We will also be assessing safety in this study similar to our TRD trials, and we will make use of an independent data safety monitoring board to monitor both blinded and unblinded data.

As is the case with our TRD program, we will be conducting the study to the highest standards and align with the FDA guidelines for psychedelic treatment development. We've selected a CRO. We are now in the process of selecting sites and investigators for the program, and we expect to start screening patients this quarter. As a physician, it is truly a privilege to have the opportunity to address such significant mental health challenges. That is the program right now for PTSD.

And now let me turn to a little bit on treatment-resistant depression. As a preface, let me first discuss the significant unmet medical need in TRD. Today, approximately 23 million adults experience major depression in the U.S. Of those, we estimate that about 4 million are failed by two or more MDD indicated products. And with only two drug treatments approved for TRD and generally only one that is utilized, the challenge to bring safe and efficacious option to patients is significant, and this is our focus.

With that, let me introduce you to Dr. Gary Small, who will provide his perspective on the treatment landscape. And thank you again for your attention. So Dr. Small is a Director of Behavioral Health Breakthrough Therapies at Hackensack University Medical Center, one of our collaboration partners. He has extensive experience with TRD and with a variety of interventional treatments, including Spravato. And with that, Dr. Small, the meeting is yours.

Thank you, Michael. I'm going to be talking about unmet needs and the treatment landscape for TRD. Next slide, please. Just to begin my potential conflicts of interest and disclosures. Next slide. So with TRD, the general consensus for definition is that these patients have an inadequate response to two or more antidepressants despite adequacy of treatment and adherence to treatment. And this accounts for about 1/3 of patients with major depression. And we heard earlier that it affects about 4 million people in the U.S. If you look at the worldwide prevalence, it's estimated 100 million people. But it's not only the numbers. It's the direct and indirect costs. It accounts for more than half of these costs of major depression. So it's not surprising that it leads to significant personal, familial, and societal burdens.

Next slide. So if we take a moment to look at the current treatments used for major depression and TRD, with major depression, as we know, most of these treatments are based on monoaminergic mechanisms, affecting serotonin, norepinephrine, and dopamine. And there's been limited innovation in this space. With TRD, most of the strategies are ineffective and they're inefficient, and what we generally do is to extend the treatment of the antidepressant, combine it or switch it, or use psychotherapy. It requires daily chronic use with the medications. And of course, this imposes ongoing side effect risks. If we use neuromodulation in these cases, that treatments like ECT or electroconvulsive therapy or transcranial magnetic stimulation, that brings up issues of accessibility and tolerability.

Next. So what about the management of TRD? Let's look a little bit more at the data on that. If we extend antidepressant trials, systematic review of the available studies on response after 4 weeks indicates that about 20% of patients respond during weeks 5 to 8, and only 10% respond during weeks 9 to 12. Now depressed patients, they prioritize rapidity of antidepressant action. When you're depressed, you want to feel better. It's really debilitating. You want to feel better now rather than later. Despite that, it's a big problem. These people are reluctant to get into these prolonged trials.

What about switching antidepressants? If you look at the meta-analysis on the data available, it's conflicting as to whether switching antidepressants increases the likelihood of response or not. With combining antidepressants, you run into the problem of polypharmacy, which increases the risk for drug-drug interactions and further side effects. And actually, there are a few relevant studies that have been conducted in this population to show that this is effective despite the fact that doctors often use this approach.

Next slide. Let me hand it off now to Steve Levine.

Thank you, Dr. Small. Sorry for the delay. I'm Dr. Steve Levine, Chief Patient Officer. And in this segment, we'll be discussing what we believe are the key clinical advantages of COMP360 psilocybin treatment compared with the current standard of care for TRD based on the developing profile from data to date. We'll give an overview of the existing therapeutic landscape, the limitations patients and clinicians currently face, and discuss how the emerging profile of COMP360 potentially represents a meaningful advance both clinically and commercially.

Having founded a national interventional psychiatry network 15 years ago and being one of the first networks to prescribe Spravato when it launched, I'm intimately familiar with the challenges and opportunities of providers and patients, and I'm passionate about leveraging my prior experience to help launch and scale COMP360, if approved. To understand where COMP360 potentially fits, it's important to start with the current pharmacologic landscape.

As said before, for MDD, there are more than 50 approved pharmacologic treatments. These therapies are daily chronic treatments. They require consistent adherence, yet they bring daily side effects. And when studied in TRD, they have failed to prove efficacy. This leads to a paradox in clinical practice. While existing treatments may help some patients, many patients are expected to continue in long-term treatment with medications that aren't providing relief while accumulating the risks and side effects associated with ongoing exposure.

When we narrow the focus specifically to TRD, which is defined as patients who have been failed by 2 prior treatments, the picture becomes even more constrained. While numerous MDD agents are used after failure of first or later line treatments, we have only two approved products explicitly for TRD with proven clinical efficacy. And in practice, only one is commonly prescribed, Spravato or intranasal esketamine. Spravato has proven to be commercially successful despite operational and economic challenges for healthcare providers and significant burden to patients and their caregivers. Its administration requires numerous 2- to 3-hour appointments.

Dosing is twice weekly for the first 4 weeks, meaning 8 treatments in the first month alone. This is followed by weekly dosing in weeks 5 through 8 and then ongoing weekly or biweekly maintenance, leading to 25 to 35 treatments per year or more. Patients cannot drive themselves home, so the burden of treatment frequently also falls to caregivers. And for patients and caregivers, they are unlikely to return to work that day, so a day is a day. The frequency of these logistical demands significantly limits adoption and adherence even in motivated patients and imposes substantial operational burden on clinics.

Another important constraint is that there are no dedicated current procedural terminology codes or CPT codes, which are the codes submitted by providers for reimbursement of medical services that adequately reimburse providers for the monitoring and clinical time required for Spravato treatment. Providers use general evaluation and management codes that do not fully capture all of the work performed and the practice expenses required.

Within a day, they must schedule 2 to 3 patients for a room to be fully reimbursed for the day. Turning the room over multiple times requires cleaning and paperwork for multiple patients, adding cost and operational complexity. And during the time in between patients, that room is not being paid for, creating gaps in reimbursement for the room. The economics are more favorable for patient occupying that room all day versus 2 to 3 patients for 2 to 3 hours each. COMPASS learned from some of the challenges of the Spravato launch and designed new CPT codes specific for psychedelics that capture the full cost of treatment, monitoring and practice expenses and can be reimbursed on an hourly basis. So for COMP360, the full 6 to 8 hours could be reimbursed, filling the gaps in reimbursement that practices currently have between patients for Spravato and minimizing the administrative burden of multiple patients in a day.

These CPT codes are already approved and are ready for providers to use once COMP360 is launched. This is an essential step towards enabling scalable clinical delivery and appropriate reimbursement for providers. There are now more than 6,800 interventional psychiatry centers delivering Spravato. But despite all of this, there is currently no treatment in TRD that offers both rapid and durable symptom reduction. This is a major unmet need, both for patients and for the healthcare system that supports them.

Against this backdrop, COMP360 presents an emerging differentiated profile that may address many of these limitations. Our Phase IIb data, together with top line results from the 005 Phase III study demonstrate two critical features: one, immediate robust response; and two, durability of that response after a single dose. In fact, in the 005 study, a single administration of COMP360 showed an effect size at week 6 that is comparable to the effect size of Spravato, which requires 10 treatments to get to 6 weeks. So what we've already seen to 6 weeks could be paradigm changing in practice.

Sustained efficacy following a single administration that may be deepened by a second initial administration as being tested in 006 represents a fundamentally different treatment paradigm for TRD. Safety is equally important. In Phase IIb, most adverse events were mild to moderate. They generally resolved the day after administration and treatment adherence was 100% since it was a single dose.

For those who have been distracted by multitasking, here are five key takeaways. First, Spravato, while approved, requires frequent dosing to maintain treatment effect and can be highly burdensome to both patients and their caregivers. Second, there is currently no existing drug treatment indicated for TRD that offers both rapid onset and durability. Third, COMP360's emerging profile across efficacy, durability, safety, adherence, and patient experience positions it as a potentially transformative treatment option in TRD. Fourth, the current interventional psychiatry treatment center infrastructure is already set up to support new multi-hour treatments like psychedelics. This includes an available and trained workforce, operational know-how and rapidly growing capacity.

And importantly, CPT codes specifically designed for monitoring psychedelic treatments means that provider economics will not be impacted regardless of treatment time required. As we look ahead, these clinical advantages form the basis for a compelling opportunity to set a new standard of care for patients who have not found relief with existing options. And what better way to begin to understand the treatment delivery landscape than to hear directly from three of our strategic collaboration partners that are currently delivering interventional psychiatry treatments, including Spravato.

We are pleased to have with us today Dr. Geoffrey Grammer, Chief Medical Officer of Greenbrook Neuronetics. With over 90 sites in the U.S., Greenbrook is one of the top providers of Spravato. Myriam Barthes, Co-Founder and CEO of Journey Clinical, which operates a decentralized network of thousands of therapists supported by a central medical team, delivering ketamine-assisted therapy and Spravato; and Dimitri Cavathas, CEO of HealthPort, a Maryland-based certified community behavioral health clinic or CCBHC, that provides comprehensive care to underserved populations.

Thank you all for being with us today. I have a number of questions for the group. So let's go with a fireside chat format.

To start, and this is a question for each of you. Can you please briefly share an overview of your organization and the approach you take to treating patients with TRD.

Let's start with Dr. Grammer, and then Myriam and then Dimitri.

Thank you, Steve, for that. I appreciate it. So Greenbrook Wellness Center, which is a subsidiary of Neuronetics, we've been in this treatment-resistant space since 2011. And we currently operate 95 centers. On any given day, we will do 800 TMS treatments and we will do 400 Spravato treatments. We remain committed to being able to leverage new modalities and technologies to helping patients who have not gotten adequate relief from either medications and/or psychotherapy. We are positioning ourselves now to continue to plug in new modalities such as COMP360 into our armamentarium to try to help patients. And our whole philosophy is overcoming barriers to care, including awareness, geographic proximity, and fiscal viability.

Thank you, Dr. Grammer. Myriam?

Today, Journey Clinical is the leading care delivery platform and marketplace for FDA-approved psychedelic informed care. Our platform gives licensed therapists, everything they need to deliver these treatments in their practice, including access to a medical team, education, insurance, and community. Through our unique collaborative care model, we partner with over 3,000 therapists to help patients who suffer from depression and anxiety with insurance covered ketamine-assisted psychotherapy, Spravato and medication management. So far, we have delivered about 500,000 hours of treatment, and given the rapid antidepressant effects of ketamine alongside therapy pre and post treatment, we have successfully treated thousands of patients with TRD.

Thank you. And Dimitri?

Thank you, Steve, for having me here. Honored to be here. HealthPort is a rural safety net health and housing provider, providing behavioral healthcare and primary care for the lower Eastern shore community in Maryland. And at any given time, we served about 2,000 people in 4 counties with significant health professional shortages as well as a disproportionate number of people on Medicaid and Medicare.

For 45 years, our organization is providing a full continuum of support services to individuals with psychiatric and addiction issues as well as disabilities and other disadvantages. We have a unique platform with social determinants of health interventions, which allows us to offer a variety of programs, tailor people's needs and in particular, the kinds of issues that need to be addressed with treatment-resistant depression.

Amazing. I think we can see that this group represents really the gamut of where people with TRD receive their care today, including those who are historically underserved. So maybe coming back over to Dr. Grammer, you're not only the Chief Medical Officer of Greenbrook, you're a practicing psychiatrist who cares for TRD patients everyday. So I'm curious, what you're seeing as far as awareness and interest in psychedelic treatments from your patients that are currently receiving Spravato and TMS?

Yes, absolutely. It's a great question. And I don't think I can overstate the enthusiasm, to be honest. What I have seen in the 30 years that I've been doing psychiatry is there have been a few pivotal moments of paradigm changes. One of those was when TMS was initially cleared by the FDA back in 2008. The next one was when Spravato received FDA clearance, and COMP360, in my opinion, is the next large paradigm change. But in some ways, it has more enthusiasm than those other two modalities for several reasons. I think one is more practical where for decades, we had antidepressant medications and therapy as the cornerstones of treatment, and patients became acclimated to that expectation.

So when we had new treatments that were fundamentally different, it took a while for people to kind of accept that. That barrier, I think, we've broken through. But the other thing fair or not is that there is a romanticized enthusiasm for COMP360. And what I will tell you is people struggle with their own sort of existential negotiation. They struggle with their meeting of life, so to speak. And the psychedelic therapies have this idea that not only do they provide symptom relief, but for some patients, they may provide awareness.

And so what I'm seeing is an outsized enthusiasm. I mean, I do 32 hours a week of clinic. And most of the patients I treat get better with modalities they have. But even in those patients currently receiving Spravato or TMS, they are asking me, when is psilocybin coming? When is psilocybin coming? And I think it's because they want some of those answers. They want that durability. They want that quick relief, and they want to feel that sense of peace. And I don't think it's a question of, if there's going to be a demand. Quite the opposite, I think it is how well we are going to meet that demand.

One of the statements I give is we will have a line out the door of enthusiasm. Every day, I'm hearing patients asking about this, begging for it, wanting to be first in line. And so for the listeners out there, in my 30 years of experience, this is very different than anything that has preceded it.

Well, those are some great points and really sounds like a call to action. So thank you for that. Maybe turning to Myriam. Having described the model of Journey Clinical, which is certainly a very different model perhaps than Greenbrook or HealthPort, how do you see COMP360 fitting into your organization?

At Journey Clinical, we are definitely ready, willing and able to deliver COMP360 within our decentralized care model. In fact, I would really almost add that in the last 4 years, our clinicians have already been delivering psychedelic-informed care with ketamine therapy and more recently also with Spravato. So if I give you an example, today, patients would go through a medical intake to determine treatment eligibility. And if they're eligible, they receive a prescription. Then they would follow traditional follow-up consultation with our medical team to monitor outcome. And what that means is we have already built end-to-end protocols, closed-loop safety mechanism, outcomes tracking as well as insurance coverage. So we would very simply adapt our protocol to the drug profile of COMP360.

In addition to that, we would go beyond the REMS and follow the preparation, dosing, integration clinical framework. And what would happen in this case is that similarly to the way we deliver Spravato, dosing session would happen in therapy practices with monitoring and support. And while there is no active therapy during dosing session to enable patients to self-direct the work, we would provide continuity of care with psychotherapy pre and post treatment through our network of licensed mental health professionals. In the real world, truly, this model has already enabled us to scale ketamine therapy and help patients with symptom reduction, followed by deep therapeutic healing and emotional changes.

All right. Well, it sounds like Journey Clinical and your network members are chomping at the bit, so we better hurry up. Dimitri, I haven't forgotten about you. As you know, at COMPASS, we're committed to broad and equitable patient access. Historically and sadly, innovation in healthcare has often widened existing access disparities. I know you're optimistic about adoption of COMP360 by HealthPort and the nation's 500-plus CCBHCs. Can you talk a little bit about the potential you see?

Yes, Steve. Thank you so much. This is really about equitable access to the COMP360 intervention. And the safety net providers of the certified community behavioral health clinics really have a platform and an ability to educate people that are usually disenfranchised, do not have great access to care. And that is -- our job is to educate them. And this is what we've learned with Spravato. We've had a really great ability to learn from the use of Spravato in a rural environment and in an environment where people don't normally have really good access to treatment.

And the biggest fear of a COMP360 intervention is that only people with good insurance and or high net worth individuals will be able to access this. And this is something we want to change. Our model of care as a certified Community Behavioral Health Clinic allows us to create a structure, a cost structure to provide this intervention across the country. Currently, there's over 500 CCBHCs in 46 states, D.C., Puerto Rico, and Guam, serving over 3 million people. So this is an ability for these CCBHCs have amazing expertise, amazing knowledge, and an ability to engage this community to get this very, very important intervention.

Amazing. You always get me fired up, Dimitri. That's exciting. So Dr. Grammer, you talked before about the need that you're seeing in the patient population you're treating today, the patients that you see every day, and some of the awareness and the enthusiasm. Can you talk a bit about how a large organization like Greenbrook that currently delivers a lot of Spravato and TMS, how do you see COMP360 fitting into Greenbrook?

Yes. So we are all hands on deck when it comes to getting ready for COMP360, right? So at Greenbrook, we have the full continuum of care all the way from marketing for making that awareness available to patients to call centers that will instantly answer the phone and then lead to conversions into appointments and treatment starts and then all the way on the back end where we have the relationship with payers, and we're able to file those claims and get reimbursement so that we utilize people's insurance so they can have access to that care without necessarily being financially overly burdensome.

In addition, at our 95 centers, we've got square footage specifically dedicated to Spravato. We don't do the end of the hallway kind of like plastic chair kind of thing. We actually have dedicated rooms with subdued lighting and comfortable accommodations, close bathroom, the whole nine yards. And what we've been doing is in preparation for this, we're modifying those centers. We're modifying our workflows. We're coming up with a different standard operating procedures so that if this is approved/when it's approved, we will be ready on day 1 to instantly turn on the spigot and allow patients to call up and say, I'm interested in this and get them through the process without trying to invent it on the fly.

What I will tell you is I had a conversation with our Chief Executive Officer just last week, and he made it absolutely clear that from a Neuronetics Greenbrook Wellness perspective, this is his priority for 2026 is to be ready to handle the volume of patients that have come are going to come to us asking for relief from their depression. And we're up to that challenge. We've been working on it now. We'll continue to work on to it until we get that FDA approval.

Great. Well, thank you for that early work. I know the patients that are waiting very much appreciate that. So I'm going to ask one more question to each of you and maybe just kind of a brief answer off the top of your head, starting with Myriam. What excites you most about the potential of COMP360?

I think similar to you and most people, it's really what it represents for patients and for the field at large. My husband and I build Journey Clinical after personally witnessing the therapeutic potential of psychedelic medicines and with it also feeling a responsibility to create a care model that would deliver them safely, ethically and at scale.

And so COMP360 does feel like a pivotal milestone for two reasons. On the -- one, the clinical signal is very compelling with meaningful responses for TRD, and it will help millions of patients where other interventions have plateaued. Two, it will also open the door to new FDA-approved and insurance covered treatments in mental health. Patients deserve real clinical options grounded in evidence to end mental health crisis. And COMP360 is showing that this is possible. So very, very excited.

Thank you. Same question for you, Dimitri. What excites you most about the potential of COMP360?

The ability for this dose to be provided to this massive amount of people. We have 24% of people with major depression that are constantly struggling to have an intervention that works. And this is the new revolution. And for me, what's really exciting is that the revolution around Certified Community Behavioral Health Clinics marrying with this new intervention can access care for so many people that need it. And one of the things, for example, at CCBHC focuses on our veterans. It's a core service of what we do. And as everyone knows, veterans are adopting the use of psychedelics as an intervention.

So just think about all of this impact that can occur from COMP360 going across the country with really great clinicians helping people integrate this intervention and really sort of expand the ability for people to live a life that they want. And what's also really great about this, I think, is that there's a bipartisan support for this intervention. There's Republicans and Democrats and the administration supporting this COMP360 intervention. And I think that this revolution is going to be just amazing.

Terrific. And Dr. Grammer will give you the last word.

I appreciate that. Again, I cannot overstate this. Never in the history of medicine has a modality been offered that provides such quick relief and such good durability for our patients struggling with treatment-resistant depression. That does not exist. The comparable model in the medical world, and for those who don't know, I used to do internal medicine before I did psychiatry and is the cardiac cath lab.

In the old days, we used to manage angina with tons of meds. It had lots of side effects. People had to stay on them, they remain symptomatic. Now you can go to the cardiac cath lab, revascularize the heart and they're good to go. And psychiatry is changing to that model. We still will have outpatient psychiatrists doing great work, doing therapy, doing medications, like that is part of the plan, just like we have outpatient cardiologists.

But we're going to have these interventional psychiatry centers like we have catheterization labs, where we're able to do that instant cath and then sustained relief from symptoms. We are seeing an evolution in the field of behavioral health. And I think COMP360 is what finally pushes this over to the line to broad acceptance within the community and within the medical establishment. This will be a paradigm changer in my opinion.

Well said, well, there's so much more we could talk about. But in the interest of time, I want to thank you all for this lively and informative discussion. And let me now pass the program to Lori Englebert to go through our commercial preparation for COMP360.

Thanks, Steve. Hi, everyone. Thank you for joining us, and a special thank you to Dr. Small and all of our collaboration partners for being here with us today. It is great to see your eagerness to bring innovation to patients and hear your thoughts on how you see COMP360 potentially fitting into your practice. We certainly share your enthusiasm for bringing new medicines to the millions of patients who are lacking meaningful treatment options.

We are thrilled to be able to discuss our commercial launch preparations with you today. Having launched more than a dozen products in my career, several of them being first-in-class, similar to Dr. Grammer's comments earlier, the momentum and interest that is building around this exciting new class of psychedelics is unmatched to anything I've ever experienced.

Robust clinical evidence in patient populations that have limited treatment options, combined with a transformative new approach to how patients are treated represents a potentially monumental shift for the field of psychiatry. With COMP360 anticipated being first to market and first-in-class, COMPASS is at the forefront of shaping the future of psychiatry patient care. You heard earlier in the webcast about the tremendous unmet need for patients who are living with treatment-resistant depression. Prevalence is high with over 4 million patients in the U.S. alone. And once an MDD patient is considered treatment-resistant being failed by two prior treatments, the burden of disease becomes dramatically higher.

Treatment-resistant patients on average, experienced 70% greater work time loss, almost 3x longer depressive episodes and a greater than 50% increased risk of mortality due to suicide compared to MDD patients who are not yet considered treatment-resistant. The unmet need is clear, and we are focused on bringing COMP360 to patients as soon as possible. Given our recent updates on potential time lines, we are now focused on being launch-ready by the end of the year. Preparing for any launch mandates a deep understanding of the landscape and opportunity across various stakeholders, but being first to market in a new class requires an even more comprehensive approach to launch preparation.

Over the past 2 years, COMPASS has been very active with pre-commercial work, all with a focus on achieving our goal of ensuring that TRD patients can access COMP360, if approved. Pre-commercial activities have been primarily focused on engaging with, learning from and educating key stakeholders such as clinical care teams across various settings of healthcare delivery through work with our strategic collaborations, KOLs and HCPs through our medical science liaison team, federal and state policymakers through our government affairs team and patient advocacy groups.

We are also actively preparing for payer engagement and have already had preliminary introductory discussions with various payers. However, we intend to initiate more robust payer discussions after additional Phase III data, and we can fully characterize the value that COMP360 will bring to patients, providers and the payer system. With the foundational work that we are already doing, I am confident in our ability to accelerate all preparations needed for a successful launch.

Today, we are going to highlight three areas that set up the potential of COMP360 in a commercial setting. First, how COMP360 will be differentiated; secondly, how COMP360 is expected to be used in clinical practice. And finally, how COMP360 will fit seamlessly into existing infrastructure. First, regarding how COMP360 will be differentiated. As you heard, there is currently only one marketed medicine, Spravato, approved by the FDA to treat patients with treatment-resistant depression. 6 years post launch, Spravato continues to see double-digit year-over-year increases in patients treated, overall prescriptions, revenue, and new certified treatment centers added, which is an important indicator of future demand.

At launch, COMP360 will potentially be differentiated by clinical outcomes and a less burdensome patient experience. As pointed out in other areas of the discussion, our 005 6-week efficacy data is comparable to what was shown in Spravato clinical trials, but durability of effect is vastly different. The rapid and durable results at 6 weeks achieved after only 1 initial administration of COMP360 versus what would require 10 administrations over the same time period for Spravato is highly differentiated and has the potential to revolutionize how clinicians approach patient care.

From a patient perspective, you heard Steve mention earlier that 1 day of a treatment center versus 10 over a 6-week period means less days off work, less travel time and less burden on themselves and on their caregivers. In Q1, we will see 006 Part A data at the primary endpoint of 6 weeks, which will be important in helping us understand the potential increased benefit of two initial doses versus one. In Q1, we will also see 26-week Part B data for 005. Although 005 was primarily designed as per FDA guidance to get a safety baseline compared to placebo, we will learn valuable information that could help inform clinical decision-making and start to shape the product profile of COMP360. For 005 Part B, we will see the MADRS curves out to 26 weeks for the important subgroups of remitters, responders, partial responders, and nonresponders.

As a reminder, in Part B of both trials, patients who are not in remission at 6 weeks are eligible for another dose of what they were randomized to in Part A or they have the option of going back on an antidepressant. Patients who are in remission at 6 weeks and subsequently relapsed will also be eligible for another dose or to go back on antidepressants at the time of relapse between week 6 and 26. Data over the time course of 26 weeks for these subgroups will help us begin to understand potential frequency of dosing, which will be important to help inform how clinicians treat their patients and also for preliminary payer discussions.

We anticipate that prescribing and administration of COMP360 will fit seamlessly within current clinical practice. Based on the expected REMS, we anticipate prescribing of COMP360 will be by a healthcare professional licensed to prescribe medication. And on the day of dosing, we anticipate that monitoring of the patient during the treatment session will be by a licensed healthcare professional. In our clinical trials, monitoring and support was provided by a licensed therapist. But in real-world execution, based on FDA guidance, we anticipate that a patient will self-administer the capsule at the site of care and be monitored for safety over a required time period by a broader trained and licensed healthcare professional workforce.

At launch, there are expected to be thousands of available mental healthcare workers trained on how to monitor patients and support a multi-hour psychedelic experience. This workforce includes the hundreds of therapists already trained to support clinical trials as well as the many other HCPs who we expect will be trained through a standardized training program in anticipation of a COMP360 launch. For reimbursement, we expect to make COMP360 available through both specialty pharmacy shipped directly to the site of care and through buy-and-bill. Drug product reimbursement will be billed through the patient's pharmacy benefit.

As Steve mentioned earlier, we also anticipate that sites will be able to optimally bill by the hour for the clinical care team's time through a patient's medical benefit plan by using the newly formed CPT codes that were specifically created for psychedelics. At launch, we are prepared to leverage the well-established existing interventional psychiatry infrastructure. These treatment sites are designed and equipped to support products that require multi-hour monitoring, such as Spravato. With over 6,800 sites across the U.S. and growing rapidly, these centers are already equipped with the infrastructure needed and have highly trained staff with the operational know-how needed to support additional multi-hour treatments like COMP360.

Importantly, as you heard earlier, many of these sites are already scaling in anticipation of a COMP360 launch. If COMP360 is approved, it will undoubtedly bring a welcomed and meaningful new treatment option to TRD patients and their providers as effective new treatment options are desperately needed. Our launch planning efforts remain focused on ensuring sites are prepared to administer COMP360 and that TRD patients can access COMP360 upon approval.

COMP360 has the potential to fundamentally change the way that patients living with depression are cared for, and COMPASS is committing to help as many patients as possible. We understand the market. We understand the potential, and we understand what we need to do to be successful. The launch of COMP360 is poised to be one of the most highly anticipated launches in recent history, and I am looking forward to discussing our launch preparations and our commercial readiness with you over the coming year.

I will now turn it back over to Kabir to close this out.

Thanks so much, Lori. And as you heard, we really are getting on with our commercial preparation to be ready to meet the enthusiasm, the excitement and that day 1 demand you heard about from our collaborators earlier. So with numerous important value drivers in place, 2026 is positioned to be a landmark year for TRD patients and for COMPASS. In the back part of this quarter, we expect to report pivotal efficacy and safety data from Part A of the 006 trial with its two fixed doses, alongside more details from Part A of the 005 trial.

From that, as you know, we already reported that we met the 6-week primary endpoint last June. And it's going to be important to see the impact of two doses in the 006 trial at the same time as seeing those details from the single-dose trial. Given that we've already met the primary endpoint of 005, seeing a statistically significant result from the 6-week primary endpoint of 006 will more fully derisk regulatory and confirm the compelling clinical and commercial profile of COMP360.

For the 005 data from week 6 to 26 weeks, while the primary purpose is to more fully characterize safety, as Lori already described in detail, we're hoping to see on average how long patient responses from Part A last and what the curve looks like with an additional dose in Part B. This will help to inform early payer discussions as well as potential clinical practice. The remaining 26-week data from Part B of 006 is expected in early Q3 of this year, and that will help to inform dosing for labeling and is anticipated to be the last gating item to complete our NDA submission.

The entire COMPASS team is focused on disciplined execution, completing our Phase III trials, preparing for our NDA submission and continuing our commercial preparations. We continue to add resources to ensure that we're moving our NDA filing activities ahead as quickly as possible. And with significant commercial learnings already incorporated, we're confident that we'll be ready to launch on an accelerated time line.

We're encouraged by the continued increase in interventional psychiatry clinic infrastructure over the past few years, driven both by Spravato, but also, as you heard, by the growing excitement around the potential promise for psychedelic treatments such as COMP360 in the future. The learnings we're gaining through our strategic collaborations strengthen our confidence that COMP360, if approved, could be effectively integrated into that growing interventional psychiatry infrastructure and offer a differentiated and compelling treatment option for patients and providers.

And just yesterday, we announced our seventh strategic collaboration with Radial Health, a growing clinic network that is set up to optimize leveraging technology and operations expertise to optimize models of care for patients. As leaders in the field of psychedelics, we're confident in the emerging profile of COMP360 and its potential to transform the landscape for those living with TRD for a potentially rapid and durable treatment option. We also look forward to ramping up our late-stage PTSD program, another indication where we see significant potential and significant potential to impact for patients.

Once again, our thanks to Dr. Small, to Dr. Grammer, to Myriam Barthes, to Dimitri Cavathas for joining us on today's call. They will all be with us for Q&A as well the full executive team. So with that, I'll now turn the call over to the operator for Q&A.

[Operator Instructions] So our first question comes from Ritu Baral at Cowen.

To relatively concise questions. One for COMPASS as well as the center leaders. I wanted to ask about your expectations for monitoring requirements upon launch readiness and how the CPT codes may play into that? And then my follow-up question was actually also on the PTSD study that was outlined and the mention of the PCL-5, I believe, which was a key secondary endpoint. Will there be any efficacy requirements for the PCL-5? And how does it differ from the CAPS-5 that's been used in the field before?

Thanks, Ritu. So on the first one, I'll ask Steve Levine to take that. And the second, I'll ask Mike to take. So Steve?

Thanks, Kabir. Yes, the new CPT III codes, which are specific for the administration day of the psychedelic treatment are reportable on an hourly basis. Right now, in our clinical trials, the administration day has been 6 to 8 hours long. We do not yet know whether there may be a specific time requirement stated within a REMS. But it likely, whether within the REMS or not would be at least a 6-hour day. But regardless of that day, because the code is reported hour by hour, all of those hours could be accounted for. Additionally, an evaluation and management code for medical monitoring and supervision could be reported on the same day as the new CPT codes.

Thanks, Steve. Mike?

Yes. So I love the question about the PCL-5. So look, PCL-5 and CAPS-5, and again, I'm going to ask Guy and Steve to chime in if I miss something here or what our expert clinicians on the panel. They're actually complementary tools, right? The CAPS-5 is a clinician-administered fairly in-depth interview about a range of symptoms on PTSD. The PCL-5 is a self-report. And generally speaking, it's probably faster, it's shorter. And so it has a very different feel to it.

Those two of them play complementary roles in the sense that from a clinical perspective as well as a regulatory perspective, you want to have independent verification that the treatment is clinically meaningful. Can the clinician observe and elicit information that the patient -- the symptoms are better. But importantly, if not even more importantly, does the patient himself -- him or herself report to you that they're feeling better. So they are complementary tools.

The PCL-5 and the CAPS-5 have both been used in a multitude of PTSD studies. They are well-validated tools. They're part of the DSM criteria for diagnosis of PTSD, but they provide complementary information. The PCL in the study is a key secondary. So we need to hit on the CAPS-5 first and then move to the PCL for control of type 1 error, but we have not powered the study on a specific effect on the PCL. And so if I've missed something to my clinical colleagues, please, please help me here if there's something that I should have added.

Our next question comes from Paul Matteis at Stifel.

I wanted to dig in a little bit more on the upcoming 26-week data. Can you guys just like walk through what you're going to present, what you think a positive outcome is? Do you need a p-value? And then I'd love to hear from the clinicians like how are you interpreting long-term data from an intermittent antidepressant therapy. Understanding that as you follow patients for longer, there's compounds starting SSRIs, dropouts, things like that. Like what do you want to see to be comfortable with like a once quarterly algorithm or something even less free?

Thanks, Paul. So I'll start by just addressing what we are going to see, and then I'll hand it to Guy to talk a little bit more about interpretation. So again, clearly, from a regulatory perspective, let's focus on that to begin with, the 6-week primary endpoint is what counts. So we are not looking for a significance of difference between MADRS and placebo arms at any data point beyond the 6 weeks. What we will be showing though is when you see the responses from the patients in Part A segmented at 6 weeks, we will see what then happens to those patients in those cohorts over week 6 to 26. So those who were in remission, those who were responders, and those who are not recognizing that some of those will be getting a second dose in Part B because that was a matter of choice.

And that's why we say that will be highly informative around the clinical profile and what actually happens to patients after a single dose and potentially a second dose. But the purpose, again, is not to compare because the placebo arm is going to be somewhat confounded at that point. And again, from a regulatory perspective and what we need to provide from an endpoint perspective, the primary endpoint is what counts.

With that, let me pass to Guy to talk -- to address the second part of your question a little around interpretation.

Yes. Thanks, Kabir. Thanks, Paul. I think it's worth bearing in mind that at the moment, we know very little about our primary endpoint in 005. We just know the difference between the two arms. So we'll be very useful to have an effect to know the change from baseline in that trial alongside the trial 006, which represents the effect of two treatments. So I think that will be -- although it's always a little -- it's a little uncertain to compare two different trials. Nevertheless, recruitment criteria are pretty identical, and we should be able to compare, at least broadly speaking, the effects of 1 versus 2 doses at 6 to 9 weeks. So that in itself is going to be an important part of the interpretation. We don't yet know what we're going to see, but that's going to be extremely interesting.

I think in terms of the 26-week follow-up, we really don't know what we're going to see. We don't have any really -- real cues around that. We know that patients are getting -- a certain number of these patients are getting retreated. We don't know which group is mainly getting retreated. It could be the placebo group potentially. It could actually be the active group because the active group may be more willing to come for a second treatment because they've been unblinded. We don't want -- we don't argue that 005 is a fully blinded study.

We will also, of course, be getting safety, which we think is a very key part of what we get from 005. So in terms of what we want to see there, it would be great to have the safety signal that has been told. We're told we have pretty good record so far from the DSMB. We want to see that confirmed at 26 weeks. And then we want to see exactly what happens when patients get retreated. And we want to see that as an overall effect because, obviously, this is one of the ways patients probably will get treated in real life. They'll get one treatment and then there will be a second one if they need it.

And then in addition, we will have a look at whether there's a clear difference between the two arms. As Kabir has indicated, comparison of the two arms in 005 is not a straightforward thing to do because of the fact that over the course of follow-up, the patients who were in the placebo arm may get a whole range of other treatments. And so our intention to treat model, which when you take all comers will increasingly get confounded by additional treatments. There may be a limited per protocol set that we can look at.

So all of this is a little technical, but I think what would be -- what good would look like would be to see sustained effects in the groups that Kabir has described and also evidence that a second treatment has a benefit for patients in 005, and to be able to compare that with patients who get a planned double treatment in 006.

Our next question comes from Gavin Clark-Gartner at Evercore.

Thanks for putting on this really informative event. So I wanted to touch on the delivery landscape. And this is a question for the experts, and Dr. Grammer touched a little on this, but I wanted to expand a bit. So Steve Levine had mentioned how COMP360 would be similar or actually maybe slightly more favorable for practice economics and operations compared to Spravato. I'm curious if you've run some of those margin and operational analysis on your own and what you found. And I just had a follow-up.

Thanks, Gavin. So Dr. Grammer, if I may, I will pass that to you.

Well, I think until we get some final figures from payers on what the reimbursement is going to be, there will still be some uncertainty within the modeling of that. But I would say it's not a zero-sum game, right? So there's sort of two benefits. One is you have patient choice, and I'm a big fan of patient choice where people come in and the bigger armamentarium of things you can offer, the better it is for patient care. But the reality is we also just want to bring people into this ecosystem of interventional psychiatry.

The reality is only about 15% of people who could benefit from TMS have ever even been offered it, and it's even less with Spravato, I think it's like less than 5%. So we have to actually change the way that patients even think about care. And what we may find are there are some patients where they have a foundation of care that starts with like COMP360 that we layer on top of that between treatments, additional things like TMS and Spravato. So this is not one has to cannibalize the other. I actually think it's a win-win for patients as we leverage these multiple tools to get them into what we hope to be an eventual remission.

From -- Steve kind of alluded to this before, though, I think the payer structure is at least going to have to be comparable to Spravato for a room or square footage per hour basis, and it sounds like the general dialogue is headed in that direction.

All right. Great. And on that topic, more broadly, do you envision the psychedelic class supporting the growth of psych clinics? Like you mentioned the cath lab example. What about like community oncology as another example?

Yes. No, absolutely. I mean this is where psychiatry has been going. And I think we're going to continue to partner with the outpatient general providers, psychiatrists, nurse practitioners, therapists and so forth. But we're seeing in psychiatry, this subspecialty form of interventional modalities. And they do require specific training and logistical infrastructure that for the solo practice is nearly impossible to do. But again, not mutually exclusive, it actually works in concert and partnership.

I think we're going to see more and more of this idea of interventional psychiatry. I think that's actually the direction the field is going in general, like we've seen with ambulatory endoscopy clinics, ambulatory surgery. I mean, this is just the way medicine is where we're trying to make these things feasible and viable for patients who need them without the burden that would normally come with, say, hospitalization or what have you.

I'd like to just add that the Certified Community Behavioral Health Clinics have a very unique prospective payment structure that's going to allow the ability for our clinics to create a cost structure to do these interventions every day. And there's such a belief in this across the country that the Ballmer Foundation has actually invested $72 million to expand Certified Community Behavioral Health Clinics in Illinois, Michigan, and Kansas. So I'd highly encourage people to look into this new movement in the clinics because the structure is going to be a really wonderful way to facilitate this amazing intervention.

Our next question comes from Leo Timashev at RBC Capital.

I just want to follow up a little bit on Gavin's questions actually. I guess setting aside sort of the general expansion, I guess I'm curious how in each of your clinics and existing centers, you think about scaling. I guess, are you looking initially to just fill out any slack you may have in your current occupancy rates? When you think about the initial scale, is that converting a single room? Or will you be adding rooms, adding facilities? And I guess, how much of the scaling is dependent just on COMP360 success or on success of the class as a whole of the psychedelic class?

Thanks, Leo. So maybe I can ask Dimitri to go first on this one, followed by Dr. Grammer. And I don't know if Dr. Small, you want to comment on that from a Hackensack perspective. But Dimitri, perhaps we can start with you.

We've already have space for Spravato with two rooms right now. We have space already dedicated for the future of COMP360. And we also have a new building that's getting built. And again, for the CCBHCs in particular, there's an ability to sort of create a payment structure to allow for new buildings to be built. So the ability for these clinics, in particular, have a real unique gift to be able to say, we believe that we're going to have these many sessions per week. This is the space we need to do it in, and this is the cost structure. And then that is a conversation with each state to pay for that.

And again, what's really wonderful is that there's bipartisan support for CCBHCs, there's bipartisan support for the use of COMP360 and psychedelics, both sides plus the administration. So I'm very confident. I feel very optimistic that this will be able to be a very major intervention in this system of care.

Dr. Grammer?

Yes. So the question is where do we surge this and do we have existing capacity. So currently, at Greenbrook Wellness Centers, we have 170 providers. We have 95 clinics. Most of those clinics have 4 or more chairs and the average is going to be 6. Where I work in Rockville, we currently have 9, and we're expanding to 12, and we run those concurrently, okay? What we do first is we will fill the chairs per hour. When that reaches capacity, we expand the number of hours those chairs operate. And when that reaches capacity, we build out additional brick-and-mortar infrastructure to deploy more chairs.

What I will say is one of the benefits of commercialization of this is if the demand exceeds our current capacity, we build additional capacity. But do we have the ability now to fold in something like COMP360 into our Spravato footprint? Yes, we do. And if we exceed that capacity, we'll build out more capacity if we need to.

Okay. Dr. Small, perhaps?

So Hackensack Meridian Health is the largest, most integrated health system in New Jersey. We're across the state from -- we have three regions, Southern, middle region and the Northern region. We're going to start in our Spravato clinics, our eventual clinics and look at that experience and then expand out depending on the demand. So we're very excited about this. This is the health system. I mean, I'm in the California, I was so excited to come here because of the capacity to really help people across the entire state.

Amazing. You traded the weather for this opportunity. And maybe, Myriam, if I could ask, I mean, clearly, scale is somewhat different in your case, but perhaps I could just ask you to comment on that and how you're thinking about scale as well.

Yes. I think, the model at Journey Clinical is built for scale. That means that we're not limited actually by a small number of clinics, we have 3,000 therapists with 3,000 practices. That means if you're a patient, you can literally go to your local therapist office and have this treatment accessible, and we already cover -- we already have insurance. So that means scale will -- is already happening and is going to be easy.

Wonderful. Thank you Leo for the question.

Our next question comes from Judah Frommer at Morgan Stanley.

A lot of great information today. I just wanted to follow up on a comment that Dr. Grammer made about demand for COMP360. Maybe could the panel further characterize where the demand is coming from? Are these patients that have potentially tried Spravato and/or TMS or another treatment and failed? Are these patients that would be newer to TRD treatment? Just curious how you're thinking about potentially sequencing COMP360 if it's approved and how that might affect whether patients are lost to follow-up if there are failures from other treatments?

Okay. Maybe Dr. Grammer, I'll ask you to lead and then go to Dr. Small and we -- everyone can jump in.

The good news is for people who we've seen before that failed to get adequate relief from the modalities we have, we have -- we actually do periodic touch-ins with those folks. We also at Neuronetics, have a patient liaison team that goes out to referring network providers to educate them on the services we offer to facilitate referrals and so forth. And so any launch would be associated with that initiative. We have an entire marketing department to increase that awareness where we do both DTC and referral-based marketing efforts to try to increase that awareness. All those things will be turned on if there's a COMP360 approval.

As far as who's interested, it's actually fascinating because there are some people that have relief but not remission from symptoms that want more. And we certainly have those, right? We have those that didn't get better. And that makes a lot of common sense. If you didn't get all the relief you want, you're like what else is out there. But I'll tell you, and this is the thing that has me so enthusiastic about this. I have patients that are in full remission on Spravato that are asking me about psilocybin. I have patients that had a full remission with TMS that are asking about psilocybin.

When I said there's this romantic enthusiasm for this particular compound, people are drawn to it even if from a clinical perspective on validated rating scales, they're getting adequate relief from those existing modalities. And there are different reasons for that. So I think you're going to see an interest that is incredibly broad-based, not only from those who haven't gotten better, but those that are but just want something different.

Next, Dr. Small?

So we use a similar strategy at Hackensack Meridian Health, direct-to-consumer marketing. We have a very active group of primary care physicians, and we also have collaborative care where we embed mental health practitioners in the primary care settings. In addition, we have a very active clinical pathways group where we get input from experienced clinicians across the state. And so we try to have a systematic approach to treatment-resistant depression. If somebody fails one treatment, where we go next. So I think I'm very confident that we'll start low and go slow, but we'll build this out and scale it up, so it will have a real impact.

Thank you very much. And I know we've still got a few more questions. So thank you all for your patience as we stay on here through the end of this webinar. So thanks, Judah. If we could turn to the next question, please.

Our next question comes from Jay Olson at Oppenheimer.

Maybe just to focus on PTSD. Can you talk about some of the more recalcitrant symptoms of PTSD and how COMP360 may address those? And then if you could also talk about the in-clinic experience for PTSD patients on COMP360 with regards to psychotherapy, especially considering the emotional challenges of addressing acute underlying trauma.

Thanks for the question, Guy. Let me turn that to you, please.

Yes. Thanks very much for the question. It's a very good one. Our experience is based not just on rating scales. We showed the effect on the CAPS-5 and we also saw a faster effect on the PCL-5. But we did in-depth interviewing with the patients after the trial was finished. And we got some very interesting insights into how the drug appears to work. And one of the things that holds back psychotherapy in this area is exposure to the treatment to the original trauma is often part of the therapy. And it's treated as essentially an exposure experience, which allows patients to desensitize and lose the associated emotionality.

What was extremely interesting to us was that although patients came into the study expecting that, that would be kind of what happened for them under the influence of psilocybin, in about half of the patients, it didn't. And yet when they came out of the experience, they found the way they were processing the memory in a different way from the way they had done it when they went in. Other patients did have recall of the experience, but it was often less alarming than they had expected. And the key message to us was that we were preparing them for uncertainty.

We were selling them, we don't know what's going to happen, but whatever does happen, you accept it and go with it. And that retrospectively was very good, a very good way to manage the experience. So essentially, what we're saying is that preparation is key. These patients often come in high anxiety. They need reassurance that things are not going to necessarily result in a very frightening revisiting of the experience that may have brought them there, but they will be able to process what happens in a way that leaves them feeling differently about the experience. And I suppose the key thing is that we see a change, particularly in the core symptoms of PTSD.

I mean, one of the issue is that PTSD and depression have quite a major overlap. So it's extremely important in this early stage of development of the treatment that we see an effect on the core symptoms of PTSD, the most characteristic, which are the flashbacks. And of course, we would expect to see some effect of depression anyway. But the symptoms that are most troubling, the symptoms that seem to lead to social withdrawal and this sense of emptiness and really withdrawing from life, those are the fear of the return of the symptoms, the apathy. That seems to be something that patients they can reevaluate. They can -- they get into a different frame about it.

And it's very striking for people who have seen and interviewed the patients, how there's simply a different look in their eye when they come out of these experiences. So that is the promise. We have to confirm it at scale, and we will obviously be very excited in how this eventually gets implemented in the kind of services you've described. But of course, these patients will fit perfectly into services that are developed for TRD, and there will be a good deal of overlap, actually, a lot of comorbidity in the patient groups who will seek treatment in this way.

Thank you, Guy. And Jay, just to clarify one thing I wasn't sure on your question. We are not offering psychotherapy. So our COMP360 protocol includes monitoring, but it does not include psychotherapy. And perhaps I can refer back to Myriam because I think she made that articulation very clearly around there is a therapeutic container for the patients, but the actual psilocybin session itself does not. So maybe, Myriam, I can pass back to you on that.

Absolutely. And this is what we have been doing at Journey Clinical for now over 4 years. The dosing session itself does not include therapy. The patient is self-directing the experience and what can be added to the real world when COMP360 will be approved is psychotherapy before and after the dosing sessions. And that is the difference that we at Journey Clinical have designed within our care delivery model.

Our next question comes from Patrick Trucchio at H.C. Wainwright.

My first question is on the TRD program. With the understanding that COMP005 Part B is designed to inform safety and dosing rather than placebo-adjusted durability. I'm wondering what from a payer discussion perspective, would you want to see in these outputs from the remitter responder curves? What would matter most? And what should we be looking for? And then on the PTSD program, you've designed a trial to potentially support approval with a single study. What could determine whether or not this program can move forward with a single trial or if you may need an additional pivotal study?

Thanks, Patrick. Well, I'll briefly answer the second one. It will depend on the results of the study. So I think that will be the key determinant in terms of that. We'll have to see what we see and whether that's sufficient to support the dialogue with the FDA. And on the first part, let me ask Lori to address that.

Thanks, Patrick. I'll have a fairly brief response as well. 6 weeks is already -- will be meaningfully different for payers already. I think, again, back to what we -- the point we made in the presentation around Spravato is requiring 10 administrations to get to the same equivalent efficacy that we saw with one dose at 6 weeks. When we look at the 006 -- I mean, the 005, 26-week data, what we will see is the remitters, the responders, the nonresponders, partial responders and nonresponders and what those curves look like out to 26 weeks. I want to make sure everyone understands the payers, anything we see beyond 6 weeks is just going to be additional benefit for payers, for clinicians, for patients. But we really need to characterize based on each of those subgroups, what clinicians will need to look at.

Right. That's helpful. If I could also ask a few on the commercial side, more specifically on the commercial side.

Patrick, absolutely. If I may, just very -- apologies, very briefly interrupt. I know Dr. Small has to drop off. I just wanted to thank him, thank him for staying on. Thank you very much, Dr. Small. Apologies, Patrick, I will come back to you.

Thank you.

Thank you.

Sorry, Patrick, back to you.

No problem. So just on -- I think you mentioned that you'd expect a balance between specialty pharmacy and buy-and-bill distribution to evolve over time. I'm wondering if you could talk about the differences between these two? And is there potential advantages of one versus another and how we should think about this relative to Spravato? And then for the KOLs, I was wondering if you could talk about what are the remaining barriers, whether it's operational reimbursement or staffing to scaling COMP360, even with the CPT codes in place? And what, from your perspective, could the company do to help you to accelerate uptake of COMP360 in the first year of launch?

Lori first.

Yes. So from a specialty pharmacy and a buy-and-bill, you think about the benefits, the benefit is really for the provider -- the center and the provider on the buy-and-bill standpoint, if they buy and bill it, they can get some additional benefit in terms of potential profit margin. But likely, centers will not exercise the buy-and-bill option or want the buy-and-bill option if they don't have generated enough demand to get there. And so we do believe that it will be somewhat of a slower ramp to buy-and-bill.

What we know from Spravato now is about 35% to 40% of Spravato is buy-and-bill. And if you think about how Spravato is prescribed right now, highly, highly concentrated to a very small group of prescribers, but very high volume, that's likely where you're seeing a lot of that buy-and-bill opportunity go. The benefits to the patient are -- there is no benefit to the patient on either one. It's very seamless.

And Patrick, for the second part of your question, maybe I can go to Dimitri first in terms of what else you would need to see to build scale and capacity.

Yes. I mean for our journey and mission, we are focused on the Medicaid and Medicare population. And unfortunately, especially with PTSD, people who have the most significant PTSD tend to become disabled if we get them. So we have a slew of people that really need this kind of intervention. And so the ability to integrate this is not going to be a really difficult journey for us. We also have a really wonderful partnership with a specialty pharmacy, multistate specialty pharmacy that already is a large dealer of Spravato and will be able to help us facilitate the use of COMP360 in these clinics such as ours in CCBHC.

So I think that the ability of the market for Medicaid and Medicare in particular, is really strong because people tend to become disabled from most significant PTSD. So it's something that there's a lot of focus on commercial insurance, which we take also and all CCBHCs do as well. There's also a lot of focus on obviously buying directly. But the Medicaid and Medicare market, in particular, I think, is going to be quite significant.

Thank you. Dr. Grammer?

Yes. So I think it's interesting. The biggest barrier I see is changing the expectations of patients. So if you look at this TRD population, about half of those patients aren't even currently in care. For the half that are, 80% are being cared for in primary care, not by behavioral health providers. And what we have seen with TMS and Spravato is this sort of uncertainty of how to access the system. So as with any launch, I think it's going to be absolutely pivotal to make sure that not only are we doing typical ways of increasing awareness through marketing and so forth, but really, there needs to be earned media organic buzz to get the word out there to patients who have sort of dropped off the treadmill of care to let them know that there is something fundamentally different and bring them back into the system.

And then the bigger thing is or an equally important thing is making sure that aperture for entry into care is as wide as possible. You can't ask someone who's currently depressed to go through all these hoops to try to get authorization to receive the modality. So we need to build in, and we currently have that at Greenbrook Wellness Centers, but build in that infrastructure. So all they need to do is make a phone call, send a chat, fill out a form, do an e-mail, whatever, send up smoke signals and then we take it from there. So the next step for them is showing up for that treatment.

Our next question comes from Tom Shrader at BTIG.

A wonderful event. It's really been fun to listen to. Really related to Jay's question, patients in PTSD, given the potential issues, are your inclusion criteria likely to be very tight? Are there types of patients you're scared of? And I think the question is relevant to the treatment centers also. When you get a PTSD patient, is it the same as a TRD patient? Or are they kind of inherently more worrisome? And then I have a commercial question.

Yes. So maybe on the IE criteria, Mike, do you just want to address that briefly, please?

Yes. So I love the question. So I don't think there's any PTSD patient that we're afraid of. I think that we have criteria designed to make sure that we're recruiting a more real-world population than some other trials. So for example, in these studies, we're allowing some degree of alcohol and substance abuse because that's a serious concomitant comorbidity with PTSD.

Clearly, folks who've had childhood trauma or have had PTSD for an inordinate long period of time who are historically not responsive to any treatments, those patients were sort of excluded from the trial. So the criteria are generally aligned with what other studies have done. We try to liberalize it a little bit to make it a little bit more real world. So other than that, as I said, we ran the study by the FDA, and they have actually no comments or issues with the criteria that we have proposed to them.

Thank you, Mike. And Tom, I'll turn the other part of your question to Dr. Grammer and others. But just a reminder to contextualize is, there are only two very old approved medicines for PTSD. So right now, the kind of interventional psychiatry is not really set up to deal with PTSD. But I don't know, Dr. Grammer, Dimitri, Myriam, anyone who wants to take that, please?

Yes. I would just like to say that health systems have a running list of super utilizers of healthcare, people that are utilizing the ER and other health resources. And there is a significant percentage of those super cost utilizers that have PTSD. So I don't think there's any concern around the gradient of PTSD symptomology. And I think if anything, there's going to be a significant focus on people that have the most issues to get this intervention so that we can help not only the person have a much better life, but also to help drive down healthcare costs.

So CCBHCs have really great data around these kind of supports to lower healthcare costs. And we see a COMP360 intervention as a key element in helping people that are using ERs for intervention. And the other thing real quick is that we have integrated primary care and primary care is a great vehicle also to engage people and need care. Primary care still prescribes more psychiatric medications across the country than outpatient mental health clinics. So the strategy of primary care and behavioral healthcare facility is really a key to getting access for people in their care.

And real quick on the treatment landscape. The Spravato numbers, if there are 6,800 centers given the sales, that says the average center is doing about 2 a month. And we had somebody today say they're doing either 400 a day or 400 a week. What's the major sticking point to all these centers that can do it, have done it, but don't do it very much?

I don't know, Steve, perhaps you want to take that one?

Yes, happy to. I think, yes, 6,800 writing at least one prescription for Spravato, but as you said, highly concentrated. Dr. Grammer gave the example that you pointed out of one that's much higher volume than most others. Across the other types of sites, I think there's probably a diversity of reasons because there's diversity in the types of sites of care. Much of that concentration is probably in what we would refer to as interventional psychiatry sites that are specifically focused on delivering treatments like Spravato as well as typically TMS, whereas other sites may be delivering a range of services, including medication management or therapy, other psychiatric services without a specific focus on Spravato.

So in those cases, it's not necessarily a difficulty of delivering or implementing Spravato, so much as just not as much of an emphasis on exclusively delivering that as a treatment. Whereas some of the others may represent some of the smaller practices that Dr. Grammer mentioned earlier that at least at this point, do have greater difficulty with delivering a more complex interventional treatment than one with that specific expertise.

So our next question comes from Imogen Mansfield at Cantor Fitzgerald.

Thanks very much for the great session. Many of our experts on the call have talked about kind of patient-centered motivation to find access to COMP360. It will be interesting to hear what you think the barriers are for referral patterns from primary care and from traditional psychiatry and what is preventing those providers from recommending Spravato and TMS right now, given that the rates are so low? And how will that change with COMP360? Is it just awareness? Or does the time factor component also provide a meaningful benefit for those providers to refer these intervention options?

Maybe Dr. Grammer, I'll ask you to start and then go to Myriam and Dimitri on that.

It's a great question. And I think there's slight differences between traditional mental health referrals and primary care. Let's start with primary care. Again, we talked about changing the paradigm of care within behavioral health in one of the medical specialties that's been a little bit more frozen in time than others, right? And so it's taking a while for people to understand that the field has changed.

So primary care, I think one of the challenges is they're uncomfortable jumping from their level to what they see as a subspecialty within psychiatry, going -- bypassing general psychiatry. And we're working hard on trying to crack that code through a variety of different mechanisms. But that's a lot of educational awareness to that group of providers to let them know, it's okay. And that we'll send them back better and they can continue to manage as they were, but we serve as a resource for them. I think for primary behavioral health is a little bit more nuanced and complex.

Some of it is awareness, but I think some of it, unfortunately, is more primitive. When you're in the thick of it with someone trying to get them better, it's easy to kind of get lost within that battle against the depression. And to finally reach a point where you're saying, "Hey, listen, what I'm doing isn't getting you the relief that you deserve, I need to refer you out." Psychiatry is not used to that sort of method of care. Where I brought up the cardiology model before, most cardiologists, like "oh, yes I'll send you the cath lab. I got a body there we'll do that." I think in psychiatry, people are still getting used to that idea without it feeling like they have somehow let that patient down with their very well-intended efforts.

The way to overcome that is to explain to those referring providers, we're not a replacement for them. We're not a competition to them. We are an extension of their practice just like that cardiac cath lab. And so we have to have a relationship with them, which is why we have that entire dedicated staff to go out to these referring providers and establish these relationships. I think we need more of that. And I do think COMP360 is going to continue to push that boundary further down the field to where it needs to be where that's much more fluid than it currently exists.

Thank you. Myriam?

This is such a good question, and we've asked ourselves this question so many times over the years in building Journey Clinical. And the reason why we built it is because we wanted to understand what were the barriers for providers to offer ketamine-assisted psychotherapy to their existing clients. And what we have learned is those people tend to be afraid. They want access to training. They really want access to peers and community and other people who are also offering this treatment. They need help with insurance and navigating those landscapes.

And so when we came up with this concept of giving licensed mental health professional everything they need to offer these treatments into their practice, that basically opened the floodgates. And it's simply supporting and empowering them through this journey of adoption. And then what we have learned with COMP360, we've actually ran a survey about asking our 3,000 therapists if they would be interested in delivering this treatment within the Journey Clinical model in their own practice and 90% replied that they would. So we have already signaled and evidence that those people who have been offering this type of treatment are ready to start the second this is approved.

Wonderful. Thank you. Dimitri?

Yes. I echo the sentiments I've just heard, they were wonderful. And just to add, CCBHC's core service is same-day access. So people can walk in, we can engage people immediately and then get them set up pretty quickly. We have about a 3- to 4-day wait from access day to medication. So we're really aggressive about engaging people because we know from a change perspective, when people want to change, you have to get it when they're ready. And the more time you give away from that change moment, the less opportunity for that person to engage in what they need.

People don't want to spend all those hours to do Spravato. So that is a real thing. And this 1-day kind of intervention is much more palatable to people than this whole other process you have to do Spravato. So I would just say that on the patient side, the time savings is a big deal. And on the provider side, having this ability to sort of engage people quickly is a real key aspect. And referrals are always a very complicated thing, and there's nothing else I can add to what Myriam and Geoffrey said, they really hit it.

Lori, can you just very briefly address what we're doing already to build our infrastructure and capability to support referrals?

Yes, absolutely. And it is a key component and something we've been thinking about quite a bit. So you heard me mention in the remarks that our medical science liaison team has been out educating on treatment-resistant depression on psychedelics on what we've seen so far in COMP360, our trial designs.

A key element of what they're doing is obviously speaking to the psychiatry infrastructure that's already out there that could potentially be referrals into these interventional centers. But we are also expanding to the PCPs because the PCP, they already have the bulk of patients who are sitting there who are already treatment-resistant. So just some education around that is starting to happen.

So our final question comes from Sumant Kulkarni at Canaccord.

For this informative event and all the work you're putting in on behalf of patients. I have one set of -- one question for the experts and a couple for the company. For the experts, perhaps starting with Dr. Grammer, in a future scenario where COMP360 is approved and if there is another psychedelic product or 2 that are also approved for TRD, but only require patients to be in your clinics for 2 hours or less, what would be the key variables you'd consider that would make you use COMP360 over those other products?

I think that was to me. So that's a good question. I don't know that I have a good answer for you yet because we don't know the differentiators between the different molecules that may come farther down the pipeline, right? Historically, in biology, durability can be somewhat questionable with very brief interventions to things. So one of the first things that we're going to be looking at is whether or not you get the same durability with a shorter-acting compound that could be offered. The other thing is going to be subtypes of depression or other conditions that may respond to one versus the other. Until we have that data, we don't know.

But I think from a commercialized standpoint, the pool of people with treatment-resistant depression is so large. It's not like it's a finite market population. It's almost infinite is one way to think about it. So if there's a molecule that comes along that works equally as well, has the same durability, but a shorter duration of action, it's not like the business drops off. It's that we are able to continue to attend to those patients with the modality we receive. The reality is for right now, the first one up on the list is going to be COMP360. We're prepped for that. We're going to do that. We need to get that right. And as new molecules come on board, we'll kind of adjust and adapt as needed based upon what that data shows. But it's a little premature to really know how we would differentiate those out.

For the company, what would you consider a good result in terms of a major score change for Part A of COMP006 for the 25 mg versus the 1 mg? And could you put that in context versus the 3.6 point adjusted change you saw in Part A of COMP005? And given there's a commercial plans update component to this webcast, what are your latest thoughts on pricing COMP360 for TRD?

Thanks, Sumant. So the answer is statistical significance is the barrier we're looking for. in terms of the MADRS difference in 006 Part A. And I'll turn to Lori for -- it's premature to talk about pricing specifically, but I'll turn to Lori to talk about that.

Yes. You said it, Kabir. It's a little bit premature because it's hard to characterize the clinical profile of COMP360 without our 26-week data or even our 52-week data. So once we have that full picture of what COMP360 and the value that COMP360 can bring to the payer system as well as patients and providers, it's a little premature to think about pricing.

So this concludes today's Q&A session. I'll turn it back to Kabir for some quick closing remarks.

Thank you very much, indeed. And first, thank you all for staying on. I know considerable length beyond the end of the planned time. Particular thanks to our guests, to Dr. Small, Dr. Grammer, to Dimitri Cavathas, and to Myriam Barthes for their really great contributions to the discussion and the Q&A.

I think the key takeaway from today is you've heard very clearly that providers and patients are ready. They are incredibly excited about the potential for COMP360 as a new treatment option. They recognize the work that COMPASS has put in to driving this program. They're excited as we are with the data that we're going to see. And what you can take away is that we at COMPASS are truly ready for this transformational paradigm shift in the treatment of serious mental illness through interventional psychiatry infrastructure.

So again, thank you all so much for staying on. Thank you for the contributions. Thank you for your questions. And we will look forward to updating you not only with data in the back part of this quarter, but also, as Lori said earlier, as our commercial plans continue to evolve. So thank you very much, everyone. Thank you for your attention, and thank you for your time, and I wish you an excellent rest of the day.

Good morning, ladies and gentlemen, and thank you for standing by. My name is Kelvin, and I will be your conference operator today. At this time, I would like to welcome everyone to the COMPASS Pathways Third Quarter 2025 Earnings Call. [Operator Instructions]

I would now like to turn the call over to Stephen Schultz, COMPASS Pathways' Senior Vice President of Investor Relations. Please go ahead.

Welcome, all of you, and thank you for joining us today for this quarterly conference call. My name is Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways. And today, I'm joined by Kabir Nath, our Chief Executive Officer, and Teri Loxam, our Chief Financial Officer. Lori Englebert, our Chief Commercial Officer, and Dr. Steve Levine, our Chief Patient Officer, will be available for the Q&A.

The call is being recorded and will be available on the COMPASS Pathways' Investor Relations website shortly after the conclusion of the call and will be available for a period of 30 days. Before we begin, let me remind everyone that during the call today, the team will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as amended.

You should not place undue reliance on these forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those risks and uncertainties described under the heading Risk Factors in our most recent quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission and in subsequent filings made by COMPASS with the SEC.

Additionally, these forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements even if our estimates or assumptions change.

I will now hand the call to Kabir Nath.

Thank you, Steve, and thank you all for joining us for today's call. We are very excited that COMPASS continues to make excellent progress on all fronts, in particular, the potential 9- to 12-month acceleration of our launch plans that we announced today. Our first Phase III trial, COMP005, demonstrated a highly statistically significant result for the primary endpoint in June, which was an important derisking event for the company.

It was also a clinically and commercially meaningful result which points to the potentially differentiated profile that is emerging for COMP360. We're looking forward to the remaining data from our ongoing Phase III trials, especially from the second Phase III COMP006 trial with its 2 fixed doses, which will be important to help inform dosing for labeling.

Enrollment for the 006 trial continued to accelerate throughout the summer. And today, we're pleased to announce the completion of enrollment. This is great news, since it clarifies timing for the remaining Phase III data disclosures and gives us line of sight to our potential filing time line. Following the data readout in June, we had a positive and collaborative interaction with the FDA on our filing strategy for COMP360 in TRD. We're encouraged by their support for acceleration of the planned NDA filing, including the potential for a rolling submission.

To enable this, we now plan to unblind 9-week data from Part A of the 006 trial and disclose it concurrently with 26-week data from the 005 trial in Q1, which is likely to be in the later part of the quarter. The 26-week data from COMP006 is now expected in early Q3 next year, which we anticipate will be the last gating item to complete our NDA submission.

Given the accelerated time lines, we are also pulling forward our launch readiness, building on the significant progress we've already made over the last couple of years. With our strategic collaborations across a variety of care settings and our medical science liaisons interactions with KOLs, we've been very active in developing an extensive understanding of the commercial landscape and of provider sentiment and dynamics.

We've generated valuable learnings that we're incorporating into our launch plans, including insights into patient preference, patient flows and provider economics which have helped us understand how COMP360 will be differentiated from current and future treatment options if approved. We're encouraged by the continued increase in interventional psychiatry infrastructure over the past few years, driven both by SPRAVATO and the excitement around the potential promise for psychedelic treatments such as COMP360 in the future. The learnings we've gained through our commercial work strengthen our confidence that COMP360, if approved, can be effectively integrated into the growing interventional psychiatry infrastructure and offer a differentiated and compelling treatment option for patients and providers.

With significant learnings already incorporated, we are confident that we will be ready to launch on an accelerated time frame which is great news for the estimated 3 million individuals in the U.S. living with TRD. Beyond TRD, we're also finalizing the design for a late-stage PTSD trial following constructive interaction with the FDA. We look forward to updating you further on that program in the near future. As you can see, these are exciting times for COMPASS, and we are focused on translating our progress into real-world patient impact as quickly as possible as the need remains urgent.

With that, let me turn it over to Teri.

Thank you, Kabir. At the end of September, we had cash and cash equivalents of $186 million compared with $222 million at the end of the second quarter. We have continued to be disciplined in our spending, which has allowed us to maintain our cash runway into 2027. Debt under the Hercules loan facility was $31.3 million at the end of the third quarter.

Cash used in operations for the third quarter was $35 million, and we expect net cash used in operations for the full year 2025 to be between $120 million and $145 million. This range includes the amount receivable in respect to the R&D tax credit in the U.K., the timing for which is uncertain. As Kabir mentioned, our entire team is focused on strong execution, completing both of our Phase III trials, preparing for our NDA submission and continuing our commercial preparations.

We have added resources to our regulatory team to ensure we're moving our NDA filing activities forward as quickly as possible, and we have also pulled forward select commercial activities to meet our new accelerated time lines. We are confident in the emerging profile for COMP360 and its potential to transform the landscape for those living with TRD and PTSD through a potentially rapid and durable treatment option, reinforcing our leadership in the field of psychedelics. As mentioned at the beginning of the call, Lori Englebert and Dr. Steve Levine will also be available for the Q&A.

Thank you, and I'll now turn the call back to the operator for Q&A.

[Operator Instructions] Your first question comes from the line of Josh Schimmer of Cantor.

Congrats on the update and time lines. Quick question about selection of specialty pharma partner you may use to kind of support patient access. Have you identified any that you would anticipate to move forward with? And would there need to be any unique capabilities that they have in terms of offering those patient support services to psychiatrists who would be interested in prescribing psilocybin?

Thanks, Josh. It's Kabir. Just checking that you can hear us.

Yes, loud and clear.

Let me pass that to Lori.

Josh, it's Lori. Thanks for the question. We have not made a selection yet. It's a little bit too early to do that. But as Kabir mentioned in the opening remarks, we have done quite a considerable amount of work already in terms of understanding what the distribution pathway might look like to these treatment centers and how that might flow. And now that we're starting to accelerate some of those activities, you can expect that we will start narrowing down what that looks like in the coming months. With regards to your question about any special requirements, again, we're looking through what that might require in terms of how we will support patients once they get -- once we get to market. But there should be nothing unique that's psychiatrists will -- are not -- are unfamiliar with.

Okay. Got it. And then if I may ask one other quick question. You mentioned that sites that are able to administer SPRAVATO currently should be able to administer COMP360. Does that apply to every single site? Or what incremental changes to the office or practice might be needed to incorporate COMP360 into the 6,000 or so sites capable of delivering SPRAVATO currently?

Josh, thanks for that question. It's Steve Levine. The short answer is that we would expect that any site that is delivering SPRAVATO today would be capable of delivering COMP360, if approved. That doesn't mean that it's necessarily one for one in the implementation, but it's exactly why we're doing the work we are with the collaboration sites or strategic collaborations to understand what any incremental changes might be needed. But in terms of the physical infrastructure, the staffing, the capabilities, those all port over directly from their current experience with SPRAVATO.

Your next question comes from the line of Paul Matteis of Stifel.

So as it relates to this FDA meeting, I think you said previously that the thought was you were only going to be sharing with the agency the same level of granularity on the 005 data that we've seen, and I think you've still -- since just seen as well. To that point, do you feel like there's the need to have another FDA engagement after you release this much more detailed data early next year?

And then I guess as a second question related to that, can you help set up what your expectation is when we see 26-week data? And what do you think would be a positive outcome on either the frequency of retreatment or response rates for retreatment that would align with your target product profile as it relates to how -- what you're looking for durability and just kind of the commercial sort of viability and scalability?

Thanks, Paul. So yes, on the first one, you're right. From a data perspective, we have no more data in hand. But clearly, we were able to share with the agency, some of what we've announced today in terms of time lines, where we were with 006 and so on. So there was information that we were able to share at that point with them.

To your point, absolutely, we would expect with the significant data readouts in quarter 1, that would indeed be the point for another meeting with the agency really to align fully on the plan going forward in terms of rolling submission, what's going to be reviewed when and so on. So yes, that is absolutely the case.

For the profile, I'll actually hand to Lori to talk a little bit about that. And again, though, I'd just remind you, contextualize, we are now going to be announcing 26 weeks from 005 together with the 9-week data from 006.

Yes. Paul, thanks for the question. So what we expect to see, and let me just remind you, in order to achieve equivocal efficacy to SPRAVATO, SPRAVATO patients need to receive 8 to 10 treatments to our one that was already demonstrated at the 6-week time line. So already, we are quite differentiated from what's available to TRD patients right now. Everything we see in the 26-week data will only help accentuate what the clinical profile of the product is going to be. And I do want to just caveat that the 005 26-week data that we will release in quarter 1 is after one administration.

The 2 administration that we will see with 006, we will also really be looking forward to what that profile looks like at the 26-week data for 006. In terms of commercial liability, as I mentioned, we're already highly differentiated with the one administration getting such profound efficacy in a TRD indicated population. So anything on top of that in terms of durability will help accentuate that product profile.

Your next question comes from the line of Judah Frommer of Morgan Stanley.

Congrats on the progress here. Just curious if any of the interactions with the FDA included conversation around submissions for the commissioner's priority review application. I think you had said at some point, you did have interactions with the agency on that submission. And if not, has the agency pointed toward TRD versus PTSD in any way being higher areas of unmet need in their view?

Yes. So thanks, Judah. Yes, we -- as we've said before, we did apply for a CNPV but we know that hundreds, perhaps thousands of companies applied for CNPV. There was some interaction. But obviously, we've seen the first list. We're aware the commissioner said that there may be more coming. But really, I think our discussions have been with the division, and that's where we've had the very positive feedback that there is momentum there and so on.

I think -- from an agency perspective, I think they see both TRD and PTSD as areas in desperate need of new options for patients. I don't know that at the agency level as opposed to shall we say at the political level, there's any distinction there. We are clearly the most advanced with our program, which is in TRD. And that's -- I think we have a very good relationship and good understanding of the urgency of trying to move that forward, subject to data.

Okay. Maybe just a quick follow-up. Any interaction or commentary from the VA within these agency conversations? Or do those kind of weigh on their decision-making there?

So I don't think we could comment on how the VA and FDA interact, but I'll turn to Steve to talk about our interactions with the VA kind of independent of that.

Thanks, Kabir. Judah, yes, we have regular engagement with the VA and have for quite some time now. About 1 year, 1.5 years ago, the VA convened an integrated project team that is specifically tasked with thinking -- early thinking and planning for the implementation of psychedelic treatments, if approved. And that includes senior VA leadership within the Office of Mental Health. We engaged with them on a regular basis. We provided many resources for them to help guide their thinking about what they will need to ensure that there is access within the VA upon approvals. And so that's been a very positive set of interactions.

Your next question comes from the line of Gavin Clark-Gartner of Evercore ISI.

Congrats on the update. So by presenting the 006 data at 9 weeks, do you risk the integrity of the study in any way? Like I know that was part of FDA discussions previously. So I'm curious what led regulators to change their stance? And also curious if by presenting this data at an earlier time point, do you lose the commercial ability to make claims around the durability of the 2-dose regimen?

No. So to be clear, Gavin, I mean, it was our choice in the past, you'll recall that we actually changed guidance from disclosing Part A of 006 to only disclosing the 26-week data in the light of, shall we say, a lot of the confusion and commentary around Lykos at the time. A few things are clearer. First, when really -- given that CRL was published, it actually does not focus on functional unblinding and expectancy as a key issue. There were a whole lot of other deficiencies as well. Second, we will actually have the vast majority of patients through Part B of 006 by the time we disclosed data from Part A. And in our perspective, that does not, in any way, compromise what we may see in Part B, which would also be integral to claims. I don't know, Lori, if you want to just build on that?

No, I agree. And just a reminder, it is double blinded through 26 weeks. So as we present that data to the agency, there should be no hesitation in terms of how we promote based on that data.

All right. Great. That is super helpful. And just a separate topic. What's your current assumption for how the label or the REMS may read on monitoring requirements? Like specifically, I'm wondering if a single versus a group room may be required and if one health care provider can monitor multiple people simultaneously and if any of this was discussed in the Type B.

Thanks, Gavin. It's Steve Levine. It's a great question. I think what you should anticipate is that the label or REMS will not necessarily get into granular detail about the practice of medicine and the delivery of treatment to patients, so much as describing how the studies were conducted. It would be expectable that at the time closest to launch, most sites would likely deliver this treatment in the most conservative way possible with one patient occupying a private room as SPRAVATO was often delivered today.

But also taking lessons from SPRAVATO, it's also likely that as clinicians gain more experience and comfort with delivering COMP360, they likely will find additional efficiencies in delivering it and that could include group administration. It could include rooms with curtain bays, et cetera, ways that allow them to move patients efficiently through their centers. And this is also work that we've been exploring in some early work with our strategic collaborations.

Your next question comes from the line of Ritu Baral of TD Cowen.

This is Athena Chin on for Ritu. Could you please review the state of your commercialization preparation for 360 and provide more color on what activities you pulled forward given the accelerated time lines? And then I have another follow-up.

Thanks, Athena. I'll hand that to Lori.

Athena, thanks for the question. So as Kabir mentioned in the prepared remarks, we have done some really incredible work over the past couple of years, specifically with our strategic collaborations as well as our MSLs and then a whole host of other critical components of a commercial preparation such as government affairs, HEOR, we've done some market access for all of that to get prepared for a real solid understanding of what strategy should be. What that actually means is that we understand the marketplace landscape, we understand where the prescribers -- who the prescribers are, where they are, how we might want to ensure that they can seamlessly integrate COMP360 into their treatment practice as it stands today.

What we will pull forward and start shifting to is your more fundamental traditional commercial activities like marketing, messaging, figuring out how to structure a sales force, getting an IT infrastructure set up and prepare to ingest data as the sales reps are out in the field. And of course, a lot of that comes with also some market access and payer discussions around the potential to reimburse the product. So we are pulling those forward by several months.

And obviously, a lot of that will be contingent, especially the payer discussions will be contingent upon the durability data and a complete understanding of what the 006 data looks like so that we can put together a very nice picture for what the full clinical profile of COMP360 will be to engage in the payer discussions. But a lot of that does not contingent upon doing marketing activities and sales force sizing and things like that to prepare. So we will be ready based on the fact that we have a very strong strategy in place, and we are just pulling forward some of the execution activities.

Got it. And on the filing, are there any outstanding drug liking requirements that are needed or ongoing? And when can we expect those to complete?

No. So as we said on the call, we would -- we do expect 26-week data from 006 to be the final gating items. So everything else in terms of preclinical, CMC, stability, et cetera, will be well in hand before all that. So no, there are going to be no other outstanding requirements.

Your next question comes from the line of Patrick Trucchio of H.C. Wainwright.

The first question is just on the Type B meeting with the FDA. I'm wondering if there was any change from what had been discussed previously. Or just has the agency's tone or the way that they're talking to you about COMP360, has this changed from what you've heard previously, And particularly as it relates to the potential for the rolling submission and how we should think about that? And then I have a few follow-ups.

Yes. No, thanks, Patrick. So yes, I mean, I think it's fair to -- first, as we've consistently said, we have an excellent relationship with the division. We've had breakthrough designation now for a number of years. That's allowed us to have regular dialogue. I think it's been clear for some time that the division sees the potential in psychedelics in COMP360, they see the need. But at the same time, they're going to adhere to exactly the same high standards as they always have, and we're very happy with that, and we will continue to uphold those standards.

But yes, I mean, traditionally psych has perhaps not been as forward-looking in terms of rolling submissions and so on as some other divisions. And so in that sense, there was, as we've said, encouragement, a very positive spirit around the meeting. And so in that sense, something of a change in tone, but again, in the context of the relationship that's always been excellent and a very supportive division.

Right. And then as we look ahead, first, is it still the anticipation that there would be an advisory committee? And as you prepare for this anticipated outcome, what key elements of the submission or support model would address questions around safety, support, mechanism of action, any of these other questions? And maybe also as this relates to learnings from that published CRL? And then separately, just on the commercial front. I think in the past, you've said there is roughly 6,000 interventional psychiatry centers capable of administering multi-hour treatment. So I'm wondering, at the time of launch, what proportion of those would be certified and able to deliver COMP360.

Okay. So that last one, I will hand to Steve in a moment. But the question around -- so obviously, it's the FDA's determination as to whether or not they want an advisory committee, and that will depend on when they actually receive data in the review package. All I can tell you is we will be ready. We are anticipating that, that may happen, and we will be ready for that. I think clearly, obviously, we do -- everyone now has access to the Lykos CRL which is helpful. But as we've always said, we have done a comprehensive job of collecting side effects, including positive, shall we say, side effects, euphoria and so on. So I think we have the data to characterize the risk benefit of COMP360 in the way you would expect of any drug.

In addition, as we've said, the person in the room is there for safety. It's not a -- they're not there to direct therapy or to intervene, they are there for safety. We have had that then trained to a very standardized protocol consistent across every arm of each study. And as we've talked about before as well, we are doing some sampling of that to ensure that that's in line with the education we've given. So I think, obviously, as time evolves, we will look at our strategy, look at everything we're preparing in relation to the specific concerns that were raised by the agency either in the case of Lykos and other ones, but we will be ready for an advisory committee whatever happens. Steve?

Yes, this is Steve Levine. And as far as the second part of your question about the readiness of these SPRAVATO interventional infrastructure to deliver COMP360 at launch, within our strategic collaborations, there already is a high representation of this concentrated delivery network that delivers SPRAVATO today. But additionally, the bidirectional information exchange that happens within these collaborations helps us to not only understand how to best support these sites and patients at these sites so that they can be activated to deliver our treatment.

But because they share characteristics with other interventional psychiatry practices, it allows us to build templates to also be ready to support them. But you'll also note that this network of collaborations isn't exclusively interventional psychiatry. It really reflects the diversity of sites of care where patients living with treatment-resistant depression receive their care today. And although we would expect that some of the earliest adopters would be the interventional psychiatry sites, we are committed to broaden equitable access and that means enabling access in a broader array of treatment sites.

Your next question comes from the line of Sumant Kulkarni of Canaccord Genuity LLC.

Nice to see all the progress. I have a couple. As a point of clarification, what is the key variable that has allowed you to bring forward your time line for commercialization by 9 to 12 months? Is that related primarily to an ability to submit an NDA for COMP360 for treatment-resistant depression ahead of your original plans? Or is it something else? And second, is it fair to assume that you would need to have the Part A from COMP006 and Part B from COMP005 in hand to initiate a rolling NDA submission?

Thanks, Sumant. So a couple of things. First, clearly, the completion of 006 enrollment that has come ahead of expectations. So you'll know that we were guiding until now for second half of '26 for the 26-week data from 006, so we've now tightened that to early Q3. So we've gained a number of months there from there. And clearly, 006 has gone extremely well, particularly over the course of the summer with European sites in particular performing very strongly. So a big chunk of the acceleration comes from our execution on 006.

Part of it then does come from the potential to have the agency start reviewing of some modules in line with a typical rolling submission, where, as you know, you can submit preclin and CMC and so on ahead of the full package of clinical data. So there were clarifications around that in the meeting. But yes, to your point, as -- and the earlier question, we would expect another meeting with the agency in quarter 1 with the data, the 26-week data from 005 and the 9-week data from 006 in hand. And that we would expect to be another meeting which would -- actually can formalize the plan going forward.

There are no further questions at this time. And with that, I will turn the call back to the management for closing remarks. Please go ahead.

Thanks, everyone, for participating today. As you've heard, we are extremely excited about this potential acceleration of 9 to 12 months, really based both on our execution around 006, also a good positive dialogue we've had with the agency as well as the decisions we've made about unblinding 006 data in the first quarter of next year.

I'd remind you again that we will be talking about PTSD in due course. We're excited about that. We have actually now finalized the protocol on that. We have selected a CRO, the protocol is with them for costing and so on. And so we look forward to announcing that and getting on with that with the potential to have first patient in that in the first quarter of next year as well.

So very exciting times for COMPASS. We're thrilled with where we're at. We are ready to move on that accelerated time line. As you've heard from Lori and Steve as well today, a lot of activity on the commercial front, building on the learnings we already have. So we're looking forward to a very engaged and active next 12 to 15 months. Thanks, everyone, for taking part today.

Ladies and gentlemen, this concludes today's call. We thank you for participating. You may now disconnect.