Compass Pathways Plc - ADR Aktie

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.

All right. Good morning, everyone. Welcome to the session of the Morgan Stanley Global Healthcare Conference. I'm Judah Frommer, one of the SMID biotech analysts here. I'm just going to start off with a quick disclosure statement for important disclosures. Please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative.

With that out of the way, I'm excited to welcome the COMPASS Pathways team. We've got Kabir, Teri, Steve and Guy representing. So we should be able to have a fulsome discussion up here.

Maybe Kabir for those who are newer to the COMPASS story, could we start with maybe some company background and a brief overview of the COMP360 program?

Sure. Thanks, Judah. And just a reminder, we will be making forward-looking statements. So I'd just refer you to our risk factors in our many filings to the SEC. So COMPASS is a company that's dedicated to transforming the paradigm for the treatment of serious mental illnesses. Our lead product, COMP360 is a synthetic proprietary form of psilocybin, and we are currently in Phase III for treatment-resistant depression. And we'll go on to talk more about the size of that opportunity, about the lack of currently available treatment options. There's really only 1 that's currently marketed today.

And with that Phase III program, we've had the primary endpoint readout of our first Phase III study. That was the 6-week primary endpoint that came out in June of this year. With that, we are 2 for 2 in terms of highly statistically significant, clinically relevant studies in treatment-resistant depression, building on a very robust Phase IIb that came out now some 4 years ago.

We will see longer-term data from our first Phase III study in due course, and we can come back to talk more around that timing. Our second Phase III study is recruiting extremely well. Actually, the positive data from the first one has accelerated. Our ability to recruit in that. So our second study, and these are not very creatively called 005 and 006, but our second study 006 is recruiting very well, and we are confirming guidance for the full 26-week data set for the second half of next year.

Our base case has been that, that data set, the 26-week data from that second 006 trial, is the gating item for a potential NDA preparation. However, we have met with the agency in the last week under a Type B meeting. And given a lot of what we're hearing from FDA, HHS, around the potential for psychedelics and the potential for acceleration. We are engaged with the psychiatry division and a discussion around potential regulatory acceleration.

That's where we are.

Great. So maybe just a more point to follow-up on that last statement. What is your sense of FDA's current stance psychedelic therapies. It seems like it has changed with the current administration, but you're talking to them fairly routinely. So how would you kind of assess their stance?

So I would say we've obviously been working with them now for 7, 8 years on this program. We have breakthrough designation for TRD. It's been highly engaged. We've essentially been solving problems together. I think what's very interesting is just last week, the CRL for Lykos was published. First, there were no surprises in that, but that also showed us the FDA's thinking. They weren't worried about functional unblinding. They were worried about issues very specific to Lykos.

So I would say they are engaged. They see the potential. They clearly see the new for new innovative treatments. And I think also some of what we're hearing from the HHS Secretary, VA Secretary, others is clearly filtering down and is giving an impetus and a sense of urgency to move these forward. So the final thing I would say is within the psych division itself, there's actually been no changes since January. It's the same people, very engaged, very committed, and we're actually excited about the ability to collaborate and try and move with greater speed.

Okay. Great. Moving into the clinical data, you mentioned the 6-week COMP005 data. How would you say that compared versus the Phase IIb, I guess, specifically on MADRS and safety, but I think those are the 2 areas we get the most questions on. And kind of a subquestion, how has KOL versus investor reaction differed? The stock is basically back where it was prior, but maybe you can walk us through the reaction.

Yes. I think it's worth remembering that our Phase II study was quite a large study, over 20 sites, over 200 patients. So it was a little unusual for Phase II. So you might have hoped that it would be pretty predictive of what happened in Phase III. That is not always the case, of course. And it turned out it really was in this case in that we saw a difference up to 6 weeks in the Phase II study of 4.2 in our MADRS data in the Phase II. And we saw -- and we, therefore -- we -- in discussing our expected effect sizes, we emphasized that over 3 would be regarded as good by the field, by KOLs generally, and we came in at 3.6.

Now 3.6, 4.2, given the confidence intervals around those numbers are highly comparable. And the statistical significance in both those studies was 0.001. So we have highly statistically significant effects in both those studies that are greater than the 3 points that is usually regarded as the level of clinical significance.

So we felt we've done a really nice replication. Remember that the 005 that we've announced the data on was against [ inert ] placebo. That was something that the FDA had requested to give a fair safety baseline. And therefore, the second big message really from the readout that we -- the limited readout that we had was that there was no imbalance in suicidality in either the 005 at that point or indeed 006, and that came from the DSMB together with the -- time together with the readout.

So those are the 2 ways in which they're complementary to the Phase II. So we have a comparable efficacy, and we have a confirmation of greater safety perhaps than people had thought we had in the Phase II with larger numbers.

Okay. And then just maybe on kind of KOL or clinician reaction versus investors?

KOL, I mean, the evidence that the KOL reaction, our KOLs are mainly PIs and the PIs in general, regarded this as a very strikingly positive finding and the sort of proof of their conviction, we've had an acceleration in our recruitment into 006. So we've seen people actually behaving as well as saying that they think they're impressed by this.

Okay. And you touched on it, maybe just can you further emphasize the trial design differences between 005 and 006?

Of course, yes. So 005 was a single administration, 25 milligrams psilocybin COMP360 versus inert placebo and 006 is 3 doses that is 3 doses, 25 milligrams, 10 milligrams or 1-milligram, the 10-milligram really ensuring that the study is as blinded as is possible to what the true dose being received is. And that is administered twice, once at baseline, once at 3 weeks, again, with a readout, the primary outcome of 6 weeks.

And this gives us additional confidence given the size of the study; it's powered to detect pretty small effect actually. We think the effect, in fact, will be bigger because we've seen that in other people's data and indeed in data generated with COMP360. So we anticipate a larger effect in 006 and a more sustained effect. Obviously, time will tell whether we're correct in that.

Okay. Great. And I think one thing we bump up against is this perception that the 26-week data from the second Phase III trial, 006 in the back half of 2026 is the next material catalyst for the company. But there is more happening near term. Maybe would you be able to walk us through the catalyst path over the next 12 months, what we could learn from the next 005 update that could inform the 006 data?

Yes. I mean I'll just put the timing there and then turn back to Guy. So the 26 weeks of 005, I mean, clearly, people -- given that we declare the 6 weeks, people to work out mathematically, that data should be in hand roughly in first quarter. However, we have said we're going to gate that on every patient being through Part A of 006, just the first 9 weeks, so that there's no suggestion of influence. But Guy, in terms of what we can expect to see potentially in Part B of 005.

Yes. I mean one of the things that we will get is the effects of retreatment because we designed the study to allow retreatment with the original dose of the drug that patients have received. And that, of course, is going to allow us to make some predictions about the way in which the drug is likely to be used in clinical practice. So we're going to see people who've not responded particularly well to a single dose get retreated. We're going to see whether that essentially compensates for a single administration. We're going to look at durability in that phase. This will all be blinded and that gives it an additional value, of course.

Okay. And we will have a full safety data set. So that will also help, I think we will have the full safety profile.

Okay. Got it. Another area we get questions on is kind of background SSRIs. So how do you anticipate communicating exploratory data from patients who elect for SSRI treatment during 006, and could this support future combination therapy positioning?

Well, we'll have data because in the Part C of the -- both studies, patients will be eligible for an open-label administration 25 milligrams, and a number of them will have gone on to SSRIs because that's one of the options in Part B. So we will have quite a lot of experience of the safety and indeed the apparent efficacy unblinded of that treatment.

In a moment, I'll pass to Lori and Steve to talk about that what that is in the real world. But just from a regulatory perspective, though the studies are indeed monotherapy, typically, precedent would suggest the label will be broad. If you study only adjunct, you will likely get only an adjunct label. But by studying monotherapy and having SSRIs added on during the course of the study, we are likely to get a broad label on that.

Yes. And I agree it will be very important data for us to generate because that will be real-world practice, and physicians will need that guidance as they decide when to administer COMP360.

Okay. Another kind of development of the company relatively recently that ties into the regulatory environment is your decision to participate in the Commissioner's National Priority Voucher, the CNPV program for COMP360. So -- can you just walk us through the rationale for doing that? And do you have any sense on time lines or what you could potentially hear around that?

Sure. So this was something that was announced, I guess, a couple of months ago, and there are essentially 5 criteria, and you had to meet at least one of them. We clearly meet 3 of them, which is an area of significant unmet need, lacking new treatments, a public health emergency and something that is in and of itself innovative. And indeed, the criteria call out the treatment of mental health, particularly PTSD.

So the submission is actually straightforward. It's 350 words. So we assume that every biopharma company and every biotech company did indeed submit an application. I can tell you, we have had engagement, which suggests that we're not at the bottom of that list at least. So we have had engagement with the agency. There has been too and throw on that. I think just yesterday, I believe the commissioner here, we were in investor meetings, so [indiscernible] sort of barely, he said he is -- they are planning to announce 10 to 12 pilots in a matter of weeks or whatever.

I think we know there is a lot of talk about psychedelics, the desire to accelerate. Our focus as COMPASS has been, given where we are in data generation in our programs, we are the closest of any psychedelic company to a potential regulatory approval. We've also been in surround sound on the Hill to kind of make that point as well. I don't know, Lori, if you want to comment on that.

Yes, I think it's very important for us and for patients to make sure that the standards are not reduced that we are just simply talking about accelerating as fast as possible and working with the agency, and what for other divisions as normal pathways.

And so on the Hill, we have been doing just that. We've been spending a lot of time there making sure that we're educating on, we're not advocating for any exceptionalism. We are advocating really to make sure that they are aware of COMPASS, aware of the clinical trials and the rigor that we are putting behind them to ensure patient safety.

Okay. That makes sense. And then maybe just a couple of comments on how you're thinking about the ex U.S. opportunity. Has there been engagement with ex U.S. regulators outlook for potential global registration pathways?

So yes, so when we designed this 005, 006 pair of Phase III studies, we took scientific advice. We've taken supplementary scientific advice from 3 countries actually a couple of years ago. But from a regulatory perspective, these 2 trials together should be sufficient to deliver a CHMP approval potentially, obviously, subject to data and so on.

We have engaged with MHRA. We have the so-called ILAP, and I'm afraid you can't test me on what it actually stands for, but it is an innovative program that brings together MHRA and [ NEC ], and we've had positive discussions there. Beyond that, beyond Europe and that, we haven't actually engaged more broadly. And while we believe we have something that is certainly from a regulatory perspective, viable, the likelihood is at some point, we would seek to partner some of the ex U.S. opportunities.

Okay. That makes sense. I think the kind of the next area of focus tends to be potential commercial launch plan. So how many treatment centers are you targeting? How equipped are they to support an accelerated approval scenario if that's the direction that it goes?

Yes, it's a really good question. I might want to just step back a moment and paint the landscape of what the addressable patient population looks like.

So right now, there are 9 million MDD patients being treated with antidepressants. These are your antidepressants that you get in a retail pharmacy and patients take on a daily basis, sometimes twice a day.

When Spravato launched in 2019, they were effectively the only product used for treatment-resistant depression. So of those 9 million MDD patients, there are 3 million that are classified as treatment-resistant because they have been failed by 2 prior antidepressants. There are only 2 products approved by the FDA right now to treat treatment-resistant depression. There are 50-plus approved to treat MDD. And the reason that number of 3 million is so high or one of the reasons that, that number is so high is that it's very hard to prove efficacy in the treatment-resistant depression population.

So when Spravato launched in 2019, the infrastructure to have a different way of treating, so a therapy that -- or a treatment that requires hours of monitoring after administration, that was a very minimal infrastructure setup. Fast forward to now 2025, there are over 6,000 sites setup for multi-hour delivery of treatment in these centers. That number is growing very rapidly. They are 6 years post launch when they're supposed to technically be slowing down. They're growing 30% year-over-year.

So the interest in understanding the work that J&J has done, we will be able to leverage. The infrastructure is there, 6,000 sites, about 5,000 HCPs. We know who they are. We're doing a ton of work through the strategic collaborations, and Steve can speak more to that if of interest to really understand what barriers could be in place once we get to launch, we will be first-in-class. We take that very seriously. We want to make sure that any barriers are removed and part of understanding those 6,000 treatment centers, work with the strategic collaborations will help us achieve that.

Okay. Maybe you can talk about whether your initial patients need to be Spravato switches necessarily and maybe some of the dynamics at these treatment centers in terms of whether a Spravato room would have to be converted to a COMP360 room. I think there's some perception that these 6,000 centers are kind of peak potential and that the number of rooms available are currently being filled. But can you help us with some of the dynamics there? Do you need to necessarily take share from Spravato? It sounds like not.

Yes. I can speak to this from the perspective of a psychiatrist who spent 2010 to 2020 treating thousands of TRD patients through a nationwide network of interventional psychiatry practices that I had built initially delivering ketamine, but later Spravato once approved in 2019 and other interventional treatments.

Lori covered the unmet need quite well just before, underscoring that there are 3 million patients living with treatment-resistant depression, only 50,000 to 60,000 of whom are currently receiving Spravato. This does today largely happen within interventional psychiatry practices. And a Spravato room is a COMP360 room. The staffing required to deliver Spravato is the staffing required to deliver COMP360.

And so to your question about whether that requires then pulling from rooms that are currently delivering Spravato, it will likely be a mix. There's currently capacity in the system. So there isn't necessarily an immediate need to build additional capacity. It's there and waiting. It's likely that we will see some switching, but the reality is there are so many patients who are currently underserved that there doesn't necessarily need to be.

If those rooms are filled up and that would be good news for patients because it would mean that they are being better served than they are today, then these centers would likely be very happy to build additional capacity given that the economics are very favorable for them to do so.

Okay. That makes sense. And speaking of the economics, you've highlighted hourly reimbursement codes as being supportive. Can you expand on payer engagement and how reimbursement might work in practice, what's different versus what Spravato has in place for COMP360?

Maybe Lori can cover the payer engagement piece. But just in terms of the provider perspective on the provider economics of delivering this treatment, as you mentioned, a few years ago, we did work to receive new CPT codes. We applied to the AMA. Those were granted. They went live in January of 2024. These are specific to the administration of psychedelic treatments. And as you pointed out, they're reportable on an hour-by-hour basis. So regardless of the length of that administration, providers will be fully reimbursed for that time.

That relates directly to a bit of a myth that's out there that should be dispelled, which is then that shorter is better. I think because of the success of Spravato now being on a $1.7 billion run rate and that being a roughly 3-hour treatment visit, the assumption that for a psychedelic treatment to be commercially viable, it would need to fit within that time window.

The reality is, though, that, again, given that the codes are reportable hourly, if you can have one patient in that room for the day and be fully reimbursed for that time, that's actually more desirable than having a shorter-acting treatment given that with shorter-acting treatments, you would need to turn that room over multiple times in the day to realize the same revenue. That comes with significant additional operational complexity as well as administrative work and cost. You have to clean that room, there's REMS compliance, the controlled substance storage and handling, not taking, prior authorization, a lot of work goes into the care of each of these patients. So actually, it's superior to have the longer-acting treatment.

Got it. And maybe just on the...

Yes, happy to. So just to level set, the payer engagements would be to ensure that the drug is reimbursed for the patient. And those engagements -- constructive engagements are a bit premature just by the simple fact that we only have 1 data point from a Phase III, once we fully characterize what the clinical benefit will be and the economic benefit to payers will be -- then we will have more constructive discussions.

However, we are engaging with payers, mostly because, one, they psychedelic's will be first-in-class, and they need to make sure that they are aware and understand the rigor behind the clinical trials that are being conducted through COMPASS. And also, it should be noted, again, TRD is a high burden to the payer system from a patient standpoint, and I hate speaking about patients that way. But they understand that, and they understand that Spravato is the only one who's proven clinical efficacy in that patient population right now. And so we are hoping for a favorable outcome, especially if we can show durability beyond even the 6 weeks, which is already beneficial to patients.

Okay. And maybe just one more from the provider perspective. We got the question on patient monitoring, how patient monitoring is done within the trials versus how it could be done in the real world and how that might compare to Spravato or any other, like you said, longer-acting treatment in one of these centers?

Yes, I can cover that. So with -- we'll start with Spravato. Most people are familiar with the 2 hours of monitoring that's required within the REMS for Spravato. There is some additional time, which is that it takes for the patient to self-administer the nasal spray, which can take up to 20 to 30 minutes. That administration needs to be directly observed by a health care provider. At that point, the 2 hours of monitoring doesn't need to be continuously eyes on. However, there's somebody coming in and out of the room to check vital signs multiple times as well as to check on the patient. So it's pretty active in terms of the level of supervision that happens with Spravato.

We anticipate something very similar with COMP360. There's another misconception out there that there's some form of therapy happening with these treatments. But the reality is that with a classical psychedelic like COMP360 psilocybin, this is a quiet internal experience where patients are typically lying down, wearing an eye shade, listening to a playlisted music, and there is an interaction with the supporting monitor. So we do expect that the staffing, the ratios, the requirements in terms of the in-office support will look pretty comparable to Spravato.

Okay. Got it. Maybe just moving to the next potential indication. PTSD, when do you anticipate finalizing the PTSD pivotal trial protocol and what's expected time line to trial initiation there?

Yes. So we're in the process of financing. We got some agency feedback, but we are right now in that process. And we would have hoped to start a trial early next year.

Okay. Great. And can you give us any sense for, I guess, addressable market for PTSD versus TRD kind of how should investors be thinking about that?

Yes. There are 2 -- well, there's lots of components to think about, but there are several areas to think about from a commercial synergy standpoint. So these will high overlap TRD patients, very similar to PTSD patients treated in the same types of centers. So the synergistic approach from what we're rolling out and we'll roll out for TRD will apply here.

So it's about 13 million patients right now that are experiencing PTSD, may be surprising to some, but veterans is not the highest percentage of population. That population is typically around 10% to 15% of PTSD patients. Women are actually the larger component here. And so that's important to understand. The other thing that's important to understand is there's been a tremendous lack of innovation in this space. It's been 20 to 25 years since the last product was approved, and there are only 2 FDA-approved to treat PTSD.

Okay. Great. Maybe I should have asked this question earlier. But it seems there is some level of interest in nonhallucinogenic psychedelic agents. So can you help us with the therapeutic case for retaining the hallucinogenic experience in COMP360? And I guess, how do you think about kind of that comparison more generally?

Guy?

Well, I'll start, but Steve can obviously chime in as well. I mean, pragmatically, what we find is that the intensity of the most characteristic psychedelic experience is predictive of outcome in all our trials. So on the face of it, it looks pretty important. Clearly, there is associated that experience a change in brain, and it's possible that the 2 are somehow dissociable. But Optum's razor suggests you should look for one hypothesis and my hypothesis would be that the 2 are related. And therefore, I'm personally a skeptic, but I'd be convinced by different data.

Yes. Guy covered that well. The only thing I'll add is that we don't think of treatment-resistant depression as a winner takes all environment. The size of the unmet need is too large. We hope, there are multiple new treatments available for these patients. Right now, the data is very early on nonholucinogenic. So we'll see. But again, hopefully, we will, over time, see multiple approvals for this population.

Okay. And then maybe just one from the patient perspective on longer acting psychodylics versus shorter duration, whether they're psycodelic or not. I guess is there this recognition from patients that whichever therapy works regardless of how long it takes is the right way to go? Or does it seem like there's a patient preference to get in and out of the clinic. I think there's some misperception about how quickly you're back on your feet post-Spravato. So maybe just help us from a patient perspective there.

Yes. Again, both speaking from the perspective of experience as well as a lot of work that we do already with patient advocacy groups, the idea that somebody is going back to work after having Spravato or potentially one of the other shorter-acting psychedelic treatments in development, very unlikely. So for a patient, the day is a day. And there's also the consideration of their caregiver given that they need to drive patients to each of these treatments.

And so going back to where we started with our top line data from 005, the effect that we saw at week 6 after a single administration versus Spravato, where in their pivotal studies in the first 4 weeks, there were 8 administrations to get to their primary endpoint, which was comparable or 10 in the first 6 weeks. It really can't be overstated the difference in the level of burden to patients and their caregivers as well as to clinics, by the way, because that frequency of treatment can be challenging for capacity. So yes, I think for patients, a day into a day, and they tend to find the day in our trials to be an immersive, relaxing and often meaningful experience.

Okay.

And I think it's important to stress that not all psychedelics are created equal. So the patient experience between ketamine, MDMA, psilocybin, 5-MeO-DMT are radically different. And ultimately, there will be a significant degree of both patient and clinician preference also that actually drives this marketplace.

Okay. Great. And maybe just one follow-up there. We do get a question. I guess if you had to look into your crystal ball, what could, I guess, annual dosing look like? What's the range that you're thinking about?

At the moment, we're saying 3 to 5 annually. But again, the Phase III will clearly inform that. And just as a reminder, with 006, we obviously have the 2 as it were initial doses. So depending if that hypothesis does play out, if we see better efficacy and so on, it will be probably 1 or 2 initial doses followed by up to 3 or 4 in the remainder of the year. But again, we need to see the data. And there will be a wide distribution. Everyone's not get [indiscernible].

And it's highly likely that the label will not dictate what that looks like.

Got it.

And I mean, we don't know. So I should heavily caveat that. We don't know. But it is likely that it will not mostly because of the variation that we will likely see. So it will be -- the burden is on us to generate enough data to make sure that we can inform clinical decision-making along the way.

Okay. And maybe just last company specific one. Anything that we didn't discuss here maybe you could throw in cash runway and then what that's funding, but anything you'd highlight that we didn't touch on yet.

Yes. So let me just cover cash runway. We are -- we have runway into 2027. That contemplates the completion of the 2 Phase III trials, but also setting up this late-stage trial in PTSD. So I think clearly, while interest in psychedelics is increasing, I think there's an increasing understanding of the regulatory risk being discharged. We talked a little bit about that regulatory interaction. We're confident in the results of 006. So from a development perspective, we think we're in a very good place.

Clearly, the fact that we will be the first psychedelic to come to market, both first and psychedelic are carrying a fairly significant discount in some investors' eyes. And I think there, people truly understanding that the Spravato infrastructure, just how much of a leg up that actually gives to us from a point of commercial launch planning, but also the work that Lori and Steve have talked about in terms of what we're doing across strategic collaborations, the work we're doing with KOLs and so on.

So I think people perhaps don't fully perceive how these 3 legs are coming together now and putting us in a really strong position. I think the other thing to say is psychedelic drug development is hard, and you're seeing some other companies have some delays. So actually, the gap from us to others potentially coming behind, whether in TRD or MDD is actually getting bigger.

Got it. Okay. I'm going to move into kind of a mini survey that we're asking all the management teams. If there are any questions in the room, feel free to raise your hand. There are some mics if there are audience questions.

The first amount of question, I might alter it a little bit for you guys. So the first theme is Chinese biotech. So maybe you are, maybe you're not. Like it does -- the rise of Chinese biotech impact your business decisions day-to-day. But maybe I'll layer on top of that, I think kind of the one of the underlying premises of that question is an IP question. So maybe it's worth highlighting the IP for COMP360?

Yes. That's right. And yes, we are not focused on China. I'm not sure that anyone is going to be looking at mind altering something in China too soon.

Yes. So our IP is around psilocybin is clearly a known entity. We actually -- when the company was founded, the first work was to establish a novel polymorph that is stable and scalable. So we have a series of claims around actually 3 different polymorphs. Those patents as soon as they were published, were actually challenged for a PGR here on the basis of obviousness, all those challenges were beaten back. So those patents stat.

So our core is polymorph patents that last to 2038 before patent and extension. We then have formulation methods, indications behind that, but that's at the core of our strategy. We will also get NTE exclusivity presumably because we are -- if this will be the first time that psilocybin has been filed, and it is an NTE, level.

Okay. Great. Second team is AI. Is there a way that COMPASS is leveraging AI or thinking about potential for AI to disrupt the space in anyway?

So I mean, we -- like anyone, we're using it as a productivity tool. That's kind of not interesting. I mean we have done work and we actually have digital tools in terms of both an app and some technologies behind that. We are required to record all interactions. And so we have the transcripts of that and have done some very interesting work around that and actually seeing whether from what you see in sessions and so on, you can actually get to any sort of predictive power. Now in psychiatry, that's the holy grail for everyone to get to kind of predictive power or whatever. So we're doing the same as others in that space. I don't know any other AI comments anyone has.

The only thing I'd add is from a commercialization standpoint, AI could potentially help from more streamlined targeting and messaging rollout. So we will obviously be exploring that once we get closer to commercialization.

Okay. Great. And last, most relevant to you, and you certainly touched on it throughout the session. On the regulatory side of things, changes at FDA pricing, tariffs, any regulatory topics that are kind of top of mind, I would imagine FDA, but...

Yes. So I mean, obviously, as a pre-commercial biotech, neither tariffs nor MFN or pricing right now are kind of things that we're focused on back to your earlier question, as you think about a global strategy, clearly, how you think about pricing will come into that.

The big one for us is regulatory. And as I said, from a day-to-day FDA perspective, there have been no changes in the psych division. They remain engaged. It's the same people we're dealing with. But clearly, there are a number of voices talking about the potential for psychedelics. There have been public comments about the need to accelerate psychedelics. We have applied like everyone else for one of these commissioners' national priority vouchers.

I would say we are clearly seeing regulatory flexibility that is positive and a sense of urgency that's very refreshing. But to build on a point Lori said earlier, we are not asking for psychedelic exceptionalism. These need to be held to the same standard as anyone else. We are conducting 2 very large, very robust Phase III trials, and that will continue to be the standard in psychiatry.

Okay. Great. If there's nothing from the audience, we are out of time. So thanks again.

Thanks very much, Judah.

Thank you.

Thank you.

All right. Welcome, everyone. We're going to get started. I'm Josh Schimmer from the Cantor Biotech Equity Research team. Very pleased to introduce from the COMPASS Pathways. We have the management team, Kabir Nath, Chief Executive Officer; Guy Goodwin, Chief Medical Officer; and Steve Levine, Chief Patient Officer. And I just have to say like a wonderful team to be leading this field of psychedelics that started very fringe and is now going mainstream. And I think now requires a very different approach to communicating, thinking about the power of psychedelics. And why don't we start there as COMPASS -- and can you just give us a quick overview of the company. And should we be continuing to use the word psychedelic? Or do you want us to maybe move away into some other terminology?

Thanks, Josh, and thanks for the invitation. And just a reminder, we will be making forward-looking statements and refer you to the risk factors in our many SEC filings. So COMPASS is a company in Phase III for treatment-resistant depression. We have 2 ongoing Phase III studies. We put out the primary endpoint of the first of those at the end of June, which showed a highly statistically significant result, a MADRS difference between baseline -- change from baseline, a MADRS difference of 3.6, which is clinically and commercially relevant. But clearly, as a highly statistically significant study that discharged regulatory risk comes on top of our Phase IIb study that was published now 3 years ago. So we are 242 in treatment-resistant depression, which we believe is unique, but we're set up for using the word remarkable.

Our second Phase III study, 006, we are guiding to the 26-week data from that study in the second half of next year. And these 2 studies taken together are very consistent with the FDA's draft guidance around psychedelics that was published in June 2023. So we're confident both in the execution of those and in the fact that taken together, those 2 supported by a very strong Phase IIb together constitute, we believe, a really robust package of evidence for a filing, and we will talk about how we might try and accelerate that given some of what we're hearing from the administration and so on as well.

I think on your second part of the question, I mean, I'll start, but clearly, Guy and Steve should weigh in. I think for now, we are clearly leaning into the subjective experience for psilocybin because what we have demonstrated is actually certain elements of that appear to be needed to achieve the impact we're seeing in treatment-resistant depression. So with that said, I don't think we should run away from psychedelics, but where that goes over the longer term is interesting. But Guy, Steve?

Yes. I think the only thing I would add is that the use of the term psychedelic has often gone along with the term assisted psychotherapy. And I think that has been unhelpful because it's distracted attention to the psychotherapy that particularly it was used with MDMA and which is actually unnecessary for the actions of psilocybin. Psilocybin works essentially through an inward process. People are their own treatment therapist, if you like. They don't need external help. And during the actual experience, people are silent and contemplative. So I think the psychedelic psychotherapy nomenclature has been unhelpful, but I don't think we can leave behind the psychedelic experience because that does seem to be core, whether you think of it as a mental state or a brain state, it seems to be core to the efficacy of these drugs.

Okay. So maybe you can go to the 005 study. You gave us a little snapshot of the data, right? The 6-week time cut, and there's so much more to learn about the data set that hopefully is going to better frame what patients might experience. One important consideration is you looked at 6 weeks, which is pretty far out as far as depression studies go. And typically, the sooner you measure, the larger the treatment effect. So the other relevant component to this is as the treatment effect gets lost over time, is it because the placebo arm is doing better or because the patients are doing worse? As you think about kind of completing the data set, what are you hoping to see based on the data you've already generated?

Guy, you want to take that?

I mean, as you know, we do not yet know what the data will show us. So -- see this trial, it's pure speculation for us. I mean what you outlined is possible that it may be that the placebo arm starts to do better after a few weeks that is seen in other studies as well, and that's possibly why the difference wasn't as great. But there are a number of ways in which we're going to look at this data over the full 26 weeks that we have blinded information. And of course, these patients were eligible for retreatment if they didn't respond. So we're going to get a sense of what a second treatment can do if the first one doesn't achieve the full effect. And I think that's going to be very informative.

And you also haven't adjusted for rescue therapy in this trial. How do you think rescue therapy might distort the treatment effect?

Well, just judging from the 001 data, the way in which we analyzed that was allowed for the treatment effect on the one hand -- in one of the versions of the analysis and it didn't in another. The effect sizes actually were unchanged. So we don't think it makes a great deal of difference.

As we think about then the 006 trial and the questions that you're going to address with that, 2 important considerations. One is your primary endpoints at 3 weeks and the other is that you have a second dose. There's not much literature to guide certainly on the second dose dynamics, but relative kind of to the 005, at least top line data, what do you think directionally we're likely to see in 006 with those adjustments?

Well, I think our hypothesis is the effect will be larger. That's based on our own analysis of data that was available from the IMPERIAL study that compared 2 doses of 25 milligrams COMP360 with escitalopram. And in addition, there's sort of anecdotal data from other studies that suggest a second treatment may be effective in adding to the treatment benefit of the first. So we have a strong hypothesis that it's going to be a better overall treatment package to get to rather than one, but time will tell.

And we have a new FDA and HHS administration who I think are very vocally supportive of psychedelics. So as we think about your articulated time lines for data disclosure and unblinding, et cetera, is that still congruent with what might be a very accelerated path for you, particularly as you filed for a commissioner's Voucher and you're trying to do what you can to maybe lean into the receptivity of the administration for these therapies.

Yes. So the first thing to say is the first and most important thing is to get the studies done as quickly as possible. So our first internal priority is to continue to do everything we can to accelerate 006, but I can confirm we are absolutely on track for the guidance we already have. The data from 26 weeks of that in the second half of '26. So to break down your question a little, absolutely, we are encouraged by what we hear from senior figures in the administration. We seem to share with them the view that psychedelics have significant potential and that appropriate ways to try to get them to patients more quickly are worth seeking. So yes, in dialogue with the agency, that's about the potential for some regulatory flexibility. I mean the data timings I've given you are the data timing, yes. I mean that is when we will have the readouts and so on.

The question is whether given a very robust Phase IIb that is highly consistent in its findings with the first Phase III, what combination of those and the emerging data still to come from 005 and 006. Can we take together? Is there the potential for something that you might is familiar from other divisions, shall we say, a rolling submission, a rolling review, which has typically not been done in psychiatry. So that's the type of dialogue we're looking to have. I think that what's really important is no psychedelic exceptionalism. We're not asking for a different set of standards. And a key part of all our dialogue is that COMPASS is the closest to a potential regulatory approval. And the reason for that is we've actually invested more time to run really well-designed, robust large-scale clinical studies than anyone else yet in psychedelics.

Have you noticed the tenor of the conversations with the FDA has changed? And who are you able to dialogue either within the FDA or HHS, recognizing that you do have a number of allies out there now?

So profession. First, nothing has changed within the psych division or the professional staff with the FDA since January. So we continue to have very good engagement. We have breakthrough designation, which allows for a regular engagement. Within HHS, we have a number of different contacts. We have people we're talking to. Again, let's just say that translating rhetoric into action in what is a complicated administration is an interesting new challenge that we're working through.

Okay. Any sense in terms of the regulatory dialogue time lines as to when you might have clarity in terms of what the FDA really now requires between 005 and 006, if you do need anything from 006?

So I will disclose that we have just met with the FDA and just means in the last hour. And people on this platform were not all part of that meeting. So I cannot tell you what happened in the meeting. So we're not in a position to announce that until the meeting had taken place. So look, we will look for the minutes of that. Again, our going-in position was absolutely around is there flexibility? What might be the elements of that is? We're not in a position to say what came out.

Do you feel like commercially alone, you need some additional time to prepare, right, for what is a somewhat complex now delivery product profile, right? We had talked about this before, like if your regulatory time lines compress too much, are you -- have you not had enough time to get ready commercially? But I know you've been doing a lot of work commercially leading up to this.

So the easy answer is Lori and Steve will be ready whatever the time line is, but Steve?

Well, I was going to say because Lori isn't on the stage right now, I'm happy to say that we will be ready. But kidding aside, whatever the compressed time line is, and of course, we've prepared for various scenarios, we'll be ready.

All right. Excellent. So I think we've talked about a little over 6,000 centers that are equipped to administer SPRAVATO. You can multiply that by the number of days they can administer SPRAVATO, the number of times per day they can administer SPRAVATO. And there's actually a fair amount of capacity in the system, at least for SPRAVATO. It also, I think, implies there may be like 15,000 to 20,000 psychiatry practices that don't have the capability to administer SPRAVATO. So as you kind of think about this evolving landscape that you're going to be launching into, how are you thinking about the bandwidth considerations at the practices and how you can help drive that momentum, not just to 6,000 but to 12,000 and 18,000 practices?

So as you said, SPRAVATO today is being delivered in 6,000-plus sites. And as you mentioned, within those sites, there currently is slack, there is capacity. And because a SPRAVATO room looks like what's needed for COMP360, that means there's capacity for COMP360 today. Without us doing anything else, that capacity will increase. That is the trend right now in the building of psychiatry infrastructure. It's in the direction of interventional psychiatry capacity. We've seen this since 2019. At the time prior to SPRAVATO's launch, there really were no interventional psychiatry practices. There were very few rooms available. That has really taken a hockey stick like trajectory, roughly doubling each year since that time. And there's no signs of that slowing down given that -- it's not only been good for patients with good outcomes and reaching those sooner who are living with treatment-resistant depression-related conditions. But most of these practices are built in a treatment-agnostic way to capacitate new treatments as they come online. And so they will continue to build because it's their business.

Are these the ketamine clinics -- because there was a time when the ketamine clinics as we had talked about starting to decline because the business model wasn't working, but this is now a new business model that likely should work. So to what extent as we're talking about these 6,000 SPRAVATO centers, are we talking about ketamine clinics or not?

The way I would differentiate ketamine clinic from a site delivering SPRAVATO today is that ketamine clinics typically are single service line focused on delivering ketamine, typically not contracted with payers and being paid out of pocket by patients at the point of service for an off-label treatment. That is a very difficult business model to scale because it's not a true health care business as opposed to the interventional psychiatry practices, which by taking a more agnostic approach by contracting broadly with commercial and government payers, delivering a range of treatments and not being wedded to just delivering a single treatment, but rather delivering the appropriate treatment to the appropriate patient at the right time, that is a healthy, scalable business.

And so for us, as we look ahead to a commercialization along any time line, the existing SPRAVATO infrastructure is already there. That type of infrastructure is scaling. But with the work that we're doing with our strategic collaborations, which spans not just interventional psychiatry but also hospital systems and integrated delivery networks, community behavioral health, decentralized models, really the gamut of where patients living with treatment-resistant depression receive their care today, we are learning a lot every day about what it will take to implement a treatment like COMP360 and those types of sites of care as well.

I just wanted to come back to something you said earlier because one thing we clearly don't know is what the ultimate path or maximum number of treatment centers delivering treatment will be. But one thing that's clear is we're going to have to do a significant education work with that large pool of psychiatrists who will never be able to offer the treatment themselves because we can argue about why SPRAVATO's penetration is so low. But one of the key reasons is that psychiatrists are not referring to interventional psychiatry. They're not understanding [indiscernible]. So that's why we have a field medical team already, and that piece, again, of our commercial prep is fundamentally important because we have to get to those referring psychiatrists and really break out of the current paradigm that refers to interventional psychiatry only very late in the disease progression.

Can you talk more about the scalability dynamic? Because intuitively, it doesn't seem as easily scalable in the sense of if you want to add more capacity, you need to find more rooms, but you rent it out your office space and you're using it presumably efficiency. So where does that -- how do you scale that up? Do you have to open up new sites? How do you staff those new sites? Where do you find the extra rooms to handle what eventually may be millions and millions of patients of demand?

Yes. I mean, first, starting with interventional psychiatry practices. The typical footprint of one of these centers is the relatively large for psychiatry. They have multiple rooms. Typically, multiple rooms will be treating patients with SPRAVATO simultaneously, maybe one or more rooms also for some kind of neuromodulation like TMS. Sad reality, along with the tremendous unmet needs for this population is that these ultimately are patients with chronic remitting depression, relapsing remitting depression. And they will likely need multiple treatments over time. This is the management of a chronic illness. In cold business sense, that means that they have a high lifetime value if you can continue to meet their needs. There's also a relatively low cost to acquire these patients. And it is a relatively low cost to build one of these centers or to add space in one of these centers and to operate them on a monthly basis.

So the economics -- and again, I don't like to talk about treatment-resistant depression in this way, but the economics favor building additional capacity if you are reaching capacity. Today, there's a lot of slack anyway. Now these are the larger, more organized, oftentimes public or venture capital or private equity-backed businesses. There are today many smaller psychiatry practices, the more traditional chair desk phone, single psychiatrist or small group. recognizing the need to build additional capacity for the new treatments coming. There also are a number of companies now that are focusing on building the back end to support smaller practices to be able to deliver treatments like COMP360.

It gets so nuanced and fascinating too, right? Like does the psychiatrists need to be there on site? Or if you're a pioneering psychiatrist, can you have satellite offices administrating? Like again, because this is really getting to that question of how do you scale? Steve, you said it's easy to add rooms, but how is it easy to add rooms when you rented out your little office space and now have to wait for another segment of the building to open up to lease.

Yes, you're waiting for spacing your building to open up perhaps or within the same city, perhaps you're building a new site. And depending upon the size of the city, there's potentially room to have multiple centers within a single city if there is that demand. As far as the staffing, going back to the structure I was describing before of these being platforms that deliver multiple treatments, I think you want to think about this not just in terms of delivering COMP360 or having the capacity to deliver multiple COMP360 treatments, but how these centers need to be staffed to deliver a range of treatments. And today, what they typically look like is one prescriber, either psychiatrist or a psychiatric nurse practitioner on site with a multidisciplinary team supporting them that can include technicians and nurses and other health care providers.

So we haven't really focused on the psychiatric nurse practitioner component, right? Because, again, for a psychiatrist to open up multiple sites, he can only be on one. But if he's got a team of nurse practitioners, that can actually extend the reach and again, help with the scaling process. So how many psychiatric nurse practitioners are there? What's the growth rate of even the treating physician and nurse practitioner demographics here?

There are the numbers today, and then there's the reality that the numbers are actually growing pretty rapidly. There's an increasing popularity of psychiatry as a choice of residency amongst graduating physicians. There is an increasing number of psychiatric nurse practitioners entering the workforce and also physician assistants who are at a similar level to nurse practitioners, although historically, they focused on surgical subspecialties or primary care. We're seeing a tremendous trend towards physician assistants now being trained specifically to deliver psychiatric treatment. So today, those numbers look something like 35,000 to 40,000 psychiatrists. There are 6 figures plus of nurse practitioners, probably about 20,000 or so of them specifically focused on psychiatry. And then again, a rapidly growing number of physicians assistants and a rapidly growing number of psychiatrists in training now who will soon enter the workforce.

So in terms of the increase in training, are centers or academic institutions now expanding their residency programs with this in mind? Or has it just become a more popular specialty, as you point out. And so now the available slots are being filled more consistently?

It's both. Available slots are being filled more consistently, but also [ ACG&E ] over the past several years has approved more psychiatry residency slots, and those are being filled too. And yes, perhaps that is in part because of excitement around psychedelic treatments to come.

Okay. Got it. Maybe talk a little bit about pricing considerations, what the pricing benchmark products that you're looking at might be?

So it's premature to speculate on that because until we complete the Phase III, understand durability and so on better, we need that to do that. But clearly, we know what SPRAVATO is and in SPRAVATO, net is going to be depending on the number of administrations somewhere between $25,000 and $45,000 a year in that range. So you can clearly see that as a benchmark. But again, much will depend on the actual profile, what we see for durability, need for repeat doses and so on.

So now and assuming approval relatively imminently, which whatever that actually means, Lori is ready to go from day 1. If you got approved tomorrow, in theory, how do we think about that early rollout? Like what are the steps that need to happen post approval to the first patient being actually treated in the clinic? What there might be DEA scheduling considerations to address. There might be counseling considerations, preparatory sessions. Maybe give us a sense of what that entail.

So I'll just start with kind of the big budget regulatory and so on and then Steve and Guy weigh in. And so first, there would need to be rescheduling. So federal rescheduling, the DEA has 90 days after an approval. As an industry, we are working to actually bring that in parallel with the final stage of FDA review because there is no reason for that to have to be a sequential 90-day. So the industry association has made that one of their key asks. But there's federal rescheduling, there's then state level rescheduling, which we've talked about before. 50% of states have an automatic trigger with federal rescheduling. The other half don't.

And so we have already now for nearly 2 years, been working to ensure that we can enable whatever legislative needs are at those states so that, that can happen as well. But you need that state level rescheduling before you can deliver product. So that's kind of the formal piece. I'll ask Steve and Guy to talk about some of the things on the education and how to get ready side that will need to be in place. Also, we have to assume we will have a REMS. So an approval will come with a REMS and rolling out a REMS is a nontrivial exercise as well as part of this.

Yes. Certainly, as you would expect, we'll have some traditional commercialization efforts that we'll have to prepare as well as far as the sales force and increasing the size of our medical science liaison team, the other things that will be part of any commercial launch. But specifically to the point about preparing sites, getting them ready for compliance with the REMS or understanding the training that they may require, et cetera. This is part of the learnings that we get right now from our work with our strategic collaborations because part of what they're sharing with us would be what is their current staffing, who's involved in the care of their patients, what kind of training do they already receive? How do they handle additional trainings if they do need training beyond whatever it is that they are already using to care for their patients, how they would handle things like preparatory sessions, would they do those one-on-one, would they do them remotely or face-to-face, would they do them in groups, et cetera.

So these are a number of the things that we're working through. And of course, this would apply not only to the specific collaboration group that we're working with. But because they're representative of broader phenotypes, it's allowing us to build templates to get ready to understand how to educate and support these sites at that moment of launch.

It's interesting, right, because for the clinical trial program, the centers had to go through a fairly rigorous training period. Is that -- how do you see that evolving in the commercial phase? Are they going to have to go through the same kind of protocol training to be able to prescribe in which case, it may be kind of center of excellence type delivery, but that seems to be a very limited paradigm relative to the unmet need that needs to be addressed.

Much of -- and Guy is weigh in here, too, but much of the need for the training that we provide in our clinical trials is just consistent with the rigor with which we approach every other facet of running these trials. It's to ensure that there's consistency site to site, that there's compliance with our protocol that the people involved in supporting these patients aren't doing more than they should do in this trial and introducing additional variables. If it's a therapist who's part of the study team, we don't want them doing therapy during these studies because that's not part of this protocol.

Once we enter the real world, much of that becomes less important to real-world care delivery, where there's less of a requirement to have that high level of standardization site to site. So there will be basic principles that these sites will need to understand. Much of that can be incorporated within the training that's part of a REMS. We are working out what other third parties might be involved to help these sites understand the minimum training requirements and core competencies and so forth, but we don't anticipate a rigorous many hour training like we've had.

Yes. And I think I would just add, Josh, that what -- the feedback we get from PIs is that they get this training, which in some ways they find rather scary. And when they actually come to deliver the treatment, it's actually kind of easier than they expected. And so there is that sort of element to it, which is quite reassuring to us that we set very high standards and it's sort of make it difficult for people. When they actually do it, they do find that the experience the patient has is pretty gentle, it's pretty manageable. And for the staff running the place, it's not a big strain. And that may not be true of all the psychedelic treatments that get developed.

So there's another important leg to the stool that's starting to spread in the PTSD indication. I think you just published some of the Phase II data. When are we likely to hear a little bit more about that program? And what are the gating steps to advancing?

Yes. So we are in the final stages of designing a late-stage study for that. We did get some agency feedback on that, which we're incorporating into that. So I mean, I would hope that in relatively short order, we'll be in a position to announce how we're taking that forward.

Right. Excellent. And then maybe in the final seconds here, over the next 12 to 18 months, just kind of frame for us some of the milestones we should be looking for.

So we will, in due course, announce the completion of enrollment in 006, and that's going to be important both to demonstrate that we are sticking on time with that and delivering on our commitment for that time line. But also that will then clearly allow us -- require us to tighten the guidance both for the 26-week data of 006, but also for the 26-week data of 005, which is going to be, as I said, hooked to -- based on the timing for the 9 weeks of that. So that's one. Then we do expect that 26-week data from 005 realistically early next year and then the second half of next year, the 26-week data from 006. And somewhere in this relatively short time frame, we will also announce the PTSD design.

And then at some point, some regulatory update on the requirements. I think we're out of time. Thank you so much the COMPASS Pathways team for joining. I think we also have -- we recently did a webinar together under our let's do some psychedelics framework. And I think we're going to come back after we get some more color on PTSD and dive in there because there is a huge unmet medical need that is so poorly served currently. So all right. Thanks, everyone, for joining.

Hello, everyone, and welcome to COMPASS Pathways Second Quarter 2025 Earnings Conference Call. Please note that this call is being recorded. [Operator Instructions]

I'd now like to hand the call over to Steve Schultz, Senior Vice President of Investor Relations. You may now go ahead, please.

Welcome all of you, and thank you for joining us today for our second quarter 2025 results conference call. Again, my name is Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways.

Today, I'm joined by Kabir Nath, our Chief Executive Officer; and Teri Loxam, our Chief Financial Officer, who will have prepared remarks. In addition, Dr. Guy Goodwin, our Chief Medical Officer; Dr. Steve Levine, our Chief Patient Officer; and Lori Englebert, our Chief Commercial 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 in 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 over to Kabir Nath.

Thank you, Steve. Good day, everyone, and thank you for joining us. Let me begin by welcoming Justin Gover to the COMPASS Board of Directors. Justin was the CEO and one of the founders of GW Pharmaceuticals, and we're truly excited to have access to his expertise. Under Justin's leadership, Epidiolex, the first cannabis plant-derived medicine to be approved by the FDA had a successful commercial launch.

I look forward to leveraging his expertise as we embark on a similar path to gain FDA approval and launch COMP360 for TRD. In addition to announcing the addition of Justin to the Board earlier this week, we announced that Dr. Linda McGoldrick will be retiring from the Board at the end of October after a transition period. I'd like to thank Linda for her service on the Board over the last 5 years where she was instrumental in supporting the growth of the company through the IPO and subsequent developments.

Turning now to our operations. This has been an exciting year for COMPASS. In late June, we announced the successful achievement of the primary endpoint of the COMP360, 005 trial, the first of our 2 pivotal Phase III trials. The positive results were highly statistically significant demonstrating a clinically meaningful reduction in depression and no unexpected safety findings based on the latest data reviewed by the independent DSMB.

This assessment included all data reviewed by the DSMB to date from both the 005 and 006 trials going beyond the 6-week time point for 005 alone. There was a 3.6 point difference in change from baseline in mattress between the 25-milligram and the placebo arms at 6 weeks, exceeding the 3-point difference that is both clinically meaningful and commercially viable.

While cross-trial comparisons are always challenging, this difference sustained to 6 weeks with a single administration of COMP360 is similar to the difference seen at 4 weeks in the pivotal trials for the blockbuster drug SPRAVATO, which required 8 administrations. So we believe the result that we have seen at 6 weeks with COMP360 is both clinically and commercially compelling.

With this positive data, COMPASS has delivered 2 for 2, announcing positive, highly statistically significant results from 2 robust late-stage studies of over 230 patients each in a very difficult-to-treat patient population in depression.

Given the track record of previous studies in psychiatry, particularly in severe depression, our achievement of 2 positive late-stage studies is remarkable and provides important clinical validation for COMP360 treatment potential in TRD.

We plan to meet with the FDA to discuss these results and explore next steps in getting COMP360 to patients as rapidly as possible, patients who so desperately need new treatment options. The second pivotal Phase III trial, COMP006 continues to recruit well and we confirm that we're on track to disclose the 26-week data in the second half of next year.

As a reminder, the protocol for this trial has a second dose after 3 weeks with the 6-week primary endpoint assessment, therefore, only 3 weeks after the second administration. We should also get some good information on the effects of a second dose as part of the 26-week 005 data given that subject to specific retreatment criteria, participants can get another dose in Part B, which runs from the 6-week time point through 26 weeks.

To prepare for a potential commercial launch, our team continues to work with a broad array of mental health care providers, both through our strategic collaborations and through our field medical team to refine our understanding of how COMP360 treatment will fit into existing setting of care.

We're frequently asked by investors how COMP360 will be viewed by providers who are used to the approximately 3 hours SPRAVATO treatment window. Through our discussions with these providers, we know that patient preference will be a driving factor in treatment selection.

As you're well aware, SPRAVATO patients need to be driven to the clinic frequently, which is a burden to the patient and caregiver and generally, they're not able to return to work that day. In addition, we believe that the added administrative burden and the work required to turn a room potentially multiple times may actually favor COMP360 from a practice standpoint.

Finally, the CPT 3 code specific to psychedelics that were put in place back in early 2024, provide for hourly reimbursement. So regardless of the length of the administration for COMP360, the provider will be covered. Steve and Lori can go into much more detail on all of this.

Beyond TRD, we're also excited about the potential for COMP360 and PTSD. We're in the final steps of designing a late-stage clinical program in PTSD, and we look forward to updating you when that design is finalized and once we've reviewed it with the FDA. Given the high unmet need and limited current treatment options, we see a significant commercial opportunity in PTSD.

In addition, as you know, we have been running a small Phase II study in anorexia. This was a double-blind, randomized, controlled Phase II clinical trial, investigating the safety and efficacy of COMP360 psilocybin treatment in participants with anorexia nervosa. It was a multicenter study, which enrolled 32 participants. The study has now completed, and we recently received the data.

From an efficacy standpoint, there was an encouraging positive signal in the reduction of eating disorder and depressive symptoms in the 25-milligram arm, which was sustained through 12 weeks. However, the low overall numbers of participants and the high number of dropouts in the control arm limited statistical power.

The safety profile was aligned with the high-risk patient population in anorexia and no unexpected safety signals were reported. As we've discussed before, this is a difficult condition to study. We're proud of the data that we've been able to generate, and we'll publish or present the full data set in future.

With that, let me now hand the call to Teri to go through some financial updates before we move on to Q&A.

Thank you, Kabir. At the end of June, we had cash and cash equivalents of $222 million, which we expect to fund our operations into 2027. This compares with $260 million that we had at the end of the first quarter. Debt under the Hercules loan facility was $30.9 million at the end of the second quarter. Cash used in operations for the second quarter was $38.7 million, and we expect net cash used in operations for the full year 2025 to be within the range of $120 million to $145 million.

We're energized by the positive 005 primary results which we believe has derisked the company from a regulatory and commercial perspective. And we look forward to the upcoming 26-week data from both Phase III trials. We are finalizing a PTSD study and look forward to updating you soon on that design and time line.

2025 has already been an important year for the company. And the remainder of this year and 2026 is shaping up to be even more exciting. We are heads down focused on continuing to execute on our pivotal program while exploring all opportunities to get COMP360 to patients suffering from hard-to-treat depression in PTSD as quickly as possible.

As mentioned in the beginning of the call, Dr. Guy Goodwin, Dr. Steve Levine and Lori Englebert will also be available for Q&A. Thank you, and I'll now turn the call over to the operator for a Q&A.

[Operator Instructions] Your first question comes from the line of Paul Matteis of Stifel.

Paul Matteis from Stifel here. I was curious if you could expand upon the engagement you've had with the FDA since the data. What do you think the scenarios are here where you could have an accelerated path for a filing. And the same scenarios, I guess, do you think you actually could move quickly enough where the second Phase III study wouldn't read out before you submit or during the review? I guess like is there a real way to actually move ahead of that data? Or are we going to ultimately, of course, get that data before there is any sort of regulatory decision in any scenario?

Thanks very much, Paul. It's Kabir. I'm just checking, you can hear me clearly.

Yes.

Thanks, Paul. So thank you for the question. So as we've said, we have requested and we will be meeting with the FDA in this quarter. As we said on the call, we are 2 for 2 now in treatment-resistant depression. So Phase IIb with over 230 patients, this Phase III with the primary endpoint data, 250 patients, and importantly, consistent data across the trials. While the IIb, of course, the primary endpoint was at 3 weeks. As you know, at 6 weeks, we did see a statistically significant difference. And actually, it's a pretty similar difference to what we've seen here in the Phase III.

So we are 2 for 2, we believe, in a very hard-to-treat patient population and one in urgent need of new interventions. So to your point, it clearly is the right thing to ask what accelerated pathways may be available, and that's exactly what we are planning to do. I'm not at this stage going to handicap the chances and obviously, we need to have that meeting with the agency in quarter 3, see what their view is.

We're obviously encouraged by the fact that there are other leaders within the administration more broadly, who seem to share our view in the potential and share our view that there are grounds to move this more quickly. But in terms of specifically which elements of 005 or whether part of 006 will be needed, that really depends on our discussions with the agency.

Kabir, just on your last comment there, understanding you request a meeting and meet with folks with the psychiatry division, are there plans or expectations or you'll be engaging with others that are more senior at the FDA or within HHS as well?

Yes. But I'm not going to go into details of those, but yes, absolutely. We recognize that this needs to be a concerted approach using whatever levers we can. But I might just ask Lori to comment on some of the work we have been doing around the broader engagement of stakeholders, not just in the administration, but actually in the political environment as well because we recognize that's also a critical part of this.

Yes. Thanks, Kabir. Paul, so obviously, we are very encouraged by statements that have been made by Secretary Kennedy as well as the Commissioner. They -- as Kabir stated, they're very clearly viewing psychedelics as a potential to treat these patients who have otherwise limited options. We've seen that through examples of them appointing Matt Zorn, Mike Davis, this seems all very positive for the industry in and of itself.

We also have been spending quite a bit of time in D.C. as the potential first-to-market company in the psychedelic space. We do find -- we do take it very seriously that we want to make sure that everyone is well educated and informed. And so we've been spending quite a bit of time there.

And what we're finding is that members of Congress are also highly receptive not only to the BA sector, which, of course, they care very much about and gets a lot of commentary, but also for the broader patient population. So we are encouraged by the conversations that we're having and continue -- we want to continue our efforts there.

And Paul, one thing I should have said and to add, you'll be aware that last week, the formal application process for the Commissioner's National Priority Review Voucher, the one that promises a very accelerated time line open. So we have submitted our application for that along, I'm sure with many other companies, but we did do that as well.

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

This is Luis in for Patrick. I would like to ask a little bit on the collaboration, the strategic collaborations that you are putting in place for the interventional psychiatry treatment centers. How are they progressing? What feedback have you received about readiness for COMP360 deliveries approved? And how confident that the existing network of centers that you've already engaged with will support the delivery of 360 if approved?

Luis, I'll pass to Steve to answer that.

Thanks. Luis, thanks for the question. Yes, we have been engaged now in the work with these collaborations for the past couple of years. As a reminder, they are representative of the broad swath of sites of mental health care delivery in this country, including hospital systems, interventional psychiatry networks, community behavioral health and others.

And what we are finding in this work, and as a reminder, some of them deliver SPRAVATO today and those that do are high representative of the 6,000 centers that are currently delivering SPRAVATO around the country. And one thing is abundantly clear. It's that this work is reinforcing our conviction that COMP360, if approved, fits directly into the infrastructure that is delivering SPRAVATO today.

If you look at a SPRAVATO room, it looks like what is necessary for COMP360, the staffing of these centers is what we believe will be required to deliver COMP360. And so we are very confident that the network is ready if and when we get approval. And even if that approval is accelerated, it is weighted in.

Your next question comes from the line of Gavin Clark-Gartner of Evercore ISI.

Congrats on the progress. First, I was just curious if you've seen a pickup in 006 enrollment following the 005 data? And then secondly, just following off your last point on the commercial side of things, do you have an estimate for what percent of SPRAVATO use is given in single rooms versus kind of group room settings where multiple people can be monitored at the same time?

Thanks, Gavin. So I'll take the first one. So the 005 data has been viewed very positively by investigators not only in 005 and 006, we're now in that kind of the really steeper center point of the 006 recruitment, and it's going extremely well, which is why we're able to reconfirm our guidance for data in the second half of next year. But yes, I would say, in general, the reception from investigators to the data has been very positive and has reinforced their belief in the potential of 006 and frankly, the derisking both from a clinical and regulatory perspective.

And I'll hand to Steve for the second question.

Gavin, regarding your question about whether SPRAVATO is currently delivered in individual rooms versus in group settings, it is primarily in individual rooms, and that is another reason why we believe that infrastructure is in place. There is the likelihood that adds these products mature in the market, and they are commonly delivered, sites may look at various models to deliver them. But again, currently, today, it's primarily in individual rooms and ready to deliver COMP360 when available.

Next question comes from the line of Ritu Baral of TD Cowen.

This is Athena Chin on for Ritu Baral. Are you guys pursuing the Commissioner's National Priority Voucher? And what is your understanding of the criteria to meet eligibility?

Athena, yes, if I did actually just confirm that in an earlier question, we did submit our application. We also do as part of our briefing book for the meeting with the FDA, raised that question. So in terms of the criteria, I believe there were 5 priorities listed, and they include significant need public health crisis, both of which we clearly hit, innovative treatments also.

There are also ones around manufacturing and global pricing, which are less relevant to us, but it's clear that the criteria don't expect a company to hit all 5 of those, and we believe on 3 of them, we very clearly tick those boxes. It also requires you to be ready to start submitting elements of a finding package, and we clearly are in terms of CMC and some of our other preclinical and so on. We're in very good shape with that.

So we think we're a great candidate. We recognize that there are, in theory, only 5 pilots that we would be taken forward. And we also recognize that the decisions were due to be made by the CMO, but it appears that the CMO at the FDA is currently a vacant position as of Monday night. So what the process is, we don't know. But we believe absolutely meet the criteria, and that's why we submitted.

Next question comes from the line of Judah Frommer of Morgan Stanley.

Just following up on kind of your commentary regarding interactions with the agency. It seems like there is some high-level connectivity. But are you able to comment on consistency of interaction with kind of mid and lower level members at the agency. Just curious if there's been consistency within team makeup in the teams that you're talking to?

Thanks, Judah. And nice to meet you. And the answer is absolutely. So as a reminder, we have breakthrough designation. And as we've always said, we have consistently had excellent engagement with the psychiatry division. Currently, we've seen no change to either the staffing, the level of engagement, the responsiveness and so on. So at the day-to-day level with the FDA, we remain very tightly aligned with the good relationships and no changes.

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

I had one on safety, especially as it relates to redosing. So I guess, how are you guys thinking about the risk of suicidality or any elevations in suicidal ideation? Are you thinking that after -- that could occur after every dose of COMP360 or potentially every dose of placebo? Or is it just something that occurs after the first dose on the study? I guess do you have any data that you can speak to with respect to that? And then relatedly, I know in the anorexia study, you said there were no unexpected safety signals. I wonder if you could just talk a little bit more about what you saw in terms of safety from the anorexia study, especially on suicidality.

Thanks, Leonid. And I'll pass to Guy in a moment, but first, just as we've always said, the statement we made last month from the DSMB did refer to all data they were seeing today from both 005 and 006, so including the study that has the second dosing. But let me hand to Guy for more -- importantly a broader discussion of that. Guy, please.

Yes. I think we have to be a bit -- we don't have a detail on the time course of the suicidality that is being seen in 005 and 006. All we know is that there's no imbalance between the arms. So I can't really comment on directly to your question except to sort of be reassuring about the fact that there isn't a clear effect of the drug that's much more likely to be an effect of the illness, and that will depend obviously on how people have responded and how the response is maintained.

So we will certainly have all that information in due course, but not at the moment. It's a good question about the anorexia group. This was a small study, remember, but it was clear that we saw higher rates of suicidality than we are used to see just measured as events in that group. That was true in both the arm receiving 1 milligram and the arm receiving 25 milligrams.

So again we have no imbalance between the arms, but higher overall rates, reflecting the fact that it's a more dangerous condition from the point of view of mortality. It has the highest mortality of any psychiatric disorder. And suicide is one of the leading causes along with the physical problems that patients also encounter. So the safe -- relative safety of our treatment in this high-risk group is, again, a reassuring thing really for the whole program.

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

What is the earliest that you could file a new drug application for COMP360? And how should we think about when you might announce a time line for reporting Part B from the COMP005 trial? And then I have a follow-up.

Thanks, Sumant. So again, I'll refer you to my earlier answer until we've met with the agency. It's premature to speculate on exactly what that could be because we really need to reach alignment on what data they would like to see and the process for that.

As we have said before, we will, in due course, announce the full enrollment of 006. As and when we do, that will be the point at which we can all look at our calendars and project forward because as a reminder, we have said 26 weeks of 005, Part B of 005, we will only release once all patients are through Part A of 006 in order to avoid any potential suggestion that there's a compound between those 2 sets of data.

Got it. And how onerous is the process to submit an application for the Commissioner's Priority Review program in terms of any trial data necessary? And is there any Phase III related efficacy or durability data in that application or your briefing book that investors are not seeing yet?

So in terms of what was required to submit for it, it's a 350-word abstract. So I could safely say that there was no data included in that. And again, I think as we're all aware, it's unclear what the selection criteria are actually going to be for the pilots. And no, to confirm, I mean, we have no more Phase III data than is out in the public domain, and that we have already released.

I'd now like to hand back the call over to the management for final remarks.

Thank you very much. So thanks, everyone, for your attention this morning. We're excited about the progress that we have made and the progress we're continuing to make. We've delivered 2 positive late-stage studies in treatment-resistant depression, which is remarkable and likely a unique achievement.

With that, we're also very encouraged by the signals we're hearing from within the administration and more broadly about them sharing our belief in the potential for these transformative treatments for patients who have so few options, and we're committed to working with the appropriate regulatory and administration authorities to see what we can do to advance COMP360 for treatment-resistant depression.

In addition, we will be, in due course, announcing the design of a PTSD study. I think particularly with recent events, again, at the agency, it's very clear that there is an urgent need for new treatments for PTSD, and we're excited to move COMP360 forward in that as well.

So thanks again for your attention this morning. I wish everyone a good day.

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