All right. Thanks for joining, everyone. Next up, we have COMPASS Pathways. Really excited to be joined by the team here. Fresh off a big year this- year and another really big year ahead. We have CEO Kabir Nath. We do not have Lori up here, despite what the sign says. But we do have Steve Levine, Chief Patient Officer, and Teri Loxham, the CFO. Thanks so much for joining. Let me just turn it over to you, Kabir, for kind of an overview of the company, where things stand today. Then we'll get into it.
Thanks very much, Gavin. Just a reminder, we'll be making forward-looking statements. Please do refer to our various risk factors in our SEC disclosures. We announced last month some very exciting news. First, we've completed recruitment in the second phase 3 study, 006, and that was significantly ahead of expectations. We also had a very positive meeting with the agency with the primary endpoint data from 005 of our first phase 3 study. That meeting with the psychiatry division resulted in a discussion around a potential for rolling submission and rolling review. That's obviously fairly standard practice within the agency, but not so much within psychiatry. That was really positive for us.
With that and with the acceleration of 006, what that enables us to do is to look to disclose in first quarter of next year both that primary endpoint data from the second study, so the nine-week Part A, which includes the primary endpoint at six weeks of 006, as well as the 26-week data from the first study, 005. That was an update in guidance because before we were going to hold 26-week data of 006 till 26 weeks. Once we saw the LICOS CRL, saw that there was actually no agency issues around functional unblinding, that enabled us to put that together simultaneously. With that as the likely trigger for a rolling submission, that's enabled us to bring the whole process of NDA submission, potential approval, and launch forward by 9 to 12 months from earlier expectations.
Awesome. All right. Let's start off with that first quarter update then. Is that going to be both of those data sets for 006, 005 coming together or sequenced separately?
Yes, it is. What we will see there is first from 005, we'll see the full analysis of the six weeks. Of course, we only put out a single data point. We will also then have the Part A analysis of 006. That will really see both primary endpoints together for both 005 and 006. That really, from a regulatory perspective, assuming positive data from 006, truly discharges regulatory risk because then we will actually see those together. We will also have from the 26 weeks of 005 safety data because that was designed principally as a safety study. From an agency perspective, that's the key thing there.
Perfect. All right. Let's start off on the 005 26-week data. What I had in my notes for what I'm looking for was durability, redosing rates, % responder or super responder. I also just checking the box on the safety side. We laying out all of those metrics, anything else we should be looking for with that update?
As I say, the focus will be on the safety side in terms of how we're looking at other parts of that. Let me turn to Steve.
Yeah, thanks, Kabir. As a reminder, the design of 005 and 006, frankly, in Part B really does not allow for a determination of durability per se because past the primary endpoint, moderacy becomes meaningless. There will be so much noise in this data. Patients will be taking many different paths at this point. If they meet criteria, which would be not yet having remitted or having subsequently relapsed, they are eligible for the choice of a single retreatment still on a blinded basis or starting an antidepressant as of the beginning of Part B, but it could really be at any point during Part B. This means that it's going to be really a mixture of data that is not interpretable from an efficacy standpoint, really, so much as being really important commercially and for payers as well to provide information clinically about dosing and redosing.
The safety data from that portion will be very important for FDA in terms of the ultimate outcomes of these patients as they move through Part B. That is clinically and commercially meaningful. I think it's also worth saying that what we've already seen from the single data point we released for 005 shows us that there is a clinically meaningful effect at six weeks following a single administration, which is already highly differentiated from the only comparator that will exist when they come to market, which is Spravato, which would have had 10 treatments at that point.
I think it's probably worth just reemphasizing from an expectation-setting perspective, after Part A, we won't be looking at MADRS. You should not expect to see MADRS beyond Part A. Right? To Steve's point, Part B from both 005 and 006 will help in ultimately us teasing out what's the ultimate dosing paradigm over time, right, and not from a regulatory perspective. This is more as they're talking about payers down the line as we're thinking through pricing down the line. I know there's lots of chatter about durability, but that's all it is right now is chatter. We've already shown the durability that we need from a regulatory perspective and that is extremely meaningful from a commercial side. Anything beyond this just helps to inform how many doses per year on average would a patient get.
There are expectations that it'll be highly variable patient to patient.
All right. That makes sense. Just to be clear, are you presenting the MADRS data at all? Not at all?
No, it's not in our stats plan or anything.
Okay.
There'll be a data point at 26 weeks, which is the end of the fully blinded period, but MADRS at 26 weeks is going to be completely irrelevant.
Okay. All right. That's helpful. All right. 006 then, where we will be looking at MADRS for sure.
Not necessarily. No, we'll be looking at Part A MADRS.
Yes.
Yes. We will be looking at Part A MADRS for COMP005 as well.
Yes.
Yeah.
Exactly. All right. 006, Part A specifically then for the first quarter.
For the first quarter, yep.
Yeah. All right. For that update, do you expect a deeper response with the two doses?
The hypothesis is that you may see a deeper response, and there is some evidence from the Imperial College London study, from EPIsoDE, and some other very small data sets, yes.
Again, the important thing, let's go back. Maybe Steve, you can comment on what we need to see, right, because what we need to see both from there's a regulatory perspective and then the commercial perspective. From a regulatory perspective, it needs to be highly statistically significant, which is what we saw for the primary endpoint for 005 already. We need to see something similar. From a MADRS perspective, again, something similar to 005, which was similar to the six weeks in Part B or in phase 2b. Steve, maybe you can expand on that, why we believe that having a MADRS in the range of Spravato is so compelling for us.
Yeah. I mean, as a psychiatrist, as somebody who's treated thousands of TRD patients, differences of two to three points on MADRS are literally life-changing and probably life-saving for these patients. To Teri's point, what Spravato showed in their two out of five positive studies was a MADRS difference between three and four. In 005, we saw essentially exactly the same effect size as Spravato. Spravato was measuring their primary endpoint at week four, which was after eight administrations. We measured at week six after a single. By the time you get to week six with Spravato, you've had 10 treatments. It really can't be overstated the amount of burden that places on patients and their caregivers who need to drive them to every one of those appointments. Showing that durability at week six after a single administration are already highly differentiating.
If we can show a comparable MADRS difference in 006, again, three would be clinically meaningful, and it's highly stat-sig, then that's exactly what we need to see.
Perfect. This is going to be a fully unblinded data presentation for 006, right, including full safety tables and everything?
Yeah. We will have certainly MADRS at all the time points, full safety. We may not have all the key secondaries, all the secondary scales and so on, but yes, I mean, everything that's essential both from a regulatory and to really understand the profile, yes.
Great. What's your latest thinking on the subtherapeutic 1 milligram control versus placebo control, which is still kind of an open debate as to what that will actually do to that control arm? What's your current thinking there?
I think it's hard to speculate given we have the 1 milligram from the phase 2b, we have some placebo data from COMP005. We did some analysis around the phase 2b, but I think where we are confident is that the primary analysis, which is two 25s against two 1s, should show a significant difference, and that's where we're focused.
Yeah. Remember that the primary endpoint in 006 is at six weeks, which is only three weeks after the second dose, right? That is also helpful. Now being able to see Part A of 006 at the same time as Part A of 005, we will be able to answer that question all at once, right? The need for that speculation will all be answered at the same time, which is great.
Awesome. All right. Let's switch gears. Let's move on from the data. Let's kind of go towards commercial preparedness, that side of things. As we're thinking about the label, what's your expectation on the monitoring requirements? Will it be specifically listed who can do the monitoring, anything about number of people one person can monitor, the setting, whether it's in a singular group room, really just label questions around monitoring in general?
Steve?
Yeah. You did not ask, but maybe I can also include REMS as part of that.
Yeah.
Because in the label itself, we would expect a fairly broad label, an indication of adults with treatment-resistant depression. We would not expect any language that in any way, particularly to the level of granularity that you just stated, would talk about who is supporting patients, how they are monitored, et cetera. For expectations around what a REMS might look like, I think that it would be helpful to look at the existing Spravato REMS as well as what FDA prepared in their briefing materials for the LICOS Adcom. What you will see in both of those cases is language around the availability of a prescriber, availability of a licensed healthcare provider, but not down to the detail of talking about a room, who is in the room, et cetera.
Ultimately, we expect that an existing Spravato room is a COMP360 room and the staffing of these centers that deliver Spravato to be adequate to deliver COMP360.
Do you think the label will be aligned to the clinical trial criteria, or could it be kind of a broader depression treatment label?
I think one area which we do expect, we expect it to be both monotherapy and adjunct. Typically in this situation, the precedent is even though we studied monotherapy populations, we're generating a significant amount of adjunct data during the 52 weeks of both trials. In that sense, we would expect it to be a broad label. In terms of what it says about frequency, we expect something like episodic dosing as needed at physician determination.
Okay. That's helpful. Do you know how much Spravato is given in single rooms versus group rooms?
Yeah, it's primarily single rooms. There are examples out there of larger rooms that are subdivided, but it's primarily single rooms.
That's helpful. Do you have hard metrics on that? Have you guys done market research projects on that?
We know that, frankly, through knowing most of the centers that are delivering Spravato today, it is highly concentrated. It is about 6,000 centers delivering Spravato, but 80% of the prescriptions are from less than 20% of those less than 1,000 sites. Frankly, 20% of those prescriptions are from, I believe, less than 100. Whether it is those that are already included within our strategic collaborations or other centers that we have also gotten to know well, I have probably physically seen most of those sites.
Yeah. I guess for those a little above 1,000 kind of priority highest volume sites, how long do you think it'll take to reach them from launch and kind of get them activated and ready to go?
They are highly motivated, and that is one of the reasons why we do the work we are doing right now with our strategic collaborations. That includes some of the sites that we would anticipate to be the earliest adopters and are the most prepared today, which are the interventional psychiatry practices. As a reminder, our collaborations do include other sites of care, types of sites of care like hospital systems and integrated delivery networks, decentralized models, community behavioral health like HealthPort in Maryland. They are already hearing a lot of grassroots clamoring for these treatments from their existing patients. They get calls for these treatments. There are not many changes they need to make because the rooms are the same, because the staffing is the same. That is very helpful in terms of our preparations as we are now building our commercial infrastructure.
We see the high-volume Spravato sites today very quickly starting to write prescriptions for COMP360.
We also have a team of MSLs who are already doing a significant amount of disease education and so on, and clearly subject to gating that to positive data and so on. We would expect to expand the medical field team as we head towards a potential filing and approval. That would be a key element of actually getting that awareness out. I think, as Steve said, we're also realistic that a potential approval of psilocybin will probably attract more attention than some other drug approvals might in the current environment.
Yeah. That makes sense. Thinking about the practice economics and making it work for them, how important is the buy-and-bill component? Do we know how much Spravato is going through buy-and-bill today? How much is that a part of your own commercial strategy?
I can take that one. It's a good question. J&J hasn't published the percentage of buy-and-bill versus specialty pharmacy, but we believe it's somewhere in the neighborhood of 35%-45% at this point, and it took some time to build there. We think independent of buy-and-bill revenue that this will be attractive to healthcare providers and likely more so than Spravato given the dedicated CPT codes that are ready to provide that reimbursement framework. Yes, buy-and-bill does represent additional opportunity on top. Certainly, if we look at other fields of medicine like oncology and rheumatology and so on, that winds up being a big part of the business. Frankly, it's why there's a lot of PE interest and activity right now to get into building infrastructure.
Steve, it may be helpful to go through some of that provider economics while you're on it because I think there's a lack of understanding out there of why we think it's so beneficial for them for COMP360.
Yeah. I mean, there has been a lot of chatter about it being necessary for any psychedelic treatments to fit into the delivery window for Spravato, and it just doesn't hold up actually when you look at the details of that because starting with the reimbursement framework that Spravato does not have dedicated CPT codes. They leverage just existing evaluation and management codes, which really don't capture all of the work done or the practice expenses that need to be accounted for. So they're adequately reimbursed for delivering Spravato. It's not ideal because it's a shorter treatment. They are pressured, though, to turn that room over quickly and to get multiple patients within the same room in a day. You can never simultaneously have a patient leaving and a patient coming. There's always going to be a gap in between. That is time that sites aren't paid for.
is also the additional operational complexity of turning a room over multiple times, cleaning the room, the additional administrative work of the paperwork, of prior authorization, et cetera. Actually knowing that you can fill that room for an entire day to have optimal codes that maximally reimburse you on an hourly basis for that time to be reimbursed regardless of the length of that administration and not to have unpaid time because of turnover makes this very attractive for providers.
Yeah. Awesome. I wanted to squeeze in a PTSD question in here. When are you having the end of phase two meeting, and is your expectation to run one single registrational efficacy study at this point?
We're planning a large potentially registrational study so that we've actually got a protocol aligned. We have chosen a CRO. We're in the final process of actual site selection and validation and so on. We expect to launch that early next year. At this stage, we believe that there's a very clear translation of the safety profile from TRD to PTSD. We're confident given the very strong signal we saw in our phase 2a that we can design a robust large registrational trial. At the moment, we're focused on that one trial.
There's also a lot of comorbidities across TRD and PTSD, so a lot of overlap there as well.
Which also leads to commercial considerations because there are a lot of synergies here. Patients are treated in the same settings of care. They often have these conditions comorbidly.
A very large population.
13 million.
Yeah. Awesome. All right. That is going to be for more discussion next year. Maybe we can just wrap up and kind of say, "Hey, what are you guys most excited for in 2026?
We're excited for the data that we see coming in Q1 and for the potential for that to really be the trigger for a rolling submission that gets us to completing a submission in the latter part of next year and really a very engaged dialogue with the agency about how we might get this medicine to patients. A lot to look forward to in 2026.
Awesome.