Thanks very much, everybody. It's my pleasure to be moderating this chat with the Compass Pathways team. With me is Teri Loxam, Lori Englebert, and Steve Levine. I'm sure most folks in the audience know Compass decently well, but do you want to kick it off, Teri, and maybe just give a quick update overview, and then we'll do Q&A? Sound good?
Yeah, absolutely. Thanks for having us, first of all. Just to satisfy the lawyers in our company, I will say we may be making forward-looking statements. Refer to our risk factors on our website. Now check that box. Now we can get on to the good stuff. Yeah, as Paul mentioned, we actually had some pretty significant announcements last week during our earnings and gave an update on the company. For those who don't know Compass Pathways, we are moving forward with synthetic psilocybin for the treatment of treatment-resistant depression to start, as well as PTSD. We are nearing the completion of our phase III trials. Some of that was part of the updates that we made last week where we announced that we have completed enrollment for the second phase III trial, which was a big milestone for us.
That really locked in the timing of the remaining data that will roll out. We also announced that after our first data that we put out in June, which was the top line for our 005 trial, which was highly statistically significant, very de-risking for the company. Coming out of that data in June, we had requested a Type B meeting with the FDA, and it had been granted that meeting. Came out with really collaborative discussion with the FDA and a very positive discussion, which has that along with our completed enrollment for 006 has really accelerated our timelines. We now have the potential for a rolling submission and a review. To facilitate that potential rolling submission, we are now pulling forward the disclosure of part A of our 006 trial, which is the second phase III trial.
We'll now be disclosing that data, which is nine-week data, alongside both part A and part B of the first trial, 005. We'll be disclosing that in Q1 of next year, just a few months away here. The 26-week data, which is the completion of part B for that second trial, is now pulled forward to early Q3 of next year. We anticipate that that will be the last data that we need to complete our submission. We're really moving everything forward. That was a big timing update for us. We think we've accelerated our launch by about 9-12 months. We are now ramping up our commercial efforts even more, which is why it's great to have Lori and Steve here. We can talk through a lot of the commercial activities that we're doing.
We are really well positioned to be the first psychedelic, hopefully to be approved. We've got two very large, well-controlled trials in our phase III program. So far, safety has been clean based on DSMB feedback. We are very well positioned.
Great. Awesome. Maybe we can go through, just quickly preview the data you're going to be disclosing early next year from the 005 and 006 studies. I have some follow-up questions on that.
You want to start, Steve?
Yeah, I'll start there. Yes, in the latter part of Q1, we'll be disclosing both parts A and B from 005, our first phase III study, along with part A, the first nine weeks of 006, the second study. We had previously disclosed just the top line of part A of 005. That was this past June. That was just the MADRS delta between the two arms, along with the statement from our independent DSMB about safety. With the disclosure in Q1 coming up, we'll be able to give you much more detail on that part A from 005, all of the time points leading up to the primary at week six, along with part B from that study, which runs out to week 26 and includes a single potential retreatment.
The first nine weeks, again, the part A of 006, which includes the six-week primary endpoint and then the key secondary at week nine, given that in the second study we have two initial administrations on a fixed interval three weeks apart. Maybe worth mentioning that with the full part A of 005, it will really give an opportunity to make a comparison of one initial administration in 005 versus the two initial administrations in 006, with the hypothesis that that second administration may lead to an increased depth of response or durability, potentially elicit more responders who could benefit from a second initial administration. That part B in 005 will allow us to see the trajectory, the longer-term effects of that first administration in 005, that single administration, as well as the effects of a potential second administration in part B.
Really, what's going to be interesting from 005 is to look at the curves of how responders continue to benefit over the course of that 26 weeks.
I'll just add on to that. The 005 trial, as a placebo-controlled trial, had been done based on feedback from the FDA. They wanted us to do that primarily for safety. That 26-week follow-up from 005 is a really important safety benchmark for the FDA. We'll also have that longer-term safety.
Yep. OK, great. As it relates to efficacy, what is your base case in the real world for how often this will be used? What do you want to see in the 26-week data to affirm that that base case is realistic?
Yeah, it's a good question, Paul. I mean, it starts with what we already know from 005 after the disclosure of the primary, because that showed us that at week six, following a single administration, we saw a highly statistically significant and clinically meaningful outcome that we believe is highly commercially viable, because there is only one pharmacologic product in the market right now being used for people with treatment-resistant depression, and that is Spravato. We saw a very comparable effect size at week six after a single administration to what Spravato demonstrated at week four after eight administrations. It would be 10 at week six. That is already highly differentiated. It already shows a durability of initial treatment that has never been seen in a treatment-resistant depression population.
We also know from our large phase two B study, 233 patients, that for those who met response criteria at the primary endpoint of week three, the vast majority of them sustained that through the end of that study at week 12. From our long-term extension in a subset of those patients, many of them were able to sustain that out to six months. We will need to see the durability data from part B in phase III to fully characterize the profile of this drug. Based upon what we've seen so far, we think it's likely that patients will have treatments somewhere in the neighborhood of two to five times per year.
Two to five times per year. OK.
Just one other point to add on there. We're not looking for a specific MADRS score after the primary endpoint. After the primary endpoint, it's going to be really hard, especially with 005 against placebo, but even in 006. It's not like we're looking for a specific score, because the arms are going to be diverging with the different treatments that the various patients are going to be getting. Some will be getting another dose in part B. Some will be going on antidepressants. It's not a hard metric that we're going to be looking at for part B of either 005 or 006. It's back to Steve's point. It's really for those who responded or had a partial response, on average, what does that look like over time? What can we deduce around the dosing schedule based on that?
SSRIs are really, really good maintenance drugs to the point that maintenance studies just do not fail. In the real world, do you see most patients being on an SSRI between treatments? That is probably something that actually extends this dosing interval further than trials.
You know, SSRIs are used for a number of indications. Patients with treatment-resistant depression have typically many comorbidities. There may be any number of reasons why a patient might be on an SSRI in the longer term. Our studies are designed as monotherapy studies, so patients are initially withdrawn from their antidepressants. However, we have generated some adjunctive data already from a small open-label study that we ran in phase two. Also, in part B of both of our phase III studies, for those who have not yet remitted or have but have subsequently relapsed, they are given a choice either to have a single retreatment in part B on a blinded basis or to restart an antidepressant from a pre-specified list.
We anticipate that many patients will opt for that antidepressant and still be eligible in part C for the open-label 25 milligram administration, which means we're going to be generating a significant amount of additional adjunctive data, which means that there will be a lot of information available to prescribers who may or may not want to withdraw patients from their antidepressants or continue them in the maintenance period.
Yep.
Just to add on, Paul, a lot of the data that we're collecting after part A is really to help guide clinical decision-making. It really, from a sales rep standpoint, what they're educating the physicians on, this is what that data is going to inform. I'm willing to bet a good amount of money that the first question they're going to ask is, can they stay on their SSRI or can I restart an SSRI? Mostly because these patients are treatment-resistant and they have somewhat seen some minimal to partial response on an SSRI. It would be very important for us to make sure that we have that data, to Steve's point, that we can discuss with the physicians.
Yep. Can you talk about your retreatment criteria in this study? How do you think this all fits into what an FDA label will look like and how to guide retreatment?
Yeah, the criteria for retreatment in both part B and part C is MADRS-driven. There is a threshold. We haven't disclosed that cutoff score. It is driven by the MADRS. It is those who've not yet remitted or have subsequently relapsed. Their MADRS has returned above a threshold. In terms of how that will inform a label or inform clinical practice, we would expect a pretty broad label that has language to the effect of one or two initial administrations, depending upon what we see in 006, and then episodic retreatment.
Yep. Yep. OK.
There will be such a wide variability between patients. Having that information come out, it really is, like I mentioned before, just to guide clinical decision-making, not necessarily specific to the label.
Makes sense. For the 006 study, you've talked about this hypothesis that a second dose may be better, which I think is intuitive, more medicine, better. Why do you think that with the way you've been dosing this with the single dose approach that you're not already at the top end of the sort of response curve over a short period of time?
Yeah, we have a few pieces of information for that. I mean, first, coming off of our phase IIb study, we had some feedback from PIs and also participants that they felt that a second administration might have been helpful, that having the first experience under their belt, they felt more ready for a second administration after that. They thought they might get some additional benefit. We did also supply COMP360 to the Imperial College study that looked at COMP360 versus escitalopram. That was two administrations four weeks apart, which indicated that there may have been some additional benefit of the second administration. There was also the episode study in Europe with a different psilocybin product that gave two administrations and showed additional benefit from that second administration. We do not have the answer yet as to the reason to run the trial.
We think there's good reason to believe that the second may have added benefit.
OK. OK. I guess taking a step back, your guys' original disclosure plans were very conservative to avoid that any early disclosure might bias longer-term follow-up and to kind of, I guess, mitigate the risk of functional unblinding. Maybe some of this, I think, was a company-driven sort of reaction to what happened with Lykos. How has that thinking evolved? What makes you comfortable that now disclosing all this data early next year is not going to create any sort of regulatory problems?
I can start if you want. So a couple of things. First is that now with the timing of 006 being completed, 005 and 006 are traveling on top of each other. By the time that we get to releasing the 26-week 005 data, we're now also able to release the top line for, sorry, the primary endpoint data in part A for 006. They're coming out together is one thing. At that time that we expect to disclose, the majority of patients, upward in the neighborhood of 80% of patients in the 006 trial, will have already been through part B. That also, it's a very large trial. We're up in the neighborhood of 600 patients, so 585 patients. A good portion of patients will already be past any second dose that they would have received in part B.
That gave us increasing confidence that there would not be a potential for any unblinding or even the optics for potential unblinding, which is what we are trying to protect against. Just because of the timing now of these trials, and then also just the ability now to unblind part A of 006 greatly facilitates a potential rolling submission. All of that just was able to come together really nicely.
Right. OK. OK, great. Anything else to add around the clinical side before we talk about commercial? Anything I missed?
Only other thing I will say is just on the safety side, just really quickly, is that, as Steve had mentioned before, we put out a statement along our top line with 005 from a DSMB, which had been looking at both 005 and 006, very clean. DSMB meets regularly. They have met recently. They continue to tell us to continue with the trials ongoing. We're nearing the completion of these trials. We feel really good about where we are from a safety standpoint.
You'll be able to give us more granularity on specific AEs with this release early next year?
Absolutely. Yeah, we're still working through the CRO. The CRO has to now do two data sets on top of each other. We are trying to prioritize which exact data points will come out in Q1. Having safety is important both for investors, but also for the FDA, given that 005 is primarily a safety trial. We will be providing some of that granularity as well in that output.
OK. OK.
Maybe before we go to commercial also, PTSD, just a quick update there. Yeah. We had last year announced positive data from a phase two A study in PTSD. It was designed as a safety and tolerability study, but with an efficacy endpoint. We were really encouraged by what we saw in that study, both in terms of the tolerability of COMP360 for those with PTSD, as well as a very exciting efficacy signal. With that, we have been really motivated to move PTSD forward as quickly as possible. We have finalized a design of a late-stage trial. We will be announcing the details of that coming up. We have met with the FDA. We have gotten feedback from them on the design, incorporated that. The design will be forthcoming.
OK. Awesome. Look forward to that. On the commercial side, I feel like the bear case on psilocybin centers around just the scalability of it. And this idea that with Spravato, yes, it's more frequent, but a center might be able to churn through, I don't know, 15 patients in a day if they stick three people in the same room. And so what would you say to that? How do you think about the scalability of this? And what's the Compass counterpoint to this line of questioning?
Yeah, I can start with that. I answer this both from personal experience of my background prior to Compass, of founding and leading a large national network of centers that delivered interventional care, including Spravato, as well as deep work we've been doing with a range of strategic collaborations over the past couple of years that span interventional psychiatry practices, hospital systems, integrated networks, community behavioral health, et cetera, to really understand where patients with TRD are receiving their care today, what the infrastructure looks like, their experience of delivering Spravato, the economics of delivering these treatments, and what it would look like for them to deliver COMP360, and so on.
Yes, to answer your question about this chatter out there about the need to fit into the delivery window for Spravato really does break down pretty quickly, because the existing situation for providers with Spravato is that because patients are typically treated in a private room and they want to be maximally reimbursed for that room in a day, they have to be extremely efficient in turning those rooms over to get as many patients in there as possible. Usually, it's two. Sometimes they can fit in a third.
There is time in between those patients where the room is being cleaned and administrative work is being done and so on that cuts down on the efficiency of how many hours they can bill for that room, as well as adding administrative cost for the REMS requirements and the drug storage and handling and note-taking, prior authorization, et cetera. With the CPT codes that we applied for a few years ago and went live in January of 2024, that are reportable on an hourly basis and specific to psychedelic treatments, and including all of the work being done, including practice expenses for delivering these treatments, much more comprehensively than can be billed for Spravato right now, actually, it is economically favorable for sites to be able to bill hourly for the entire day for one patient for that room rather than having to inefficiently turn that room over multiple times.
Right. Right. Do you think that in the real world we'll see multiple patients with 360 sharing a room?
I think what we can expect is that at the period of time closest to launch, sites will deliver this pretty conservatively in kind of a maximalist way and have one patient in a private room. I think that as they gain comfort and experience, which I think is a pretty quick learning curve, because ultimately these are pretty quiet and calm experiences that patients are having, sites will start to look for efficiencies. That could be leveraging waiting rooms and common areas for the last few hours where patients aren't having much of a psilocybin experience. It could be using larger spaces that are subdivided. There are many ways they can think about this.
I still get the question from some investors that say, Compass, isn't that going to require a therapist? How confident are you that it won't?
It won't.
It will not.
Yes. We can just say it won't. Full stop. There is no therapy involved in delivering COMP360. There is monitoring and support. The activities, which really are very inactive because it's a quiet internal experience, can be accomplished by any health care provider. The way that interventional psychiatry practices are staffed and the other centers that deliver Spravato today is a team-based approach. There are multiple patients receiving treatment simultaneously, a range of treatments, typically one prescriber, maybe a nurse, medical assistant, some administrative support.
I mean, there is the integration meetup after. And my mom was a therapist. That's a very therapy word, the integration. Is that a piece of this, you think, in the real world?
Integration is a therapy-sounding word. What it means in our trials is a safety follow-up to ensure that there's resolution of the psychedelic experience and to monitor for suicidality.
You think that can be done by any sort of trained professional?
It can. Now, it's possible that there may be added benefit from doing psychotherapy in the period following COMP360. That's an area that's an opportunity for further research down the road. I think therapists and patients may be very interested in continuing to do therapy at that point in time. It's not directly a part of delivering COMP360.
OK. OK. Lori, do you want to talk about the other commercial prep work you're doing and who your initial targets are at launch? How big is we know TRD is enormous, right? But how big is the actual treater pool and the patients under the care there that could be potential early adopters?
Yeah, it's something we've been thinking about for a while. We've been doing a lot of work over the past two years, which is quite far in advance of a potential launch. We were doing that very intentionally, given the fact that this will be a new class. We will be first in class. We've had medical science liaisons out in the field doing a lot of work, speaking to KOLs, understanding what potential barriers may be there at launch so that we can be prepared for how we can help alleviate those. We've also had HEOR working to make sure that we have and can produce really solid evidence on payer coverage to secure payer coverage at launch. Most importantly, when we think about doing the more traditional type commercial build-out and preparedness, you really want to focus on who your high potential prescribers are.
Spravato right now has about 5,000 prescribers. 80% of the volume comes from less than 1,000 of those. The concentration of prescribing is really, really small. We will know quite easily how to deploy sales reps at launch and where we will need to educate. There is one thing I want to just mention. Right now we do know and believe, based on the 6,000 sites that are currently administering Spravato, that there are likely a bolus of patients ready, willing, excited about the potential for COMP360 to come to market. We will need to continue to fill that funnel of patients eventually once we get to scale. In order to do that, we will need to expand to referring physicians. We can talk about that in three years.
OK. OK. Sounds good. We have a few minutes left. Anything else you guys want to talk about or add?
I think that the only thing is probably just to put a finer point on some of what we had talked about last week in our earnings, which is just how close we now are to launch and how excited the company is, both by the profile of COMP360 that is emerging and the work that Lori and Steve and the team have been doing out in the field with the providers and with our strategic collaborations. Just the excitement that has been building across so many different stakeholders for COMP360 has been really encouraging. We hear from patients all the time just how much unmet need there is. We do think that this could be a really important treatment option if approved. We are really excited. We have done the work.
We will be ready for launch, even though it's now quite ahead of schedule now. We said last week we expect that we're pulling this in by 9-12 months. We are really ramping up on the commercial. We're pulling forward all of that commercial work into next year. We've got really exciting milestones ahead with the data in Q1, the final data from 006, early Q3. We've got PTSD coming up, potential submission next year. A lot is coming up. It's going to be a really exciting time, both for COMP360 and Compass, but I think for patients out there to potentially get a new treatment option that's much needed.
Awesome. All right.