Compass Pathways at RBC Capital: Strategic Moves in Depression Treatment

On Tuesday, 20 May 2025, Compass Pathways (NASDAQ:CMPS) presented at the RBC Capital Markets Global Healthcare Conference 2025. The company shared updates on its clinical trials for COM360, a treatment for treatment-resistant depression (TRD), and outlined plans for its commercialization. While challenges in patient recruitment were noted, the firm expressed confidence in its clinical data and strategic commercialization efforts.

Key Takeaways

• Compass Pathways is advancing clinical trials for COM360, with data from the COMM-five trial expected soon.
• The company plans to leverage SPRAVATO’s infrastructure for COM360’s commercialization.
• Enrollment challenges in the US have been addressed, accelerating trial recruitment.
• A Phase 3 study for PTSD is planned, expanding the potential use of COM360.
• The Drug Safety Monitoring Board has recommended proceeding with trials without changes, indicating a positive safety profile.

Operational Updates

• COMM-five Trial Enrollment: Completion of enrollment was announced, with upcoming data release.
• COMM-six Trial Recruitment: Ongoing across 14 countries, with 26-week data expected in the second half of next year.
• Patient Record Acquisition: Challenges in the US resolved using third-party vendors to obtain medical records.
• Commercial Collaboration: Strategic partnerships with mental health care sites are in place to understand TRD patient care pathways.
• SPRAVATO Infrastructure Leveraging: Plans are underway to use existing infrastructure for COM360’s launch, requiring only minor adjustments.

Future Outlook

• COMM-five Data Release: Anticipated soon, focusing on the primary efficacy endpoint at six weeks.
• COMM-six Data Release: Planned for 26 weeks to maintain study integrity.
• Commercial Launch: Preparations for launching COM360, with potential expansion into PTSD treatment.
• PTSD Trial: A Phase 3 study is set to begin later this year.
• Regulatory Environment: Monitoring changes to expedite patient access and state rescheduling efforts.

Q&A Highlights

• Efficacy Threshold: A three-point difference on the MADRS scale at six weeks is deemed clinically meaningful.
• Safety Profile: No safety concerns have been reported by the DSMB.
• Suicidality Risk: Expected black box warning due to suicidality, but the risk profile differs from traditional antidepressants.
• Blinding Strategy: Strict blinding maintained in trials to ensure data integrity.
• Commercialization: The SPRAVATO network will be utilized for COM360’s market entry.

Readers are encouraged to refer to the full transcript for a detailed account of the conference call.

Full transcript - RBC Capital Markets Global Healthcare Conference 2025:

David, Interviewer: By their CEO, Kabir their chief financial officer, Terry and their chief patient officer, Steve. So thanks all for being here.

Kabir, CEO: Thanks, David. So

David, Interviewer: maybe we’ll just jump right in. I mean, data from COMP-five is imminent. So can you walk us through the trial design, what you’re seeing with respect to the type of patients you’ve enrolled, and

Terry, Chief Financial Officer: I guess

David, Interviewer: how confident you are that you can get the right patients to reproduce the Phase II data?

Kabir, CEO: Yes. So as a reminder, the design is a single dose of twenty five milligrams of COM360 against the placebo. And the primary endpoint that we’ll be declaring next month is at six weeks. So the IE criteria are very, very consistent with the Phase 2b. So this is really very consistent in terms of patient population.

The only difference that we’ve made really is in the phase 2b. We had capped prior experience with psychedelics at ten percent, and we actually had around six percent with prior experience. In the phase three across both trials, we’ve increased that So we will have a handful more patients likely with prior psychedelic experience. You know, in terms as I say, in terms of the IE criteria, it is very similar.

We obviously are on a blinded basis just tracking epi at the moment, but there’s no reason to suppose that we’ve had anything different by way.

Steve, Chief Patient Officer: Only thing I’d add is that screening and the qualification qualification of the population for these studies consistent with Phase IIb, we are getting medical and pharmacy records to confirm that these patients have had adequate trials. These are truly treatment resistant depression.

David, Interviewer: One of the aspects that investors have talked a lot about is how long they can enroll. And on one hand, that speaks to the diligence in enrolling the right kind of patient. So can you speak a little bit more about some of the challenges and maybe why those have been overcome, how those have been overcome? And whether there’s any risk that patients who may have been enrolled at the start of the trial are different than the ones that you’re enrolling now?

Kabir, CEO: Yes, I can speak to that and then ask Steve to comment on why that doesn’t translate into broader concerns. But yes, to Steve’s point, we require this is a very strict regulatory definition of treatment resistant depression, which requires that subjects have failed at least two and not more than four courses of a specific medicine for a specific duration with documentation that they have failed to respond. That requires not only prescribing records, dispensing records and so on. And in The US system, those are hard to get. So what we actually discovered was actually putting all those together was taking us a very long time.

So what we put in place was traditional third party vendors who with the patient consent actually go and gather all those records for you. And that was the key thing that enabled us to significantly shorten that time. As a reminder, the Phase 2b was 50% ex U. S, Fifty Percent U. S, although it had some of the same issue.

This by being 100% U. S. Study that really compounded it. And just as a note on that as we six, the other study goes extensively into Europe. We are again discovering as we did in the past that it’s much easier in those payer systems and those government run systems to actually get all that data.

So really, it was an old fashioned legwork in terms of actually making sure that we got all those records. Do I think that has made any difference to the nature of the patient? No. What it enabled us to do was just accelerate the recruitment over time.

Steve, Chief Patient Officer: Yeah. And so then the second part about whether there’s any read through, any any implications of the challenges of gathering those records in The US in a commercial environment post approval? No. You know, necessarily in our trials, we need to be extremely rigorous about enrolling the right patients. That means gathering all of these records in the real world that’s not what is typically done.

It is a clinic clinical decision as to whether this is an appropriate patient. Typically, it’s not required to gather those records. And so along with some of the other relaxations of the standardizations in our trials, which are necessary to have reproducibility across all of our sites, in the real world, it is much more relaxed.

David, Interviewer: So on the efficacy profile of COMM-three sixty, what you’re looking for from COMM-five, can you talk about what your expectations are? I think we hear from physicians, from other investors, the range on moderate to anything from four to six points, what people might think is meaningful over standard of care, and this patient population much lower than that. What do you think you need to show to be exciting?

Kabir, CEO: Yeah. So I mean, just as a reminder, this is the treatment resistant depression population. This is chronic refractory depression. So this is not MDD. So we see a difference of three at six weeks will be clinically meaningful, and we will be happy to get into that four to six.

Steve, Chief Patient Officer: And if you look at, you know, other analogs out there, of course, there’s only one currently marketed pharmacologic drug for treatment with depression, esketamine. Across their studies, it was anywhere from two to five. So to Kabir’s point, showing a three point difference in the population will correlate with a highly clinically meaningful change.

Terry, Chief Financial Officer: Got it. Then the other aspect is, of course, the safety profile.

David, Interviewer: Can you talk about anything that’s come out of recent DSMB meetings since you’ve had the last ones in February? And then maybe we can dive into some of the more specific AEs that people have questions.

Kabir, CEO: Yes. So I mean, the good news is nothing has come out of the DSMB today other than proceed as bad. So there have been no specific concerns or no recommendations to change protocol or change course. The DSMB sees SAE data on a regular rolling basis unblinded. So at any point they’ve seen up to the last month’s data.

And again, nothing has come out of this point that suggests that they are seeing any imbalance or that there’s any recommendation for us to change trial combo.

Terry, Chief Financial Officer: I think worth noting that the DS-1B is across both five and six. And so they’re seeing the full spectrum of data, which is quite a large number of patients at this point.

David, Interviewer: Got it. That’s helpful. I think one aspect of the safety profile that people are most interested on is the suicidality. So there’s a number of reasons that there may have been some elevation in the Phase II. On the other hand, effective antidepressants tend to lower the risk of suicidal.

So can you maybe talk about what happened in the Phase II and sort of what your expectations are for risk of suicidality in five? And then ultimately, what’s acceptable in the real world given the treatment

Kabir, CEO: Let’s start with that last one. So as a reminder, this is a treatment population that sadly is a high risk suicidal behavior. So as a reminder in the Phase 2b, seventy percent had lifetime history of suicide ideation or suicidal. In the Phase 2b in the context of the safety events reported on the day of dosing and subsequently, we saw no we saw a low rate of suicidal ideation that was consistent across the arm. What we did see was more than a month after dosing, three non responders in the twenty five milligram arm with signs of suicidal behavior.

Non responders, as I say, and in our view, that was largely a random event. They happen to be in that. That’s the view that the agency has taken as well. They had no concerns about that in terms of how we designed and are executing phase three. They had no concerns about how we’re tracking this.

Steve, Chief Patient Officer: Clearly by studying close to 900 patients across two Phase three studies, we’ll actually see if there is any specific signal there. But I think in our view that was underlying disease reasserting itself. We do expect a black box warning for suicidality as every other antidepressant. And what related to that black box warning, I think it’s an important distinction to draw to point out that that primarily relates to more traditional antidepressants that often have a significant delay to effect if they will ultimately be effective of several weeks. And in the early period of having started that drug, there’s often some activation that, in some cases, can enable somebody with having those thoughts to act upon them.

There are also a period of time where there can be some worsening of mood directly related to the daily administration of that drug. That is very different than what we saw in phase two, where we have a drug that is very quickly cleared metabolically and where we saw a significant delay weeks beyond that period of time when we had those incidences of suicidality, all in nonresponders, all with a history of suicidal ideation behavior prior to the trial.

Kabir, CEO: One other thing to note, actually, one of those three patients has been written up as a significant case study that was published in the British Journal of Psychiatry earlier this year, and this patient has been very public about her experience as well. And while acknowledging that pattern of suicidal behavior after four weeks, at the end of a year has changed her life around, is in a much better place mentally, and clearly states that she would do it again.

David, Interviewer: Yes. That’s really interesting. Another aspect of the COMM three sixty profile that warrants a lot of discussion is the durability. And

Terry, Chief Financial Officer: to that

David, Interviewer: end, you recently published some follow-up data from the Phase II. Just can you highlight maybe the key takeaways on what that data means for durability? And then in addition, there was some dose ranging there. Obviously, how that speaks to the appropriate doses that you brought forward?

Kabir, CEO: Yes. So what we published was the data from four, which was the follow on study from one and indeed three, which was a small 19 patient adjunct study that we did at the same time. What we published recently was when you look at that entire cohort of whom the majority terminated at the end of one or three at the end of twelve weeks. But when you look at the entire cohort, including those who did go on to consent into the next study, we saw a time to depressive event for twenty five milligrams of ninety two days. And the depressive event is a specific score on Madras.

It’s a specific example of behavior. So what we saw was that for the whole population. But to be clear, most of that population is artificially sensitive twelve week because most did not actually roll into the longer term study. Of those who did, and we were doing this during COVID, so we got a relatively low percentage we did if we ate patients. What we saw there was that those on twenty five milligrams actually went one hundred and eighty milligrams before the question of that.

However, we have to recognize there were some survival bias for those who actually did roll into that. But I think the core data coming back to that ninety two days, as I say, an artificially sensitive number because most patients stopped at twelve weeks. That suggests significant durability. When you actually look then at the significant differences from 25 to either one or 10 in terms of Madras effect, we’re very confident that twenty five milligrams is the appropriate dose to carry forward. In o o six, as you’ll be well aware, we are still studying two tens as well, and that was, you know, a number of investigators and others felt we should do that.

Plus, frankly, from a confounding expectancy and therefore maintaining blinding, having the ten milligrams in as an intermediate dose is a very effective strategy for that. Our expectation is that two twenty five will clearly demonstrate superiority to one.

Steve, Chief Patient Officer: The only thing I’ll add is that although it is in parts b and c of these trials, both five and six, that we are examining longer term durability as well as the effective retreatment, even with our primary endpoint at week six following a single administration in five, two, and six. The demonstration of response out to week six in either of these trials would already be highly differentiated from any option available today, incredibly meaningful, we believe, to both patients and healthcare.

David, Interviewer: And I think maybe another point of debate, there’s a lot of them in the psychedelic fields, has been how to prevent unblinding and the functional unblinding. And you guys have been very strict about making sure that you keep the blind. So can you talk about what’s been driving that? Has that been internal? Has it come from the FDA?

And sort of as we sit in a regulatory landscape that’s evolving, I mean, do you think that ultimately there may be some flexibility around that back towards the loosening?

Kabir, CEO: Yes. So I mean, I think, first, just on that point, we pioneered that design of three separate doses in our Phase IIb. We continue to believe that particularly with the 10 and the fairly overlapping distribution of responses that the 10 and the 25 that is a very effective strategy as I say for compounding expectation and maintaining blinding. And that’s why six, the bigger trial in Phase three maintains that same strategy. Obviously, five is against placebo, and we recognize that the vast majority of patients will therefore know which arm they’re on.

As a reminder, we’re doing that study at the behest of the agency to get a true safety baseline, probably necessarily a study we would have chosen to do ourselves. With that said, clearly, the Lycos Advisory Committee, there was a lot of discussion both there and subsequently as to what impact this may or may not have on the agency’s interpretation. In many ways, it’s absurd because all psychiatry trials including specifically esketamine have been unblind until now. But let’s recognize that the psychedelics, this has become a major issue. With that in mind, we had always intended for five to disclose six week data, but we’ve been very clear that it is going to be a very limited release.

It is just going to be the primary efficacy endpoint and a single statement from the DSMB to preserve the integrity between six weeks as much as possible. For six, we did make the decision to actually disclose only after twenty six weeks. So we had originally said again, we would disclose the primary endpoint at six weeks. We made the decision to hold that all the way through the twenty six. I don’t think we know enough yet to know how the agency may be evolving their thinking around unblinding specifically.

I think obviously there are straws in the wind out there that suggest this new administration is thinking about how could we potentially get these drugs to patients more quickly and that’s something we’re very keen to capitalize on. But I don’t think we can say yet have a sense of how that thing is different. One final thing to say, in Phase 2b, we did not ask patients ahead what they expected. In Phase three, we so we are asking patients what they expect and what would you expect?

David, Interviewer: Now that five is almost done recruiting, we’ve been talking a lot about I guess it is done recruiting. Yes. It is done recruiting. Can you talk about what your expectations are for how quickly we can get six recruited? Especially, you talked about more EU patients, and maybe learnings and being able to pull through patients faster.

So what can we expect from that?

Kabir, CEO: So for now, we’re very confident to reconfirm the guidance that we will see twenty six week data in the second half of next year. Clearly, it is our intent to tighten up that guidance and indeed we’ve also said we will definitely disclose when we have completed improvement in our zone. But just to build on that, we are now in 14 countries. We have a very significant number of sites open essentially what we always committed to our investor deck in terms of number of sites for six. As we’ve said, some of the better performing five sites from The US are moving into six as well and that process is well underway, not fully complete yet because five is only just finished up.

So we are very confident in that guidance at the moment. Six is recruiting well. I think one factor is it does indeed have three doses of ptilocybin. So it is an easier trial to recruit into than a placebo controlled trial.

David, Interviewer: I know it’s still early days, but you guys must be thinking about the commercial model. So I’m curious, just at a high level on how do you stage an initial launch of the drug profile like this? I guess, how do you see that working in the real world, in a psychiatrist clinic where patients will get the therapy?

Steve, Chief Patient Officer: Yeah. You know, with without significantly investing in this area, we’ve been able to do a lot of work already. Still early days, but some things to highlight. We’ve made a number of announcements of strategic collaboration, are with live sites of mental health care delivery that span the gamut of where mental health care services are delivered today from hospital systems, integrated delivery networks, decentralized models, importantly, the interventional psychiatry infrastructure. My most recent announcement was with a CCDHC, Certified Community Behavioral Health Clinic, to specifically address where those who are underserved, receive their care.

And it’s really allowing us, especially over the past year as we’ve we’ve we’ve dive deeper into this work, to get really important understandings of the TRD population, their experience, the patient care pathways. We’ve been able to learn a lot from the sites that have implemented SPRAVATO about the operational and administrative capabilities they’ve needed to build, their early experience and how that’s evolved over the past few years of delivering that treatment, the economics associated with delivering it. We’ve also focused on how these organizations currently manage training and continuing education for their workforce. On top of that, you know, as we have announced long ago, we did work on reimbursement codes, CPT codes, that are specific to psychedelic treatments. We have laid the groundwork for the reimbursement framework there.

An area where we have made more investment is at the state level. As a reminder, as a Schedule I substance, after an FDA approval, federal DEA will have ninety days to reschedule a product, but it will then still need to move to the states. About half of the states have so called trigger laws where they were somewhat automatically followed federal guidance on their own rescheduling. The others require some administrative or legislative activity. And so we’ve, started the work there to ensure that there is minimal gap in that in time of rescheduling in those states so they can very quickly ship to all 50 states.

Terry, Chief Financial Officer: And, Steve, it may be helpful just to expand on the fact that we think we can, leverage this Bravado network that has been built. Just

Steve, Chief Patient Officer: Yeah. Important point, Terry. You know, when SPRAVATO launched in 2019, there was essentially zero infrastructure to deliver interventional psychiatry. Today’s SPRAVATO is being delivered in about May interventional psychiatry centers, prescriptions written by 4,000 plus health care providers, much of that concentrated in about 20% of those sites, with SPRAVATO at a run rate now of $1,300,000,000 So there’s been a rapid increase, rapid building, because of the presence of SPRAVATO in the market to deliver interventional psychiatry treatments. The trend is is to grow further.

That is a scaling sector of mental health care service delivery. And the jump from no interventional psychiatry infrastructure and and no capabilities to being able to deliver SPRAVATO versus the very tiny incremental adjustments they may need to make to deliver COMM three sixty gives us a lot of confidence that there will be readiness at the time of launch.

Kabir, CEO: I can just add one other point to scaling that I know investors sometimes focus on, which is the role of the person in the room because there is a view that needs to be a psychotherapist, and there aren’t enough of those at scale. So a couple of points of that. First with psilocybin, the experience for the patient is a largely in a directed, self directed experience. We now have clear data that actually shows what we’ve always said. There is no active therapy happening.

In fact, for a six hour session, typically four to five hours, they’re almost complete. So there is no active therapy happening. Second, the agency, the FDA is very clear that they do not wish to regulate therapy. They see what happens alongside the drug as a matter of clinical practice that is not in their purview to regulate. And so in our discussions with them, as we think about label REMS and real practice, We believe as long as there is a licensed HCP in the room who is able to monitor for safety, that is where we will add.

But that clearly opens up the pool of people able to be in the room massively, the nurses, other workers, potentially licensed social workers, and so on. So, again, very engaged dialogue around that and moving that beyond this notion that it needs to be apparent.

Steve, Chief Patient Officer: And just to put a fine point on that and put some numbers to it, you know, although there’s, you know, a lot of talk about limitations of workforce to deliver care, people with mental health conditions, with what Kabir is describing, the expansion of the pool of health care providers who will be able to care for patients receiving COM three sixty, the expansion of that, that represents many hundreds of thousands of health care workers who could support it.

David, Interviewer: Have shown promising data in PTSD as well. So I wanted to touch on that in maybe the last ninety seconds that we have left. I guess, how are you thinking about the level of evidence for the drug’s activity in PTSD? And how are thinking about next steps?

Kabir, CEO: Yes. So you’re right. We had a 22 patient global label study, which showed a very, very strong efficacy. In fact, at twelve weeks, it showed a much stronger efficacy signal. The maps was able to generate at eighteen weeks for Transcend more recently in their study.

So we are very working assiduously on designing a robust late stage study, which we should be able to talk about relatively soon, once we’re passed over five data, which is the primary focus. And we believe that not only that signal of efficacy, but also in terms of how I was just describing a psilocybin experience, the experience for both therapist and patient is much easier than one, let’s say, with MDMA. And we’re excited to design a robust Phase three study and that’s something we will be looking to move forward in the latter part of this year.

Steve, Chief Patient Officer: There’s also high rates of comorbidities of PTSD and DV or TRD. So in some ways, you know, we think of this as a relatively similar population. And then, of course, should we have an approval in that indication as well, there are there’s a high degree of synergy in terms of where these patients are treated.

David, Interviewer: Well, I think we’re basically up on time. Thank you all for being here, and

Terry, Chief Financial Officer: thanks, everyone, in the audience for listening.

Kabir, CEO: Thanks, Leo.

Terry, Chief Financial Officer: Thanks, Leo.

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