Compass Pathways at Stifel’s 2025 Virtual CNS Forum: Strategic Insights on Psilocybin Trials

On Tuesday, 18 March 2025, Compass Pathways (NASDAQ: CMPS) presented at Stifel’s 2025 Virtual CNS Forum, shedding light on their strategic initiatives and upcoming Phase 3 trials for their psilocybin formulation, COM360, targeted at treatment-resistant depression (TRD). The company expressed optimism about their timelines and highlighted the potential of psychedelics in addressing unmet medical needs, while also acknowledging challenges such as placebo responses and commercialization strategies.

Key Takeaways

• Compass Pathways is on track to release Study 5 data by the end of the next quarter and Study 6 data in the second half of 2026.
• The company is focused on robust clinical trials and strategic regulatory interactions.
• Emphasis was placed on managing expectations regarding placebo responses and safety signals.
• Commercial strategies are being developed, including reimbursement models similar to SPRAVATO.
• The company is working to establish CPT codes to support provider economics.

Operational Updates

• Study 5: A single-dose, placebo-controlled trial with a six-week primary endpoint. Optional retreatment and antidepressant initiation are allowed after six weeks, with open-label 25mg COM360 available at 26 weeks. The trial extends to 52 weeks for safety data collection.
• Study 6: Involves three doses with a repeat fixed dose at three weeks. Data is expected in the second half of 2026. Recruitment is active in the U.S., Canada, and Europe, with half of the participants from the U.S.

Future Outlook

• The company aims to refine the timeline for Study 6 data release.
• Efforts are underway to establish CPT codes, ensuring economic viability for providers.
• Learnings from current trials and collaborations will help optimize real-world COM360 administration.

Q&A Highlights

• Placebo Response: Concerns were discussed about the design and outcome definition.
• Antidepressant Initiation: Patients can resume antidepressants after six weeks if needed.
• Safety and Suicidal Ideation: Regular DSMB reviews have not raised concerns.
• Commercial Scalability: A therapist may not be needed for patient monitoring in real-world settings.

In conclusion, for a detailed understanding, readers are encouraged to refer to the full transcript.

Full transcript - Stifel’s 2025 Virtual CNS Forum:

Paul: Excellent. Thanks, everybody, for continuing to listen to our great panels today. It’s my pleasure to be introducing the COMPASS Pathways team. We’re going to talk a lot about the upcoming Phase three readouts and some of their preparation on the regulatory and commercial side. Before that, maybe we can start, Kabir, thank you so much for joining.

You can just give us a quick snapshot of COMPASS and the update on the five and six studies and timelines and then we’ll dig in. So, thank you again.

Kabir, COMPASS Pathways: Thanks very much, Paul. Thanks for the invitation. And just as a reminder, we’ll be making some forward looking statements. So I’d refer you to our risk statements and our various filings with the SEC. So yes, we are very much in the middle of Phase three with COM three sixty, our proprietary synthetic formulation of psilocybin for treatment resistant depression.

The first of those studies, five single dose placebo controlled, we will see six week primary endpoint data towards the end of next quarter. The second of those studies, six, which is the three doses with a second repeat fixed dose of three weeks, for that study, we are expecting twenty six week data in the second half of twenty twenty six. And I’m happy to confirm that we are on track for both of those timings at this point.

Paul: Excellent. So, maybe let’s start just with a broader question on psychedelics. You know, since you joined Compass, how has the landscape changed? And where do you think we are currently? And just the world’s acceptance of psychedelics as a class when you think about all your stakeholders, right, patients, physicians and bigger, more traditional pharmaceutical companies?

Kabir, COMPASS Pathways: Yes. So, I think the good news is what you’ve seen over the last few years is not only us, but a number of other companies are now really generating robust clinical evidence. I mean, the whole thrust in this field has been to move beyond what was kind of anecdotal experience to the type of robust evidence that can be delivered to regulatory authorities with the potential ultimately for approval of reimbursement. And not only us, but other companies are moving forward on that. And I think you’re seeing a clear separation of those companies that are doing that.

I think I’ll actually hand to Guy and Laurie also to talk about what they’re seeing from a physician and commercial perspective. I think you’re clearly seeing a lot of interest from physicians and patients, but also a desire to see data. So, you know, there’s an acknowledgment that we’re still relatively early in understanding the appropriate use of whether it’s of psilocybin or these other things as well. And on the commercial side, clearly, the development of SPRAVATO and the fact that that’s now a blockbuster is a good leading indicator of why psychedelics could go. But let me just ask Guy and Laurie to add their comments on that and how they see the field overall.

Guy?

Guy, COMPASS Pathways: Yes. Thanks, Kabir. Yes, I think one is very conscious of the interest and excitement in the academic sector if one goes to conferences, indeed conferences where there are not just academics, but also clinicians, the sessions about psychedelics are always packed out. So there is that interest, but frankly, there is not really the knowledge yet to see translation into real world. And I think that is where I can segue to my colleague, who can talk a little bit about that.

But the enthusiasm, no problem. Actually, the knowledge of how to use these drugs, that is that is the task and Laurie’s the best person to tell us how to address it.

Laurie, COMPASS Pathways: Yeah. Hey, thanks, Guy. And and I agree with you, Paul. I think the the landscape has definitely shifted and there’s probably good reason. There’s been quite a significant lack of innovation in the mental health space, especially in these difficult to treat patient populations for quite some time now.

And if you think about what the psychedelics are actually studying and generating data and, you know, in some cases, like selfishly, TRD, for example, there are only two pharmacologic products approved right now, to treat TRD. And if you think about PTSD, again, only two that are approved, but it’s also been thirty years since the last one was approved or thirty plus years since the last one has been approved. So really, I think the psychedelic space and the data that these molecules are starting to generate is is what’s causing some of the the excitement. But on top of that, let’s not forget, I think the FDA also is starting to shift and become pretty excited about psychedelics as well. By my account, there are, what, five molecules being developed that have breakthrough therapy designation, which is fairly impressive, in in this space.

And as a reminder, breakthrough therapy designation, you know, helps advance the development and the the the speed to market, on products that show promising data above and beyond what’s available right now.

Paul: Yeah. Yeah. Okay. Great. So maybe let’s go through a couple of questions on the upcoming five readout.

Maybe just set the stage on the design of this study and what are the couple key questions you’re trying to answer with this trial specifically?

Guy, COMPASS Pathways: Well, this trial is a single administration of twenty five milligrams GOM360 compared with a MINERT placebo. That is not a design we would have favored from the point of view of validity because it’s quite likely to be unblinding. But nevertheless, it’s one that we were obliged to do to get a true safety baseline from the placebo arm. Its primary outcome is at six weeks, and the primary outcome measure is the Madras, which is assessed remotely so that the assessor is blind to the status of the patient. The trial continues out to twenty six weeks as a blinded activity And during that time, patients are eligible for retreatment.

So we’re getting going to get some sense of how treat how retreatment optional retreatments can operate. Patients who elect not to have retreatment with the original dose, which is effectively the design, can elect to go on to antidepressants at that point. And they continue to the twenty six week time at which all patients become eligible for an open label twenty five milligram dose of COM360. So what we will get in that extended run follow through is evidence of the tolerability of twenty five milligrams open label in patients who are taking antidepressants. We’ll get some sense of open label versus blinded, which is actually something that’s almost never been done in this field.

And of course, we’ll get the full fifty two week safety data that we think is also important for understanding and contextualizing the benefits of treatment with this drug.

Paul: Yeah.

Guy, COMPASS Pathways: So that’s five.

Paul: Yeah. Makes sense. Does I know it’s a different trial, right, but does the complete like a placebo response in GH’s Phase 2b make you more confident in the odds of success in this study and further inform your view that the five study might be the easier of the two given again this point around functional blinding?

Guy, COMPASS Pathways: I think there are some unique features to the GH approach. First being that the primary outcome is defined at eight days. That seems a little short. A placebo response to in those circumstances, particularly when patients know that they will get an active treatment almost immediately after it is very much like a waiting list control rather than a true placebo comparison. The difficulty with and indeed what we saw effectively was a nocebo response in the placebo treated patients because again of the design of multiple administrations on the day, patients will become I think will be 100% certain that they have received an inert placebo.

The difficulty is that the active arm is difficult to interpret because it consists we always think of active arms of consisting of the drug effect and a placebo effect. And of course, we’re not getting any control for the placebo component of the active arm. So at some point, one is going to have to see a more valid placebo to evaluate the true strength of that effect observed in the existing study.

Paul: And how are you handling antidepressant initiation in this trial understanding again that if I, you know, if me or someone I knew came into the study, they’re expecting a psychedelic experience, they don’t get one, they still feel awful, right? I mean, there’s an ethical issue there. How does that play into this?

Guy, COMPASS Pathways: Well, we’re encouraging patients to stay with it through the six weeks, which is tough for some patients. It certainly will be. Obviously, if clinical needs supervenes, they can have any treatment that’s necessary. But patients are given form consent, they know that they’re doing what is effectively an experiment and we thank them very much for their altruism in that respect. When they qualify for having the option to go back onto antidepressants, we expect quite a number of them will and we assume that will be particularly noticeable in the placebo arm.

We have specified a list which gives a certain amount of freedom of choice and of course they can then continue on that drug, which may very well give some sort of partial response, it remains to be seen. But that’s the way we’ve handled it ethically. We’re trying to offer patients as early as is practical the option of going back onto antidepressants. But at the same time, we want them not to because essential as late as possible because we want a valid comparison at six weeks. Right.

Paul: Yes. And there’s a way to handle that statistically if they do go on one, like you’ve I know you’ve shown multiple analyses in the last trial. Can you just review that for people? This is still I think a point of confusion out there.

Guy, COMPASS Pathways: Yes, I know. Our primary analysis last time did interpolate for patients going back onto antidepressants. In other words, if you went back onto an antidepressant, it was assumed you might improve due to it. So the scores were worsened systematically for patients who did go back onto antidepressants. In the end at the end of the day, this didn’t actually change the primary comparison very much from if you didn’t do that.

So we have elected in both the new Phase three trials to simply treat patients in an intention to treat basis without interpolation. So it will be easier for people to understand, but we accept that for those patients going back on to antidepressants, they may be weakening the effect that we would have seen in an ideal world, but that’s we think that’s probably more sensible just because it’s more understandable.

Paul: Yes. Okay. The other thing too, and I know you guys have done a good job of being very consistent about this, but it’s still it never ceases to surprise me and how people end up being surprised about these things. You’ve been very specific about the top line disclosure, what you’re comfortable disclosing, and what you don’t wanna disclose. Right?

And as I understand it, right, like, the the holdback, right, is is really related to you preserving the integrity of some of the other data we’re going to get in the six trial and just overall maximizing the regulatory probability of success here. Can you expand upon that? And is my interpretation correct? And where does this kind of thought process stem from?

Kabir, COMPASS Pathways: Yes. I’ll start and Guy, please build on it. So it is I mean, it’s preserving the integrity not only of the second trial, but indeed within five itself. So as Guy said, the trials do run fully blinded all the way through to twenty six weeks. And therefore, in making the determination to disclose the primary endpoint data only of five, again, to your point, it will literally just be that primary endpoint.

It will be the difference in the change from baseline between the arms with the associated P value and confidence interval. The reason we’re doing that is exactly to preserve the integrity of that line on five, but also to minimize any impact on six. As a reminder, 04/2006, the second study, which owing to its design with the three different doses is one that we actually do believe addresses many of the agency’s concerns around functional unlearning. For that, we will only be looking at data at twenty six weeks, not at six weeks of the primary endpoint. And again, that’s exactly to preserve the integrity of that all the way through to twenty six weeks because those claims in the second part of six are gonna be material to our profile and our label.

Paul: Yeah. Yeah. Okay. Fair enough. You know, the other disclosure, right, that we’re all looking forward to is relates to safety in the top line and the whole question around suicidal ideation.

I guess two questions there. One is, I think you’ve said that the DSMB is going to opine on their perspective as to whether or not there is a signal. So I’d be curious kind of, you know, how you think about where the line is for the DSMB given that they’re small numbers. Right? Like, if there’s two events on drug and one on placebo, is that a signal?

Is that noise? And then just second, what’s the team’s confidence? Or where does the team’s confidence come from that there’s not a real signal here and this was more just kind of an artifact of noise and small numbers in the last trial?

Guy, COMPASS Pathways: Well, essentially, I think whenever one looks at an adverse event in which suicidality is implicated, and bear in mind, these are often quite complicated events. So it might be admission to hospital and that admission to hospital may very well be due to worsening, and that worsening may include suicidality, but may not be uniquely suicidality. It’s essential that the DSMB look at the events in that way in clinical judgment, taking each case in its own context and make a judgment about whether they think it seems to represent some specific risk to either design of our study or to the drug that we’re studying. Simple numbers won’t do it. So, you know, that’s essentially the reason why we’re require requiring clinical judgment to evaluate.

The second part of your question, which is how will we get comfortable about the quality of risk as it were, you have to go to something more sensitive than serious adverse events because they’re too infrequent, and they’re much more likely to be driven by simply chance. And so for that reason, we are systematically collecting data on a scale, the Columbia Suicidality Severity Rating Scale, and we will use that to look at what are effectively sub threshold changes in suicidality, which we can then relate to changes also in depressive symptoms. And it will be equal scores, if you like, on those sub threshold measures in all of the patient populations that will give us some confidence about the the true underlying risk relating to dose or relating to the arm of the study.

Paul: Right. Right. Okay.

Kabir, COMPASS Pathways: Okay. The only thing I would add is, obviously, the DSMB is conducting regular reviews of both studies. The most recent was February. So if there had been any sign of an imbalance that they actually had clinical concern around, they would have told us by now whereas here the two it’s just been perceived as planned.

Paul: Great. Good clarification. So, I guess, we’ll look forward to getting more color there really soon. Maybe just broadly, in psychiatry, I feel like there’s often a fixation in the investor community on the bar. And sometimes it frustrates me when it feels like for the market, there’s a big emotional difference between a three point mattress difference and a four point difference and a two point difference when most of the prescribers of Prozac probably didn’t realize the drug failed and more trials than it worked in.

And so but nonetheless, these headlines matter and they’re how they’re reported and they’re how they’re described. I mean, and when you think about a therapy like COP360, right, which is certainly more complicated to use than Zoloft, do you feel like the efficacy bar for this to be an exciting commercial product is higher, like it has to have an elevated effect size that is materially better than average for an antidepressant?

Kabir, COMPASS Pathways: So I’ll start and then hand to Guy and Laurie. The only place I’ll start is a reminder that we’re talking about treatment resistant depression or MDD. Yes, so we’re talking about people who have typically been failed by multiple drugs at this point. And therefore, I would argue that the bar in TRD is different from that in MDD. But Guy?

Guy, COMPASS Pathways: Yes, I think that’s right. I mean, in truth, it’s very tricky to extrapolate from Phase three trials to the real world, and the patient satisfaction with the overall experience, etcetera, etcetera. It’s hard to do. I don’t think we should be setting the bars higher. I don’t think that’s reasonable.

Just the nature of these trials as we know they’re quite prone to failure, they’re difficult to conduct, and I think piling more pressure on to do better is unreasonable frankly. So I’m certainly not looking at looking at our results in that way personally, and I don’t expect the field to, frankly.

Paul: Yeah. Okay. Fair enough. So we’ll get some more data soon. And then, you know, I think the other just kind of couple of development questions before I want to ask a few in the commercial to wrap things up.

Just Just as it relates to enrollment, right, and you’ve given us color, right, later 2Q for this first five readout. But for six, what can you say about just where you are and your comfort that that readout is not going to slip?

Kabir, COMPASS Pathways: Yes. It’s a good question, Paul. So what I would say is while we hadn’t thus far disclosed numbers, we are well underway with recruitment. And just clarification, these it did start while five was underway. These are not sequential studies.

So six is already recruiting aggressively not only in The U. S. And Canada, but in a whole host of European countries. And as a reminder, five was U. S.

Only. Six in terms of distribution looks much more like one with around 50% U. S, fifty % ex U. S. And just by the nature of TRD where the patients are the medical systems in Europe, recruitment tends to be significantly quicker in Europe than it is in The U.

S. We’ve also said as five wraps up imminently, the best performing sites from five will move into six in The U. S. They haven’t had to stop screening in five, so there’s a bonus of patients there for six. It’s the same indication.

So for now, we are very confident on that second half twenty six guidance, recognizing it’s a wide guidance, and we would hope over the course of the remainder of this year to narrow that down somewhat.

Paul: Yeah. Okay. Makes sense. And then the o six study, how different is it from the phase 2b?

Guy, COMPASS Pathways: Not very, except, of course, that it lasts for blinded up to twenty six weeks and for full observational reasons up to fifty two. But the design otherwise is very similar in that we’re going for a comparison between one, ten and twenty five. The ten is a psychoactive dose that we believe is unlikely to be efficacious, but therefore sits in and kind of keeps everybody uncertain about what the dosing is for any individual patient. There are two administrations of the drug, which is the key change. And that means we’re expecting a larger benefit.

That was something that was predicted by the PIs and many of the patients commented in one that they thought two treatments would help them. We’re going to be very excited to see that. I think otherwise, we made minimal changes to the entry criteria. I suppose a little difference is that we’re having a few more patients with previous experience with psychedelics and with psilocybin in particular, and that will allow us has allowed us to stratify the randomization on that past history. And so we will get some sense of whether those patients are different in any way from the group who who who claim to be naive to the to the drug.

So, you know, those are those are the very, very minor changes that we’ve made. The double treatment is the thing that’s really interesting.

Paul: Yes. Okay. Okay. Great. All right.

Two commercial questions or I guess one of them is sort of regulatory sort of commercial and then we can wrap up. And hopefully, it’s okay if you go a minute or two over since we started a couple of minutes late. But just as it relates to the monitoring in the real world, can you talk about why the team is comfortable that you’re not gonna need a therapist in the real world for patient monitoring? And when you think about the commercial scalability of this, how important is it in getting regulators onboard globally that this is really not therapy guided efficacy and that the therapy piece or the therapist piece is really just about caution, safety, monitoring, etcetera.

Laurie, COMPASS Pathways: Yeah. I do wanna speak about it from a clinical standpoint, and then I can certainly answer from a commercial standpoint.

Guy, COMPASS Pathways: Yeah. I think, I mean, we’ve I think I think, obviously, the need for psychotherapists was driven by the FDA. And in Europe, we didn’t we are not necessarily using psychotherapists. We’re using nurses, in particular, and other healthcare professionals. I think essentially we think that the key thing is the preparation for the experience.

That’s not something that we would want to diminish, but we don’t see that as requiring a psychotherapist. That can be delivered in part with a really good psychoeducational package and also someone in person who is gonna sit with the patient on the day. And we think that relationship helps a good deal to make sure that patients feel safe, and therefore are more able to relax and accept the experience. So those are, I think, the component components that are important. How they’re delivered, I know that Laurie is thinking a lot about that, maybe you I should hand over the thinking to her.

Laurie, COMPASS Pathways: Yeah. Thanks thanks, Guy. You know, we are obviously learning a lot through what’s happening in the clinical trials, and we’re working with our, you know, collaboration partners as well to understand, you know, what will happen in a real world setting. Given that, you know, especially during the administration period, the therapist is really there just for safeguarding and monitoring. We feel pretty comfortable that we will only be limited to, a health care provider during that time period.

And that can be, obviously, whatever the list is, at the site’s discretion. You know, a good analog is is Spervato. Right? So Spervato REMS just as limited to a health care provider being present during administration and available during the monitoring session. So so we feel like it will be a very comparable situation.

Paul: Yeah. Okay. And then I realized that a couple of minutes left doesn’t do this question, Jeff. This is Laurie, so I’m sorry. But I think the one most interesting commercial question that I regularly get just honestly relates to the economics.

I mean, it feels like figuring out the economics and the reimbursements for Lotto has been key to it taking off. I mean, I think that that’s been a big part of it. And so as it relates to Comp three sixty, given the longer duration, how might the economic model here be similar or different? And how what are the implications for scalability?

Laurie, COMPASS Pathways: Yeah. We agree. Provider economics is going to be important to the adoption of the product. So, obviously, something we’re spending quite a bit of time thinking about and working through. Again, we’re kind of leaning on learnings from our collaboration partnerships that we have in place, as well as, you know, additional, you know, just commercial preparation work.

You know, if you think about Sverdato, best case scenario for Sverato is, you know, potentially three patients per day per room. You know, if you think a two hour administration session, turnover, administrative burden of of scheduling, That is how, you know, their day kind of looks. Hours and some of the work that I was most impressed with when I came on board to Compass was the work that was done around getting the CPT three codes adopted, and, you know, the adoption of those, obviously, after approval. But having those set up in place allows for the centers to bill for the administration and support time. So, effectively, if it’s an eight hour six to eight hour administration time period, the center can bill exactly the same time that they would take as cycling patients through.

So, you know, from a provider economics, we think it will be highly comparable. We also know Sravato is, you know, especially the high volume centers are doing buy and bill, and we we don’t see any reason to believe that

Kabir, COMPASS Pathways: they wouldn’t do the same for

Paul: country 60. Great. Makes sense. Well, thank you. I know we could easily talk for another half hour, about more of your data and commercial and stuff, but I really appreciate it.

And we look forward to your results about two to three months away. So best of luck, and thanks so much.

Kabir, COMPASS Pathways: Thank you, Paul. Thanks very much.

Paul: All right. Good seeing you. Thank you. Thank you. Thanks everyone for joining.

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