Phase 3 Program Investigating COMP360 Psilocybin for Treatment-Resistant Depression: Breaking Poster Data From the 2026 ASCP Annual Meeting

Compass Pathways shared late-breaking poster data at the 2026 ASCP Annual Meeting in Miami, FL, on their phase 3 program investigating COMP360 psilocybin for treatment-resistant depression.^1-3 Study COMP005 compared a 25 mg dose with a placebo over 26 weeks and 2 doses (1, 10, or 25 mg) against each other. Both studies COMP005 and COMP006 showed highly statistically and clinically significant results, with significant improvements in the Montgomery-Åsberg Depression Rating Scale (MADRS) score. The cohort included patients with severe depression and many lifetime depressive episodes and chronic current episodes. Investigators also noted that 2 treatments were generally better than 1, and that some patients benefited dramatically from a single treatment. These studies aimed to address skepticism by recruiting a valid population without prior psychedelic use and by conducting rigorous, large-scale trials.

Guy Goodwin, MD, the chief medical officer at Compass Pathways, sat down with Psychiatric Times to share his insights on this data.

Psychiatric Times: Can you talk to us about your late breaking poster data at the 2026 ASCP meeting?
Guy Goodwin, MD: I would be delighted. We have 3 posters at that meeting; they present the data baseline for the demographics and the trial design. This is our phase 3 program to investigate COMP360 psilocybin in treatment-resistant depression. There are 2 trials and we describe the baseline characteristics. We then go on and look at the actual outcomes, particularly in the first of the studies, which compares inert placebo with 25 mg of COMP360 over 26 weeks, and then we present the primary outcome for both that study and the second of the studies that compares 2 doses of either 1, 10, or 25 mg. All of those primary outcomes are determined at 6 weeks from baseline. We are delighted to say that both these studies are highly statistically significant, and the differences from the comparator are also clinically significant in terms of the magnitude of the change in MADRS score, which is one of the standard metrics in this area.

PT: These trials show a picture of a fairly severe cohort with a pretty high number of lifetime depressive episodes and chronicity of the current episode. We also noted there was a requirement for at least 8 weeks of antidepressant treatment, which is a much higher threshold than typically seen in a lot of treatment-resistant depression trials. Do you think this reflects how psychedelics like COMP360 psilocybin are truly meeting a huge unmet need?

Goodwin: Yes, absolutely. I think we are also studying the most refractory patients, so as you rightly just noted, that is a very high bar to set that requires long proof of nonresponse, more than has often been done previously. That means we have recruited a group who are not just resistant to treatment but also chronic in their experience of depression. The average duration of the index episodes that we are treating is more than 3 years; these are very tough to treat patients, and therefore the improvements that we see, which are, as I said, highly statistically significant differences, and are very good proof of concept and proof that this is an effective treatment for a significant number of patients. I think the other interesting feature is that we seem to have evidence that 2 treatments are probably going to be better than 1 for the majority of patients. Some patients benefit dramatically from a single treatment, and that seems also to show considerable durability, speed of response, maintenance of the effect over a period of time, and this proof of a separation from a comparator, all of which are very key ingredients of these clinical trials.

PT: We also noted that patient prior use of classic psychedelics in both COMP006 and COMP005 was pretty low. Do you think the lack of exposure to psychedelics plays any part in the response?
Goodwin: We simply do not know. We actually set a limit of 15% but it came in appreciably lower than that; It came in at only about 5% of the patients. I think this represents the fact that we are dealing with a group of people, average age of 45, who have not actually used these drugs and have not sought them for treatment of their depression. I think that represents a very large percentage of the chronically depressed or treatment-resistant population, so I think this is highly representative, and it means not so much that we can predict response from this, but that the validity of the clinical trial is reinforced, because there's been suspicion in some previous studies. High rates of previous use of psychedelics is really, first of all, profoundly under-blinding, and secondly, it shows a sort of a psychedelic-seeking behavior on the part of the participants, and that really cannot be said of our cohorts,;they truly represent more realistic clinical practice.

PT: Since we have last spoken, President Trump signed an executive order directing the FDA to issue national priority vouchers for breakthrough breakthrough therapy designated psychedelics. How do you see this impacting access to and research on psychedelics?
Goodwin: We remain committed to a high-quality research program. We have not cut any corners. We are delighted to see this pressure emerging, which will mean that, if we are successful in submitting a valid file, it will be looked at quickly, and that is good news for patients. It also means that we are likely to see commercialization earlier than would otherwise have been possible with the the common rate at which applications were assessed by the FDA. We are delighted to see it.

PT: We have heard some hesitancy on the part of clinicians about this fast track order. Clinicians want psychedelics accessible, but they want them through the regular, rigorous approval process. What do you have to say to people who still have doubts about psychedelics?
Goodwin: We designed these studies to meet as many of the possible objections from the doubters as we possibly could. We designed these studies to recruit a valid population of patients without previous exposure to psychedelics and who are not psychedelic seeking. We have taken a clear major unmet need, which is treatment-resistant depression. Patients are already suffering and there is clearly a need for improved practice. Finally, we have done trials at scale, and randomized now over 1000 patients into our phase 3 study. What we believe is we can present an entirely conventional package of drug development to the FDA, and that allows them to look at what we've done, assess it, and use the same kind of criteria as they would for any other drug. That is key to credibility for us, for the use of these drugs generally, and for the field. We have never attempted to cut corners, or asked for special treatment, and have always gone to look for the most rigorous way of proving our point, which is that these drugs have value in treatment-resistant depression. They probably have a value in other indications as well, which we will need to study in the same responsible and disciplined way.

PT: With the 2026 ASCP posters, was there any particular data point that surprised you, or anything you would like to highlight?
Goodwin: I would like to highlight the speed of response. We had seen that before, but to see it at scale in this way is remarkable. It means, for a clinician, and indeed for patients, that if they are better almost immediately, they are probably going to stay well, because we see this durability. The early response seems to predict the durability and the benefit from the drug, and that I think is remarkable, and we are delighted to see it. The other thing is the durability that we see in our 26 week data, in the in the 25 mg vs placebo arm; to see that separation over 26 weeks is extremely unusual in trials in depression, particularly in TRD. Other companies have tried to treat patients and see benefit in TRD with their products, and they have not been able to do it. One has to bear in mind that these patients are very difficult to treat. Demonstrating these benefits is very exciting to us, and I think will be turn out to have an important benefit for patients.

PT: Do you think that is what differentiates COMP360 from other psychedelics
that are in the pipeline?
Goodwin: I think we will have to see. We are at a later stage. It is very difficult to compare efficacies across phase 2 studies because they tend to be smaller, and they are subject to certain kinds of biases, which may inflate effect sizes. We need to be clear that our evidence is based solidly on phase 3 data, which is clearly generalizable. It has been studied in the United States, in Europe, and in many different centers, in patients without previous psychedelic experience, so it is the generalizability, at the moment, that gives us an edge. We will have to see what happens when other compounds go through the same journey in phase 3.

PT: Is there anything you wish clinicians knew about COMP360?
Goodwin: I think most clinicians are not quite aware that we may be quite close to approval. If we have the good fortune to be approved, it may be as soon as the end of this year, or the beginning of next year, that we are able to launch. I do not think most people appreciate we are as close as that.

The other thing is to emphasize that we are working very hard to ensure that when the drug is available, we will be able to advise clinicians how to use it, where to use it, and which patients would most benefit. All of that work is being done now, and it sets us up for a very exciting 12 months coming up.

PT: Any concluding thoughts?
Goodwin: I want to express our appreciation to the patient population and their families who have helped us by participating in trials. I cannot say enough about how much we value that, and how sometimes how demanding our studies are. So, thank you to them in particular.

Dr Goodwin is the chief medical officer at Compass Pathways, as well as the Emeritus Professor of Psychiatry and NIHR Emeritus Senior Investigator at the University of Oxford, UK.

References

1. Hewitt N, Taylor RW, Marwood L, et al. Demographic and clinical characteristics of participants receiving COMP360 psilocybin treatment for treatment-resistant depression across two pivotal phase 3 trials. Poster presented at: 2026 ASCP Annual Meeting; May 26-29; Miami Beach, FL. Accessed March 15, 2016.

2. Goodwin GM, Marwood L, Hewitt N, et al. Durability of efficacy and safety of COMP360 psilocybin for treatment-resistant depression (TRD) across 26 weeks in a double-blind, randomized, controlled phase 3 study. Poster presented at: 2026 ASCP Annual Meeting; May 26-29; Miami Beach, FL. Accessed March 15, 2016.

3. Goodwin, GM, Marwood L, Hewitt N, et al. Efficacy and safety of COMP360 psilocybin for treatment-resistant depression (TRD) in two phase 3 double-blind randomized controlled studies. Poster presented at: 2026 ASCP Annual Meeting; May 26-29; Miami Beach, FL. Accessed March 15, 2016.