Compass Pathways Successfully Achieves Primary Endpoint in First Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression

Business Wire

23-06-2025

LONDON & NEW YORK--(BUSINESS WIRE)--Compass Pathways plc (Nasdaq: CMPS), a biotechnology company dedicated to accelerating patient access to evidence-based innovation, announced today the successful achievement of the primary endpoint in the ongoing Phase 3 COMP005 trial, the first of two Phase 3 trials evaluating COMP360, a synthetic, proprietary formulation of psilocybin, for treatment-resistant depression (TRD). The primary endpoint is the difference in change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores between the active treatment group and the placebo group at week 6. A single dose of COMP360 25 mg versus placebo demonstrated a highly statistically significant reduction in symptom severity with a p-value of <0.001 and a clinically meaningful difference of -3.6 in change at the primary endpoint. The Company plans to discuss these preliminary COMP005 data with the U.S. Food and Drug Administration (FDA), which has not yet reviewed the data.
The ongoing Phase 3 COMP005 trial is the first study of an investigational, synthetic psilocybin, and the first classic psychedelic to report Phase 3 efficacy data. This randomized, double-blind, placebo-controlled study, which dosed 258 participants with TRD across 32 sites in the United States, aims to assess the efficacy and safety of a single dose of COMP360 25 mg versus placebo for reducing symptom severity in TRD.
Key COMP005 Findings:
Efficacy Data (MADRS): Single dose of COMP360 25 mg versus placebo with a mean treatment difference of -3.6 points, 95% CI [-5.7, -1.5]; p<0.001
Safety Data (statement provided by the DSMB chair): Based on the latest review of the data for the 005 and 006 studies, safety findings are consistent with previous studies of COMP360 and there are no new or unexpected safety findings. From this review of the data, there is no evidence of a clinically meaningful imbalance between treatment arms in suicidality in either study. 4
'The positive top-line results at week 6 from the COMP005 trial underscore the innovative potential of psilocybin treatment in mental health care for which Compass Pathways continues to pave the way,' said Kabir Nath, Chief Executive Officer of Compass Pathways. 'We are proud of this significant progress, which reflects our scientific rigor, operational excellence and steadfast commitment to serving patients living with TRD. We eagerly anticipate further insights once we have the full dataset, and also look forward to findings from COMP006, which will explore the efficacy of two fixed doses. We remain focused on our goal of transforming the landscape of mental health treatment.'
'As we continue our Phase 3 program, we are very encouraged by the initial positive results and the highly statistically significant and clinically meaningful change in the MADRS score between the arms of the study 6 weeks after a single administration of COMP360,' said Guy Goodwin, MD, Chief Medical Officer of Compass Pathways. 'This progress marks an important milestone for patients living with TRD and highlights the groundbreaking work Compass Pathways is doing to bring innovative treatments to those who have been failed by multiple currently approved available treatment options. This achievement provides hope that they can finally receive appropriate care and live the life they deserve. We are incredibly grateful to the participants, investigators and clinical sites for their invaluable contributions to this study.'
About the COMP360 Phase 3 Program
The COMP360 program aims to evaluate the safety and efficacy of COMP360 psilocybin, a synthetic, proprietary formulation of psilocybin under investigation for difficult-to-treat mental health conditions. There are two pivotal Phase 3 trials, COMP005 and COMP006, evaluating the efficacy of COMP360 for treatment-resistant depression (TRD).
The ongoing COMP005 trial is a randomized, double-blind, placebo-controlled study, which has dosed 258 participants with treatment-resistant depression across 32 sites in the United States and aims to assess the efficacy and safety of a single dose of 25 mg COMP360 versus placebo for reducing symptom severity in TRD. The trial is comprised of three parts: Part A, which has recently concluded and was blinded through 6 weeks; Part B, which remains blinded through week 26; and Part C, which contains an open-label treatment part from week 26 to 52.
The COMP006 trial, running in parallel to the COMP005 trial, is a randomized, double-blind study with 568 planned participants from North America and Europe and aims to compare the safety and efficacy of two fixed doses, taken three weeks apart, of 25 mg COMP360 to 10 mg COMP360 and 1 mg COMP360. The trial is comprised of three parts: Part A, which is blinded through 9 weeks, Part B which remains blinded through week 26, and Part C, which contains an open-label treatment part from week 26 to 52.
Compass Pathways anticipates sharing 26-week data for COMP005 once all participants in the COMP006 trial have completed part A of the COMP006 trial. The 26-week data from COMP006 is expected in the second half of 2026.
About treatment resistant depression (TRD)
The United States is in a mental health crisis, and depression is one of the most common mental health disorders. Depression significantly impacts relationships, work performance, overall quality of life, and is associated with an increased risk of suicide. Major depressive disorder (MDD) has been ranked as the third cause of the burden of disease worldwide in 2008 by the World Health Organization (WHO), which has projected that this disease will rank first by 2030. An estimated 21 million adults in the United States suffer from major depression, and approximately 9 million are drug treated.
Due to the limitations of approved existing MDD medications, approximately one-third of patients with MDD will develop TRD. TRD is broadly defined as an inadequate response to two or more appropriate courses of approved medications. TRD has a significantly greater impact on individuals compared to MDD, leading to residual symptoms, poorer quality of life, increased comorbidities, higher mortality, and an increased risk of suicide compared to non-treatment resistant MDD.
About Compass Pathways
Compass Pathways plc (Nasdaq: CMPS) is a biotechnology company dedicated to accelerating patient access to evidence-based innovation in mental health. We are motivated by the need to find better ways to help and empower people with serious mental health conditions who are not helped by existing treatments. We are pioneering a new paradigm for treating mental health conditions focused on rapid and durable responses through the development of our investigational COMP360 synthetic psilocybin treatment, potentially a first in class treatment. COMP360 has Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) and has received Innovative Licensing and Access Pathway (ILAP) designation in the UK for treatment-resistant depression (TRD).
Compass is headquartered in London, UK, with offices in New York in the U.S. We envision a world where mental health means not just the absence of illness but the ability to thrive.
Forward-looking statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. In some cases, forward-looking statements can be identified by terminology such as 'may', 'might', 'will', 'could', 'would', 'expect', 'intend', 'plan', 'objective', 'anticipate', 'believe', 'contemplate', 'estimate', 'predict', 'potential', 'continue' and 'ongoing,' or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. Forward-looking statements include express or implied statements relating to, among other things, statements regarding our business strategy and goals; our plans and expectations regarding our Phase 3 trials in TRD, including our expectations regarding the time periods during which the 26-week results of the two Phase 3 trials will become available; the potential for the pivotal Phase 3 program in TRD to support regulatory filings and approvals; our expectations regarding the safety or efficacy of our investigational COMP360 psilocybin treatment, including as a treatment for treatment of TRD; our expectations regarding the enrollment of our Phase 3 COMP006 trial; any implication that past results will be predictive of future results; and statements related to the innovative potential of psilocybin treatment in mental health care. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Compass's control and which could cause actual results, levels of activity, performance or achievements to differ materially from those expressed or implied by these forward-looking statements.
These risks, uncertainties, and other factors include, among others: uncertainties associated with risks related to clinical development which is a lengthy and expensive process with uncertain outcomes, and therefore our clinical trials may be delayed or terminated and may be more costly than expected; the full results and safety data from this Phase 3 study in TRD or the results and safety data from our second Phase 3 study in TRD, COMP006, may not be consistent with the preliminary results to date; our need for substantial additional funding to achieve our business goals and if we are unable to obtain this funding when needed and on acceptable terms, we could be forced to delay, limit or terminate our clinical trials; our efforts to obtain marketing approval from the applicable regulatory authorities in any jurisdiction for our investigational COMP360 psilocybin treatment may be unsuccessful; our efforts to commercialize and obtain coverage and reimbursement for our investigational COMP360 psilocybin treatment, if approved, may be unsuccessful; and those risks and uncertainties described under the heading 'Risk Factors' in Compass's most recent annual report on Form 10-K or quarterly report on Form 10-Q, and in other reports we have filed with the U.S. Securities and Exchange Commission ('SEC'), which are available on the SEC's website at www.sec.gov. Except as required by law, Compass disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Compass's current expectations and speak only as of the date hereof.
References
Data on file
For the definition of classic psychedelic, see Vollenweider, F.X. and Smallridge, J.W., 2022. Classic psychedelic drugs: update on biological mechanisms. Pharmacopsychiatry, 55 (03), pp.121-138.