COMPASS Pathways (NASDAQ:CMPS) used an investor update webinar to highlight positive results from its Phase III COMP005 and COMP006 pivotal trials of COMP360 psilocybin for treatment-resistant depression (TRD), emphasizing rapid onset, durability, and a safety profile the company described as consistent with prior experience. Executives said the dataset now includes more than 1,000 participants across the two Phase III studies and a prior Phase IIb trial, with the company meeting its primary endpoint “three for three” with high statistical significance.
Unmet need and trial program overview
CEO Kabir Nath framed the opportunity around what the company called a large unmet need in TRD, citing an estimate that more than 4 million U.S. adults live with TRD each year. He said many therapies have failed in this population and noted that only one marketed medicine is currently approved and used for TRD.
Goodwin said the COMP006 design used 1 mg as an active comparator rather than an inert placebo to reduce unblinding and strengthen claims of pharmacologic effect. MADRS assessments were conducted remotely by blinded raters.
Efficacy: rapid onset and durability
Company leadership repeatedly underscored what they characterized as unusually rapid response. Nath said the key takeaway for COMP360 is that it is “safe to try” and that for those who respond, “on average, you do so on day one.” Goodwin said in COMP005 the treatment effect was observed the day after administration and remained statistically significant versus placebo at each measured time point through six weeks.
Newly presented COMP005 Part B data extended the blinded follow-up to 26 weeks. Goodwin said the trial showed “numerical separation at all time points up to 26 weeks,” with most retreatments occurring between weeks 10 and 14. He cautioned that further analysis is needed for full understanding given options for retreatment, antidepressant use, and withdrawals, but called the intention-to-treat durability signal “very striking.”
Goodwin described a planned analysis splitting the 25 mg COMP005 arm into remitters, responders/partial responders, and non-responders, noting that a subset showed sustained remission out to 26 weeks after a single administration. He also said that among those receiving a second 25 mg dose in Part B, over 40% achieved remission after the second dose.
Across trials, Compass highlighted the proportion achieving what it defined as a clinically meaningful reduction in MADRS at week six:
- COMP005: 25% of patients in the 25 mg arm achieved a clinically meaningful reduction at week six, sustained through 26 weeks, according to management’s summary.
- COMP006: 39% achieved a clinically meaningful reduction at week six, which management linked to the fixed second dose in the trial design.
In COMP006, Goodwin said 25 mg showed statistically significant differences versus the 1 mg comparator at every time point beyond baseline, with a numerical dose-response pattern (25 mg > 10 mg > 1 mg) at one, three, and six weeks. He noted the week-six effect size of -2.5 on MADRS, while statistically significant, was below a commonly cited threshold of three points for clinical significance. He added that 1 mg appeared to perform better than inert placebo would, which the company said was expected given the active-comparator design.
Safety: no new signals in >1,000 patients
Discussing COMP004/005/006 collectively, Goodwin said COMP360 was generally well-tolerated, with most adverse events occurring on the dosing day and resolving within a day. He reported no new safety signals in the database.
On suicidality, Goodwin said serious adverse events (SAEs) of suicidal ideation were under 1% across available data, with one SAE of suicidal behavior occurring in the 1 mg arm of COMP006. He said the data safety monitoring board (DSMB) found no evidence of a clinically meaningful imbalance between arms in suicidality. He also stated there have been no attempted or completed suicides to date in these studies.
During Q&A, Goodwin described examples of transient suicidal ideation occurring in temporal association with dosing in COMP005, saying they lasted hours and resolved by the next day, and he contrasted these with suicidality seen in non-responders as part of ongoing depressive illness. He also said blood pressure elevations were observed as expected with the drug class but described them as not concerning and within ranges seen with moderate exercise, with no subsequent consequences reported.
Regulatory and commercial plans
Nath said the company has submitted the Phase III data to the U.S. Food and Drug Administration and requested a meeting to discuss an NDA filing strategy, including potential rolling submission and review. He said the FDA has shown interest in an “aggressive filing strategy,” and Compass plans to request expedited review tied to its Breakthrough Therapy designation, which he said the company believes is likely to be granted.
Management said 26-week COMP006 data expected in early Q3 would be the “last gating item” to complete the NDA package under a rolling strategy. Nath and Chief Commercial Officer Lori Englebert said Compass is preparing to be launch-ready by the end of the year, while clarifying in Q&A that the company is not providing guidance on an approval date and is preparing commercial operations to be ready if timelines move quickly.
Englebert said launch planning is designed to leverage existing interventional psychiatry infrastructure, citing more than 7,000 U.S. sites that already support multi-hour monitored treatments such as Spravato. She also outlined distribution and access considerations, including the need for DEA rescheduling after FDA approval and subsequent state-level rescheduling to enable prescribing and distribution. Englebert said the DEA has 90 days after FDA approval to reschedule a product and that the company is engaging with regulators and states to support timely execution.
About COMPASS Pathways (NASDAQ:CMPS)
COMPASS Pathways (NASDAQ: CMPS) is a clinical-stage biotechnology company focused on the development and commercialization of psilocybin therapy for mental health disorders. Founded in 2016 and headquartered in London with additional offices in the United States, COMPASS Pathways is pioneering the use of synthetic psilocybin combined with psychotherapy to address treatment-resistant depression. The company’s flagship program is a Phase IIb clinical trial evaluating COMP360, its proprietary psilocybin formulation, which has received Breakthrough Therapy designation from the U.S.
