Compass Pathways Targets Q4 2026 COMP360 NDA Completion, H1 2027 Launch

Compass Pathways (NASDAQ: CMPS) said in its Q3 2026 investor presentation that the rolling U.S. new drug application submission and review for COMP360 in treatment-resistant depression are underway, with the final portion of the submission expected in the fourth quarter of 2026. The company is preparing for a potential U.S. launch in the first half of 2027, subject to approval by the Food and Drug Administration and the required rescheduling of the psilocybin treatment.

The regulatory effort is supported by two positive Phase 3 trials, COMP005 and COMP006, which met their primary endpoints and showed statistically significant reductions in depressive symptoms. The FDA has granted COMP360 Breakthrough Therapy designation, rolling review and a National Priority Voucher for treatment-resistant depression, or TRD. Compass cautioned that rolling review and the voucher may not result in a faster review or approval.

Phase 3 results support regulatory filing

COMP360 is Compass Pathways’ investigational synthetic formulation of psilocybin. The company is developing it as an infrequently administered treatment for mental health conditions, with TRD as the lead indication.

In COMP005, which enrolled 258 participants, a single 25-milligram dose produced a least-squares mean difference of 3.6 points on the Montgomery-Åsberg Depression Rating Scale compared with placebo at Week 6, meeting the primary endpoint with a p-value below 0.001. The treatment difference was statistically significant beginning on the day after administration.

In the 581-participant COMP006 trial, patients initially received two doses of 25 milligrams, 10 milligrams or 1 milligram, with the second dose administered at Week 3. At Week 6, the 25-milligram arm showed a 3.8-point least-squares mean improvement in MADRS relative to the 1-milligram control arm, also with a p-value below 0.001. Statistically significant differences between the 25-milligram and 1-milligram groups were observed at every measured time point after administration through the primary endpoint.

The studies enrolled patients with chronic depression and substantial prior treatment exposure. In COMP006, current depressive episodes had lasted more than three years on average, while participants had experienced more than six lifetime depressive episodes on average.

Compass said separation between the 25-milligram and control groups was maintained through Week 26 in both trials. In post hoc analyses, 39% of participants in the COMP006 25-milligram arm and 25% in the COMP005 25-milligram arm achieved at least a 25% reduction in MADRS at Week 6 and, on average, maintained that improvement through Week 26.

Retreatment was available under prespecified criteria during the follow-up periods, and protocol-permitted antidepressants could be used in later portions of the studies. In COMP006, 58% of patients in the 25-milligram group were retreated after Week 9. In COMP005, 70% of the 25-milligram group and 53% of the placebo group received a second administration after Week 6. The presentation noted that no statistical analyses were conducted in COMP005 after the Week 6 primary analysis.

Open-label COMP005 data extended to Week 52. Among participants originally assigned to 25 milligrams who continued into Part C, 80% received another dose, and the group recorded an average 13-point MADRS reduction from baseline at Week 52. Participants originally assigned to placebo who later received their first 25-milligram dose in Part C showed an average 10-point reduction from baseline at the end of that period. These later-stage findings were based on observed open-label data rather than the initial randomized comparison.

Safety and commercial preparations

Compass characterized COMP360’s Phase 3 safety profile as generally well tolerated, with no new safety signals identified. Most adverse events were transient and occurred on dosing days.

Through Week 26 in COMP006, treatment-emergent adverse events were reported by 94.6% of patients in the 25-milligram arm, compared with 86.7% in the 1-milligram arm. Serious treatment-emergent adverse events occurred in 5.7% and 6.3% of those groups, respectively. The most frequent events in the 25-milligram group included nausea, headache, anxiety, visual hallucinations, fatigue, perceptual disturbances and dizziness.

In COMP005, 84.8% of participants receiving 25 milligrams experienced a treatment-emergent adverse event through Week 26, compared with 59.8% of placebo recipients. Serious events were reported in 4.7% and 2.3%, respectively. Headache, nausea, visual hallucinations and anxiety were the most common events occurring in more than 10% of the 25-milligram group.

Ahead of a possible launch, Compass said it is holding payer discussions, enabling product distribution, establishing patient-support mechanisms and preparing its commercial field organization. The company expects treatment to be delivered at certified centers where a patient would self-administer an oral capsule while being monitored by a licensed healthcare professional.

Compass believes COMP360 could fit within the existing interventional psychiatry infrastructure, which already includes dedicated treatment areas and staff for therapies requiring several hours of monitoring. However, the company said coding and reimbursement arrangements for COMP360 have not been established and remain subject to change.

PTSD program broadens development pipeline

Compass is also evaluating COMP360 for post-traumatic stress disorder. A Phase 2a open-label study involving 22 participants found sustained improvements on PTSD and disability measures through Week 12 after a single 25-milligram administration. CAPS-5 response rates were 81.8% at Week 4 and 77.3% at Week 12, while remission rates were 63.6% and 54.5%, respectively. No treatment-emergent serious adverse events were reported in the study.

A randomized Phase 2b/3 PTSD trial is underway in 300 adults. The primary endpoint will compare two 25-milligram administrations with two 1-milligram administrations based on the change in CAPS-5 scores at Week 8. A 10-milligram arm is included to help preserve blinding and assess that dose as a secondary outcome, followed by an open-label extension through Week 52.

The company’s outlook remains dependent on clinical, regulatory and commercial execution. Full Phase 3 results may differ from preliminary findings, and the FDA may not approve COMP360 on an accelerated basis or at all. Even if approved, the treatment contains Schedule I controlled substances and would need to be rescheduled by the U.S. Drug Enforcement Administration and individual states before commercialization. Compass also identified funding needs, potential clinical delays, reimbursement and adoption challenges, and its ability to transition from a clinical-stage to a commercial-stage organization as material uncertainties.