COMP360 · program

Psilocybin (COMP360) for Treatment-resistant depression

Phase 3ActiveCOMPASS Pathways plc (CMPS)
  • Breakthrough Therapy
  • FDA Rolling Review
  • Commissioner's National Priority Voucher
  • ILAP (UK)

Indications for COMP360: Treatment-resistant depression · Phase 3 Anorexia nervosa · Phase 2 Post-traumatic stress disorder · Phase 2/3 Major depressive disorder · Phase 2

Both pivotal Phase 3 trials (COMP005, COMP006) met their primary MADRS endpoints (p<0.001). As of mid-2026 the program is in the regulatory-filing window: a rolling NDA is underway, full submission targeted Q4 2026, with FDA Breakthrough Therapy designation and an April 2026 Commissioner's National Priority Voucher that could compress review.

Data current as of

Development timeline

Phase 3Jun 2025 – Dec 2026
  1. UpcomingFull NDA submission targeted (FDA rolling review underway).↗
  2. FDA granted rolling NDA review; Compass awarded Commissioner's National Priority Voucher.↗
  3. metCOMP006 met its primary endpoint: -3.8 MADRS (two 25mg doses vs 1mg) at Week 6 (p<0.001).↗
  4. metCOMP005 met its primary endpoint: -3.6 MADRS vs placebo at Week 6 (p<0.001).↗

Readouts

  • fourth quarter 2026AnticipatedRegulatory

    Full NDA submission targeted (FDA rolling review underway). ↗

  • 2026-02-17ReportedTopline datametNCT05711940

    COMP006 met its primary endpoint: -3.8 MADRS (two 25mg doses vs 1mg) at Week 6 (p<0.001). ↗

  • 2025-06-23ReportedTopline datametNCT05624268

    COMP005 met its primary endpoint: -3.6 MADRS vs placebo at Week 6 (p<0.001). ↗

Clinical trials in Treatment-resistant depression

NCT05711940COMP006Phase 3Activen=572

Phase III, Randomised, Double-blind, Controlled Study of Two Administrations of COMP360 in Treatment-resistant Depression

Started Feb 2023· Primary completion Feb 2026· 📍 116 sites across 12 countries (United States, United Kingdom, Canada, Czechia)

metprimaryMADRS change at Week 6 (two 25mg doses vs 1mg) — -3.8 points (<0.001)

Second pivotal Phase 3; two doses 3 weeks apart. 95% CI [-5.8, -1.8]. Magnitude noted as modest by some analysts.

NCT05624268COMP005Phase 3Activen=255

Phase III, Randomised, Double-blind, Placebo-controlled Study of COMP360 in Treatment-resistant Depression

Started Jan 2023· Primary completion May 2025· 📍 40 sites across 1 country (United States)

metprimaryMADRS change at Week 6 (single 25mg vs placebo) — -3.6 points (<0.001)

First pivotal Phase 3; first Phase 3 efficacy readout for a classic psychedelic. 95% CI [-5.7, -1.5].

NCT03775200COMP001 (P-TRD)Phase 2Completedn=233

The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression

Started Mar 2019· Primary completion Jul 2021· 📍 25 sites across 10 countries (United States, United Kingdom, Netherlands, Canada)

metprimaryMADRS change at Week 3 (25mg vs 1mg) — -6.6 points (<0.001)

Phase 2b dose-ranging; single 25mg dose significantly reduced MADRS vs 1mg at Week 3. Published NEJM (Goodwin 2022).

Formulations

FormulationRouteRegimenPharmacokinetics
COMP360 oral capsule (25 mg)Immediate-release solid oral capsule (synthetic crystalline psilocybin), administered once with psychological support
25 mg single oral dose (also studied at 1 mg and 10 mg comparator doses)
OralSingle doset½ 3 h · Tmax 2 h · F 52.7%

Mechanism of action (compound-wide)

Psilocybin is a prodrug rapidly converted in vivo to psilocin (4-OH-DMT), the active serotonergic agent. Effects are driven primarily by 5-HT2A partial agonism, with additional agonism at 5-HT2C, 5-HT1A and 5-HT2B and weaker activity at TAAR1. Reported affinities vary widely across assays.

TargetActionAffinity
5-HT2AprimaryHTR2APartial agonistpEC50 7.6ⓘ
5-HT1AHTR1AAgonist—ⓘ
5-HT2BHTR2BAgonistpKi 8.33ⓘ
5-HT2CHTR2CAgonistpKi 6.85ⓘ
TAAR1TAAR1AgonistKi 1.4 nMⓘ

← Full COMP360 compound page (identity, identifiers, all indications)

Sources

  1. 5-HT2A/2C/1A and TAAR1 in the head-twitch response (psilocybin) — Int. J. Mol. Sci.
  2. COMP001 / P-TRD (NCT03775200) — ClinicalTrials.gov
  3. COMP005 (NCT05624268) — ClinicalTrials.gov
  4. COMP006 (NCT05711940) — ClinicalTrials.gov
  5. COMP360 Phase 3 (COMP006) efficacy data — Psychiatric Times
  6. Compass Pathways Successfully Achieves Primary Endpoint in First Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression — Compass Pathways IR
  7. Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression — Compass Pathways IR
  8. FDA rolling NDA review + Commissioner's National Priority Voucher — Business Wire
  9. psilocin — IUPHAR/BPS Guide to Pharmacology (Ligand 11291) — IUPHAR/BPS
  10. psilocin — Ligand Activity Charts — IUPHAR/BPS
  11. Psilocybin — Wikipedia
  12. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression (Goodwin 2022) — NEJM