AtaiBeckley eyes Q4 data from BPL-003's two-dose TRD cohort as Phase 3 launches
The open-label Phase 2a readout comes as AtaiBeckley runs a separate, larger placebo-controlled Phase 3 program testing the same drug in treatment-resistant depression.
Executive Summary
- AtaiBeckley expects to report data from a two-dose induction cohort of its open-label BPL-003 study in treatment-resistant depression before year-end, a smaller mechanistic extension running alongside its pivotal Phase 3 program for the same drug.
- Earlier cohorts of the same trial showed a rapid antidepressant response after single intranasal doses that held up through twelve weeks, without serious safety findings, setting the bar the new cohort must clear.
- The trial's completion date has been pushed back repeatedly since it started, and the recruiting status has toggled between active and closed, though the current guidance window remains open and enrollment has held steady at target.
- The real test for BPL-003 sits in a separate, larger, placebo-controlled Phase 3 program now underway, making this readout informative for the drug's dosing strategy rather than decisive for its regulatory prospects.
The catalyst
AtaiBeckley said it expects initial data from the Part 4 cohort of its open-label Phase 2a study of BPL-003 in treatment-resistant depression (TRD) in the fourth quarter of 2026. The cohort is testing a two-dose induction regimen, 8 mg followed by 8 mg, within NCT05660642, a UK-based Phase 2 study that has run since February 2023. The company said the first patient was dosed in this cohort in its March 2026 business update. AtaiBeckley+1AtaiBeckley Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business ...Mar 6, 2026An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant DepressionNCT05660642
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the trial has already shown
The same trial has already produced results from earlier cohorts. In the monotherapy cohort, a mean 12.6-point reduction on the Montgomery-Asberg Depression Rating Scale (MADRS, a standard depression severity score) was reported by Day 2 and sustained through 12 weeks. In the SSRI-concomitant cohort of 12 patients, a single intranasal dose produced a 66.7% Day-2 antidepressant response rate in both the 10 mg and 12 mg groups; response was maintained at Week 12 in 5 of 6 patients on 10 mg and 4 of 6 on 12 mg, with no serious adverse events and a mean discharge time of about 100 minutes post-dose. The trial's registered primary endpoint is safety and tolerability of single or multiple intranasal doses, not a formal efficacy comparison against placebo. AtaiBeckley+1AtaiBeckley Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business ...Mar 6, 2026An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant DepressionNCT05660642
Timing and protocol history
The trial's primary completion date has moved three times since 2023: from October 2023 to November 2024, then to July 2025, then to its current November 2026 date. Its recruitment status also shifted from Recruiting to Active, not recruiting in June 2025 and back to Recruiting in November 2025. Enrollment has held at its 64-patient target since September 2024, with no change accompanying the most recent completion-date shift. AtaiBeckley has repeated the same October-to-December 2026 guidance window across three separate disclosures since March 2026. NCT05660642+1An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant DepressionNCT05660642AtaiBeckley Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business ...Mar 6, 2026
The larger stake
The Part 4 readout arrives as AtaiBeckley runs a separate, larger Phase 3 program for BPL-003 in the same indication. ReConnection-1, roughly 350 patients randomized 2:1:2 across 8 mg, 4 mg, and placebo, and ReConnection-2, roughly 300 patients on a two-dose Day 1/Day 15 schedule against placebo, both use change from baseline in MADRS total score at Week 4 as the primary endpoint, and both began following a completed End-of-Phase 2 meeting with the FDA. Topline data from those core studies is not expected until early 2029. The Phase 2a Part 4 cohort tests the same two-dose concept ReConnection-2 will use, without a placebo arm. AtaiBeckleyAtaiBeckley Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business ...Mar 6, 2026
The competitive field
Treatment-resistant depression carries an active pipeline of small-molecule mechanisms in Phase 2 and Phase 3, including NMDA-modulating agents such as esketamine, D-cycloserine, and zelquistinel, an orexin antagonist in seltorexant, and other novel mechanisms such as osavampator and navacaprant, none of which share BPL-003's mechanism. No direct comparator trial sharing BPL-003's mechanism and modality was identified in the current competitive field, leaving BPL-003's dosing-regimen question to be answered largely on its own evidence rather than against a same-mechanism precedent.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.