In an open-label Phase 2a study of 13 patients with treatment-resistant depression, intranasal mebufotenin benzoate (BPL-003) delivered a mean MADRS reduction of 13.3 points by Day 2 after an initial 8 mg dose and 12.9 points by Day 8. A second 12 mg dose at Week 2 deepened the effect to a 19.0-point reduction one week later, with a 13.7-point reduction sustained at Week 12. Remission rates were 25% one week after the first dose, rising to 50% at Week 8 and 42% at Week 12. Adverse events were mild to moderate with no severe drug-related events, and patients met discharge readiness within two hours post-dose.
The core development is atai Life Sciences and Beckley Psytech’s proof-of-concept readout for a two-dose induction regimen of BPL-003, designed to augment and extend antidepressant effects without prolonging clinic time. The small, non-concomitant antidepressant cohort mirrors active doses from the sponsors’ blinded Phase 2b core study, which previously showed significant effects for single 8 mg and 12 mg doses versus a 0.3 mg comparator through Day 57. The open-label extension of the Phase 2b trial—testing a 12 mg administration eight weeks after the initial dose—has completed dosing with data expected in October. The companies intend to engage the FDA on the Phase 3 design, targeting first-half 2026 for initiation pending feedback.
Strategically, the two-dose induction is a bid to balance efficacy with operational efficiency. Mebufotenin’s short-acting psychedelic profile and intranasal delivery aim to sidestep the staffing and chair-time burdens common to longer-session modalities, positioning BPL-003 closer to interventional psychiatry workflows already familiar with two-hour monitoring windows. The use of a nasal device platform with prior regulatory precedent could streamline scale-up and site onboarding. Against a crowded TRD field, the sponsors are betting that a brief clinic footprint coupled with rapid onset and re-dosing optionality will differentiate the program. The pending all-share combination of atai and Beckley Psytech adds context: consolidating psychedelic assets and late-stage spend into a single vehicle signals a push to prioritize candidates with clearer development pathways and commercial operability.
For sites, an induction model of two visits within two weeks, each requiring roughly two hours of observation, fits capacity-constrained clinics better than full-day psychedelic sessions and may reduce the need for intensive psychotherapy infrastructure. Standardization of psych support and safety monitoring remains critical, but the procedural load resembles existing interventional protocols rather than bespoke psychedelic clinics. For CROs, shorter visit times and intranasal dosing reduce logistical complexity relative to infusion- or multi-hour session-based studies, but trials will still demand robust central rater oversight and expectancy-mitigation tactics, particularly because early data are open-label. Regulators are likely to scrutinize durability beyond eight weeks, functional outcomes, suicidality monitoring, and generalizability across patients on background SSRIs. Comparator strategy in Phase 3—active control, optimized SOC, or low-dose comparator—will shape both assay sensitivity and payer narratives.
The immediate watch items are the Phase 2b open-label extension readout, which will test whether re-dosing at eight weeks sustains or amplifies response, and FDA guidance on whether Phase 3 proceeds with single-dose, two-dose induction, or a maintenance framework. Expect clarity on psychotherapy requirements, monitoring duration, and any risk management obligations that could affect site throughput. Operational risks include small-n, open-label bias in the current dataset, potential unblinding in future studies, and the need to lock in device supply and manufacturing for a combination product. If regulators accept a streamlined protocol with limited clinic time and standardized support, BPL-003 could shift psychedelic-acting therapies toward scalable interventional delivery. If not, the operational edge narrows, and the program will have to compete primarily on durability and safety in a crowded TRD landscape.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
