BPL-003 Nasal Spray Shows Quick and Enduring Effect in Treatment-Resistant Depression

BPL-003, mebufotenin benzoate nasal spray, showed reduced depressive symptoms and sustained response rates in patients with moderate to severe treatment-resistant depression.¹ Further cohort data from the 4-part phase 2a trial have been published showing efficacy and safety of the medication in this unique form.²

Recently published data were gathered from cohort 1 of the phase 2a study, which included 12 participants with treatment-resistant depression in a 12-week, open-label trial. Participants included 2 women and 10 men of ages 31 to 55, and all completed the trial. Participants were not taking any concomitant antidepressants. A 10 mg dose of intranasal BPL-003 was administered, then change in Montgomery-Asberg Depression Rating Scale (MADRS) score and remission were measured at days 2, 8, 29, 57, and 85 post-dose.

The phase 2a study showed a mean MADRS score reduction of 12.6 points from baseline to day 2, and the improvement was sustained over 12 weeks. From the day after dosing to day 85, a response rate (MADRS reduction of 50% or greater) continued to show in 54.5% of patients. Over 63% of patients achieved remission (MADRS score of 10 or less) at one or more measured timepoints. Also at day 85, mean Snaith-Hamilton Pleasure Scale scores were improved, from average 8.4 at baseline to 1.5, indicating a lack of anhedonia.

No serious adverse events were reported and no treatment withdrawals due to adverse events occurred. Adverse events were transient and mild to moderate, including mostly increased blood pressure (resolved within observation period), nausea, and nasal discomfort. In terms of discharge after treatment, 10 participants were ready after 90 minutes post-dose (as measured by the Readiness for Discharge Questionnaire). Median time from dosing to discharge was 98 minutes, with a range of 95 to 167 minutes.

“The publication of these findings in the Journal of Psychopharmacology is an important scientific milestone. In this first cohort, we saw a rapid 12.6-point mean reduction in MADRS scores by day 2, which was sustained through 12 weeks on a single dose,” said Srinivas Rao, MD, PhD, cofounder and chief executive officer of AtaiBeckley.¹ Rao added that the company is “proud to be advancing a novel treatment designed to deliver rapid, durable results and integrate conveniently into clinical care. With phase 3 on track to initiate in Q2 2026, these peer-reviewed results reinforce our confidence in BPL-003’s potential to meaningfully address a critical unmet need for patients living with treatment-resistant depression.”

BPL-003 is an intranasal formulation of mebufotenin benzoate, designed to provide rapid relief and continuing effects. It is also being investigated as a treatment for alcohol use disorder and has been granted Breakthrough Therapy designation by the US Food and Drug Administration (FDA).

Cohort 4 in phase 2a has also begun, with evaluation of a 2-dose regiment of BPL-003 in treatment-resistant depression for patients taking specified antidepressants.^1,3 Developers of the drug reported a successful end-of-phase 2 meeting with the FDA in March, and the phase 3 program for BPL-003 is planned to begin in the second quarter of 2026.

References

1. BPL-003 demonstrates rapid and durable antidepressant effects in treatment-resistant depression; phase 2a data published in journal pf psychopharmacology; phase 3 program on track for Q2 2026 initiation. Press release. March 17, 2026. Accessed March 17, 2026. https://www.biospace.com/press-releases/bpl-003-demonstrates-rapid-and-durable-antidepressant-effects-in-treatment-resistant-depression-phase-2a-data-published-in-journal-of-psychopharmacology-phase-3-program-on-track-for-q2-2026-initiation

2. Roberts C, Seynaeve M, Ermakova AO, et al. A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in patients with treatment-resistant depression. J Psychopharm. 2026.

3. An open-label study to evaluate the safety, tolerability and pharmacodynamics of BPL-003 in patients with treatment resistant depression. ClinicalTrials.gov. November 28, 2025. Accessed March 17, 2026. https://clinicaltrials.gov/study/NCT05660642