BPL-003 for Treatment-Resistant Depression: New Positive Phase 2a Data

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atai Life Sciences and Beckley Psytech shared positive data from a proof-of-concept study investigating a 2-dose induction regimen of intranasal mebufotenin benzoate (BPL-003), in patients with treatment-resistant depression (TRD).¹

In the open-label phase 2a study (NCT05660642), investigators enrolled 13 patients with TRD who were not on concurrent antidepressants, and 12 met the criteria for per-protocol analysis. Participants were given an 8 mg dose of BPL-003, followed by a 12 mg dose 2 weeks later. Safety, tolerability, and efficacy assessments were conducted at various timepoints for 12 weeks following the initial dose using multiple validated depression rating scales, such as the Montgomery-Asberg Depression Rating Scale (MADRS). The results show that a second dose of BPL-003 at week 2 has the potential to induce greater antidepressant effects without impact on the safety and tolerability profile of the treatment.

Following the initial 8 mg dose, participants experienced a mean MADRS reduction of 13.3 points from baseline at day 2 and a mean MADRS reduction of 12.9 at day 8. One week after the second 12 mg dose, there was a further decrease in MADRS score to a total of a 19.0-point reduction from baseline, with sustained antidepressant effects observed through week 12 (13.7 points from baseline). These findings suggest that a second dose of BPL-003 may further enhance the clinical response beyond what is achieved with a single administration, and effect are sustained for up to 3 months. Also, participants met discharge readiness criteria within 2 hours after dosing for both doses, which makes administration more practical.

Furthermore, the second dose of BPL-003 increased the proportion of participants meeting response and remission criteria for depression. Remitter rates 1 week after the initial 8 mg dose were 25%, with rates doubling to 50% at week 8 (6 weeks after the second dose administration), and 42% at week 12.

As to safety and tolerability, BPL-003 was shown to be generally well-tolerated, with all adverse events classified as mild to moderate, and there were no severe or serious drug-related adverse events reported. These findings are consistent with those seen in other previously reported studies of BPL-003.

“These results underline BPL-003’s potential to offer a rapid, well-tolerated and durable treatment option for patients with treatment-resistant depression. They suggest that a second dose of BPL-003 not only maintains, but potentially deepens, antidepressant effects while remaining well-tolerated. Importantly, the findings are consistent with results from earlier phase 2a cohorts, including studies in patients who were taking antidepressants (SSRIs), where a single dose of BPL-003 produced rapid and sustained improvements for up to 3 months,” said Cosmo Feilding Mellen, the chief executive officer and cofounder of Beckley Psytech. “Together with the results from our phase 2b program, these data provide a strong foundation of evidence to design our phase 3 program, and we are grateful to the patients, investigators, and sites who have made this progress possible.”

This research builds upon previous phase 2b findings. In July 2025, atai and Beckley Psytech shared results from an 8-week, quadruple-masked, dose-finding, core stage of the phase 2b clinical trial evaluating the efficacy and safety of a single dose of BPL-003 in patients with TRD. Investigators found that BPL-003 demonstrated rapid, robust, and durable antidepressant effects with just a single 8 mg or 12 mg dose.²

“This proof-of-concept study provides compelling evidence that a 2-dose induction regimen for BPL-003 may optimize outcomes for patients with treatment-resistant depression. This dosing approach could be further explored in phase 3 studies, subject to discussions with regulators,” said Srinivas Rao, the chief executive officer and cofounder of atai Life Sciences.

atai and Beckley Psytech are finalizing plans to engage with the US Food and Drug Administration to discuss the design of the phase 3 clinical trials for BPL-003 in patients with TRD, which is set to initiate in the first half of 2026.

References

1. atai Life Sciences and Beckley Psytech report positive phase 2a data demonstrating improved outcomes with a two-dose induction regimen of BPL-003 in patients with treatment-resistant depression. News release. September 23, 2025. Accessed September 23, 2025. https://ir.atai.life/news-releases/news-release-details/atai-life-sciences-and-beckley-psytech-report-positive-phase-2a

2. Kuntz L. Positive results from the phase 2b study of BPL-003 in patients with treatment-resistant depression. Psychiatric Times. July 1, 2025. https://www.psychiatrictimes.com/view/positive-results-from-the-phase-2b-study-of-bpl-003-in-patients-with-treatment-resistant-depression