Positive Results From the Phase 2b Study of BPL-003 in Patients With Treatment-Resistant Depression

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atai Life Sciences and Beckley Psytech today jointly announced positive topline results from the 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 (intranasal mebufotenin (5-MeO-DMT) benzoate) in patients with treatment-resistant depression (TRD).¹

The phase 2b clinical study is the largest controlled clinical study to investigate mebufotenin and the only blinded phase 2b study of mebufotenin to include the United States. It was conducted at 38 sites across 6 countries and enrolled a total of 193 participants with moderate-to-severe TRD (NCT05870540). Participants were randomly assigned to receive a single 12 mg (n=73), 8 mg (n=46), or 0.3 mg comparator (n=74) dose of BPL-003. Investigators followed participants for 8 weeks, conducting efficacy assessments via centralized, blinded raters using the MADRS at day 2, day 8, day 29 and day 57.

The study met its primary and all key secondary endpoints, and BPL-003 demonstrated rapid, robust, and durable antidepressant effects with a single dose. For the primary endpoint, at day 29, a single 12 mg dose of BPL-003 demonstrated a statistically significant reduction in depressive symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), with a mean decrease of 11.1 points from baseline compared with a 5.8 point reduction in the 0.3 mg comparator group (P = 0.0038). For the key secondary endpoints, a single 8 mg dose of BPL-003 also showed significant improvement at day 29, with a mean MADRS score reduction of 12.1 points (P=0.0025 for change vs 0.3 mg control). Investigators noted that both the 8 mg and 12 mg doses of BPL-003 showed statistically significant improvements in MADRS scores as early as a single day after dosing and maintained effects until week 8.

“The achievement of our primary and secondary endpoints in this study represents an important milestone in the development of BPL-003 and reinforces its potential to be a viable treatment option for patients and health care systems. We are particularly encouraged that a single 8 mg or 12 mg dose of BPL-003 showed rapid and durable efficacy results, favorable tolerability, and a short time in-clinic, giving us important flexibility in optimizing the design of future trials,” said Cosmo Feilding Mellen, the chief executive officer and cofounder of Beckley Psytech.¹

BPL-003 was generally well-tolerated at all doses. More than 99% of treatment-emergent adverse events were mild or moderate and there were no drug-related serious adverse events. However, the 8 mg dose was better tolerated than the 12 mg dose, as suggested by dose related increases in administration site discomfort, nausea, headache, blood pressure, and anxiety. Additionally, investigators noted that no participants in the 8 mg nor 12 mg arms had any instance of treatment-emergent suicidal intent or behavior. The average time to discharge across all arms was within 2 hours of dosing. Most participants were deemed ready for discharge 90 minutes post-dose.

“What stands out in these results is that a single administration of BPL-003 in patients with treatment-resistant depression was generally well tolerated and produced a robust antidepressant effect that emerged rapidly and was solidly sustained for at least 2 months. Notably, the acute psychedelic effects were shorter than with most other psychedelics studied clinically, suggesting potential for a quicker functional recovery for patients and a reduced need for prolonged monitoring. If a treatment with this profile were available today, it would immediately become my treatment of choice for TRD,” said David Feifel, MD, PhD, Professor Emeritus of Psychiatry at the University of California, San Diego and director of the Kadima Neuropsychiatry Institute.¹

The safety and efficacy data from this study support the advancement of the 8 mg dose of BPL-003 into phase 3 clinical studies. atai and Beckley Psytech will engage with the US Food and Drug Administration (FDA) and other agencies to plan the phase 3 trial design for patients with treatment-resistant depression.

“These findings strengthen our confidence in the potential of BPL-003 to be a transformative psychedelic therapy, offering rapid and durable antidepressive effects with minimal in-clinic time for patients with treatment-resistant depression. We look forward to engaging with the regulators later this year to advance this innovative treatment into phase 3 clinical development,” said Srinivas Rao, the chief executive officer and cofounder of atai.¹

Follow-up in the 8-week open-label extension (OLE) stage of the study is ongoing. The OLE study is designed to evaluate the safety and efficacy of a second 12 mg dose of BPL-003 administered to patients 8 weeks after dosing in the core study. Approximately 85% of eligible subjects from the core stage of the study have enrolled into the OLE. Data from the OLE study is expected in the third quarter of 2025 and will provide additional insights into the safety and tolerability of repeat dosing, as well as the durability of BPL-003’s antidepressant effect.

Earlier in June 2025, atai and Beckley Psytech announced their intention to strategically combine the companies, creating a global leader in short time in-clinic psychedelic-based mental health therapies.² Based on this positive phase 2b news, this is now expected to progress to shareholder approval stage.

“Thank you to all of the patients and study partners who participated in this study. We now look forward to preparing for end-of-phase 2 meetings with regulators and moving forward with our strategic combination with atai Life Sciences to form atai Beckley, a global leader in psychedelic-based mental health treatments," said Mellen.¹

References

1. atai Life Sciences and Beckley Psytech announce positive topline results from the phase 2b study of BPL-003 in patients with treatment-resistant depression. News release. July 1, 2025. https://ir.atai.com/news-releases/news-release-details/atai-life-sciences-and-beckley-psytech-announce-positive-topline

2. atai Life Sciences and Beckley Psytech to combine creating a global leader in psychedelic mental health therapies. News release. June 2, 2025. Accessed July 1, 2025. https://ir.atai.com/news-releases/news-release-details/atai-life-sciences-and-beckley-psytech-combine-creating-global