Phase 2b Study of Psychedelic BPL-003 Shows Rapid, Persistent, and Significant Improvement in Treatment Resistant Depression

A single dose of the investigational psychedelic compound BPL-003 produced rapid, durable, and statistically significant reductions in depressive symptoms in patients with treatment-resistant depression (TRD), according to topline data from a phase 2b clinical trial announced July 1 by atai Life Sciences and Beckley Psytech.

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The randomized, quadruple-masked, 8-week study including 193 participants demonstrated efficacy with both 8 mg and 12 mg doses of intranasal BPL-003, a formulation of mebufotenin (5-MeO-DMT) benzoate. The 8 mg dose is being advanced to phase 3 pending regulatory discussions, the companies stated.

At day 29, participants assigned to receive 12 mg of BPL-003 showed a mean 11.1-point reduction from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS), compared to a reduction of 5.8 points for the participants in the control group receiving 0.3 mg (P = .004). The 8 mg dose produced an even more pronounced MADRS reduction of 12.1-points (P = .003 vs 0.3 mg control).

The antidepressant effects emerged rapidly, with both the 8 mg and 12 mg doses showing statistically significant improvements in MADRS scores as early as day 2 post-dosing, according to the statement. At this early timepoint, participants in the 8-mg group achieved a mean MADRS reduction of 8.8 points from baseline, while the 12-mg group reached an 8.9-point reduction, compared with 3.9 points in the control group. These effects increased by day 8, with mean reductions reaching 11.1 points for those taking 8 mg and and 10.8 points for participants taking 12 mg.

Durability of the antidepressant response was notable, with effects maintained through the 8-week follow-up period. At day 57, both groups achieved additional improvement, with the 8-mg group reaching a mean reduction of 10.8 points from baseline, and the 12-mg group showing a 10.2-point reduction, compared with 5.2 points in the comparator group.

atai Life Sciences and Beckley Psytech stated that there were no drug-related serious adverse events (AEs) and that more than 99% of treatment-emergent adverse events were mild or moderate. There were no observed suicide-related safety signals in either active dose group. The phase 2b safety and tolerability findings are consistent with earlier phase 1 and phase 2a studies of BLP-003 and with other psychedelic studies within the drug class, according to the atai statement.

The clinical practicality of BPL-003 administration aligns with existing interventional psychiatry treatment paradigms, atai pointed out. The majority of participants met readiness for discharge criteria at the 90-minute post-dose assessment, with average discharge readiness occurring within 2 hours across all treatment arms. The compound uses a nasal spray device from a previously approved drug product, which along with the discharge readiness outcome, could potentially facilitate integration of BPL-003 into current treatment workflows established by esketamine (Spravato).

“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 two months,” David Feifel, MD, PhD, professor emeritus of psychiatry at the University of California, San Diego, said in the statement. “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.”

“We are particularly encouraged that a single 8 mg or 12 mg dose of BPL-003 showed rapid and durable efficacy results, favourable tolerability and a short time in-clinic, giving us important flexibility in optimising the design of future trials,” Cosmo Feilding Mellen, CEO and cofounder of Beckley Psytech, noted.

The companies plan to advance BPL-003 into Phase 3 development and have triggered the next step in their strategic combination, forming a global entity focused on short-duration psychedelic-based mental health treatments. An open-label extension study evaluating a second 12 mg dose at 8 weeks is ongoing, with approximately 85% of eligible participants from the core study enrolled. Results are expected in the third quarter of 2025.

References

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. atai. July 1, 2025. Accessed July 1, 2025. https://ir.atai.com/news-releases/news-release-details/atai-life-sciences-and-beckley-psytech-announce-positive-topline

atai Life Sciences and Beckley Psytech to Combine Creating a Global Leader in Psychedelic Mental Health Therapies. News release. atai. June 2, 2025. https://ir.atai.com/news-releases/news-release-details/atai-life-sciences-and-beckley-psytech-combine-creating-global

Patient Care Editorial Staff. FDA approves esketamine for adults with treatment-reistant depression. Patient Care. January 21, 2025. https://www.patientcareonline.com/view/fda-approves-esketamine-as-monotherapy-for-adults-with-treatment-resistant-depression