BPL-003: Positive Phase 2b Open-Label Extension Study Data

AtaiBeckley today announced positive topline results from the open-label extension (OLE) study of a phase 2b clinical trial (NCT05870540) of intranasal mebufotenin benzoate (BPL-003) in patients with treatment-resistant depression (TRD). Investigators found that a 12 mg dose of BPL-003 administered 8 weeks after a 0.3 mg, 8 mg, or 12 mg dose of BPL-003 was generally well-tolerated and provided additional rapid, clinically meaningful antidepressant effects, which were sustained for up to 8 weeks.¹

“These new data provide compelling support that redosing with BPL-003 may deliver additional and durable antidepressant effects in patients with treatment-resistant depression while maintaining a favorable safety and tolerability profile,” said Srinivas Rao, MD, PhD, the chief executive officer and cofounder of AtaiBeckley. “Importantly, 2 doses, given 8 weeks apart, provided antidepressant effects lasting up to 4 months, further supporting the viability of an intermittent-dose treatment paradigm with a short psychedelic duration, which has the potential to fit within the existing health care infrastructure and could minimize the burden on patients and providers.”

The phase 2b clinical trial of BPL-003 was conducted in 2 parts: an 8-week, quadruple-masked, dose-finding core study designed to evaluate the efficacy and safety of a single 0.3 mg, 8 mg, or 12 mg dose of BPL-003 in patients with TRD, followed by an 8-week OLE study to assess the safety and efficacy of a second subsequent 12 mg dose, given 8 weeks after the initial dose, regardless of the patient’s Montgomery-Asberg Depression Rating Scale (MADRS) score. A total of 126 participants completed the blinded core study and were eligible to enroll; of those, 107 participants continued into the extension study.

Investigators found that participants who initially received a 0.3 mg dose of BPL-003 in the core study of the phase 2b trial (n=47) saw a mean reduction in MADRS score of 14.0 points at day 57 in the OLE compared with their baseline at the start of the core study. This is in line with the antidepressant effects seen in patients who received a single active dose in the core study. Then, participants who initially received an 8 mg dose of BPL-003 in the core study of the phase 2b trial (n=23) saw a mean reduction in MADRS score of 22.3 points at day 57 in the OLE (or week 16 of the phase 2b clinical trial) compared with their baseline at the start of the core study. The responder rate (≥50% improvement in MADRS total score) in the OLE was 81% at day 57 and the remission rate (MADRS score ≤10) was 67% at the same timepoint.

The pooled population of participants who received an active dose (either 8 mg or 12 mg) of BPL-003 in the core study of the phase 2b trial (n=60) saw a mean reduction in MADRS score of 19.0 points at day 57 in the OLE compared with their baseline at the start of the core study. The responder rate in the OLE was 63% at day 57 and remission rate was 48% at the same timepoint.

As to safety and tolerability profile, it was largely consistent with prior studies of BPL-003 and is in line with other previously reported studies of the psychedelic class, showing BPL-003 to be generally well-tolerated. Most adverse events occurred on the day of dosing and were classified as mild or moderate in severity and transient in nature. The most commonly reported adverse effects included nausea, headache, administration site pain, administration site discomfort, blood pressure increases, and anxiety. One serious drug-related adverse event was reported 8 days following administration of the second dose and was resolved with additional in-patient monitoring and support. No other drug-related serious adverse events were reported in the study. Average time to meet readiness-for-discharge criteria was within 2 hours of dosing, supporting the potential of BPL-003 to fit within the existing interventional psychiatry treatment paradigm.

“With a significant need for more effective therapies, our priority, following end-of-phase 2 discussions with the FDA, is to advance BPL-003 into phase 3 clinical trials with the hope of bringing this promising treatment option to patients as swiftly as possible,” concluded Rao.¹

This research builds upon previous phase 2a findings. In September 2025, atai and Beckley Psytech shared results from a phase 2a study that showed that a 2-dose regimen of BPL-003 improved outcomes for patients with TRD, inducing 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).²

References

1. AtaiBeckley announces positive topline data from the phase 2b open-label extension study of BPL-003, supporting safety and efficacy of a second dose in patients with treatment-resistant depression. News release. November 10, 2025. Accessed November 10, 2025. https://www.biospace.com/press-releases/ataibeckley-announces-positive-topline-data-from-the-phase-2b-open-label-extension-study-of-bpl-003-supporting-safety-and-efficacy-of-a-second-dose-in-patients-with-treatment-resistant-depression

2. Kuntz L. BPL-003 for treatment-resistant depression: new positive phase 2a data. Psychiatric Times. September 23, 2025. https://www.psychiatrictimes.com/view/bpl-003-for-treatment-resistant-depression-new-positive-phase-2a-data