Intranasal Psychedelic Shows Promise for Treatment-Resistant Depression in phase 2 study

Safety and efficacy results from this study support the selection of the 8 mg dose of BPL-003 for advancement into Phase 3 clinical studies. atai and Beckley Psytech plan to engage with the U.S. Food and Drug Administration (FDA) and other applicable agencies regarding the Phase 3 trial design for patients with treatment-resistant depression in the coming months.

With these positive Phase 2b results, the pre-agreed success criteria for the proposed strategic combination between atai and Beckley Psytech, which was announced in June 2025, has been achieved and the strategic combination is now expected to progress to atai shareholder approval stage. The atai Beckley combination is expected to create a global leader in short time in-clinic psychedelic-based mental health therapies.

Cosmo Feilding Mellen, Chief Executive Officer and Co-Founder of Beckley Psytech, said: “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 healthcare systems. 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. 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.”

The Phase 2b clinical study was conducted at 38 sites across six countries and enrolled a total of 193 patients with moderate-to-severe TRD (defined as non-response to two or more prior treatments in the current depressive episode) (NCT05870540). It is the largest controlled clinical study to investigate mebufotenin and the only blinded Phase 2b study of mebufotenin to include the United States. Patients were randomized to receive a single 12 mg (n=73), 8 mg (n=46), or 0.3 mg comparator (n=74) dose of BPL-003 and were followed for eight weeks with efficacy assessments conducted by centralised, blinded raters using the MADRS at Day 2, Day 8, Day 29 and Day 57.

Key efficacy findings:

• A single 12 mg dose of BPL-003 led to a mean reduction in MADRS score from baseline of 11.1 points compared with 5.8 points in the 0.3 mg comparator arm (p=0.0038) at Day 29, with the 8 mg dose arm showing a mean MADRS reduction from baseline of 12.1 points versus the 0.3mg comparator arm (p=0.0025) at that same timepoint.

• The 8 mg and 12 mg doses of BPL-003 demonstrated equivalent efficacy suggesting the 8 mg dose may be sufficient to achieve therapeutic benefit from a single dose.

• The difference in MADRS scores between the 8 mg and 12 mg doses versus the 0.3 mg dose were statistically significant in both active arms from as early as Day 2, with mean MADRS reductions from baseline of 8.8 points in the 8 mg group and 8.9 points in the 12 mg group observed at that timepoint, compared to a reduction from baseline of 3.9 points in the 0.3 mg group. These mean reductions from baseline increased to 11.1 points in the 8 mg group and 10.8 points in the 12 mg group at Day 8.

• A durable effect was also observed for both higher doses, with the 8 mg group showing a mean reduction of 10.8 points from baseline at Day 57 and the 12 mg group showing a mean reduction of 10.2 points from baseline compared with the 0.3 mg group (5.2 point reduction). These findings highlight the potential of BPL-003 to be a durable treatment for patients with TRD.

Key safety findings:

• BPL-003 was generally well-tolerated at all doses. More than 99% of treatment-emergent adverse events (TEAEs) were mild or moderate and there were no drug-related serious adverse events (SAEs).

• Dose related increases in administration site discomfort, nausea, headache, blood pressure and anxiety suggest the 8mg dose was better tolerated than the 12mg dose.

• No participants in the 8 mg nor 12 mg arms had any instance of treatment-emergent suicidal intent or behaviour, indicating no suicide-related safety signal observed to date.

• The average time to meet readiness for discharge criteria across all arms was within two hours of dosing, with the majority of patients deemed ready for discharge at the 90 minutes post-dose assessment. This, alongside the administration of BPL-003 via a previously approved nasal spray device, supports the potential of BPL-003 to fit within the existing interventional psychiatry treatment paradigm that has been successfully established by Spravato®.

• The study had a low drop-out rate with 90% of patients completing the core study.

• These findings suggest a favourable tolerability profile which are consistent with earlier Phase 1 and Phase 2a studies of BPL-003, as well as other psychedelic studies within the class.

Additional data from the core study is expected to be shared through publications and medical meetings in the future.

Dr David Feifel, Professor Emeritus of Psychiatry at the University of California, San Diego and Director of the Kadima Neuropsychiatry Institute said: “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. 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.”

Follow-up in the eight-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 eight weeks after dosing in the core study. 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.

Commenting on the news, Srinivas Rao, Chief Executive Officer and Co-Founder of atai, said: “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.”