BPL-003 for Treatment Resistant Depression Continues to Show Sustained Symptom Reduction

Results of part 2 from the phase 2a study pf BPL-003 for treatment-resistant depression showed rapid and sustained reductions in symptoms. The data included participants taking selective serotonin reuptake inhibitors (SSRIs), and part 2 analysis has been published in CNS Drugs.

The phase 2a study was a 12-week open-label, ascending-dose trial with 12 adult participants aged 18 to 75 with moderate to severe major depressive disorder and treatment-resistant depression. The severity of the disorder was classified by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 24 or higher. All participants had a history of 2 or more failed courses of antidepressants and continued on a stable dose of an SSRI (citalopram, escitalopram, sertraline, or fluoxetine) throughout the study. Half of participants received a single 10 mg dose of BPL-003, while half received a single 12 mg dose. Participants were then monitored for 12 weeks.

Part 2 of phase 2a showed 66.7% of participants achieving a greater than 50% reduction in MADRS scores from a single dose compared with baseline at day 2. Durability of treatment at day 85 was present in 83% of responded in the 10 mg cohort and 66.7% of responders in the 12 mg cohort. In the 10 mg group, the average reduction in MADRS score was 19.2 to 6.2, and the 12 mg group decreased from 21 to 9.3. No serious adverse events occurred, with most drug-related adverse being transient and resolved the same day as treatment. The average time to readiness for discharge was about 100 minutes post-dose.

Srinivas Rao, MD, PhD, cofounder and chief executive officer of AtaiBeckley, noted in a press release that "a 66.7% day 2 response rate with a single intranasal dose of BPL‑003, maintained through week 12 in the 10 mg cohort, represents a compelling clinical signal in patients who remained on their baseline SSRI therapy. Combined with our statistically significant double-blind, randomized phase 2b results in 193 participants and our recent [US Food and Drug Administration] end‑of‑phase 2 alignment, these phase 2a data reinforce the potential of BPL‑003 to transform the treatment paradigm for [treatment resistant depression] as we prepare to initiate phase 3 in Q2 2026.”

BPL-003 is an intranasal spray formulation of mebufotenin benzoate (5-MeO-DMT), designed to provide rapid relief and continuing effects. The drug is a %-HT1A and 5-HT2A agonist associated with rapid onset and treatment experience of about 2 hours. It is also being investigated as a treatment for alcohol use disorder and was granted Breakthrough Therapy designation by the FDA in October 2025.

Kevin Craig, MD, chief medical officer at AtaiBeckley, added “this study provides the first Phase 2a evidence that BPL‑003 can be administered alongside SSRIs without compromising efficacy or safety, a meaningful advance given that many TRD patients remain on chronic SSRI therapy.” He continued, “the rapid resolution of acute effects and ~100‑minute discharge readiness further support the feasibility of integrating BPL‑003 into existing interventional psychiatry settings.”

Top line data from part 3 of this study were announced in September 2025, and part 4 is ongoing with initial data expected toward the end of 2026. Developers of the drug reported a successful end-of-phase 2 meeting with the FDA in March, and the phase 3 program for BPL-003 is planned to begin in the second quarter of 2026.

References

1. AtaiBeckley’s BPL-003 shows rapid, durable antidepressant response in treatment-resistant depression patients on SSRIs; phase 2 data published in CNS Drugs. Press release. April 8, 2026. Accessed April 8, 2026. https://ir.ataibeckley.com/news-releases/news-release-details/ataibeckleys-bpl-003-shows-rapid-durable-antidepressant-response

2. Walters J. BPL-003 nasal spray shows quick and enduring effect in treatment-resistant depression. Psychiatric Times. March 18, 2026. https://www.psychiatrictimes.com/view/bpl-003-nasal-spray-shows-quick-and-enduring-effect-in-treatment-resistant-depression