mebufotenin benzoate (BPL-003) / AtaiBeckley, Eli Lilly - LARVOL DELTA

Next-Generation Pharmacotherapies for Unipolar Mood Disorders: A Leading Article on Phase II/III Drug Development Across Diverse Mechanisms. (PubMed, CNS Drugs) - "Following the US Food and Drug Administration (FDA) approval of esketamine and brexanolone in 2019, industry investment in therapeutics with novel mechanisms for mood and anxiety disorders has expanded, catalyzing a new wave of innovative interventions...The drug names discussed are ALTO-100, ALTO-203, ALTO-207, ALTO-300, BHV-7000, BI-1569912, BPL-003, COMP360, DT120, ELE-101, GATE-251, GH001, GM-1020, GM-2505, HLP003, MK-1942, NBI-1065845, NBI-1070770, NV-5138, PIPE-307, SEP-363856, SPT-300, VLS-01, and XEN1101. The US Clinical Trials registry (clinicaltrials.gov), MEDLINE, conference proceedings, and company communications such as press releases were consulted to obtain up-to-date trial information and reported outcomes. Overall, the therapeutic landscape shows an expanding range of clinical compounds under active development; nonetheless, persistent challenges remain, including approaches to therapeutics where functional unblinding may occur, the ways in which to..."

Journal • P2/3 data • Review • CNS Disorders • Mood Disorders • Psychiatry

Psychological change processes in alcohol use disorder: A qualitative study of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) with cognitive behavioural therapy. (PubMed, Addiction) - "Participant and therapist accounts indicate that a single dose of 5-methoxy-N,N-dimethyltryptamine, when embedded in a relapse-prevention cognitive behavioural therapy programme, can support meaningful shifts in self-appraisal, emotional regulation, and behavioural patterns associated with alcohol consumption."

Journal • Addiction (Opioid and Alcohol) • Cognitive Disorders

AtaiBeckley’s BPL-003 Shows Rapid, Durable Antidepressant Response in Treatment-Resistant Depression Patients on SSRIs; Phase 2a Data Published in CNS Drugs (AtaiBeckley Press Release) - "AtaiBeckley Inc...announced peer-reviewed Phase 2a results (NCT05660642) in CNS Drugs demonstrating that a single intranasal dose of BPL-003 (mebufotenin benzoate), which holds FDA Breakthrough Therapy Designation, achieved rapid and sustained reductions in MADRS scores from baseline in participants with treatment-resistant depression (TRD) who remained on stable SSRI therapy throughout the study (n=12). A 66.7% antidepressant response rate (≥50% reduction from baseline MADRS score) was observed at Day 2 in both the 10 mg (n=6) and 12 mg (n=6) cohorts, with 83% (5/6) of participants in the 10 mg cohort and 66.7% (4/6) of participants in the 12 mg cohort maintaining a response at Week 12. BPL-003 was generally well tolerated with no serious adverse events reported...Phase 3 studies are on track to initiate in Q2 2026 following recent FDA End-of-Phase 2 (EOP2) alignment."

New P3 trial • P2a data • Depression

A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in patients with treatment-resistant depression. (PubMed, J Psychopharmacol) - "Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, suggesting BPL-003 could be beneficial in TRD, warranting investigation in larger controlled trials."

Journal • P2 data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) for alcohol use disorder: An open-label, phase 2, proof-of-concept, clinical trial. (PubMed, Addiction) - "A first phase 2a clinical trial of 5-methoxy-N,N-dimethyltryptamine (BPL-003 10 mg) in the context of a 10-week programme of CBT demonstrated acceptable safety and tolerability and provided preliminary evidence of efficacy for reducing alcohol craving and consumption. These findings support progression to larger, controlled trials of BPL-003 for the treatment of alcohol use disorder."

Journal • P2 data • Addiction (Opioid and Alcohol) • Cognitive Disorders • Pain

An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant Depression (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: Beckley Psytech Limited | Active, not recruiting ➔ Recruiting | Trial completion date: Jul 2025 ➔ Nov 2026 | Trial primary completion date: Jul 2025 ➔ Nov 2026

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

Mapping the phenomenology of intranasal 5-MeO-DMT in psychedelic-naïve healthy adults. (PubMed, Sci Rep) - "5-MeO-DMT has a distinctive profile of subjective effects relative to published reports of other psychedelics, with a short duration of action, relative lack of visual effects, strong emotional or bodily experiences and the potential to elicit therapeutically relevant content, such as emotional breakthroughs and personal insights. These findings inform therapeutic applications, participant preparation, and future research on 5-MeO-DMT."

Clinical • Journal

atai Life Sciences and Beckley Psytech Announce U.S. FDA Breakthrough Therapy Designation Granted to BPL-003, Underscoring its Potential in Treatment-Resistant Depression (GlobeNewswire) - "FDA designation follows previously announced Phase 2b topline data which showed rapid and durable antidepressant outcomes following a single dose of BPL-003....'BPL-003 is well-positioned for Phase 3 trials which are expected to initiate in the second quarter of 2026, subject to alignment with the FDA'."

Breakthrough therapy • New P3 trial • Depression

The efficacy of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) on anhedonia in patients with treatment resistant depression: a phase 2a open label study (ECNP 2025) - P2 | "The mean number of failed antidepressants in the current episode was 3.2 (range of 2-5), with citalopram and sertraline the most frequently failed antidepressants. The observed improvements in functional outcomes, as measured by the SDS further underscore the potential impact of BPL-003 beyond symptom reduction. The convergence of symptom and functional improvement in this study suggests that BPL-003 may exert therapeutic effects that are rapid, sustained and multidimensional."

Clinical • P2a data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

BPL-003 Efficacy and Safety in Treatment Resistant Depression (clinicaltrials.gov) - P2 | N=196 | Completed | Sponsor: Beckley Psytech Limited | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Mood Disorders • Psychiatry

An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant Depression (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: Beckley Psytech Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Depression • Mood Disorders • Psychiatry

BPL-003 Efficacy and Safety in Treatment Resistant Depression (clinicaltrials.gov) - P2 | N=196 | Active, not recruiting | Sponsor: Beckley Psytech Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Depression • Mood Disorders • Psychiatry

atai Life Sciences Announces Completion of Enrollment in Phase 2b Clinical Trial Evaluating BPL-003 for Treatment-Resistant Depression (GlobeNewswire) - "atai Life Sciences...today announced the completion of patient enrollment in the eight-week, double-blind, core stage of the global Phase 2b clinical trial evaluating BPL-003 (mebufotenin benzoate) in patients with treatment-resistant depression (TRD)...Topline results from the core stage of the Phase 2b clinical trial are expected in mid-2025...Data from the Phase 2b clinical trial will be used in conjunction with data from the Phase 2a study of BPL-003 in patients with TRD to support end-of-Phase 2 meetings with regulatory bodies and Phase 3 planning in the second half of 2025."

Enrollment closed • New P3 trial • P2b data • CNS Disorders • Depression

atai Life Sciences Announces Positive Topline Results from Beckley Psytech’s BPL-003 (intranasal 5-MeO-DMT benzoate) Phase 2a Open-Label Study for Alcohol Use Disorder (GlobeNewswire) - P2 | N=13 | NCT05674929 | Sponsor: Beckley Psytech Limited | "The results showed that a single dose of BPL-003, in combination with relapse prevention cognitive behavioral therapy, induced meaningful and sustained reduction in alcohol use and heavy drinking days (HDDs) in patients with moderate to severe AUD out to 12 weeks...Mean number of alcohol units consumed per day decreased from 9.3 units to 2.2 units at Week 12; Mean percentage of HDDs, defined as consuming seven or more units of alcohol per day for women and nine or more units of alcohol per day for men, declined from 56% to 13% at Week 12; Mean number of abstinent days increased from 33% to 81% at Week 12; 50% of the patients remained completely abstinent through the 12-week study...Beckley Psytech plans to evaluate future development options for BPL-003 in substance use disorders and anticipates reporting additional clinical data from this study in publications and conferences in 2025."

P2 data • CNS Disorders

BPL-003 Efficacy and Safety in Treatment Resistant Depression (clinicaltrials.gov) - P2 | N=225 | Recruiting | Sponsor: Beckley Psytech Limited | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Oct 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

An Open-Label, Single Dose Study in Patients With Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: Beckley Psytech Limited | Active, not recruiting ➔ Completed

Trial completion • Addiction (Opioid and Alcohol)

Blinding in psychedelic studies: comparison of placebo and sub-perceptual dose of intranasal 5-Methoxy-N,N-dimethyltryptamine in healthy volunteers (ECNP 2024) - "This was confirmed by the SDI Results , where 80% of subjects receiving 0.3mg of BPL-003 thought they had a possible effect. Based on these Results 0.3mg of BPL-003 is well suited to be used as a sub-perceptual dose (i.e. active placebo) in future clinical trials."

Clinical • CNS Disorders • Pain

Rapid antidepressant effect of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in treatment-resistant patients: a phase 2a open label study (ECNP 2024) - P2 | "Several studies have recently demonstrated the beneficial effects of psychedelics, such as COMP360 [1] and GH001 [2] for depression...The mean number of failed antidepressants in the current episode was 3.2 (range of 2-5), with citalopram and sertraline the most frequently failed antidepressants...This indicates a single dose every 3 months or later may be the appropriate dosing regimen. Dose optimisation, to maximise the therapeutic effect is ongoing, with doses up to 12 mg being explored in a Phase 2b TRD study (BPL-003-201)."

Clinical • P2a data • CNS Disorders • Depression • Psychiatry

An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients with Treatment Resistant Depression (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: Beckley Psytech Limited | Trial completion date: Nov 2024 ➔ Jul 2025 | Trial primary completion date: Nov 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

An Open-Label, Single Dose Study in Patients with Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=13 | Active, not recruiting | Sponsor: Beckley Psytech Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Addiction (Opioid and Alcohol)

atai Life Sciences Announces Dosing of First Patient in Part 2 of Beckley Psytech’s Phase 2a Study Exploring BPL-003 Adjunctive to SSRIs in Patients with Treatment Resistant Depression (GlobeNewswire) - "atai Life Sciences...announced that the first patient has been dosed in Part 2 of Beckley Psytech’s Phase 2a study, evaluating BPL-003 (intranasal 5-MeO-DMT) in patients living with Treatment Resistant Depression (TRD)....Initial results are expected in H1 2025....The BPL-003 Phase 2b study is currently underway, evaluating the effects of a single medium or high dose of BPL-003 against a sub-perceptual dose in TRD patients (NCT05870540). Initial results from that study are expected in H2 2024."

P2a data • P2b data • Trial status • CNS Disorders • Depression

Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. (PubMed, J Psychopharmacol) - P1 | "The short duration of action and induction of mystical experiences suggest clinical potential, warranting further trials. NCT05347849."

Journal • P1 data • PK/PD data • CNS Disorders • Depression • Pain • Psychiatry

atai Life Sciences Announces Positive Initial Results from Beckley Psytech’s Phase 2a Open Label Study of BPL-003 (Intranasal 5-MeO-DMT) in Treatment Resistant Depression (GlobeNewswire) - P2a | N=52 | NCT05660642 | "atai Life Sciences...announced positive initial results from Beckley Psytech’s Phase 2a open label study of BPL-003 in Treatment Resistant Depression (TRD), a condition that affects approximately 100 million people worldwide....Initial analysis showed that a single dose of BPL-003 induced a rapid antidepressant response in 55% of patients on the day after dosing. The antidepressant effect was durable, with a 55% response rate maintained at week 4, which continued to week 12. There were 55% of patients in remission3 at week 4 and 45% in remission at week 12. These findings represent the longest known follow-up of depression outcomes in a clinical study of 5-MeO-DMT."

P2a data • CNS Disorders • Depression • Mood Disorders

Single Ascending Dose Study With BPL-003 in Healthy Subjects (clinicaltrials.gov) - P1 | N=62 | Completed | Sponsor: Beckley Psytech Limited | Recruiting ➔ Completed

Trial completion

An Open-Label, Single Dose Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant Depression (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: Beckley Psytech Limited | Phase classification: P2a ➔ P2 | N=12 ➔ 52 | Trial completion date: Oct 2023 ➔ Nov 2024 | Trial primary completion date: Oct 2023 ➔ Nov 2024

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry