BPL-003 Efficacy and Safety in Treatment Resistant Depression

Inclusion Criteria:

1. At least moderate major depressive disorder.

2. Diagnosed with TRD defined as failure to respond to an adequate dose and duration ofat least 2 pharmacological treatments based on the MGH ATRQ assessment.

3. Hamilton Depression Rating Scale score ≥19 at Screening and Baseline.

4. CGI-S ≥4 at Screening and Baseline.

5. If currently taking antidepressant medications, willing and able to discontinuecurrent antidepressants.

Exclusion Criteria:

1. Current or past history of schizophrenia, psychotic disorder including psychoticdepression, bipolar disorder, delusional disorder, schizoaffective disorder, or anyother severe psychiatric disorder.

2. Current personality disorders.

3. First-degree family history of schizophrenia, bipolar disorder, delusional disorder,or schizoaffective disorder.

4. Current alcohol or substance use disorder (other than caffeine or nicotine).

5. A participant who at any time has been unresponsive to ketamine, esketamine, anadequate course of treatment with electroconvulsive therapy, or has received vagalnerve stimulation or deep brain stimulation.

6. Suicidal ideation or behavior within the 12 months prior to the start of Screeningor on Day 1 prior to dosing.

7. Suicide attempt and/or self-injurious behavior within the last 12 months prior toScreening.

8. Uncontrolled medical conditions e.g. hypo/hyperthyroidism, diabetes, renal failure.

9. History or current uncontrolled hypertension.

10. Seizure disorder or any seizure in the 2 years prior to Screening.

11. Has clinically significant results on ECG during the Screening.

12. Any nasal obstruction, blockage, or symptoms of congestion at the time of dosingthat in the investigator's opinion may interfere with the administration of thestudy medication.

13. Female participants who are pregnant, lactating, or of childbearing potential andnot willing to use adequate forms of contraception during the study.

14. Male participants who are sexually active and not willing to use adequate forms ofcontraception during the study.