An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients with Treatment Resistant Depression

Inclusion Criteria:

1. Diagnosed with Major Depressive Disorder.

2. Diagnosed with TRD defined as failure to respond to an adequate dose and duration ofat least 2 pharmacological treatments in the past 5 years prior to screening, atleast one of which is during the current episode.

3. Montgomery-Asberg Depression Rating Scale score ≥24 at Screening.

4. Clinical Global Impression - Severity ≥4 at Screening.

5. Willing and able to discontinue current pharmacological anti-depressant therapy.

6. On current stable dose of pharmacological antidepressant therapy limited to one of 4SSRIs (Arm B), i.e. either citalopram, escitalopram, sertraline or fluoxetine.

Exclusion Criteria:

1. Current or 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,personality disorders 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 with the intent to act or suicidal behaviour within the 12 monthsprior to the start of Screening or on Day 1 prior to dosing.

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

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

9. Seizure disorder or history of seizures (including febrile seizures).

10. Abnormal and clinically significant results on the physical examination, vitalsigns, electrocardiogram, or laboratory tests at Screening Baseline.

11. Any nasal obstruction, blockage, or symptoms of congestion at the time of dosing,that in the Investigator's opinion may interfere with administration of the studydrug.

12. Currently receiving lithium, antipsychotics, serotonergic drugs (excluding thepermitted SSRIs for arm B), psychostimulants, or any other prohibited medication.

13. Female patients who are pregnant or lactating, or of childbearing potential and notwilling to use adequate forms of contraception.

14. Male patients who are sexually active and not willing to using adequate forms ofcontraception.