A Phase 2a Study to Evaluate the Safety and Tolerability of GM-2505 in Patients With MDD

Key Inclusion Criteria:

1. Patients are male or female, of any ethnic origin.
2. Patients are aged between 18 to 65 years, inclusive.
3. Patients have a body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.
4. Patient is ≥50 kg.
5. Patients meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for recurrent MDD without psychotic features, as assessedwith the Mini-International Neuropsychiatric Interview (MINI) at Screening. Comorbidanxiety disorders (e.g., social anxiety disorder, panic disorder, generalised anxietydisorder, specific phobia, agoraphobia) and cluster C personality disorders (avoidant,dependent and obsessive compulsive) are allowed, provided that MDD is considered theprimary diagnosis.
6. Current moderate to severe MDD diagnosis confirmed with a MADRS-SIGMA total score >22and total score CGI-S score > 3 at Screening and Day -1.
7. Concomitant depression therapy:
8. Patients need to be stable and must not have taken any SSRI or SNRI for at least 6 weeks prior to Screening and must be willing to avoid starting a newpharmacological treatment for MDD until the end of the study procedures andassessments. Discontinuing current treatment is not allowed if done for thepurposes of achieving eligibility for this study.
9. Patients receiving any form of psychotherapy or counselling must have beenreceiving therapy at Screening and must be willing to remain in therapy until theend of the study procedures and assessments.

Key Exclusion Criteria:

1. Patient has current or past primary DSM-5 diagnosis of a psychotic disorder or MDDwith psychotic features, bipolar, or related disorders. A current diagnosis of PTSD,complex PTSD and borderline personality disorder are exclusionary. Other psychiatricdisorders besides MDD should not be the primary disorder.
2. In first degree relatives, a history of schizophrenia, psychosis, bipolar disorder,delusional disorder, paranoid personality disorder or schizoaffective disorder.
3. Patient has undergone involuntary psychiatric hospitalisation in the current episode.Patients with previous involuntary hospitalisation should be carefully considered andonly included at the discretion of the Investigator.
4. Current or prior (six weeks before Screening) use of any SSRI/SNRI medication.
5. Current or prior (five weeks before Screening) use of any monoamine oxidase inhibitor ([MAO-I]; including phenelzine, tranylcypromine, isocarboxazid, iproniazid,selegiline, rasagiline, the reversible MAO-I moclobemide and the antibioticlinezolid).
6. Patient has a history of non-response to Electroconvulsive Therapy, Vagus NerveStimulation, repetitive Transcranial Magnetic Stimulation, or ketamine/esketamine, andpsychedelic 5-HT2A receptor agonists used in a clinical trial setting.
7. History of alcohol and/or drug use disorder according to DSM-5 within the last 12months, or intake of >21 units of alcohol weekly, and the inability to refrain fromalcohol use from 24 hours before Screening and each scheduled visit until dischargefrom the CRU. One unit is equivalent to a 285 mL glass (half-pint) of 3% beer or 1 (25mL) measure of 40% spirits or 1 small glass (125 mL) of 9% wine.
8. Current or a recent history of clinically significant suicidal ideation or behavioursas defined by:
9. Suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within 1 year priorto Screening or on Day -1, or
10. Suicidal behaviours within 1 year prior to Screening, or
11. Clinical assessment of significant suicidal risk. Patients with a prior suicideattempt of any sort, or prior serious suicidal ideation/plan >6 months ago,should be carefully screened for current suicidal ideation and only included atthe discretion of the Investigator.
12. Clinically relevant history of abnormal physical or mental health interfering with thestudy as determined by medical history and physical examinations obtained duringScreening as judged by the Investigator (including [but not limited to], cardiac,cardiovascular, pulmonary, gastrointestinal, endocrine, haematologic, rheumatologic,or metabolic, any inflammatory illness, hepatic, or renal disorder).
13. Patient has personal or familial history of epilepsy or other convulsive conditions,moderate to severe brain injury or other factors predisposing to seizures.
14. Any other concomitant disease or condition that could interfere with, or for which thetreatment might interfere with, the conduct of the study as outlined in this Protocol,or that would, in the opinion of the Investigator, pose an unacceptable risk to thepatients with a MDD diagnosis in this study.
15. History or clinical evidence of any disease and/or existence of any surgical ormedical condition which might interfere with the ADME of IV GM-2505.