Study of ABX-002 for the Adjunctive Treatment of Major Depressive Disorder (AMPLIFY)

Inclusion Criteria:

• Meets the DSM-5 criteria for Major Depressive Disorder, with a current majordepressive episode duration of > 6 weeks and ≤ 18 months.

• A score of ≤ 22 (midrange mild/moderate) on the Hamilton Anxiety Rating Scale.

• Montgomery-Asberg Depression Rating Scale total score of > 24 [indicating moderateto severe depression] at Screening and at Baseline.

• Subject is compliantly using a single selective serotonin reuptake inhibitors /serotonin norepinephrine reuptake inhibitor antidepressant for at least 6 weeks fortheir current episode of depression, with an adequate dose, and with an inadequateresponse as defined by the Antidepressant Treatment Response Questionnaire. Thedosage of the current antidepressant must have been stable for the past 4 weeks, andthe dosage and specific antidepressant used should remain the same from Screeningthrough the end of the Follow-up Period.

Exclusion Criteria:

Note: History implies lifetime history, unless otherwise specified

• History of schizophrenia or other psychotic disorder, major depressive disorder withpsychotic features or concomitant DSM-5 depressive disorders, bipolar I or IIdisorder, cyclothymic disorder, delirium, dementia, amnestic disorder, or cognitivedisorder.

• Current diagnosis or active symptoms within the last 2 years of obsessive-compulsivedisorder, posttraumatic stress disorder, panic disorder, or eating disorder,according to DSM-5 criteria.

• Primary diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, orhistrionic personality disorder, according to DSM-5 criteria. Current or historywithin the last 2 years of self-injurious behavior is exclusionary.

• Has failed more than 2 single selective serotonin reuptake inhibitors / serotoninnorepinephrine reuptake inhibitor antidepressant treatments, including the currentserotonin reuptake inhibitors / serotonin norepinephrine reuptake inhibitor, duringthe current depressive episode, despite an adequate dose (per AntidepressantTreatment Response Questionnaire) and duration (at least 6 weeks).

• Failure to respond to triiodothyronine or thyroxine augmentation for the treatmentof depression.

• Started new psychotherapy or had a change in the intensity of psychotherapy within 8weeks before Screening.

• Is suicidal at Screening or Baseline

• History or current evidence within previous 3 months before Screening ofuncontrolled, clinically significant neurological, gastrointestinal, respiratory,renal, hepatic, immunological, hematological, or other medical disorder, includingcancer, that would jeopardize the safe participation of the subject in the study (inthe opinion of the Investigator).

• History of thyroid disease

• History of multiple endocrine neoplasia syndrome

• Diagnosis of epilepsy or history of convulsions, including childhood febrileseizure. Use of co-administered drugs that may lower seizure threshold is excluded.

• Females who are pregnant, intend to become pregnant or are breastfeeding.

• Antidepressants: Prior use of psychedelics, ketamine, or esketamine, for thetreatment of Major Depressive Disorder.

• Antidepressants: Current use, or use within 4 weeks prior to Screening, of any otheraugmentation agents for Major Depressive Disorder (e.g. second-generationantipsychotics [SGA], monoamine oxidase inhibitors [MAOI], tricyclic antidepressants [TCA], lithium, or bupropion)

• Current or prior use of treatment for hypothyroidism including but not limited tosynthetic or natural thyroid hormone, triiodothyronine and/or thyroxine.

• Concomitant use of biotin of any dose and in any preparation 14 days prior to Day 1until after the last study visit at Week 8 (Day 56).

• Medications that are strong cytochrome P450 3A4 inhibitors or strong cytochrome P450 3A4 inducers are not allowed.

• Prescription drug/controlled substance abuse, or illicit substance use within 1 yearof Screening or positive urine drug results at Screening or Baseline for an illicitsubstance.

• History or presence of cataract on ophthalmic examination (including slit-lamp),glaucoma, inflammatory eye disease or prior ophthalmic surgical procedures or lasersurgery in either eye