Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression

Key Inclusion Criteria:

- Signed informed consent.

- Male and female subjects, 18 to 65 years of age (inclusive) at screening.

- DSM-5 defined major depressive episode at the time of screening

- Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 24 at baseline

- Failure to respond to two or more antidepressant treatments, at least one of which is
in the current depressive episode, with adequate dose and duration.

- Stable dose of psychotropic drugs at screening defined as no changes in dose or type
of antidepressants, antipsychotics, or mood stabilizers for at least 2 weeks prior to
randomization if applicable.

- No new antidepressant initiated 4 weeks or less before baseline, and 6 weeks or less
before baseline if subject is initiated on fluoxetine

- At least one prior clinical depressive episode (recurrent major depressive disorder).

- Able to communicate well, and to understand and comply with study requirements

Key Exclusion Criteria:

- Any prior or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective
disorder at screening.

- Current alcohol or substance use (other than nicotine or caffeine) meeting DSM-5
criteria for addiction, within the past month.

- Prior suicidality caused by or associated with ketamine, as identified by prior
psychiatric history assessed by the investigator, and augmented by medical records and
third party report (family, friends, clinician-treaters) where available.

- Acute serious and/or imminent suicidal ideation and/or intent within the prior 2
weeks, or any suicide attempt within the prior 4 weeks at screening.

- Use of other investigational drugs at the time of randomization, or within 30 days or
5 half-lives of randomization, whichever was longer; or longer if required by local
regulations at baseline.

- Current pregnancy or lactation.

- Positive HIV, Hepatitis B or C test.

- Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment baseline

- History of multiple and recurring allergies or allergy to the investigational
compound/compound class being used in this study.

- History of malignancy of any organ system (other than localized basal cell carcinoma
of the skin or in-situ cervical cancer), treated or untreated, within the past 3
years, regardless of whether there is evidence of local recurrence or metastases.

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 1 week after stopping of investigational drug.

- History of hypersensitivity to any of the study treatments or excipients or to drugs
similar to chemical classes.

- Current diagnosis of borderline personality disorder or antisocial personality
disorder, based on DSM-5 criteria.

- Current acute depressive episode lasting longer than two years continuously, defined
as no two week or longer period where depressive symptoms are subsyndromal in severity
for a full DSM-5 acute major depressive episode.

- Considered by the investigator, for any other reason, to be an unsuitable candidate
for the study.