To Evaluate the Effects of NMRA-335140 on Symptoms of Major Depression in Participants With Bipolar II Disorder.

Inclusion Criteria:

1. Have a primary Diagnostic and Statistical Manual of Mental Disorders Fifth EditionText Revised (DSM-5-TR) diagnosis of BP II disorder with a current major depressiveepisode (MDE), without psychotic features confirmed by Structured Clinical Interviewfor DSM 5 Disorders, Clinical Trials Version (SCID-5-CT) at screening (this may be afirst or recurrent episode).

2. Participant's current MDE and lifetime history of hypomanic episodes must beconfirmed by independent assessment.

3. The symptoms of the current MDE have been present for more than 4 weeks prior to theScreening Visit, but no longer than 12 months prior to the Screening Visit.

4. Have a MADRS total score of 25 or higher at Screening and Baseline.

5. A change in MADRS total score between Screening and Baseline of ≤20%.

Exclusion Criteria:

1. Have failed 2 or more courses of antidepressant (adequate dose and duration, i.e.,minimum 6 weeks) or mood stabilizer/antipsychotic treatment (each or in combination)for treatment of depressive symptoms in the current MDE.

2. Have currently or in the past year any of the following DSM-5-TR disorders: bipolarepisodes with mixed features (including the current MDE), bipolar II with rapidcycling pattern (4 or more distinct mood episodes during a 12-month period).Participants with comorbid generalized anxiety disorder, social anxiety disorder,simple phobias, panic disorder, for whom bipolar II MDE is considered the primarydiagnosis are not excluded.

3. Have a lifetime diagnosis of bipolar I disorder (manic episode schizophrenia,schizoaffective disorder, schizophreniform disorder, anorexia nervosa, bulimianervosa, cluster B personality disorder, post-traumatic stress disorder (PTSD), orobsessive- compulsive disorder.

4. Have moderate to severe substance or alcohol use disorder, per DSM-5-TR criteria,within the 12 months prior to screening (excluding nicotine).

5. Are actively suicidal (e.g., any suicide attempts within the past 12 months) or areat serious suicidal risk as indicated by any current suicidal intent, including aplan, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) (score of "YES" on suicidal ideation Item 4 or 5 within 3 months prior to Visit 1 [screening])and/or based on clinical evaluation by the Investigator; or are homicidal, in theopinion of the Investigator.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.