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

Inclusion criteria

• Have a primary Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) diagnosis of BP II disorder with a current major depressive episode (MDE), without psychotic features confirmed by Structured Clinical Interview for DSM 5 Disorders, Clinical Trials Version (SCID-5-CT) at screening (this may be a first or recurrent episode).
• Participant's current MDE and lifetime history of hypomanic episodes must be confirmed by independent assessment.
• The symptoms of the current MDE have been present for more than 4 weeks prior to the Screening Visit, but no longer than 12 months prior to the Screening Visit.
• Have a MADRS total score of 25 or higher at Screening and Baseline.
• A change in MADRS total score between Screening and Baseline of ≤20%.

Exclusion criteria

• 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.
• Have currently or in the past year any of the following DSM-5-TR disorders: bipolar episodes with mixed features (including the current MDE), bipolar II with rapid cycling 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 primary diagnosis are not excluded.
• Have a lifetime diagnosis of bipolar I disorder (manic episode schizophrenia, schizoaffective disorder, schizophreniform disorder, anorexia nervosa, bulimia nervosa, cluster B personality disorder, post-traumatic stress disorder (PTSD), or obsessive- compulsive disorder.
• Have moderate to severe substance or alcohol use disorder, per DSM-5-TR criteria, within the 12 months prior to screening (excluding nicotine).
• Are actively suicidal (e.g., any suicide attempts within the past 12 months) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, 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 the opinion of the Investigator.

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