A Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 in Major Depressive Disorder

Key Inclusion Criteria:

• Be properly informed of the nature and risks of the study and given written informedconsent.

• Male or female, aged 18 through 65 years (inclusive) with a body mass index (BMI) ≤35 kg/m².

• Subject must meet the Diagnostic and Statistical Manual of Mental Disorders, FifthEdition (DSM-5) criteria for current MDD and currently in a moderate to severe majordepressive episode (MDE), confirmed using the Mini International NeuropsychiatricInterview (MINI).

• Current MDE duration ≥2 months and <24 months at the time of screening.

• Current illness severity that is at least moderate, defined as a score of ≥20 on theHAM-D17 at screening and on Day 1.

• Score ≥20 on the SHAPS at screening and on Day1.

• Must be willing to comply with the study protocol for the full term of the study.

Key Exclusion Criteria:

• A primary psychiatric diagnosis other than MDD as defined by DSM-5 (comorbid anxietydisorders [including agoraphobia, generalized anxiety disorder, social anxietydisorder, post-traumatic stress disorder (PTSD), and panic disorder] are allowed).

• Concomitant use of antidepressants and/or other disallowed pharmacotherapy (including benzodiazepines).

• History of schizophrenia or other psychotic disorder, MDD with psychotic features,bipolar I or II disorder, or MDD with mixed features.

• History of non-response to >1 antidepressant drug due to lack of efficacy in thecurrent MDE.

• Failing >3 antidepressant drug trials, for any reason, in the current MDE.

• History of non-response to electroconvulsive therapy (ECT) in the past 10 years.

• Active suicidal plan/intent in the past 6 months, or more than 1 lifetime suicideattempt.

• Females who are pregnant, breastfeeding, or planning to become pregnant during thefirst administration of study drug until 3 months after the last dose of study drug.

• Meets criteria for a substance use disorder within the past 12 months, with theexception of tobacco use, and/or has a positive urine toxicology screen for drugs ofabuse.

• Any medical condition or personal circumstance that, in the opinion of theinvestigator, exposes the subject to unacceptable risk by participating in the studyor prevents adherence to the protocol.