A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy

The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind,
placebo-controlled, multicenter study to evaluate the clinical efficacy, safety and
tolerability of XEN1101 administered as adjunctive treatment in adult patients aged 18 to 75
years diagnosed with focal epilepsy. Approximately 300 patients will be randomized in a
blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion
(XEN1101 25 mg : 20 mg : 10 mg : Placebo). After screening, patients will have 8 weeks of
baseline to assess frequency of seizures, followed by 8 weeks of treatment and a 4-week post
treatment follow-up period. In order to be included in the study, patients must already be
treated with a stable dose of 1 to 3 allowable current anti-epileptic drugs for at least one
month prior to screening, during baseline, and throughout the duration of the study. During
the treatment period, patients will be given XEN1101 or placebo once daily in the evening.

Key Inclusion Criteria:

- Be properly informed of the nature and risks of the study and give informed consent in
writing, prior to entering the study

- BMI <35 kg/m2

- Diagnosis (≥2 years) of focal epilepsy according to the International League Against
Epilepsy [ILAE] Classification of Epilepsy (2017)

- Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month
prior to screening, during baseline, and throughout the duration of the study

- Must be willing to comply with the contraception requirements

- Able to keep accurate seizure diaries

Key Exclusion Criteria:

- History of pseudoseizures, psychogenic seizures, primary generalized seizure, or focal
aware non-motor seizures only

- Presence or previous history of Lennox-Gastaut syndrome

- Seizures secondary to other diseases or conditions

- History of repetitive seizures within the last 12 months where the individual seizures
cannot be counted

- History of neurosurgery for seizures <1 year prior to enrollment, or radiosurgery <2
years prior to enrollment

- Schizophrenia and other psychotic disorders, or active suicidal plan/intent in the
past 6 months, or a history of suicide attempt in the last 2 years, or more than 1
lifetime suicide attempt

- History or presence of any significant medical or surgical condition or uncontrolled
medical illness at screening, or history of cancer within the past 2 years, with the
exception of appropriately treated basal cell or squamous cell carcinoma

- Any clinically significant abnormalities on pre-study physical examination, vital
signs, laboratory values or ECG indicating a medical problem that would preclude study
participation

- Past use of vigabatrin without stable visual fields tested twice over the 12 months
after the last dose of vigabatrin (concomitant use of vigabatrin is not allowed)

- If felbamate is used as a concomitant AED, patients must be taking it for at least 2
years, with a stable dose for ≥49 days and acceptable hematology and LFT values (or
discontinued felbamate no less than 49 days) prior to Screening.

- Have had multiple drug allergies or a severe drug reaction to an AED(s), including
dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity
reactions

- Current use of a ketogenic diet