Study of ANAVEX2-73 in Patients With Rett Syndrome

This Phase 2 safety, tolerability and efficacy study is designed as a double-blind,
randomized, placebo-controlled study.

This is a 7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of
patients with RTT 18 years or older. A voluntary option will be offered for all patients who
meet the exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.

Inclusion Criteria:

- Aged ≥ 18 years, inclusive.

- Diagnosis of classic RTT, according to 2010 criteria (Neul et al., 2010), and a MECP2
mutation.

- Current pharmacological treatment regimen, including supplements, has been stable for
at least 4 weeks.

- If on antiepileptic drugs (AEDs), 1-4 AEDs allowed. Treatment must be stable (drug,
dose, interval of administration) for 30 days prior to enrollment.

- Ability to keep accurate seizure diaries or have caregiver who can keep accurate
seizure diaries.

- Confirmation from the participant that, if of childbearing potential is not pregnant
through urine pregnancy testing. Female patients of childbearing potential and at risk
for pregnancy must agree to abstinence.

- Prior to the conduct of study-specific procedures, the subject's parent/caregiver/LAR
must provide written informed consent. If applicable, the research team must attempt
to obtain consent from both parents.

Exclusion Criteria:

- Patients who have a progressive medical or neurological condition that in the opinion
of the Investigator would interfere with the conduct of the study.

- Current clinically significant systemic illness that is likely to result in
deterioration of the patient's condition or affect the patient's safety during the
study.

- History of clinically evident stroke or clinically significant carotid or
vertebrobasilar stenosis or plaque or other history of neurologic (e.g., head trauma
with loss of consciousness) or psychiatric condition that the Investigator deems may
interfere with interpretability of data.

- Indication of liver disease, defined by serum levels of ALT (SGPT), AST (SGOT), or
alkaline phosphatase above 3x upper limit of normal (ULN) as determined during
screening.

- Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within
the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for
asthma are permitted) or chemotherapeutic agents for malignancy within the last 3
years.

- Other clinically significant abnormality on physical, neurological, laboratory, or
electrocardiogram (ECG) examination (e.g., atrial fibrillation) that could compromise
the study or be detrimental to the participant.

- Any known hypersensitivity to any of the excipients contained in the study drug or
placebo formulation.

- Other co-morbid or chronic illness beyond that known to be associated with RTT.

- Subjects who plan to initiate or change pharmacologic or nonpharmacologic intervention
during the course of the study.

- Subjects on potent CYP 3A4 and CYP2C19 inhibitors and inducers.

- Subjects taking another investigational drug currently or within the last 30 days.

- Any other criteria (such as a clinically significant screening blood test result),
which in the opinion of the Investigator could interfere with the study conduct or
outcome.

- Patients with hepatic and renal impairment.