A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

Rett syndrome is a neurodevelopmental disorder primarily affecting females. The disorder is
characterized by apparent normal development in early infancy (6-18 months), followed by a
period of regression with onset of systemic and neurological signs. The CNS symptoms of Rett
syndrome include learning disability, autism symptomatology and epilepsy and these can be
severe and highly debilitating. Affected individuals also show signs of autonomic
dysfunction, reflected in cardiovascular and respiratory abnormalities. There is no currently
effective treatment for Rett syndrome.

This study will investigate the safety, tolerability and blood pharmacokinetics of treatment
with oral administration of NNZ-2566 at 50 mg/kg, 100 mg/kg, 200 mg/kg BID, or placebo BID,
in children and adolescent females with Rett syndrome. The study also will also investigate
measures of efficacy and biomarkers during treatment.

Inclusion Criteria:

- Diagnosis of classic/typical Rett syndrome with a documented mutation of the MeCP2
gene.

- Age 5 - 15 years.

- Weight at Screening and Baseline between 15.0 kg-100.0 kg (at least 15.0 kg and no
greater than 100.0 kg).

- Each subject must be able to swallow the study medication provided as a liquid
solution, or via gastrostomy tube.

Exclusion Criteria:

- Actively undergoing neurological regression

- Abnormal QT interval, prolongation or significant cardiovascular history.

- Current treatment with insulin.

- Anti-convulsants with liver enzyme inducing effects.

- Unstable seizure profile.

- Excluded concomitant medications.

- Current clinically significant (as determined by the investigator). cardiovascular,
renal, hepatic, or respiratory disease.

- Gastrointestinal disease which may interfere with the absorption, distribution,
metabolism or excretion of the study medication.

- History of, or current cerebrovascular disease or brain trauma.

- History of, or current clinically significant endocrine disorder, e.g. hypo- or
hyperthyroidism, or diabetes mellitus.

- History of, or current, malignancy.

- Significant hearing and/or visual impairments that may affect ability to complete the
test procedures.

- Allergy to strawberry.