A Safety Study of NNZ-2566 in Patients With Rett Syndrome

Rett Syndrome is a developmental disorder primarily if not exclusively 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 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 and tolerability of treatment with oral
administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescent or adult females with
Rett Syndrome. The study also will also investigate measures of efficacy during treatment.

Inclusion Criteria:

- Diagnosis of Rett Syndrome with proven mutation of the MeCP2 gene

- Age 16 to 45 years

- Severity rating of between 10 and 36 (Rett Syndrome Natural History/Clinical Severity
Scale)

- Concomitant medications must be stable for >4 weeks prior to enrollment. The
following concomitant medications are permitted: anticonvulsants which do not have
liver inducing effects; beta-blockers; medications for the treatment of
gastroesophageal reflux disease (GERD); medications for the treatment of chronic
respiratory conditions such as asthma; medications for the treatment of anxiety, of
depression and of psychosis, hormonal contraceptives. Melatonin for difficulties with
sleep onset.

- Ability to swallow study medication provided as a liquid solution, or via gastrostomy
tube

Exclusion Criteria:

- No detectable abnormality of the EEG during screening period

- Actively undergoing regression

- QTcF exclusions (any of the following): baseline/screening QT/QTcF interval of 450
msec; history of risk factors for torsade de pointes (e.g. heart failure, hypokalemia
(serum potassium at screening < 3.0 mmol/L) or family history of long QT syndrome;
QT/QTcF prolongation previously or currently controlled with medication

- Current treatment with insulin

- Hgb A1C values outside the normal reference range at screening

- Current or past treatment with IGF-1

- Current or past treatment with growth hormone

- Current treatment with N-methyl-D-aspartate (NMDA) antagonists

- Current or planned use of non-medication based interventional therapy during the
period of the study (defined as 4-6 week screening period followed by 4 week dosing
and 2 week follow-up period)

- Current clinically significant cardiovascular, renal, hepatic or respiratory disease

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

- History of, or current cerebrovascular disease or brain trauma

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

- History of, or current malignancy

- Clinically significant abnormalities in safety laboratory tests, vital signs or ECG,
as measured at screening or baseline

- Confirmed pregnancy

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

- Enrollment in another clinical trial within the previous 30 days

- Previously randomized in this clinical trial

- Allergy to strawberries