A Study of RG1662 in Adults and Adolescents With Down Syndrome (CLEMATIS)

Inclusion Criteria:

- Individuals aged 12-30 years of age inclusive

- Clinical diagnosis of Down syndrome (trisomy 21) confirmed by chromosomal analysis
(karyotyping)

- Males, or non-pregnant, non-lactating females. For females of childbearing potential,
strict contraceptive prevention is required.

- Body-mass Index (BMI) 18-42 and 15-30 kg/m2 inclusive for adults and adolescents
respectively

- Ability to complete the Clinical Evaluation of Language Fundamentals (CELF)-preschool
2 word classes task

- Subjects must have a parent, or other reliable caregiver who agrees to accompany the
subject to all clinic visits, provide information about the subject as required by the
protocol, and ensure compliance with the medication schedule

- Study participants must have sufficient language, vision and hearing to participate in
study evaluations, as judged clinically by investigator

Exclusion Criteria:

- Subjects with a current DSM 5 diagnosis of any primary psychiatric diagnosis
(including ASD or MDD)

- Subjects with a history of infantile spasms, of West syndrome, Lennox-Gastaut
syndrome, Early Infantile Epileptic Encephalopathy or any treatment-refractory
epilepsy associated with cognitive or developmental regression, of severe head trauma
or CNS infections (e.g. meningitis)

- Subjects with a known or suspected clinical seizure event of any type within 24 months
prior to screening

- Clinically relevant ECG abnormalities at screening or baseline; QTcF above 450 ms;
personal or family history (first degree relatives) of congenital long QT syndrome

- Inadequate renal or hepatic function