Autism Biomarker Consortium for Clinical Trials

The specified aims of this study are to accelerate the development of effective treatments
for social impairment in ASD by validating outcome measures that will be sensitive and
reliable assessments of response to treatment and electroencephalography (EEG) and
eye-tracking (ET) biomarkers. These hypothesized outcomes could then be used to reduce the
heterogeneity of samples via stratification, could possibly indicate early efficacy, and/or
demonstrate target engagement. The consortium will conduct a naturalistic, longitudinal study
of preschool and school-aged (6-11 years) children with ASD and typical development (TD) with
intelligence quotient(s) (IQ) ranging from 50-150. Children will be assessed across three
time points (Baseline, 6 weeks and 24 weeks) using clinician, caregiver and lab-based (LB)
measures of social impairment, along with a battery of conceptually related EEG and ET tasks
and independent ratings of clinical status.

Inclusion Criteria:

For All Subjects:

- Males and Females Age 6 - 11 (<11:5 at timepoint #1 unless all study procedures will
be completed before the participant turns 12.0 and prior approval by the Principal
Investigator is obtained).

- Written parental consent obtained prior to any study procedures.

- Participant and parent/guardian must be English speaking.

For TD Participants:

• IQ 80-150 as assessed by the Differential Ability Scales (DAS)- 2nd Edition

For ASD Participants:

- Diagnosis of ASD based on Diagnostic and Statistical Manual of Mental Disorders
(DSM-5), the Autism Diagnostic Observation Schedule (ADOS-2), and the Autism
Diagnostic Interview-Revised, short form (ADI-R). Diagnostic evaluations will be
completed by research staff and supervised by a licensed psychologist.

- IQ 60-150 as assessed by the Differential Ability Scales (DAS)- 2nd Edition

- If parents are biological, a minimum of the child and one parent (if accompanying the
child at study visits) will be required to participate in the blood draw procedure. It
is preferred that the child and both biological parents participate in the blood draw
procedure, but the inability to obtain blood samples from trios will not be
exclusionary.

Exclusion Criteria:

For All Subjects:

- Known genetic or neurological syndrome with established link to autism (in addition to
ASD for ASD participants), but not events in which the link to ASD is less well
known/established (e.g., 16p11.2 CNVs, CHD8 mutations, Trisomy 21, 22q deletion
syndrome)

- History of epilepsy or seizure disorder (except for history of simple febrile seizures
or if the child is seizure free (regardless of seizure type) for the past year).

- Motor or sensory impairment that would interfere with the valid completion of study
measures including significant hearing or vision impairment not correctable by a
hearing aid or glasses/contact lenses. Children who wear bifocal or progressive lenses
are not eligible.

- Medication is not exclusionary. Children taking neurological or psychiatric
medications, including anti epileptics and psychopharmacological agents, must be
stable on the medication and dose for 8 weeks prior to T1D1.

- History of significant prenatal/perinatal/birth injury (birth <36 weeks AND weight
<2000 grams (approximately 4.5lbs)).

- History of neonatal brain damage. (e.g., with diagnoses hypoxic or ischemic event)

- Any other factor that the investigator feels would make assessment or measurement
performance invalid.

For ASD Participants:

• Any known environmental circumstances that is likely to account for the picture of autism
in the proband (severe nutritional or psychological deprivation etc.)

For TDs Participants:

- Known historical diagnosis of ASD or a sibling with ASD.

- Active psychiatric disorder (depression, anxiety, ADHD, etc.) and/or any current
treatment (medication or other treatment) for a psychiatric condition. Participants
will be screened using the Child/Adolescent Symptom Inventory (CASI-5). Due to the
measurements sensitivity, any score in the clinical range will be reviewed by research
staff for determination of eligibility.