Clinical Study Of caNNabidiol in childrEn and adolesCenTs With Fragile X (CONNECT-FX)

This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the
efficacy and safety of ZYN002, a pharmaceutically manufactured CBD, formulated as a
transdermal gel, for the treatment of children and adolescent with FXS. Approximately 204
male and female patients, ages 3 to < 18 years, will undergo a screening process. Eligible
participants will be randomized 1:1 to either trial drug or placebo and will undergo a
14-week treatment period. Randomization will be stratified by gender, weight category and
geographic region. All participants may receive placebo during the trial. Participants who
are taking anti-epileptic drugs may undergo an additional 1-2 weeks of blinded treatment to
taper off study drug treatment. The assignment will be done by a computer generated system
and neither the study doctor or the participant or their caregivers will know which treatment
is being given to them. The dose of the treatment will depend on the weight of the
participants. If the participants weigh less than or equal to 35 kg, they will receive 2
sachets of the gel twice a day (1 sachet approximately every 12 hours) and if they weigh more
than 35 kg, they will receive 4 sachets of gel per day (2 sachets approximately every 12
hours). Parents/ caregivers will be instructed on proper application of the gel. The gel will
be applied to clean, dry, intact skin of the upper arms/ shoulders.

Blood samples will be collected for safety analysis of ZYN002. An independent analytical
laboratory will also perform CGG repeat and methylation status analyses. Additionally, the
parents/caregivers will be asked to complete some questionnaires. There will be other
questionnaires and scales that will be completed at the site by the study doctor.

After the final dose, patients will be followed weekly for 4 weeks by telephone, prior to
discharge from the study.

Inclusion Criteria:

- Male or female children and adolescents aged 3 to less than 18 years, at the time of
Screening.

- Diagnosis of FXS through molecular documentation of FMR1 full mutation.

- Judged to be in good health based on physical exam, 12-lead ECG and clinical
laboratory test results.

- Patients must be assessed by the Investigator as being moderately to severely impacted
due to FXS.

- Patients taking psychotropic medication(s) should be on a stable regimen of not more
than two such medications for at least fours weeks preceding Screening and must
maintain that regimen throughout the study.

- If patients are receiving non-pharmacological, behavioral and/or dietary
interventions, they must be stable and have been doing so for three months prior to
screening.

- Patients and parents/caregivers must be adequately informed of the nature and risks of
the study and given written informed consent prior to Screening.

- In the Investigator's opinion, patients and parents/caregivers are reliable and
willing and able to comply with all protocol requirements and procedures.

Exclusion Criteria:

- Females who are pregnant, nursing or planning a pregnancy.

- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin
levels greater than or equal to 2 times the upper limit of normal or alkaline
phosphatase levels greater than or equal to 3 times the upper limit of normal.

- Use of a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4.

- Use of minocycline for 30 days prior to screening or throughout the study.

- Use of any benzodiazepine at screening or throughout the study.

- Use of THC or CBD-containing product within three months of Screening Visit or during
the study.

- Change in pharmacologic or non-pharmacologic intervention during the course of the
study.

- Any skin disease or condition including eczema, psoriasis, melanoma, acne, contact
dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may
affect treatment application, application site assessments or absorption of the trial
drug.

- Patient is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate
or vigabatrin.

- Patients has an advanced, severe or unstable disease that may interfere with the study
outcome evaluations.

- Patient has acute or progressive neurological disease, psychosis, schizophrenia or any
other psychiatric disorder or severe mental abnormalities (other than FXS) that are
likely to require changes in drug therapy or interfere with the study objectives or
ability to adhere to protocol requirements.

- Patient has suspected or confirmed cardiovascular disease, advanced arteriosclerosis,
structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities,
coronary artery disease, cardiac conduction problems, exercise-related cardiac events
including syncope and pre-syncope, risk factors for Torsades de pointes (e.g. heart
failure, hypokalemia, family history of Long QT Syndrome) or other serious cardiac
problems.

- History of treatment for, or evidence of drug abuse within the past year.

- Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or
at any time on study.