A 2-Period Crossover Study of BPN14770 in Adults Males With Fragile X Syndrome

A total of 30 subjects will be enrolled. The study consists of a screening period of up to 28
days prior to initial treatment, followed by two double-blind treatment periods, each 12
weeks long. A final follow-up visit or phone contact for safety is planned one week after the
conclusion of Period 2.

Eligible subjects will be randomized in a blinded, balanced (1:1) fashion to receive either
25 mg BPN14770 capsules or matching placebo capsules during Period 1, followed by the
opposite treatment during Period 2. One capsule will be taken twice daily during both
double-blind periods.

Subjects will return to the clinic at the end of Weeks 2, 6, and 12 of each study period.
Cognitive and behavioral evaluations will be repeated at Weeks 6 and 12 of each Period.
Additionally, patients will be monitored for adverse events via a telephone call at the end
of Week 1 of each Period, and one week following completion of Period 2 or following early
discontinuation.

During clinic visits, adverse effects will be assessed, and laboratory measures, vital signs,
and ECGs will be performed. Suicidality risk will also be evaluated at each clinic visit; if
a concern is detected, the subject will be referred for further evaluation and treatment.
Cognitive and behavioral assessments will be performed during each clinic visit.
Pharmacodynamic measures of CNS function will be obtained to evaluated effects of the drug in
the brain. Pharmacokinetic samples will be collected to confirm that study drug is present
and to estimate plasma exposure at Week 12 of each Period.

Inclusion Criteria:

1. Subject is male aged 18 to 45 years, inclusive.

2. Subject has Fragile X Syndrome with a molecular genetic confirmation of the full
Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repetitions).

3. Current treatment with no more than 3 prescribed psychotropic medications. Anti-
epileptic medications are permitted and are not counted as psychotropic medications if
they are used for treatment of seizures. Anti-epileptics for other indications, such
as the treatment of mood disorders, count towards the limit of permitted medications.

4. Permitted concomitant psychotropic medications must be at a stable dose and dosing
regimen for at least 2 weeks prior to Screening and must remain stable during the
period between Screening and the commencement of study medication.

5. Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks
prior to Screening and must remain stable during the period between Screening and the
commencement of study medication.

6. Subjects with a history of seizure disorder who are currently receiving treatment with
anti-epileptics must have been seizure-free for 3 months preceding Screening, or must
be seizure-free for 3 years if not currently receiving anti-epileptics.

7. Behavioral and therapy treatments/interventions must be stable for 4 weeks prior to
Screening and must remain stable during the period between Screening and the
commencement of study medication, and throughout the study. Minor changes in hours or
times of therapy that are not considered clinically significant will not be
exclusionary. Changes in therapies provided through a school program, due to school
vacations, are allowed.

8. Subject must be willing to practice barrier methods of contraception while on study,
if sexually active. Abstinence is also considered a reasonable form of birth control
in this study population.

9. Subject has a parent, legal authorized guardian or consistent caregiver.

10. Subject and caregiver are able to attend the clinic regularly and reliably.

11. Subject is able to swallow tablets and capsules.

12. For subjects who are not their own legal guardian, subject's parent/legal authorized
guardian is able to understand and sign an informed consent form to participate in the
study.

13. If subject is his/her own legal guardian, he/she can understand and sign informed
consent to participate in the study.

14. If subject is not their own legal guardian, the subject provides assent for
participation in the study, if the subject has the cognitive ability to provide
assent.

Exclusion Criteria:

1. History of, or current cardiovascular, renal, hepatic, respiratory, gastrointestinal,
psychiatric, neurologic, cerebrovascular, or other systemic disease that would place
the subject at risk or potentially interfere with the interpretation of the safety,
tolerability, or efficacy of the study medication. Common diseases such as mild
hypertension, well-controlled type 2 diabetes mellitus (hemoglobin A1C [Hgb A1C]
<6.5%), etc. are allowed per the investigator's judgment as long as they are stable
and controlled by medical therapy that is constant for at least 4 weeks before
randomization.

2. Renal impairment, defined as serum creatinine > 1.25 x ULN at screening

3. Hepatic impairment, defined as ALT or AST elevation > 2 x ULN at screening. Note:

LFTs may be repeated after 1 week to evaluate return to acceptable limits; if LFTs
remain elevated, subject is ineligible to participate.

4. Clinically significant abnormalities, in the investigator's judgment, in safety
laboratory tests, vital signs, or ECG, as measured during Screening.

5. History of substance abuse within the past year, according to investigator assessment.

6. Significant hearing or visual impairment that may affect the subject's ability to
complete the test procedures.

7. Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia
or Bipolar Disorder) as diagnosed by the investigator. Subjects with additional
diagnosis of Autism Spectrum Disorder or Anxiety Disorder will be allowed.

8. Subject has active diseases that would interfere with participation, such as acquired
immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis.

9. Subject is planning to commence psychotherapy or cognitive behavior therapy (CBT)
during the period of the study or had begun psychotherapy or CBT within 4 weeks prior
to Screening.

10. Subject is related to anyone employed by the sponsor, investigator, or study staff.

11. Subject has BMI less than 18 or greater than 36.

12. Subject has participated in another clinical trial within the 30 days preceding
Screening.