Study to Evaluate Safety & Efficacy of NaBen® as Add-on Treatment for Schizophrenia in Adults

This is an adaptive, phase IIb/III, multi-center, prospective, randomized, placebo-controlled
study, in which adult subjects with schizophrenia will be enrolled. The study will include
four parts: a 2 week Screening part, a 4 week run-in part, and 8 week double-blind treatment
part, and a 52 week Open-Label Extension part.

Screening part of the study:

The subjects will be evaluated for eligibility during the Screening part of the study.

Enrichment run-in part of the study:

Subjects who are determined to be eligible will enter the Run-in part of the study. A total
of 348 Subjects will be randomized. The randomized subjects will receive 4 weeks of NaBen® or
Placebo accordingly. The subjects who have completed 4 weeks of randomized treatment in both
groups (NaBen® or Placebo) will be assessed and categorized intoresponders and
non-responders, based on 20% or more reduction from baseline in their PANSS total scores as
per the evaluations at Visit 2 and Visit 4.

Double-Blind treatment part of the study :

- Subjects who have successfully completed the Enrichment Run-in part will enter the
Double- Blind treatment part of the study per below: NaBen® treated subjects: Subjects
will continue receiving NaBen® for another 8 weeks.

- Placebo treated subjects:

- Placebo Responders: Subjects will continue receiving Placebo for another 8 weeks.

- Placebo Non-responders: Subjects will be re-randomized to receive NaBen® or Placebo
in a 1:1 ratio for another 8 weeks.

Open-Label Extension part of the study:

All subjects who have completed the Double-Blind part of the study will continue with the
Open-Label Extension part of the study to receive NaBen® for an additional 52 weeks, plus a 2
week follow-up.

Inclusion Criteria:

1. Male/female subjects between 18 and 55 years of age

2. If female and not infertile (defined below), the subject must agree for the duration
of the study to use one of the following forms of contraception 1) systemic hormonal
treatment 2) an Intrauterine device (IUD) which was implanted at least 2 months prior
to screening or 3) "double-barrier" contraception (condom, diaphragm and spermicide
are each considered a barrier). Females are considered to be infertile if they are
either a) surgically sterile or b) have had spontaneous amenorrhea for at least the
last 2 years and at least 2 years after the onset of amenorrhea while not receiving
hormone replacement therapy and had a Follicle-Stimulating Hormone (FSH) level greater
than 40 mIU/mL and an estradiol level less than 30 pg/mL

3. Subject is capable of providing informed consent and is willing to sign the ICF prior
to study Screening and agrees to comply with the study protocol requirements

4. Physician confirmed DSM-V diagnosis of schizophrenia for the past 2 years based on
subject's history and confirmed by psychiatric evaluation and MINI International
Neuropsychiatric Interview For Schizophrenia and Psychotic Disorders, version 7.0
(MINI, Version 7.0)

5. The subject is outpatient with no hospitalization for worsening of schizophrenia
within 3 months of the screening.If the subject is hospitalized during the study for
worsening of schizophrenia symptoms the subject will be withdrawn from the study

6. The subject's schizophrenia condition is clinically stable with residual symptoms.
Residual symptoms will be defined as a total score of ≤110 and ≥ 60 of PANSS per Visit
1 evaluations

7. An unchanged antipsychotic medication regimen for at least eight (8) weeks prior to
screening into the study and expected to remain unchanged during the study (longer for
depot or long-acting antipsychotics: ten (10) months for Aripiprazole and
Paliperidone; six (6) months for Olanzapine pamoate monohydrate; and at least 6 times
duration of the reported half life or minimum four (4) months for other depot or
long-acting antipsychotics)

8. In good general physical health and without clinically significant abnormalities in
physical exam, neurological exam and laboratory assessments (urine/blood routine,
biochemical tests and ECG) which would exclude the subject from the study in the
opinion of the Investigator. For ALT and AST, clinically significant is defined as
above twice the upper limit of normal.

9. BMI between 17 and 35 inclusive

10. Subject has a negative routine urine illicit drug screening test (including heroin,
amphetamines (including MDMA/ecstasy), cocaine, cannabis or PCP)

11. The subject has a caregiver or some other identified responsible person (e.g., family
member, social worker, caseworker or nurse) as determined by the Investigator and per
the local regulations. The identified caregiver should be considered reliable by the
Investigator and per the local regulations in providing support to the subject to help
ensure compliance with study treatment, study visits and protocol procedures who
preferably is also able to provide input helpful for completing study rating scales

12. The subject must not be a danger to self or others per the Investigator's judgment

Exclusion Criteria:

1. Meets the DSM-IV or V criteria at screening for intellectual disability, dissociative
disorder, bipolar disorder, major depressive disorder, schizoaffective disorder,
schizophreniform disorder, autistic disorder, primary substance-induced psychotic
disorder, dementia, or any other comorbid mental disorders that in the opinion of the
Investigator may interfere with study conduct and results interpretation

2. Subjects whose illness was resistant to antipsychotics according to prior trials of
two different antipsychotics of adequate dose

3. Subjects who have been previously treated with or are receiving clozapine

4. Initiation or dose change of lithium, antidepressant or other mood stabilizers within
16 weeks prior to screening

5. Initiation or dose change of benzodiazepines or sleep medications due to worsening of
schizophrenia symptoms or medication side effects, or any other psychotropic
medications within 4 weeks prior to screening

6. The subject has previously received NaBen®

7. History of epilepsy, major head trauma, or any neurological illness other than
Tourette's syndrome which might impair the subject's cognition or psychiatric
functioning per the investigator's judgment

8. History of allergic reaction to sodium benzoate

9. Serious medical illnesses such as end-stage renal disease, liver failure or heart
failure that, in the opinion of the Investigator, may interfere with the conduct of
the study

10. Any significant gastrointestinal disorders that, in the opinion of the investigator,
markedly alter the absorption, metabolism or elimination of sodium benzoate

11. Any movement disorders with a total score higher than 6 on SAS scale, or more than 2
on any items of the AIMS scale

12. Current substance abuse, or history of meeting criteria for moderate or severe
substance abuse (including alcohol, but excluding nicotine and caffeine) in the past
six (6) months prior to screening

13. Female subjects who are pregnant (as confirmed by urine pregnancy test performed at
Screening Visit) or are breast feeding

14. History of cancer not in remission for the last 3 years except for basal cell
carcinoma and squamous cell carcinoma

15. Participation in a clinical trial within 3 months prior to screening or more than two
clinical trials within 12 months

16. Electroconvulsive Therapy within 6 months prior to screening

17. The subject started a new non-medication treatment for schizophrenia or other
psychiatric condition within the last 3 months prior to screening

18. The subject's anti-EPS medications dose or regimen has changed within 2 weeks prior to
screening