NRX-1074 in Early Course Schizophrenia

Investigators propose to conduct a 4-week, randomized, double-blind, placebo-controlled
trial in which NRX-1074 will be intravenously administered twice. Subjects will be 62 stable
patients ages 18-50 within five years of onset of schizophrenia, treated with any
antipsychotic except clozapine at an adequate, stable dose for at least 8 weeks. This study
will be conducted by the Schizophrenia Program of the NYU Langone Medical Center and at the
Psychiatry Outpatient Clinic of Bellevue Hospital located in New York, NY.

Upon signing consent, patients will undergo screening procedures to assess eligibility. A
diagnosis of schizophrenia or schizophreniform disorder will be determined by the Structured
Clinical Interview for DSM IV (SCID) completed by a research clinician using all available
clinical data and will be confirmed by consensus diagnosis. A comprehensive medical review
and physical exam, including routine laboratory tests, will be completed to identify
unstable medical illness. A urine toxicology screen and, in females, a pregnancy test will
also be performed. A research assistant will complete the Logical Memory Test portion of the
Weschler Memory Scale-III (WMS-III).

Subjects who meet study eligibility criteria will complete the baseline visit which will
include a one minute infusion of NRX-1074 and the following clinical assessments: Brief
Psychiatric Rating Scale (BPRS), Clinical Assessment Interview for Negative Symptoms
(CAINS), Calgary Depression Scale for Schizophrenia (CDSS), InterSePT Scale for Suicidal
Thinking (ISST), Clinical Global Impression (CGI), and Systematic Assessment for Treatment
Emergent Events (SAFTEE). The BPRS, SAFTEE, and ISST will be conducted twice, both before
and after the infusion. The remaining assessments will be conducted before the infusion. A
cognitive assessment, the Logical Memory Test of the WMS-III, will also be conducted after
the infusion.

Patients will return for a visit one day after their baseline infusion, where the BPRS,
ISST, CGI, and Logical Memory Test will be conducted. Their next visit will be one week
later, where they receive their second NRX-1074 infusion, and will be similar in format to
the first baseline infusion with the exception of CAINS and CDSS. One day after the second
infusion, patients will be administered the BPRS, CAINS, CDSS, ISST, CGI, and MATRICS
Consensus Cognitive Battery (MCCB). Patients will then return weekly for three weeks until
Day 28.

The BPRS and ISST will be conducted during the Baseline, Day 1, Day 7, Day 8, Day 14, Day
21, and Day 28 visits. The CGI will be administered during Baseline, Day 1, Day 7, Day 8,
Day 14, and Day 28. The CAINS and CDSS will be administered at Baseline, Day 8, Day 14, and
Day 28. The SAFTEE will be conducted on Baseline, Day 7, Day 14, Day 21, and Day 28. The
Logical Memory Test will be administered during Screening Visit 1, Screening Visit 2,
Baseline, and Day 1. The MATRICS will be conducted on Day 8 and Day 28.

The primary outcome measure is the change in BPRS total score from Baseline to 24 hours post
infusion on Day 8. Secondary outcome measures include the positive and negative symptom
subscales on the BPRS, the CAINS total score, the composite score on the MATRICS 24 hours
after the second infusion and the Logical Memory Test compared to placebo one hour after the
first infusion (Baseline).

Inclusion Criteria:

- Age 18-50

- Diagnosis of Schizophrenia, Schizophreniform, or schizoaffective disorder as per
DSM-V criteria

- Within five years of onset of illness

- Treated with any antipsychotic agent except clozapine at an adequate, stable dose for
at least 8 weeks.

- A score of at least 4 (moderate) on at least one BPRS negative symptom item.

Exclusion Criteria:

- Serious or unstable medical illness

- Pregnant or nursing

- Abuse of substances except nicotine in the previous 6 weeks (excluding cannabis use)

- Positive urine toxicology at screening

- Experiencing serious suicidal or homicidal ideation within six months

- Treatment with clozapine