Restoring Cognitive Control in Acute Nicotine Withdrawal

This study is a Phase 2A, randomized, double-blinded, placebo-controlled, two-period
crossover study to evaluate the effect of two doses of SXC-2023 on measures of impulsivity
and inhibitory control, urge for cigarettes, and mood in non-treatment seeking smokers who
are abstaining from smoking. The study consists of a screening period of up to 30 days, a 5
day randomized double-blind treatment period, a 9 day washout period, followed by a second 5
day randomized double-blind treatment period, with a safety follow-up period 8 days after the
last dose of study medication.

Inclusion Criteria:

1. Adult, female or male, 28-55 years of age, inclusive at screening.

2. Has provided signed written informed consent and has willingness and ability to comply
with all aspects of the protocol, including abstaining from the use of tobacco for two
5-day periods.

3. Non-treatment seeking smokers regularly using tobacco with a FTND score ≥4 at
screening and self-reported use of ≥10 cigarettes/day at screening.

4. Has smoked for >5 years.

5. Meets Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)
criteria for tobacco use disorder.

6. Must have an expired-air CO level ≥10 ppm during initial screening visit.

7. For a female of childbearing potential: either be sexually inactive (abstinent as a
life style) for 28 days prior to the first dosing and throughout the study or be using
one of the following acceptable birth control methods:

- Oral contraceptives used for at least 3 months prior to the first dose.

- Non-hormone releasing intrauterine device for at least 3 months prior to the
first dose and with either a physical (e.g., condom, diaphragm, or other) or a
chemical (e.g., spermicide) barrier method from the time of screening and
throughout the study.

- Double physical barrier method (e.g., condom and diaphragm) from 14 days prior to
the first dose and throughout the study.

Exclusion Criteria:

1. Subject is mentally or legally incapacitated or has significant emotional problems or
clinically significant abnormality at the time of the screening visit or expected
during the conduct of the study.

2. Meets DSM-5 criteria for Axis I or II psychiatric disorder (except for tobacco use
disorder).

3. Subject suffered a concussion 6 months or less prior to screening.

4. Females who are pregnant or breastfeeding.

5. Positive for hepatitis, human immunodeficiency virus (HIV), coagulopathy, or hepatic
illness.

6. Use of any psychiatric medications (e.g., selective serotonin reuptake inhibitors
[SSRIs], antipsychotics, etc.) or antiepileptics within 30 days prior to the first
dose.

7. Use of NAC within 30 days prior to the first dose.

8. Use of Chantix or related smoking cessation medications within 30 days prior to the
first dose.

9. Use of sulfasalazine (Azulfidine®) within 30 days prior to the first dose.

10. DSM-5 criteria for alcohol/substance use disorder (except for tobacco use disorder).

11. History or presence of clinically significant psychiatric condition (except for
tobacco use disorder) or disease in the opinion of the PI or designee.

12. History of any illness that, in the opinion of the PI or designee, might confound the
results of the study or poses an additional risk to the subject by their participation
in the study.

13. History of seizures.

14. Any history of psychiatric hospitalization in the past year.

15. Currently participating in a clinical study.

16. Previously participated in this Phase 2A study.

17. FTND score <4 at screening or expelled CO levels <10 ppm at screening.

18. Any clinically significant laboratory, ECG and/or vital sign abnormalities at
screening.

19. Unable to read/understand/speak English.