Multiple Ascending Dose to Study the Safety, Tolerability, PK and PD Effects of AEF0117

The overall goal of this protocol is to evaluate the safety, tolerability, pharmacokinetics
(PK) and pharmacodynamics (PD) of escalating multiple oral doses of AEF0117. This will be a
single center study in healthy male and female subjects. The study design will be a
double-blind, randomized, placebo-controlled, single period, parallel group, multiple dose
escalation with AEF0117.

Three dose levels are planned for the study with 8 subjects (6 active and 2 placebo) per dose
level:

Dose Level I - 0.6 mg multiple oral dose of AEF0117 given on the morning of Day 1 to Day 7
Dose Level II - 2 mg multiple oral dose of AEF0117 given on the morning of Day 1 to Day 7
Dose Level III - 6 mg multiple oral dose of AEF0117 given on the morning of Day 1 to Day 7

The planned dose escalation schema may be amended based on the emerging PK and safety data,
and an additional cohort may be added. Smaller dose escalation increments can also be
implemented based on safety and PK results of previous dose levels. Each subject will
participate in only one dose group.

Administration of AEF0117 to each dose cohort should not occur before participants in the
previous dose cohort have been treated and data i.e. safety results and PK from those
participants are reviewed in accordance with the protocol. Eligible subjects will be admitted
to the research clinic at midday prior to dosing (Day -1) and remain in house until Day 14.
Subsequently subjects will return to the research facility on an outpatient basis to have PK
and safety assessments at 216 and 264 hours (Day 16 and Day 18) after the last dose (Day 7).
PK samples and safety assessments will be done pre-dose and at different times post-dose.

Randomized subjects will receive a single oral dose per day on Days 1 through 7. Serial PK
and PD blood samples and urine PK collections will be performed for 24 hours after the first
dose administration (Day 1). Pre-dose PK and PD blood samples will then be obtained on Days
3, 4, 5 and 6 prior to the daily dose administration. Serial PK and PD blood samples and
urine collections will be also performed for 48 hours after the last dose (Day 7), and blood
samples will be obtained at 72, 96, 120, 144, 168, 216 and 264 hours after the last dose (Day
7).

Safety monitoring (physical examinations, vital sign measurement, 12 lead ECGs, clinical
safety laboratory tests, and adverse event monitoring) will be performed throughout the
study. Psychometrics tests (Bond & Lader VAS, ARCI, POMS) will be performed on D1 and D7 at
pre-dose, tmax and 24 hours post-dose. CSSRS test will be performed at pre-dose of D1 and at
D8. tmax will be determine according to PK results obtained in the AEF0117-101 clinical
study. Subjects will have a final follow up/Study termination safety evaluation on Day 18.

Inclusion Criteria:

1. Be a healthy, non-smoking or smoking (<10 cigarettes per day) male of any race, at
least 18 years old and no more than 55 years old, inclusive. As the effect of the
study drug on sperm is still unknown, male subjects should refrain from donating sperm
or plan a pregnancy with their partner throughout the study and after 90 days, and
must report immediately to the study doctor if its partner becomes pregnant during the
study and after 90 days. The male subject will have to use double-barrier
contraceptive methods: male condoms and spermicide.

2. Be a healthy, non-smoking or smoking (<10 cigarettes per day) female of
non-child-bearing potential between 18 years of age and 55 years of age, inclusive.
Females may be accepted if they are documented to be surgically sterile (e.g.,
hysterectomy, tubal ligation) or post-menopausal [amenorrhea >1 year and FSH
>25.8mlU/mL, cut off from Labcorp] with a negative pregnancy test. At least 30% of
female.

3. Have a body weight ≥50 kg, with a body mass index (BMI) calculated as weight in
kg/(height in m)2 from 18 to 30 kg/m2 (inclusive) at screening.

4. Have no significant diseases in the medical history and no clinically significant
findings on physical examination including ECG, BP, HR, RR, temperature, C-SSRS test.
Routine laboratory values should be within normal ranges or considered as NCS by the
investigator. The Non Clinical Significant nature of the deviation will result from
the integration of a full clinical examination with physical examination and lab tests
in that contest by a certified physician.

5. Be informed of the nature of the study and provide written informed consent.

6. Be legally competent and able to communicate effectively with study personnel.

Exclusion Criteria:

1. Allergies to the Investigational Medicinal Product (IMP) or placebo and its excipients
and known allergies to pregnenolone or its matching placebo or its ingredient

2. Acute signs of intoxication at screening or baseline assessment due to opiates or any
type of stimulants, causing cognitive impairments

3. Severe learning disability, brain damage or pervasive developmental disorder ( as this
may affect one of the end point that is being targeted)

4. Any disease or condition that might compromise the cardiovascular, hematological,
renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes),
central nervous, or gastrointestinal (including an ulcer) systems.

5. Have abnormal baseline values for the steroid hormones: cortisol, testosterone,
estradiol and progesterone in accordance to their reproductive status (for example but
not limited to surgical sterile or post-menopausal).

6. A history of alcoholism or drug addiction within the past 2 years, recent use (in the
last month) of any recreational drugs, or positive results from a urine screen for
substances of abuse or positive alcohol test.

7. A history of or current serious mental illness including active or recent suicidal
ideation, severe psychological distress (e.g., active suicidal plans, psychosis,
debilitating panic disorder) or/and an abnormal C-SSRS result.

8. A history of difficulty donating blood or inadequate venous access.

9. The donation of blood or plasma within 30 days prior to receiving study medication or
received any blood and plasma for medical/surgical reasons or intention to donate
blood or plasma within one month after receiving the study drug.

10. A positive hepatitis screen that tests for both hepatitis B surface antigen (HBsAg)
and antibody to hepatitis C (HCV).

11. A positive test result for HIV antibody by enzyme immunoassay which is confirmed by
Western immunoblot.

12. Ingestion of an investigational drug or product, or participation in a drug study
within a period of 30 days prior to receiving study medication (for investigational
drugs with an elimination half-life greater than 10 days, this will be extended to 60
days).

13. Use of any prescription or over-the-counter (OTC) drug therapy, including herbal,
homeopathic, vitamins, minerals and nutritional supplements, bodybuilding supplements
unapproved by the sponsor, within 2 weeks prior to receiving the study medication (for
drugs with an elimination half-life greater than 10 days, this will be extended to 60
days). The use of any food supplement or body cream containing pregnenolone or any
other steroid including phytosteroids.

14. Use of a drug therapy known to induce or inhibit hepatic drug metabolism within 30
days prior to receiving study medication or during the study.

15. Use of psychoactive and/or psychotropic medication (including sedative, antidepressant
and antipsychotics), or medication that alters the hypothalamic pituitary adrenal
(HPA) Axis functioning and any medications that alter heart rate or skin conductance
monitoring

16. Unable to follow the restrictions outlined in the protocol.

17. Legal status that would interfere with participation

18. Employed by the contract research organization (CRO) or are family members of the
staff at the CRO

19. Previous participation in a cohort for any dose level of AEF0117.