Healthy Adults

Primary Objectives: • To determine the safety and tolerability of J4 Dry Powder Capsule after single and multiple oral doses in healthy subjects. Secondary Objectives: • To determine the single dose pharmacokinetics (PK) of J4 Dry Powder Capsule in healthy subjects in a single ascending dose (SAD) study. • To determine the repeat dose PK of J4 Dry Powder Capsule in healthy subjects in a multiple ascending dose (MAD) study. • (Optional) To determine the effect of food on the bioavailability of J4 Dry Powder Capsule in healthy subjects.

capsule

JMF3464

130

5mg/capsule

3.1 Primary Endpoint
Safety and tolerability assessment will be based on medical review of adverse event reports,
clinically significant laboratory assessments, vital sign measurements (blood pressure, heart rate,
body temperature, respiratory rate, oxygen saturation), electrocardiogram (ECG), Columbia-
Suicide Severity Rating Scale (C-SSRS) scores (MAD only), and physical examinations. The
incidence of adverse events will be tabulated and reviewed for potential significance and clinical
importance.

1. Healthy male and female subjects between 18 and 64 (inclusive) years of age at the time
of consent.
2. Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive); male subjects must
weigh a minimum of 50 kg while female subjects must weigh a minimum of 45 kg.
3. Healthy subjects as determined by no clinically significant deviation from normal in
medical history, physical examination, vital sign measurement, ECG, and clinical
laboratory test results.
4. Male subjects with a female partner of childbearing potential are eligible to participate if
they meet either of the following conditions:
- They are surgically or biologically sterile (surgically sterile is defined as vasectomy with
documented negative semen analysis/azoospermia).
- They commit to the use of highly effective methods of contraception (defined as those
that, alone or in combination, result in a failure rate less than 1 percent per year) from
study Day -1 until 90 days after the last dose of the study drug. Male subject must use a
condom, and the subject’s female partner must use one of the following contraceptive
measures.
a. Intrauterine device.
b. Oral, implantable, or injectable contraceptives.
- They are abstinent from intercourse from study Day -1 until 90 days after the last dose
of the study drug.
5. Male subjects must agree to refrain from sperm donation and females refrain from ova
donation from Study Day -1 until 90 days after the last dose of the study drug.
6. Female subjects of childbearing potential (which is defined as any woman or adolescent
who has begun menstruation) are eligible to participate if they meet either of the following
conditions:
- They are surgically of biologically sterile. (surgically sterile is defined as the subject has
one of the following: documented hysterectomy, documented bilateral salpingectomy,
documented bilateral oophorectomy). If they have undergone tubal ligation, the
procedure must have occurred at least 6 weeks prior to the 1st study drug administration.
- They commit to use of highly effective methods of contraception, starting from at least
30 days prior to 1st study drug administration and continuing for at least 90 days after

Subject with any of the following will be excluded from the study.
1. Female who are pregnant or breastfeeding or have a positive pregnancy test at screening,
admission or prior to study drug administration.
2. A history of any significant medical illness, including but not limited to neurological,
cardiovascular, hematological, psychiatric, hepatic, gastrointestinal, pulmonary, endocrine,
immunologic or renal disease; a history of cancer within the past 5 years.
3. Any clinically significant ECG abnormalities at screening (e.g., QTcFd > 440 ms in men or
QTcFd > 460 ms in women)
4. Subjects with blood pressure outside the normal range of 90-140 mm Hg for systolic or
50-90 mm Hg for diastolic at screening
5. Subjects with a history of cardiovascular disease, such as arrhythmia, hypertension,
hypotension, angina pectoris, myocardial infarction, or heart failure
6. Any significant laboratory abnormalities, including those suggesting clinically significant
hepatic abnormalities (ALT, AST, or TBL ≥ 1.1 x ULN) or renal dysfunction (Cr ≥ 1.5 mg/dL)
at screening.
7. Clinically significant acute illness or infection within 14 days prior to Day -1.