Phase 1 Study on the Safety, Tolerability, and Pharmacokinetics of JST-018 in Healthy Adults

Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of JST-018 in Healthy Adults

The goal of this clinical trial is to learn if a single dose of the study drug, JST-018, is safe and tolerable when administered by injection into the arm or thigh muscle of healthy men and women aged 18 to 55. The main questions it aims to answer are:

• Is a single administration of JST-018 safe?
• What is the concentration of the JST-018 in the blood over time?
• Do antibodies to JST-018 develop following a dose of JST-018? Researchers will compare JST-018 to Placebo to see if there are any differences in the safety and tolerability of a single dose at different dose levels.

Participants will be confined to the clinic for the first 3 days. They will receive an injection on the second day, and then return for 9 more visits over the period of 1 year for:

• Physical exam with vital signs
• Electro-cardiogram (ECG)
• Bood collection for clinical labs and research samples
• Urine sample
• Assessment of potential adverse effects and medications taken

This is a Phase 1, first-in-human (FIH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) study to assess the safety, tolerability, and PK of a single dose of JST-018 administered IM to healthy participants.

The study will be comprised of a minimum of 3 cohorts (Cohorts A, B, and C, with 12 participants per cohort), each evaluating a single dose of JST-018 administered IM. In each cohort, 2 sentinel participants will be randomized 1:1 such that one participant receives JST-018 and 1 participant receives placebo. Following a favorable blinded safety review committee (SRC) review of sentinel safety data collected through Day 8, the remainder of the cohort (10 non-sentinel participants) will be randomized 4:1 to JST-018 or placebo, and will be dosed.

All safety data for all participants in the current cohort through Day 8 will be reviewed by the SRC in a blinded fashion for each dose cohort before escalating to the next dose cohort (for escalation from Cohort A to Cohort B and escalation from Cohort B to Cohort C); A recommendation on whether to implement Cohort D (along with a recommended dose of JST-018 to be evaluated in Cohort D) may be provided by the SRC following review of blinded safety data from Cohorts A, B, and C.

Inclusion Criteria:

1. Healthy men or women 18 to 55 years of age
2. BMI between 18 and 32 kg/m2
3. Negative serum pregnancy test
4. Use of highly effective birth control method(s) for a minimum of 60 days prior to consent and is willing to continue use for at least 12 months, or abstinence
5. In good general health as determined by medical history, exams and tests

Exclusion Criteria:

1. Acute illness or fever (≥100.4°F) within 7 days prior to dosing

2. Any history of receiving treatment, vaccine, or monoclonal antibodies (mAbs) against smallpox, monkeypox, or other orthopox viruses.

3. Receipt of any vaccine within 30 days prior to Screening, planned receipt of any vaccine prior to Day 1, or planned receipt of any vaccines before 45 days post-injection.

4. Any medical condition for which IM injections would be contraindicated in the opinion of the investigator (eg, bleeding disorders, anticoagulant therapy, and severe thrombocytopenia)

5. History of congenital or acquired immunodeficiency syndrome, , including positive human immunodeficiency virus (HIV-1/-2) antibody result

6. Prior solid organ or bone marrow transplant

7. Clinically significant corneal or lens abnormality as determined by history, clinical examination, or diagnostic imaging. Including, but not limited to:

   • Corrected vision of less (worse) than 20/40
   • History of any clinically significant history of eye trauma, in the opinion of the investigator
   • History of cataracts or current cataracts
   • Lens opacity greater than NC2, C2, or P0 as determined by the Lens Opacities Classification System (LOCS) III
   • History of uveitis (including acute)
   • Use of ocular or inhaled prescription steroids within 1 year prior to Screening nasal steroids are permissible). A single short course (ie, less than 14 days) of systemic steroid therapy is allowed provided it is concluded more than 6 months prior to Screening.
   • History of diabetes

8. Use of immunosuppressive agents, anticoagulants, or antiarrhythmics within 1 year prior to Screening. Nasal steroid use is permissible.

9. Upper arms and thighs are with insufficient muscular tissue for IM injections or is obscured by tattoos or rash

10. Use of any medications started within 30 days prior to Day -1, including prescription medications, nutritional supplements, and over-the-counter medications

    • Vitamin supplements are allowed
    • Recommended doses of acetaminophen are allowed, except for 24 hours prior to dosing
    • Recommended doses of non-steroidal anti-inflammatory drugs (NSAIDs) (eg, aspirin, ibuprofen) are also allowed, except for 7 days prior to dosing

11. Positive hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C antibody

12. Positive urine drug test or cotinine (indicating active current smoking) at Screening or Day -1, positive alcohol breath test at Screening or on Day -1, or suspected/known drug abuse and/or alcohol use disorder

13. Smoking or has used nicotine or nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months before study drug dosing

14. Dosing in any clinical research study evaluating another investigational drug or therapy within 30 days or at least 5 half-lives (whichever is longer) of receiving the investigational drug prior to Screening

15. Progressive, unstable, or uncontrolled medical conditions that have required medical attention or changes to medication for medical reasons within 90 days prior to consent

16. History of allergic reactions or hypersensitivity reactions to other therapeutic antibodies or immunoglobulins

17. Receipt of any mAbs in the 12 months prior to Screening

18. High blood pressure

19. Women who are either pregnant or breast-feeding

20. Vulnerable individuals (eg, military recruits, persons in compulsory detention, those with limited legal capacity)

21. Receipt of immunoglobulins or any blood products within 90 days prior to consent or planned receipt during the study period

22. Donation or loss of >500 mL of blood within 30 days or plasma within 7 days of Day 1; any planned donation of blood or plasma during the study period

23. History of any malignant neoplasm within the last 5 years, with the exception of adequately treated localized or in situ non-melanoma carcinoma of the skin or the cervix

24. Strenuous activity or contact sports within 48 hours before study drug dosing and through Day 8

26. History of relevant drug and/or food allergies