Study of the Safety, Tolerability and Pharmacokinetics of TMB-607 in HIV-Negative Volunteers

This study uses a sequential dose-escalation design for single dose subcutaneous and
intramuscular administrations in HIV-negative volunteers. The study investigates seven
TMB-607 dose groups: Cohort 1: 200 mg subcutaneously (Arm A), 500 mg subcutaneously (Arm B)
and 1,000 mg subcutaneously (Arm C); Cohort 2: 100 mg intramuscularly (Arm A), 400 mg
intramuscularly (Arm B), 800 mg intramuscularly (Arm C) and 1,500 mg intramuscularly (Arm D).
Five participants will be enrolled in each dose group, and will be randomly assigned in a 4:1
ratio to receive TMB-607 or placebo in a double-blinded fashion (four participants per group
assigned to active TMB-607; one participant per group assigned to placebo). In each group, a
single dose injection of TMB-607 or placebo will be administered at Day 0. The first three
Day 0 injections administered in each dose group must be given at least 24 hours apart.
Subjects will be enrolled sequentially so that a maximum of three subjects in each Cohort is
dosed within any 24-hour period. All subjects will be monitored for 24 hours after study drug
administration, with vital signs and ECGs checked hourly, and intensive pharmacokinetic
samples collected during this period. Study drug will only be administered on Mondays to
prevent weekend days from interfering with the daily assessments closest to the time of
dosing. Participants will be followed for 10 weeks after receiving study drug.

Inclusion Criteria:

- Participants must meet all of the following criteria to be included in the study:

1. Male or female between 18-55 years of age on the day of screening

2. HIV-negative volunteers, willing to undergo HIV testing and counseling, and
receive HIV test results

3. Normal 12-lead ECG at Screening and on Day 0, including normal sinus rate and
rhythm, QTc interval ≤440msec, PR interval ≤200msec, and lack of any evidence of
heart block, or left or right bundle branch block

4. Willing to comply with the requirements of the protocol and available for
follow-up for the planned duration of the study

5. In the opinion of the principal investigator or designee, has understood the
information provided; written informed consent needs to be given before any
study-related procedures are performed

6. Agrees to use a barrier form of contraception if engaging in sexual activity at
any time throughout the study (males and females) - two reliable forms of barrier
contraception diaphragm, Intra Uterine Device (IUD), spermicides or condoms) must
be used if participants engage in sexual activity that could result in pregnancy;
hormonal contraception (e.g., oral contraceptive pill, injectable or implantable
contraceptive) must not be relied upon while in this study; all female
participants must be willing to undergo urine pregnancy tests at time points
indicated in the Schedule of Events and Procedures

7. For females of reproductive potential, negative urine pregnancy test at screening
and within 96 hours prior to randomization; female participants of reproductive
potential are defined as women who have not been post-menopausal for at least 24
consecutive months (i.e., who have had menses within the preceding 24 months) or
have not undergone surgical sterilization (e.g., hysterectomy, or bilateral
oophorectomy, salpingectomy, or tubal ligation)

Exclusion Criteria:

- Participants having or meeting any of the following conditions or characteristics will
be excluded from the study:

1. Confirmed HIV-1 or HIV-2 infection

2. Currently pregnant or breastfeeding

3. Known allergy/sensitivity or any hypersensitivity to components of study drug or
its formulation, or known allergy to sulfonamide drugs

4. History, or family history of Short of Long QT syndrome, Wolff-Parkinson-White
Syndrome, or congenital heart disease

5. Family history of sudden cardiac death, or unexplained cardiac death in an
otherwise healthy individual between the ages of 1 and 40 years

6. History of syncope, palpitations, unexplained dizziness, hypokalemia, heart
arrhythmias, or significant cardiac disease

7. Major psychiatric illness including any history of schizophrenia or severe
psychosis, bipolar disorder requiring therapy, suicide attempt in the previous 3
years

8. Serious illness requiring systemic treatment and/or hospitalization within 21
days prior to randomization

9. Receipt of immunomodulatory agents (e.g., interleukins, interferons,
cyclosporine, systemic corticosteroids), HIV vaccine, systemic cytotoxic
chemotherapy, or investigational therapy within 180 days prior to study entry

10. Any clinically significant acute or chronic medical condition requiring care of a
physician (e.g., diabetes, coronary artery disease, rheumatologic illness,
malignancy, substance abuse) that in the opinion of the investigator would
preclude participation

11. Any laboratory value of Grade 1 or higher according to the NCI Common Toxicity
Criteria (Appendix A)

12. Confirmed diagnosis of hepatitis B (surface antigen, HbsAg), or hepatitis C (HCV
antibodies)

13. Current confirmed STD infection

14. In the opinion of the investigator, unlikely to comply with protocol