3BNC117-LS First-in-Human Phase 1 Study

The proposed study is a Phase 1, open label, dose escalation cohort study of 3BNC117-LS
administered intravenously in HIV-uninfected and HIV-1 infected participants.

Study participants will be administered a single intravenous infusion of 3BNC117-LS at one of
three increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg) and will be followed for 48
weeks after 3BNC117-LS administration.

This trial will enroll 15 to 30 participants into 5 study groups.

First, eligible participants will be enrolled in Group 1A (n=3-6; HIV-uninfected, 3 mg/kg)
and participants will be administered 3BNC117-LS at least one day apart. No more than 2
participants in Group 1A will be administered 3BNC117-LS in a given week.

Enrollment in Group 1B (n=3-6; HIV-uninfected, 10 mg/kg) and Group 2B (n=3-6; HIV-infected on
or off ART (antiretroviral therapy), 10 mg/kg) will begin after participants enrolled in
Group 1A reach day 42 with ≤ 1 dose limiting toxicity (DLT: any adverse event of grade 3 or
greater toxicity, if the study investigators recognize a probable or definite attribution to
3BNC117-LS). Participants will be administered 3BNC117-LS at least one day apart.

Enrollment in Group 1C (n=3-6; HIV-uninfected, 30 mg/kg) will begin after participants
enrolled in Group 1B reach day 42 with ≤ 1 DLT. The first 3 participants enrolled in Group 1C
will be administered 3BNC117-LS at least one day apart, and no more than 2 participants will
be administered 3BNC117-LS in a given week. After the first 3 participants enrolled in Group
1C reach day 42 with ≤ 1 DLT, the remaining 3 participants will be enrolled, and administered
3BNC117-LS at least one day apart.

Enrollment in Group 2C (n=3-6; HIV-infected on or off ART, 30 mg/kg) will begin after
participants enrolled in Group 2B reach day 42 with ≤ 1 DLT. The first 3 participants
enrolled in Group 2C will be administered 3BNC117-LS at least one day apart. After the first
3 participants enrolled in Group 2C reach day 42 with ≤ 1 DLT, the remaining 3 participants
will be enrolled, and administered 3BNC117-LS at least one day apart.

Following 3BNC117-LS infusion, study participants will return for safety assessments at weeks
1, 2 and 4 following infusion, then bi-monthly or monthly until the end of study follow up.

Serum samples for PK (pharmacokinetic) measurements will be collected before 3BNC117-LS
infusion, at the end of the infusion, and at multiple time points during study follow up.

Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS
infusion (screen, pre-infusion and day 0) and at all follow up visits in Groups 2B and 2C.

All participants will be followed for 48 weeks after 3BNC117-LS infusion.

Inclusion Criteria:

Groups 1A-1C (HIV-uninfected):

1. Males and females, age 18 to 65

2. Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent
with low risk of HIV exposure.

3. If sexually active male or female, and participating in sexual activity that could
lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom
with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based
contraceptive with condom) from 10 days prior to and until seven months after
3BNC117-LS infusion, and agrees to safer sex counseling at each visit.

- Female study participants of reproductive potential are defined as pre-menopausal
women who have not had a sterilization procedure (e.g. hysterectomy, bilateral
oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal
if they have not had a menses for at least 12 months and have a FSH of greater
than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24
consecutive months.

Groups 2B-2C (HIV-infected):

1. Males and females, age 18 to 65.

2. HIV-1 infection confirmed by two laboratory assays.

3. HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels <
100,000 copies/ml by standard assays (ART-naïve or off ART due to intolerance or by
choice), or on ART with HIV-1 plasma RNA levels < 20 copies/ml. HIV-1 RNA levels
should be measured on 2 occasions, at least 1 week apart. At least one measurement
must be performed within 49 days prior to enrollment (day 0).

4. Current CD4+ T cell count > 300 cells/μl.

5. If sexually active male or female, and participating in sexual activity that could
lead to pregnancy or transmission of HIV, agrees to use two effective methods of
contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting
IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven
months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.

Exclusion Criteria:

Groups 1A-1C (HIV-uninfected):

1. Confirmed HIV-1 or HIV-2 infection.

2. History of immunodeficiency or autoimmune disease; use of systemic corticosteroids,
immunosuppressive anti-cancer, or other medications considered significant by the
trial physician within the last 6 months.

3. Any clinically significant acute or chronic medical condition (such as autoimmune
diseases) that in the opinion of the investigator would preclude participation.

4. Within the 12 months prior to enrollment, the participant has a history of sexually
transmitted infection.

5. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen
(HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.

6. Laboratory abnormalities in the parameters listed:

- Absolute neutrophil count ≤ 1,500 cells/µL;

- Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;

- Platelet count ≤ 125,000 cells/µL;

- Alanine transaminase (ALT) ≥ 1.25 x ULN;

- Aspartate transaminase (AST) ≥ 1.25 x ULN;

- Alkaline phosphatase ≥ 1.5 x ULN;

- Total bilirubin > 1 x ULN;

- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.

7. Pregnancy or lactation.

8. Any vaccination within 14 days prior to 3BNC117-LS infusion.

9. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in
the past.

10. History of severe reaction to a vaccine or drug infusion or history of severe allergic
reactions.

11. Individuals with known hypersensitivity to any constituent of the investigational
product.

12. Receipt of another investigational product currently or within the past 12 weeks, or
expected concurrent participation in another study in which investigational products
will be administered.

Groups 2B-2C (HIV-infected):

1. Have a history of AIDS-defining illness within 3 years prior to enrollment.

2. History of systemic corticosteroids, immunosuppressive anti-cancer, or other
medications considered significant by the trial physician within the last 6 months.

3. Any clinically significant acute or chronic medical condition (such as autoimmune
diseases), other than HIV infection, that in the opinion of the investigator would
preclude participation.

4. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen
(HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.

5. Laboratory abnormalities in the parameters listed below:

- Absolute neutrophil count ≤ 1,000 cells/μl;

- Hemoglobin ≤ 10 gm/dL;

- Platelet count ≤ 100,000 cells/μl;

- ALT ≥ 1.5 x ULN;

- AST ≥ 1.5 x ULN;

- Alkaline phosphatase ≥ 1.5 x ULN;

- Total bilirubin > 1 x ULN;

- eGFR < 60 mL/min/1.73m2.

6. Pregnancy or lactation.

7. Any vaccination within 14 days prior to 3BNC117-LS infusion.

8. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in
the past.

9. History of severe reaction to a vaccine or drug infusion or history of severe allergic
reactions.

10. Individuals with known hypersensitivity to any constituent of the investigational
product.

11. Receipt of another investigational product currently or within the past 12 weeks, or
expected concurrent participation in another study in which investigational products
will be administered.