First in Human Study to Assess Safety of VIS649 in Healthy Subjects

On Day 1, a single dose of VIS649 or placebo will be administered IV. Pharmacokinetics
sampling will start with a collection prior to the start of infusion and at multiple
timepoints throughout the study. Pharmacodynamics sampling will occur at baseline and
multiple timepoints throughout the study.

Sentinel subjects will be utilized; the first two subjects in each cohort will be randomized
to receive either VIS649 or placebo and will receive study drug at least 24 hours before the
remaining subjects in the cohort are dosed.

The safety profile of these subjects over the 24 hour post-administration period will be
reviewed to determine whether it is appropriate to proceed with enrollment of the remaining
subjects in the cohort as planned. This will occur for each dose escalation.

The maximum duration of participation (Screening through End-of-study) for individual
subjects will be approximately 20 weeks (5 months). The scheduled final visit will occur 16
weeks post-dosing (112 days).

Inclusion Criteria:

1. Subject voluntarily agrees to participate in this study and signs an Institutional
Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form
prior to performing any of the Screening Visit procedures and be able to sign and date
an appropriate Health Insurance Portability and Accountability Act (HIPAA)
authorization form or subject privacy form, if appropriate.

2. Male and female subjects between 18 to 55 years of age, inclusive, at the Screening
Visit.

3. For Japanese subjects: Subject is of Japanese descent as evidenced by verbal
confirmation of familial heritage (a subject has all four Japanese grandparents born
in Japan).

4. For non-Japanese subjects: Subjects must be of non-Asian descent, as evidenced by
verbal confirmation that all four grandparents are non-Asian.

5. The following applies to female subjects:

- Non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal
ligation]) for at least 6 months, or postmenopausal ≥ 1 year, or

- Non-pregnant, non-lactating females of childbearing potential must report prior
use (over the 28 days prior to dosing of study drug) of medically acceptable
forms of birth control (hormonal contraception, abstinence, diaphragm with
spermicide, condom with spermicide or intrauterine device, or partner with
vasectomy), with agreement to continue to use a medically acceptable form of
birth control (as described) through the end of their participation in the study.
Alternatively, a reported history of abstinence beginning at least 28 days prior
to study drug dosing, with agreement to continue abstinence through the end of
their participation in the study are required. Females of childbearing potential
must also have a negative serum human chorionic gonadotropin (hCG) pregnancy test
at Screening and a negative urine hCG pregnancy test at Baseline (Day -1). Female
subjects must also agree not to donate eggs/bank eggs for the duration of their
participation in the study.

6. For male, subject and/or his partner must use a highly effective form of contraception
(i.e., double-barrier as described above, have had a vasectomy, or have a female
partner of non childbearing potential) or agree to abstinence following study drug
dosing, through the end of the subject's participation in the study. Male subjects
must also agree to not donate sperm for the duration of their participation in the
study, following study drug dosing.

7. Screening laboratory values must meet the following criteria:

- White blood cells 3,000 12,000/mm3

- Platelets >150,000/mm3

- Hemoglobin >13 gm/dL for male and>11 gm/dL for female

- Estimated glomerular filtration rate >80 mL/min/1.73 m2

- Serum creatinine <1.25x Upper Limit of Normal (ULN)

- Blood Urea Nitrogen (BUN) ≤25mg/dL

- Aspartate aminotransferase (AST) ≤50 U/L

- Alanine aminotransferase (ALT) ≤67 U/L

- Alkaline phosphatase ≤150 U/L

- Total Bilirubin ≤1.4 mg/dL unless patient has Gilbert Syndrome, in which case
direct bilirubin must be within normal range

- Glucose (fasting) <115 mg/dL

- Drug and alcohol screen Negative

- Serum Immunoglobulin G (IgG) >750 mg/dL (7.5 g/L)

- Serum Immunoglobulin M (IgM) >55 mg/dL (0.55 g/L)

- Serum IgA >80 mg/dL (0.8 g/L)

8. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the Screening Visit.

9. Healthy, determined by pre-study medical evaluation (medical history, physical
examination, vital signs, 12-lead ECG, and clinical laboratory evaluations), as judged
by the Investigator.

10. Is willing and able to comply with study restrictions and to remain at the central
processing unit (CPU) for the in-patient duration of the study and return for all
follow-up outpatient visits.

11. QTcF or QTcB < 450 msec at Screening (may be repeated once).

Exclusion Criteria:

1. Is participating in another clinical study of any investigational drug, device, or
intervention or has received any investigational medication during the last 30 days or
five half-lives, whichever is longer, before Baseline (Day -1).

2. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for
the study.

3. Subject has a history or current evidence of a serious and/or unstable cardiovascular,
respiratory, gastrointestinal, hematologic, autoimmune, blood dyscrasias or other
medical disorder, including psychiatric disorders, cirrhosis or malignancy. History of
minor skin cancers (not including melanoma) or surgically treated, limited cervical
carcinomas (i.e., carcinoma in situ) are not exclusionary.

4. Subject has a history or presence of proteinuria, chronic kidney disease, disease
requiring immunosuppressive therapy (including systemic steroids), or is considered to
be immunosuppressed for any other reason.

5. Previous receipt of antibody or biologic therapy whether licensed or investigational
(immunoglobulin products, monoclonal antibodies or antibody fragments) within 30 days
prior to dosing or 5 half-lives within the dose of Investigational medicinal products
(IMP), whichever is longer.

6. History of a previous severe allergic reaction with generalized urticaria; angioedema
or anaphylaxis.

7. Blood pressure >160/100 mmHg or <90/50 mmHg (may be repeated once if abnormal), at the
Screening visit and Day 1.

8. Known hypoglobulinemia disorder (i.e., common variable immunodeficiency), X linked
agammaglobulinemia, selective IgA deficiency, selective IgM deficiency).

9. History of pre-existing latent infections (e.g., tuberculosis) or any infection
requiring hospitalization or treatment with antivirals or antibiotics, or vaccination
within 30 days prior to administration of study medication.

10. Concomitant use of marketed or investigational systemic immunosuppressive or
immunomodulatory medications (e.g., corticosteroids, methotrexate, azathioprine, etc.
and/or biologics) is prohibited and require a washout period prior to Screening (30
days or 5 half lives, whichever is longer).

11. Has received any prescription or non-prescription (over-the-counter [OTC]) except
acetaminophen or ibuprofen, including hormonal contraceptives, topical medications,
vitamins, dietary or herbal during the last 30 days or 5 half-lives, whichever is
longer, preceding Baseline (Day -1).

12. Subjects who consume more than 21 units of alcohol per week (7 days) or those who have
a history of alcohol or drug/chemical abuse; one unit of alcohol is equivalent to
eight ounces of beer, 4 ounces of wine, or one ounce of spirits.

13. Subject is a user or former user of nicotine-containing products (including but not
limited to cigarettes, cigars, and chewing or dipping tobacco) who stopped use or
consumption (i.e., smoking, chewing, or pinching) of these nicotine-containing
products less than 3 months before study drug administration or is using or has used
topical or oral nicotine preparations for smoking cessation within the past 90 days
before study drug administration.

14. Subjects who consume greater than 500 mg of caffeine or xanthine-containing products
per day (e.g., coffee, tea, soft drinks, energy drinks, or chocolate).

15. Subjects who refuse to abstain from alcohol, xanthine-containing or
caffeine-containing foods or beverages, or grapefruit foods or beverages, or
Seville-orange containing foods (e.g., orange marmalade) or beverages, from 48 hours
prior to check-in on Day-1 through the end of the study.

16. Subjects with a positive urine drug (inclusive of marijuana) or alcohol Screening test
result at Screening and Day -1.

17. Subjects with a positive hepatitis B surface antigen test or evidence of chronic
hepatitis C virus (HCV) infection at Screening (a negative HCV antibody assay at
screening is sufficient to rule-out chronic HCV infection for this study).

18. Subjects with a known history of a positive Human Immunodeficiency Virus (HIV) or a
positive test result at Screening.

19. Subjects who have donated >500 mL or blood within 60 days prior to start of Screening.

20. The subject has donated any plasma within 7 days prior to Baseline (Day -1).

21. Is an employee of the clinical research team (any Visterra or research site employee),
or has a family member who is an employee of these organizations.