A First-in-Human, Randomized, Double-Blinded, Placebo-Controlled Trial in Healthy Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Ascending Intravenous Dose Levels of ARGX-117 and Subcutaneous Dose Levels of ARGX-117 Co-Mixed with Recombinant Human Hyaluronidase PH20

ARGX-117 is a new compound that may be used for the treatment of diseases that
are related to the so called complement system. The complement system is part
of the immune system.

ARGX-117 is being developed to rapidly reduce tissue inflammation by inhibiting
the complement system. The complement system is part of the innate immune
system, which is not adaptable and does not change during an individual's
lifetime. Overactivation of the complement system can lead to tissue
destruction and organ damage. ARGX-117 inhibits a protein that plays an
important role in the complement system.

This is the first clinical study in which ARGX-117 is administered to humans.
It has been previously tested in the laboratory and on laboratory animals.

This is the first clinical study in which ARGX 117 is administered to humans.
The purpose of this study is to investigate how safe the new compound ARGX-117
is and how well it is tolerated when it is administered to healthy volunteers.
It will also be investigated how quickly and to what extent ARGX 117 is
absorbed and eliminated from the body (this is called pharmacokinetics). In
addition, the effect of ARGX 117 on blocking of the complement system will be
investigated (this is called pharmacodynamics).

Furthermore, the effect of the volunteers genetic information on their body*s
response to ARGX-117 will be investigated. This part of the study is not
mandatory.

This study will be performed in up to 112 healthy male or female volunteers.
The study will be performed in 2 parts, Part A and Part B.

Part A of the study will consist of up to 9 groups of 8 volunteers each.
Part B of the study will consist of up to 5 groups of 8 volunteers each.

ARGX-117 will be tested at various dose levels and via different routes of
administration. The effects of ARGX 117 will be compared to the effects of a
placebo. A placebo is a medicine without any active ingredient.

Part A:
The actual study will consist of 1 period during which the volunteer will stay
in the research center for 10 days (9 nights). This will be followed by 10
short visits to the research center. These short visits will take place at
10:30 h in the morning on Days 15, 22, 29, 36, 50,64, 92, 120, 148 , and 204.
Additionally, there is a follow-up visit on Day 260.

Day 1 is the day of administration of the study compound. The volunteer is
expected at the research center at 14:00 pm 2 days prior to the day of
administration of the study compound, so on Day -2. The volunteer will leave
the research center on Day 8 of the study.

In Groups 1 to 8, the volunteer will receive ARGX-117 or placebo as a 2-hour
intravenous infusion or the volunteer will receive ARGX-117 or placebo in
combination with rHuPH20 as an injection under the skin (subcutaneous) or
infusion under the skin over approximately1 hour. Group 9 is an optional group.
Based on results in the preceding groups, it will be determined whether ARGX
117 or placebo isadministered intravenously or subcutaneously in Group 9.

For safety reasons in Groups 1 and 2, initially 3 volunteers will receive the
study compound. Two of these volunteers will receive ARGX-117, and 1 volunteer
will receive placebo. These 3 volunteers will be dosed one by one, with 24
hours between each dosing, to monitor the safety and tolerability of the study
compound in each volunteer. If there are no concerns about the safety and
tolerability at least 24hours after 3rd volunteer has been dosed, then the
remaining 5 volunteers (4 will receive ARGX-117 and 1 will receive placebo) in
thatgroup will receive the study compound.

In all other groups, initially 2 volunteers will receive the study compound in
each group. One volunteer will receive ARGX-117, and 1 volunteer will receive
placebo. After administration, the safety and tolerability of the study
compound in these 2 volunteers will be closelymonitored. If there are no
concerns about the safety and tolerability 24 hours after administration, then
the remaining 6 volunteers (5 willreceive ARGX-117 and 1 will receive placebo)
in that group will receive the study compound.

Volunteer will be tested for the presence of coronavirus upon admission to the
research center. Until the test results are available, volunteer will be
separated from other participants and only have very limited contact with study
staff. This is to avoid virus spread from potentially infected participants to
other participants or to the study staff because, until the results are
available, it is not certain whether volunteer is infected or not and can thus
potentially infect others. The test results will be available within one hour.
If the volunteer test positive for coronavirus, he/she cannot participate in
the study.

The coronavirus test will be done at the following timepoints:
•Day -2 (admission to the research center)
•Day -1
•Day 2
•Day 260 (follow-up visit)

Part B:
For Group 1, 4 and 5 the actual study will consist of 3 periods during which
the volunteer will stay in the research center first for 11 days (10nights),
then for 4 days (3 nights), and then for 10 days (9 nights). This will be
followed by 11 short visits to the research center. These short visits will
take place at 10:30 h in the morning on Days 36, 43, 50, 57, 64, 78, 92, 120,
148, 176, and 232. Additionally, there is a follow-up visit on Day 288.

Day 1 is the first day of administration of the study compound. The volunteer
is expected at the research center at 14:00 h in the afternoon two days prior
to the first day of administration of the study compound, so on Day -2. After
the second administration of the study compound on Day 8, the volunteer will
leave the research center on Day 9 of the study. Then the volunteer will return
in the afternoon of Day 13 for the third administration of the study compound
on Day 15 and the volunteer will leave on Day 16. The third period will be from
Day 20 to Day 29, with the fourth administration of the study compound on Day
22.

For Group 2 and 3, the actual study will consist of 2 periods during which the
volunteer will stay in the research center first for 17 days(16 nights) and
then for 10 days (9 nights). This will be followed by 11 short visits to the
research center. These short visits will take place at 10:30 h in the morning
on Days 36, 43, 50, 57, 64, 78, 92, 120, 148, 176, and 232. Additionally, there
is a follow-up visit on Day288.

Day 1 is the first day of administration of the study compound. The volunteer
is expected at the research center at 14:00 pm 2 days prior to the first day of
administration of the study compound, so on Day -2. After the second
administration of the study compound on Day 8,the volunteer will leave the
research center on Day 15 of the study. Then the volunteer will return in the
afternoon of Day 20 for the third administration of the study compound on Day
22, after which the volunteer will leave again on Day 29.

In Group 1: the volunteer will receive ARGX-117 or placebo 4 times, with at
least 1 week between each administration.
In Group 2 and 3: the volunteer will receive ARGX-117 or placebo 3 times, with
at least 1 week between each administration.
In Group 4 and 5: the volunteer will receive ARGX 117 or placebo 4 times in
combination with rHuPH20 as an injection under the skin

The starting dose and the time between each administration will be confirmed
after evaluation of the results in Part A.
Volunteer will be tested for the presence of coronavirus upon admission to the
research center. Until the test results are available, volunteer will be
separated from other participants and only have very limited contact with study
staff. This is to avoid virus spread from potentially infected participants to
other participants or to the study staff because, until the results are
available, it is not certain whether volunteer is infected or not and can thus
potentially infect others. The test results will be available within one hour.
If volunteer test positive for coronavirus, he/she cannot participate in the
study.

The coronavirus test will be done at the following timepoints:
Group 1, 4 and 5: the coronavirus test is performed upon entry to the research
center on Day -2, 13, 20, and 288 (follow-up visit), and also during the
volunteers stay in the research center on Day -1, 2, 14, 16, 21 and 23.

Group 2, and 3:
Day -2, -1, 2, 20, 21, 23, and 288

Part A:
In Groups 1 to 8, ARGX-117 or placebo will be given as a 2-hour intravenous
infusion or ARGX-117 or placebo will be given in combination with rHuPH20 will
as an injection under the skin (subcutaneous) or infusion under the skin over
approximately 1 hour. Group 9 is an optional group. Based on results in the
preceding groups, it will be determined whether ARGX-117 or placebo is
administered intravenously or subcutaneously in Group 9.

Group Study compound Dose# Route of administration
1 ARGX-117 or placebo 0.1 mg/kg Intravenous
2 ARGX-117 or placebo 0.5 mg/kg Intravenous
3 ARGX-117 or placebo 2.5 mg/kg Intravenous
4 ARGX-117 or placebo 10 mg/kg Intravenous
5 ARGX-117 or placebo 30 mg/kg Intravenous
6 ARGX-117 or placebo 60 mg/kg Intravenous
7 ARGX-117 or placebo 60 mg/kg Subcutaneous
8 ARGX-117 + rHuPH20 or
Placebo + rHuPH20 80 mg/kg Intravenous
9 ARGX-117 (+ rHuPH20) or
Placebo (+ rHuPH20) 15mg/kg subcutaneous

Part B:
In Group 1: the volunteer will receive ARGX-117 or placebo 4 times, with at
least 1 week between each administration.
In Group 2 and 3: the volunteer will receive ARGX-117 or placebo 3 times, with
at least 1 week between each administration.
In Group 4 and 5: the volunteer will receive ARGX 117 or placebo 4 times in
combination with rHuPH20 as an injection under the skin

Group Day Study compound Dose# Route of administration
1 1 ARGX-117 or placebo 10 mg/kg Intravenous
8 10 mg/kg
15 10 mg/kg
22 10 mg/kg.

2 1 ARGX-117 or placebo 60 mg/kg Intravenous
8 10 mg/kg
22 10 mg/kg.

3 1 ARGX-117 or placebo 10 mg/kg Intravenous.
8 ARGX-117 or placebo 50 mg/kg Intravenous.
22 ARGX-117 or Placebo 20 mg/kg Intravenous.

4 1 ARGX-117 + rHuPH20 15mg/kg Subcutaneous.
or Placebo + rHuPH20
8 ARGX-117 + rHuPH20 15mg/kg
Subcutaneous.
or Placebo + rHuPH20
15 ARGX-117 + rHuPH20
or Placebo + rHuPH20 15 mg/kg Subcutaneous.
29 ARGX-117 + rHuPH20
or Placebo + rHuPH20 15 mg/kg
Subcutaneous.

5 1 ARGX-117 PH20 or 1200mg
Subcutaneous.
Placebo PH20
8 ARGX-117 PH20 or 1200mg
Subcutaneous.
Placebo PH20
15 ARGX-117 PH20 or 1200mg
Subcutaneous.
Placebo PH20
22 ARGX-117 PH20 or 1200mg
Subcutaneous.
Placebo PH20

Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.

In total, we will take approximately 677 milliliters (mL) of blood from you.

To make a heart tracing, electrodes will be pasted at specific locations on
your arms, chest and legs. To monitor your heart rate, electrodes will be
pasted at specific locations on the chest and abdomen. Prolonged use of these
electrodes can cause skin irritation.

Samples for the coronavirus test will be taken from the back of the nose and
throat using swabs. Taking the samples only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.