A randomized, double-blind, placebo-controlled single and multiple ascending dose study of the safety, tolerability and pharmacokinetics of oral doses of SAR443122 in healthy adult subjects.

SAR443122 is a new compound that may eventually be used for the treatment of
autoimmune diseases such as rheumatoid arthritis, an inflammatory disease. In
autoimmune diseases, the immune system sees the body's own cells and substances
as foreign and attacks them.

Rheumatoid arthritis is a long-lasting auto­immune disorder that primarily
affects the joints. Inflammation is characterized by increased blood supply and
activation of defense mechanisms, resulting in redness, swelling, heat and
pain.

The study compound that will be researched in this study, SAR443122, inhibits a
protein (RIPK1) that is involved in abnormal immune function seen in
inflammatory diseases.

This study will be performed in a maximum of 97 healthy volunteers. The study
will be performed in 2 parts, Part 1 (split up in Part 1a and Part 1b) and Part
2. A single dose of SAR443122 (or placebo [only in Part 1a]) will be
administered in Part 1 whereas multiple doses of SAR443122 (or placebo) will be
administered in Part 2.

The purpose of this study is to investigate how safe the new compound SAR443122
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 SAR443122 is
absorbed (taken up), distributed, metabolized (broken down) and eliminated from
the body (this is called pharmacokinetics). Further, the pharmacokinetics of
SAR443122 when it is administered as 2 different manufactured oral capsules
(Part 1b only). This comparison of pharmacokinetics is called relative
bioavailability. In addition, the effect of food on the absorption of SAR443122
in the body will be investigated (Part 1b only). Also, the effect of SAR443122
on certain signaling proteins in your body will be investigated (this is called
pharmacodynamics).

SAR443122 will be tested at various dose levels. The effects of SAR443122 will
be compared to the effects of a placebo (not in Part 1b). A placebo is a
capsule that does not contain any active medicine. Whether you will receive
SAR443122 or placebo will be determined by chance. Please note that when the
term *study compound* is used in this document, this can refer to SAR443122,
placebo, or both.

SAR443122 has not been administered to humans before. It has been previously
tested in the laboratory and on animals.

Part 1a
A single dose of the study agent (SAR443122 or placebo) will be given as
capsules by mouth with 240 milliliters (mL) of water. No chewing is allowed on
the capsules. The test substance will be administered after fasting for at
least 10 hours (fasting: no food or drink except water). After administration
of the test substance, volunteers will fast for a period of 4 hours until the
planned lunch. They may drink water during fasting, except from the time of
administration of the test substance until 1 hour thereafter. The actual
research will consist of 1 period during which the volunteers will stay in the
research center for 5 days (4 nights). The research center is expected at 2
p.m. in the afternoon on Day -1, the day before Day 1 (Day 1 is the day on
which the study drug is administered). They leave the research center on Day 4.

Part 1b
A single dose of SAR443122 is given in each of 3 periods: once as capsules by
mouth after fasting (fasting: no food and drink except water), once as capsules
(but with a different composition) by mouth after fasting and once as capsules
by mouth after having received a high-fat breakfast. The order in which one
receives these treatments is determined by drawing lots. There will be a period
of at least 7 days between each administration of the study compound. Each
period, SAR443122 is given as oral capsules with 240 milliliters (ml) of water.
No chewing is allowed on the capsules. The actual research will consist of 3
periods in which the volunteers will stay in the research center for 5 days (4
nights) in each period. Each volunteer is expected in the research center at
2:00 p.m. on Day -1, the day prior to Day 1 (Day 1 is the day on which
SAR443122 is administered). They leave the research center on Day 4 of each
period.

Part 2
The actual research will consist of 1 period during which the volunteers will
stay in the research center for 18 days (17 nights). They are expected in the
research center at 2:00 p.m. on Day -1, the day prior to Day 1 (Day 1 is the
day the study drug is administered). They leave the research center on Day 17.

Group 1a:
Group 1 day 1; SAR443122 10 milligrams (mg) or placebo; once fasted
Group 2 day 1; SAR443122 30 mg or placebo; once fasted
Group 3 day 1; SAR443122 100 mg or placebo; once fasted
Group 4 day 1; SAR443122 200 mg or placebo; once fasted
Group 5 day 1; SAR443122 400 mg or placebo; once fasted
Group 6 day 1; SAR443122 X mg or placebo; once fasted

Group 1b:
9 volunteers
Period 1 Once 100 milligrams (mg) of SAR443122 as capsules by mouth under
fasting conditions
Period 2: Once 100 mg of SAR443122 as capsules by mouth under fasting conditions
Period 3: Once 100 mg SAR443122 as capsules by mouth after a high-fat breakfast

Group 2
Group 8: Day 1-14; SAR443122 W mg or placebo; once a day fasted
Group 9: Day 1-14; SAR443122 X mg or placebo; once a day fasted
Group 10: Day 1-14; SAR443122 Y mg or placebo; once a day fasted
Group 11: Day 1-14; SAR443122 Z mg or placebo; once a day fasted

As SAR443122 will be administered to man for the first time in this study, side
effects of SAR443122 in man have not been reported to date. However, SAR443122
has been studied extensively in the laboratory and in animals. SAR443122 was
safe and well tolerated in animals. At very high repeated doses in 1 animal, a
potential effect on the immune system was seen, such as increased white blood
cell counts, anemia, increased spleen weight and increased cellularity
(formation of blood cellular components) in the bone marrow. You will be
monitored for effects on your immune system throughout the study. Except for
this finding, based on the animal research and knowledge about the mechanism of
action of SAR443122, no specific or pronounced side effects are expected at the
moment.

Drawing blood and/or insertion of the indwelling cannula (thin tube in an arm
vein) may be painful or cause some bruising.