A PHASE 1, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN HEALTHY VOLUNTEERS TO DETERMINE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ESCALATING SINGLE AND MULTIPLE DOSES OF SNDX-6352 OR PLACEBO ADMINISTERED BY INTRAVENOUS (I.V.) INFUSION

SNDX-6352 is a new investigational compound that may eventually be used for the
treatment of advanced cancer. SNDX-6352 inhibits the activity of monocytes (a
type of white blood cells) via binding to a signaling protein that is present
on monocyte cells (human colony stimulating factor-1 receptor [CSF-1R]).
Binding to CSF-1R is expected to disable the cells around a tumor that prevent
the human immune system to attack a tumor. Disabling this defense can
potentially slow down the disease progression and increase the effect of other
treatments. SNDX 6352 is a monoclonal antibody.

The purpose of the study is to investigate to what extent SNDX-6352 is
tolerated.

It will also be investigated how quickly and to what extent SNDX-6352 is
absorbed and eliminated from the body (pharmacokinetics). In addition, also the
pharmacodynamics of SNDX-6352 will be investigated.

The study will be performed in 2 parts, Parts 1 and 2.

For group 1 the study will proceed as follows:
The study will consist of 1 period during which the volunteer will stay in the
clinical research center in Groningen (location UMCG) for 5 days (4 nights)
followed by 6 days during which the volunteer will visit the clinical research
center in Groningen for a short visit. The short (ambulatory) visits are
planned on Day 8 (Day 1 is the day of administration of the study compound),
Day 15, 22, 29, 57, and 85 between 12:30 and 14:30 in the clinical research
center (location Martini hospital).

The volunteer is expected at the clinical research center in the afternoon
prior to the day of administration of the study compound. The volunteer will be
required not to have consumed any food or drinks during the 4 hours prior to
arrival in the clinical research center (with the exception of water).
The volunteer will leave the clinical research center on Day 4.

The post-study visit will take place on the last ambulatory visit (Day 85). The
appointments for the ambulatory visits will be made with the volunteer during
the study. During the entire study period the volunteer will be called every
week in weeks no visit is planned, to check on their well-being. These calls
will be continued until 4 weeks after the post-study visit (up to Day 113,
approximately 16 weeks after study compound administration).

Participation to the entire study, from the pre-study screening until the last
follow-up call, will be a maximum of 134 days (19 weeks, approximately 4.5
months).

During the study the volunteer will receive SNDX-6352 or placebo as an iv
infusion of 30 minutes. During the administration of the study compound and up
to 4 hours after the start of the iv infusion, the volunteer will be required
to stay in bed in semi supine position unless a different position is needed
for study procedures.

For group B the study will proceed as follows:
The study will consist of 2 periods during which the volunteer will stay in the
clinical research center in Groningen (location UMCG) for 5 days (4 nights).
The time interval between the different periods is 14 days between study
compound administrations. The study will include 7 days during which the
volunteer will visit the clinical research center in Groningen for a short
(ambulatory) visit. The ambulatory visits are planned on Day 8 (between both
periods in the clinical research center; Day 1 is the day of administration of
the study compound), Day 22, 29, 36, 43, 71, and 99 between 12:30 and 14:30 in
the clinical research center (location Martini hospital).

The volunteer is expected at the clinical research center in the afternoon
prior to the day of administration of the study compound in both periods. The
volunteer will be required not to have consumed any food or drinks during the 4
hours prior to arrival in the clinical research center (with the exception of
water).

The volunteer will leave the clinical research center on Day 4 and Day 18.

The post-study visit will take place on the last ambulatory visit (Day 99). The
appointment for the post-study visit will be made with the volunteer during the
study. During the entire study period the volunteer will be called every week
in weeks no visit is planned, to check on the well-being of the volunteer.
These calls will be continued until 4 weeks after the post-study visit (up to
Day 127, approximately 18 weeks after the first study compound administration).

Participation to the entire study, from the pre-study screening until the last
follow-up call, will be a maximum of 148 days (21 weeks, approximately 5
months).

During the study the volunteer will receive SNDX-6352 or placebo as an iv
infusion of 30 minutes. During the administration of the study compound and up
to 4 hours after the start of the iv infusion, the volunteer will be required
to stay in bed in semi supine position unless a different position is needed
for study procedures.

For part 1:
The volunteer will receive SNDX-6352 or placebo once as an intravenous (iv)
infusion of 30 minutes.
The amount of study drug given to volunteer will differ per study group as
follows:
Group A1: SNDX-6352 0.15 mg/kg* or placebo
Group A2: SNDX-6352 1.0 mg/kg* or placebo
Group A3: SNDX-6352 3.0 mg/kg* or placebo
Group A4: SNDX-6352 6.0 mg/kg* or placebo
Group A5: SNDX-6352 10.0 mg/kg* or placebo

For part 2:
The volunteer will receive SNDX-6352 or placebo twice with an interval of 2
weeks. SNDX-6352 and placebo will be given as an intravenous infusion.
The doses used in part B of the study will be based on the available results of
the single dose groups in Part A (Group B1). For the dose in Group B2 the
results of Group B1 will also be included.
Group B1: SNDX-6352 A mg/kg* or placebo
Group B2: SNDX-6352 B mg/kg* or placebo

All potential drugs cause adverse effects; the extent to which this occurs
differs. As SNDX-6352 will be administered to man for the first time in this
study, adverse effects of SNDX-6352 in man have not been reported to date.
However, SNDX-6352 has been studied in animals. The most frequently observed
adverse effects in animals were: swelling around the eyes that occurred
approximately 12 weeks after dosing began, increased liver enzyme levels that
were not accompanied by liver damage, increased risk of infections and a
decrease in markers for bone maintenance in the blood. All effects disappeared
after the end of the treatment. Swelling around the eyes disappeared in almost
all animals 26 weeks after the end of the administration. In 2 out of 36
animals (one receiving 30mg/kg/week for 13 weeks and the other 100mg/kg/week)
swelling around the eyes was still present at the end of the observation
period, which was a half year after the last dose. From observations in studies
of two similar compounds, some healthy volunteers also experienced swelling
around the eyes for extended periods, but all these events resolved. The last
swelling resolution was 4 months after the last study dose. The aforementioned
adverse effects and possibly other, still unknown adverse effects, may occur
during the study. However, with the doses used in this study no serious adverse
effects are expected.

A few drugs similar to SNDX-6352 have been administered to humans before. The
adverse effects of these drugs are similar to the findings in animals treated
with SNDX-6352. In addition, the following adverse effects were reported by
healthy volunteers: headache, common cold, stuffy nose, sore throat, itching
and fatigue.

SNDX-6352 is a so-called *biological*; given the properties of these drugs,
there is a chance that the body will develop antibodies against SNDX-6352 or
that a hypersensitivity reaction will be induced. This means that should the
volunteer need SNDX-6352 as therapy in the future, the response to treatment by
this drug may be reduced or absent, and/or the volunteer may get a
hypersensitivity reaction.

Procedures: pain, minor bleeding, bruising, possible infection.