A PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE-DOSE ESCALATION, MULTIPLE-DOSE ESCALATION, AND FOOD EFFECT STUDY OF FLX475 IN HEALTHY MALE AND FEMALE SUBJECTS

FLX475 is a new compound that may eventually be used for the treatment of
cancer. The immune system that protects the body from foreign invaders, like
viruses and bacteria, can also recognize and kill tumor cells. The immune
response is tightly controlled to prevent it from running unchecked and
attacking the body*s own cells, resulting in autoimmunity. However, these
control mechanisms can also interfere with the immune response against
tumor cells.

Treatments that act on interfering with these control mechanisms have resulted
in meaningful responses of the immune system attacking tumors. However only a
small group of patients showed a long-lasting response to these treatments.

FLX475 works via another mechanism in enhancing the immune response against
tumors. Specific immune cells, called regulatory T-cells, are recruited into
tumors, and thus suppress the immune response against tumor cells. These
T-cells are recruited into the tumor by small
signal proteins called chemokines which are produced by the tumor.

FLX475 reduces the possibility of these chemokines to bind to the T-cells and
so prevents these T-cells from being recruited by the tumor. This way FLX475
allows the immune system to elicit an antitumor response.

The purpose of this study is to investigate how safe the new compound FLX475 is
when it is administered to healthy subjects. FLX475 has not been administered
to humans before. It has been previously tested in the laboratory and on
animals. FLX475 will be tested at various dose levels.

It will also be investigated how quickly and to what extent FLX475 is absorbed
and eliminated from the body. This is called pharmacokinetics. Also, this study
will investigate how food affects the pharmacokinetics of an alternative
formulation of FLX475. In addition, the effect of FLX475 on the body will be
investigated (this is called pharmacodynamics).

The effects of FLX475 will be compared to the effects of a placebo. A placebo
is a medicine without any active ingredient. It is a *fake* medicine.

This study will be performed in up to 104 healthy volunteers divided over Part
A and Part B.

Part A will be performed in up to 56 healthy volunteers divided over up to 7
groups of 8 healthy male of female volunteers. In Part A increasing doses of
FLX475 or placebo will be investigated when administered as single doses. The
effect of giving FLX475 shortly after breakfast, as well as the effect of an
alternative formulation of FLX475 will also be investigated.

Before the study the volunteers will undergo a pre-study screening during which
they will be subjected to a number of medical examinations.
Similar examinations will be performed after the study at the follow-up visit.
This pre-study screening may be done up to 28 days before Day 1.
they will stay in the clinical research center for one period of 4 days (4
nights) from Day -1 to Day 4 (volunteers in group A4 have 3 periods).

The volunteers are expected at the clinical research center at 14:00 h in the
afternoon of Day -1. They 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 study doctor must be informed if any doses
of the own oral contraceptive were missed during the month prior to
participating in the study. They will leave the clinical research center on Day
4. An additional visit to the research center will be on Day 7. The follow-up
visit will take place on day 16 +/- Day 1. The appointment for the follow-up
visit will be made with you during the study. The participation in the entire
study, from the pre-study screening until the follow-up visit, will be a
maximum of 7 weeks (for group A1, A2, A3, A5, A6, A7) and 12 weeks (for group
A4).

In Part B will be performed in up to 48 healthy volunteers divided over a
maximum of 6 groups of 8 healthy male of female volunteers. In Part B
increasing doses of FLX475 or placebo will be investigated when administered
once daily for 14 days.

Before the study the volunteers will undergo a pre-study screening during which
they will be subjected to a number of medical examinations.
Similar examinations will be performed after the study at the follow-up visit.
This pre-study screening may be done up to 28 days before Day 1.
they will stay in the clinical research center for one period of 18 days (17
nights) from Day -1 to Day 17.

The volunteers are expected at the clinical research center at 14:00 h in the
afternoon of Day -1. They 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 study doctor must be informed if any doses
of the own oral contraceptive were missed during the month prior to
participating in the study. They will leave the clinical research center on Day
17. An additional visit to the research center will be on Day 20.The follow-up
visit will take place on day 29 +/- Day 1. The appointment for the follow-up
visit will be made with you during the study. The participation in the entire
study, from the pre-study screening until the follow-up visit, will be a
maximum of 9 weeks.

n.a.

Infection, pain, minor bleedings, bruises, possibly an infection.