A first-in-human, randomized, dose-Escalation, double-blind, placebo-controlled study to assess safety, tolerability and pharmacokinetics of APX001 administered by intravenous infusion to healthy subjects.

APX001 is a new investigational compound that may eventually be used for the
treatment of fungal infections. APX001 binds to an enzyme specific for fungi
(GWT1) and decreases the activity of this enzyme. As a result the cell walls of
the fungus will lose integrity and the growth will slow or stop. This is the
first time that this study compound is being given to humans.

The study will be performed in 4 parts, Parts A, B, C and D. The purpose of the
study is to investigate to what extent APX001 is tolerated.
It will also be investigated how quickly and to what extent APX001 is absorbed
and eliminated from the body (this is called pharmacokinetics).
This study will be performed in 120 healthy male and female volunteers, divided
over 12 groups.

The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Groningen (location UMCG for Cohort 1 to 3
and location Martini for Cohort 4 to 6) for 4 days (3 nights). This stay will
be followed by short visits to the clinical research center on Days 4 to 8 and
on Day 11, 12, or 13. During the visit on Day 8 the post-study screening will
be performed.
The volunteers are expected at the clinical research center at 14:00 h in the
afternoon prior to the day of administration of the study compound. 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). They
will leave the clinical research center on Day 3 (Day 1 is the day of
administration of the study compound).
The post-study screening will take place on Day 7 - 9 . The appointment for the
post-study screening will be made during the study.
The participation to the entire study, from the pre-study screening until the
post study screening, will be a maximum of 36 days.

The actual study for cohorts 7-10 will consist of 1 period during which
subjects will stay in the clinical research center in MZH in Groningen for 17
days (16 nights). This stay will be followed by a short visit to the clinical
research center on Day 18 and for the post-study screening on Day 21.
The participation for to the entire study, from the pre-study screening until
the post-study screening, will be a maximum of 49 days.

Part C:
The actual study will consist of 1 period during which the volunteer will stay
in the clinical research center in Groningen (location Martini) for 4 days (3
nights). This stay will be followed by short visits to the clinical research
center on Days 4 to 8 (Day 1 is the day of administration of the study
compound) and on Day 11, 12, or 13. During the visit on Day 8 the post study
screening will be performed.
The volunteers are expected at the clinical research center at 14:00 h in the
afternoon prior to the day of administration of the study compound. 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). They
will leave the clinical research center on Day 3.
The post-study screening will take place on Day 8.
The participation to the entire study, from the pre-study screening until the
post study screening, will be a maximum of 41 days.

Part D:
The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Groningen for 10 days (9 nights). This stay
will be followed by short visits to the clinical research center on Day 11 and
Day 14 (Day 1 is the first day of administration of the study compound). They
are expected at the clinical research center at 14:00 h in the afternoon prior
to the day of first administration of the study compound. 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). They will leave the
clinical research center on Day 9. The post-study screening will take place 7
days after the last administration of study compound on Day 14. The
participation to the entire study, from the pre-study screening until the
post-study screening, will be a maximum of 42 days.

SAD:
Cohort 1: 1 x 10 mg
Cohort 2: 1 x 30 mg
Cohort 3: 1 x 100 mg
Cohort 4: 1 x 300 mg
Cohort 5: 1 x 525 mg
Cohort 6: 1 x 800 mg

MAD:
Cohort 7: 1 x 50 mg
Cohort 8: tbd x tbc mg
Cohort 9: tbc x tbc mg
Cohort 10: tbc x tbc mg
Cohort 11: tbd
Cohort 12: tbd

Pain, minor bleeding, bruising, possible an infection due to blood sampling.