A randomized, blinded, placebo-controlled study to assess the safety, tolerability and pharmacokinetics of EGT710 following administration of single and multiple doses to healthy adults.

EGT710 is a new compound that may potentially be used for the treatment of
coronavirus disease 2019 (COVID 19). EGT710 works by inhibiting the coronavirus
main protease. This protease is a protein which enables the coronavirus to
replicate itself. Inhibition of the coronavirus main protease would reduce the
amount of coronavirus and could be proven an effective treatment for COVID 19.
EGT710 is found to have activity against all known human coronaviruses.

The purpose of the study is to see if the study compound (EGT710) is safe and
tolerated when given to healthy adults. The study will also look at how the
body absorbs, breaks down, and gets rid of the study treatment.

Approximately 100 healthy volunteers between the ages of 18 and 65 years are
being invited to join this study. If you wish to have further details on who
can join, please ask the responsible doctor.

Eligibility criteria for this study require that you are a healthy person. The
study compound given as part of this study is not being given to treat any
symptoms or illness. Your option is to either join or not join this study.

There are certain tests/questions you must complete to find out if you meet the
requirements to be in the study. If you do not meet these requirements, you
cannot take part in the study.

We also look at the effect of your genetic information on your body*s response
to EGT710.This part of the study is not mandatory.

We compare the effects of EGT710 with the effects of a placebo. A placebo is a
compound without any active ingredient. Please note that when the term *study
compound* is used in this document, we mean EGT710, placebo, or both.

EGT710 has not been administered to humans before. It has been extensively
tested in the laboratory and on animals.

In total, the volunteer visits the research center twice:
• once for screening.
• once for a stay in the research centre. For the study it is necessary that
the volunteer stays in the research center for a period of time.

This is for Part A: 1 period of 6 days (5 nights).
For Part B: 1 period of 12 days (11 nights)
And for Part C: 1 period of 16 days (15 nights)

We expect the volunteers for Part A and B: two days prior to the (first)
administration of the study compound in the study center.
And the volunteers for Part C: on the day prior to the (first) administration
of the study compound.

Day 1 is the (first) day on which the volunteer receives the research
compound. The Part A volunteers leave the study center on Day 4, the Part B
volunteers on Day 10, and the Part C volunteers on Day 15 of the study.

• In addition, we call the volunteer once for a follow-up check.


The study compound is given as follows:

Part A: EGT710 or placebo fasted as oral capsules with 240 milliliters (mL) of
(tap) water
The subjects will be divided into six different groups. Whether the volunteer
will receive EGT710 or placebo will be determined by chance. Per group, 6
subjects will receive EGT710 and 2 subjects will receive placebo.

Part B: EGT710 or placebo fasted as oral capsules with 240 milliliters (ml) of
(tap) water.
The subjects will be divided into four different groups. Whether the volunteer
will receive EGT710 or placebo will be determined by chance. Per group, 6
subjects will receive EGT710 and 2 subjects will receive placebo.

Part C: EGT710 or placebo as oral capsules with 240 milliliters (ml) of (tap)
water. The volunteer will also receive EGT710 or placebo as oral (test)
formulation 2, which is yet to be determined.
The subjects will be divided into six groups with 3 subjects in each. All
subjects will receive the study compound once with a breakfast and twice
without breakfast. The order in which this will occur will be determined by
chance.
The sequence in which the volunteer will receive EGT710 as an oral capsule or
as oral formulation 2 will be determined by chance. Each group will receive
EGT710 once as oral capsule and twice as oral formulation 2.

How much and how often the study compound is given:

Part A:
Group 1 will receive 80 mg EGT710 or placebo once on day 1 as oral capsules
under fasted conditions.
Group 2 will receive 240 mg of EGT710 or placebo once on day 1 as oral capsules
under fasted conditions.
Group 3 will receive 720 mg EGT710 or placebo once on day 1 as oral capsules
under fasted conditions.
Group 4 will receive NTB* mg EGT710 or placebo once on day 1 as oral capsules
under fasted conditions.
Group 5 will receive 1440 mg of EGT710 or placebo once on day 1 as oral
capsules under fasted conditions.
Group 6 will receive NTB* mg EGT710 or placebo once on day 1 as oral capsules
under fasted conditions.
* To be determined (NTB)

Part B:
Group 1 will receive 300 mg of EGT710 or placebo once daily on Days 1 to 7 as
oral capsules under fasted conditions.
Group 2 will receive 600 mg EGT710 or placebo once daily on Days 1 to 7 as oral
capsules under fasted conditions.
Group 3 will receive 1000 mg EGT710 or placebo once daily on Days 1 to 7 as
oral capsules under fasted conditions.
Group 4 will receive NTB* mg EGT710 or placebo once daily on Days 1 to 7 as
oral capsules under fasted conditions.
* To be determined (NTB)

Part C:
There are 3 treatments in this part of the study, the volunteer will receive
all three. The order in which the volunteer receives the treatments is
determined by drawing lots. There are 5 days between each dose.

- Treatment 1: EGT710 as an oral capsule after fasting
- Treatment 2: EGT710 as oral formulation 2 after fasting
- Treatment 3: EGT710 as oral formulation 2 after receiving a high fat
breakfast.

Dose escalation increments and actual doses may be revised at dose escalation
meetings based on safety, tolerability, and pharmacokinetic data from the
preceding cohort/dose level.

Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula (a tube in a vein in the arm) can sometimes lead to inflammation,
swelling, hardening of the vein, blood clotting, and bleeding in the
environment (bruising) of the puncture site. In some individuals, a blood draw
can sometimes cause pallor, nausea, sweating, low heart rate, or drop in blood
pressure with dizziness or fainting.

In total, we will take about 105 (Part A), 280 (Part B) or 225 (Part C)
milliliters (mL) of blood from screening to follow-up. This amount does not
cause any problems in adults. To compare: a blood donation involves 500 mL of
blood being taken each time at once. If the investigator thinks it is necessary
for the safety of a subject, extra samples might be taken for possible
additional testing. If this happens, the total amount of blood drawn may be
more than the amount indicated above.

Heart tracing
To make a heart tracing, electrodes (small, plastic patches) will be placed on
your arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation (rash and itching).

Meals/Fasting
The high-fat breakfast is a big breakfast containing e.g., 2 fried eggs, fried
potatoes and bacon. The volunteer must consume the whole breakfast. It can be
difficult to consume the entire breakfast, particularly for light eaters.

If the volunteer has to fast for a prolonged time during the study, this may
lead to symptoms such as dizziness, headache, stomach upset, or fainting.

Coronavirus test
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 gagging. When the sample is taken from the back of the
nose, the volunteer may experience a stinging sensation and eyes may become
watery.