A single center, randomized, double-blind, 3-arm parallel Phase I study to assess pharmacokinetics, safety and tolerability of MYL-1402O solution for intravenous infusion after 90 minute intravenous infusion at one dose level (equivalent weight-adjusted dose (1 mg/kg) compared to the EU and US marketed drug product (Avastin®) in healthy male volunteers.

Avastin® is a drug registered for the treatment of cancer. Avastin® is the
brand name; the active substance is called bevacizumab. Bevacizumab is a
humanised monoclonal antibody (a type of protein that is normally made by the
immune system to help defend the body from infection and cancer). Therefore,
bevacizumab can be called *a biological*. Bevacizumab binds selectively to a
protein called human vascular endothelial growth factor (VEGF), which is found
on the lining of blood and lymph vessels in the body. The VEGF protein causes
blood vessels to grow within tumors, these blood vessels provide the tumor with
nutrients and oxygen. Once bevacizumab is bound to VEGF, tumor growth is
prevented by blocking the growth of the blood vessels which provide the
nutrients and oxygen to the tumor.

MYL 1402O is a new investigational compound which is being developed as a copy
of Avastin®. Currently, MYL-1402O is being administered to humans for the first
time in another clinical study, which is being conducted in cancer patients.

In this study the volunteer will receive MYL-1402O, Avastin® EU formulation
(licensed product in the European Union) or Avastin ® US formulation (licensed
product in the United States of America).

The purpose of the study is to assess the concentrations of bevacizumab in the
blood at different times after the volunteers have been administered MYL-14020
or Avastin® . In addition, it will be investigated to what extent MYL-10420 is
tolerated. For the purpose of the study the concentration of bevacizumab and
the possible development of antibodies against bevacizumab in the blood will be
investigated.

The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Zuidlaren for 10 days (9 nights) followed by
a period of 76 days during which they will visit the clinical research center
on 8 occasions (on Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and
Day 85).

During the study the volunteers will receive MYL 1402O, Avastin® EU, or Avastin
® US formulation after breakfast in the morning as a 25 mL intravenous infusion
of 90 minutes. From the start of the infusion, they will be required to remain
in a lying or half-lying position for at least 4 hours.

A single dose of 1 milligram per kilogram bodyweight MYL 1402O or 1 mg/kg of
one of the two registered Avastin® formulations as a 25 milliliter (mL)
intravenous infusion of 90 minutes.

Blood sampling, indwelling cannula: During this study less than 300 mL of blood
will be drawn. An indwelling cannula will be used on Days 1 and 2 to sample
blood. In addition, from pre study screening until post-study screening
approximately 18 times blood samples will be drawn by direct puncture of the
vein. The blood samples to assess the concentrations of bevacizumab will be
drawn after the volunteers has rested for at least 15 minutes; this rest will
be in a lying position before the draws from Day 1 to Day 9 and in a sitting
position before the draws at the short visits and post study screening.

Intravenous administration: For the intravenous administration the volunteer
will have an indwelling cannula inserted specifically for this purpose in
addition to the indwelling cannula used for blood sampling on Day 1. Thus the
volunteer will have a cannula inserted in both arms during dosing. The cannula
for the intravenous infusion will be removed immediately after administration
of the infusion.

Vital signs: Respiratory rate, blood pressure, pulse rate and body temperature
will be measured regularly.

Heart trace (ECG): ECGs will be made regularly.

Infusion site local tolerance: The infusion site on the volunuteers skin will
be examined several times during the study using a special score list.

The overall risks of MYL 1402O administration are considered to be minimal,
although some are unforeseeable as the testing of this drug is still at an
early stage. Although MYL 1402O is currently being administered in a clinical
study in cancer patients, results from that study are not available yet. With
the dose used in this study no serious side effects are expected, but as all
drugs may potentially cause side effects to some extent, the occurrence of
known or other effects cannot be excluded. This means that there is a chance of
minor side effects and a remote chance of something serious happening. It is
expected that MYL 1402O, which strongly resembles Avastin®, will likely have
the same side effects as Avastin®.

Avastin® has been a registered drug for 11 years now for the treatment of
several types of cancer. The regular dose for cancer patients starts at 5
mg/kg. In this study the volunteer will receive a lower dose of 1 mg/kg. The
side effects described below were seen when Avastin® was given in cancer
patients who used the drug for a long time together with chemotherapy. In this
study only healthy volunteers will be included, who will receive a single dose.
Therefore it is thought that the probability of the side effects described
below to happen in this study is very low.

The most common side effects with Avastin are hypertension (high blood
pressure), fatigue, asthenia (weakness), feeling of numbness or tingling in
hands or feet, nausea, vomiting, diarrhoea and abdominal pain. The most serious
side effects are gastrointestinal perforation (hole in the gut), hemorrhage
(bleeding) and arterial thromboembolism (blood clots in the arteries).

The body may recognize MYL 1402O and Avastin®, as foreign. As a result an
immune response can occur, for example by making antibodies against the study
compound. However, based on experience with Avastin®, the chance of this
happening is considered very low. If the volunteer developes antibodies, this
is not expected to have consequences for the volunteer present health, but
possibly in the future.

The effects of MYL-1402O on sperm cells and a possible pregnancy are not known.
The volunteers agree to take effective measures to prevent pregnancy in a
female partner and not to donate sperm during the study and until 6 months
after administration of the study compound. Adequate contraception for the
volunteer and his fertile female partner is defined as using hormonal
contraceptives or an intrauterine device combined with at least 1 of the
following forms of contraception: a diaphragm or cervical cap, or a condom.
Also, total abstinence, in accordance with the volunteers lifestyle, is
acceptable.