1. Corporate
NC
Presenta-on
May
2014
OTCQX:BIOAF
&
TSX.V:BTI
Delivering
Breakthrough
Therapeu3cs
Across
the
Blood-­‐
Brain
Barrier

2. TSX.V:
BTI
Important
Cau-ons
Regarding
Forward
Looking
Statements
Certain
statements
in
this
presenta-on
contain
forward-­‐looking
statements
within
the
meaning
of
the
Private
Securi-es
Li-ga-on
Reform
Act
of
1995
or
forward-­‐looking
informa-on
under
applicable
Canadian
securi-es
legisla-on
that
may
not
be
based
on
historical
fact,
including
without
limita-on
statements
containing
the
words
“believe”,
“may”,
“plan”,
“will”,
“es-mate”,
“con-nue”,
“an-cipate”,
“intend”,
“expect”
and
similar
expressions.
Such
forward-­‐looking
statements
or
informa-on
involve
known
and
unknown
risks,
uncertain-es
and
other
factors
that
may
cause
our
actual
results,
events
or
developments,
or
industry
results,
to
be
materially
different
from
any
future
results,
events
or
developments
express
or
implied
by
such
forward-­‐looking
statements
or
informa-on.
Such
factors
include,
among
others,
our
stage
of
development,
lack
of
any
product
revenues,
addi-onal
capital
requirements,
risk
associated
with
the
comple-on
of
clinical
trials
and
obtaining
regulatory
approval
to
market
our
products,
the
ability
to
protect
our
intellectual
property,
dependence
on
collabora-ve
partners
and
the
prospects
for
nego-a-ng
addi-onal
corporate
collabora-ons
or
licensing
arrangements
and
their
-ming.
Specifically,
certain
risks
and
uncertain-es
that
could
cause
such
actual
events
or
results
expressed
or
implied
by
such
forward-­‐looking
statements
and
informa-on
to
differ
materially
from
any
future
events
or
results
expressed
or
implied
by
such
statements
and
informa-on
include,
but
are
not
limited
to,
the
risks
and
uncertain-es
that:
we
may
not
be
able
to
successfully
develop
and
obtain
regulatory
approval
for
p97
as
a
Physician’s
Aid
to
Diagnose
Alzheimer’s,
or
future
products
in
our
targeted
corporate
objec-ves;
our
future
opera-ng
results
are
uncertain
and
likely
to
fluctuate;
we
may
not
be
able
to
raise
addi-onal
capital;
we
may
not
be
successful
in
establishing
addi-onal
corporate
collabora-ons
or
licensing
arrangements;
we
may
not
be
able
to
establish
marke-ng
and
the
costs
of
launching
our
products
may
be
greater
than
an-cipated;
we
have
no
experience
in
commercial
manufacturing;
we
may
face
unknown
risks
related
to
intellectual
property
maPers;
we
face
increased
compe--on
from
pharmaceu-cal
and
biotechnology
companies;
and
other
factors
as
described
in
detail
in
our
filings
with
the
Canadian
securi-es
regulatory
authori-es
at
www.sedar.com.
Given
these
risks
and
uncertain-es,
you
are
cau-oned
not
to
place
undue
reliance
on
such
forward-­‐looking
statements
and
informa-on,
which
are
qualified
in
their
en-rety
by
this
cau-onary
statement.
All
forward-­‐looking
statements
and
informa-on
made
herein
are
based
on
our
current
expecta-ons
and
we
undertake
no
obliga-on
to
revise
or
update
such
forward-­‐looking
statements
and
informa-on
to
reflect
subsequent
events
or
circumstances,
except
as
required
by
law.

3. TSX.V:
BTI
Who
We
Are…
• Our
patented
“Transcend
Family”
of
technologies
allows
proven
and
experimental
drug
therapies
to
penetrate
the
blood-­‐brain
barrier
(BBB)
and
offer
poten-al
treatments
for
diseases,
such
as,
but
not
limited
to:
• Brain
Cancers
• Neurodegenera-ve
Diseases
• Lysosomal
Storage
Diseases
• The
“Transcend
Family”
is
a
Market
Leading
technology
in
BBB
transport
• New
therapeu-c
en--es
based
on
the
Transcend
Family
may
offer
hope
for
pa-ents
while
providing
value
to
industry
thru
extending
the
patent
life
of
numerous
blockbuster
drugs
• Several
drug
development
programs
are
currently
underway

4. TSX.V:
BTI
The
Blood-­‐Brain
Barrier
Challenge
• The
blood-­‐brain
barrier
(BBB)
safeguards
the
400+
miles
of
capillaries
and
blood
vessels
in
the
brain
which
carry
20%
of
the
body’s
blood
flow
• While
cancers
origina-ng
in
the
brain
are
fewer
than
in
other
regions
of
the
body,
10x
as
many
people
develop
brain
tumors
from
cancers
that
begin
elsewhere
in
the
body
(metasta-c)1
• However,
the
BBB
totally
stymies
modern
cancer
therapies
that
work
effec-vely
elsewhere
in
the
body
by
blocking
98%
of
small
molecule
drugs
and
virtually
100%
of
large
molecule
drugs1
• Crea-ng
a
‘carrier’
to
deliver
these
proven
cancer
treatments
through
the
BBB
could
not
only
save
lives,
it
could
extend
the
patent
life
of
many
of
exis-ng
drug
therapies
1) Royal
Society
of
Chemistry
The
BBB
consists
of
endothelial
cells
lining
the
blood
vessels
in
the
brain.
In
sharp
contrast
to
blood
vessels,
this
thin
layer
of
‘fortress
cells’
are
bound
together
so
-ghtly,
there
are
no
gaps
for
blood-­‐borne
materials
to
leak
into
the
brain.

5. TSX.V:
BTI
How
We
Address
this
Opportunity:
Our
Breakthrough
Solu-on
-­‐
Transcend
• Transcend
is
based
on
Melanotransferrin
(aka
“MTf”
or
“p97”),
an
endogenous
protein
that
is
ac-vely
transported
across
the
BBB
–
Transcendpep
is
a
family
of
pep-des
origina-ng
from
Transcend
offering
improved
brain
penetra-on
over
Transcend
-­‐
the
“Transcend
Family”
• The
Transcend
Family
can
uniquely
‘piggy
back’
conjugated
or
fusion
drugs
and
using
Receptor
Mediated
Transcytosis,
deliver
them
into
the
brain
• Transcend
Family
conjugates
may
have
improved
PK
and
biodistribu-on,
as
well
as
a
bePer
side
effect
profile
than
the
parent
drug
alone
• Transcend
Family
conjugates
&
fusions
may
be
designed
in
order
to
make
the
combined
therapeu3c
inac3ve
in
the
blood
un3l
processed
intracellularly
by
targeted
brain
cells
and
released
as
ac3ve
inside
the
cells
Melanotransferrin
(MTf)
Protein
Transcend
Conjugate
Transcend
in
Ac-on
Receptor
Mediated
Transcytosis
BBB

6. TSX.V:
BTI
Melanotransferrin
(Transcend)
First
iden-fied
as
cell
surface
marker
associated
with
human
skin
cancer
–
p97
Melanoma-­‐Associated
An-gen
• Belongs
to
a
group
of
iron
binding
proteins
transferrin,
lactoferrin,
ovotransferrin
(Rose
et
al.,
1985).
Shares
40%
sequence
iden-ty
with
human
lactoferrin
• 2
forms:
GPI
anchor
and
soluble
(Food
et
al.,
1994)
• Expressed
in
an
array
of
normal
-ssue,
brain
capillary
endothelial
cells,
and
reac-ve
microglia
associated
with
Aβ
plaques
in
brain
-ssues
from
AD
pa-ents
(Jefferies
et
al.,
1995;
Rothenberger
et
al.,
1995)

7. TSX.V:
BTI
Biodistribu-on
of
the
Transcend
Vector
to
the
Brain
Following
IV
Administra-on
in
Mice
This
analysis
indicated
that
there
could
be
Species
Specific
factors
in
play
hMTf
=
Human
Transcend
–
mMTf
=
Mouse
Transcend
0%
1%
2%
3%
4%
5%
6%
7%
8%
9%
0
5
10
15
20
25
30
%ID/g
BM
Time
%
Injected
Dose
in
the
Brain
hMTf
mMTf

8. TSX.V:
BTI
Transcend
is
Rapidly
Taken
up
by
the
Brain
Drug
Brain
Kin
(ml/s/g)
Reference
Glucose
9.5
x
10-­‐3
Smith
(2003)
Transcend
6.4
x
10-­‐4
Demeule
et
al.
(2002)
Morphine
2.0
x
10-­‐4
Cisternino
et
al.
(2001)
Apro-nin
*1
1.6
x
10-­‐4
Demeule
et
al.
(2008)
Insulin
Rec
An-body
*2
1.0
x
10-­‐4
Pardridge
(1997)
Leu-­‐Enkephalin
6.0
x
10-­‐5
Zlokovic
(1987)
Morphine-­‐6-­‐Glucuronide
2.4
x
10-­‐5
Temsamani
et
al.
(2005)
RAP
*3
1.0
x
10-­‐5
Pan
(2004)
Beta
Amyloid
6.5
x
10-­‐6
Banks
(1991)
DADLE
6.5
x
10-­‐6
Chen
(2002)
TNF-­‐α
4.3
x
10-­‐6
Pan
(2002)
Transport
Efficiency
More
Less
In
situ
brain
uptake
–
measurement
of
rate
of
transport
1. Angiochem
2. Armagen
Technoologies
3. Raptor
Pharmaceu-cals

9. TSX.V:
BTI
βA mAb-cy5.5 (60x)
Transcend-cy5.5 (20x) Transcend-cy5.5 (60x)§ Transcend
CONJUGATED TO
CY5.5
§ CAPILLARIES STAINED
WITH VESSEL GREEN
(FITC-LECTIN)
§ NUCLEI OF BRAIN
CELLS STAINED WITH
DAPI BLUE
Transcend-cy5.5 is localized in the brain
parenchyma in contrast to mAb against
β amyloid peptide which do not cross
efficiently the BBB and is mostly seen
associated to brain capillaries
In Capillaries
In Parenchyma
In Parenchyma
Transcend-­‐cy5.5
Located
in
the
Brain
Parenchyma
(2h
Post
IV
Injec-on)

10. TSX.V:
BTI
Transcend-­‐Rhodamine
Localizes
in
Brain
Neuron
Lysosomes
(2h
Post
IV
Injec-on)
Transcend is
associated with a
lysosomal
compartment in
neurons as shown
with co-staining of
NeuN and
cathepsin B
Lysosome in
neuron
localization
Transcend
Vessels
Cathepsin B
NeuN

11. TSX.V:
BTI
Our
Transcend
Planorm
Offers
Mul-ple
Development
Opportuni-es
We
have
conjugated
therapeu-c
compounds
that
include
an-bodies,
enzymes,
other
biologics
and
small
molecules
to
the
Transcend
Family
that
target:
a) Specific
brain
cells
(e.g.,
neurons,
astrocytes
and
tumors)
b) Certain
intracellular
compartments
(e.g.,
lysosomes,
endosomes,
cytoplasm
and
nuclei)
c) Delivery
into
the
brain
of
exis3ng
therapeu-c
drugs
currently
not
approved
for
central
nervous
system
(CNS)
indica-ons
d) Delivery
into
the
brain
of
promising
new
agents
in
development
….
and
offer
patent
term
extension
of
exis-ng
drugs
through
crea-on
of
NCEs,
combining
the
Transcend
Family
with
generic
agents
or
those
about
to
lose
exclusivity

12. TSX.V:
BTI
Chronic
Neurodegenera-ve
Disorders
• Many
biologics
in
development,
require
delivery
• Disease
modifica-on
need
is
unmet
by
current
drugs
• Direct
costs
of
trea-ng
Alzheimer’s
will
total
an
es-mated
$203
billion
in
the
US
in
2013
Stroke
&
Trauma-c
Brain
Injury
• BBB
disrupted
in
first
few
hours
but
is
intact
in
the
recovery
phase
• Clinical
need
is
unmet
by
current
drugs
• History
of
failure
of
neuro-­‐
protec-ve
drugs
in
clinical
trials
• The
direct
costs
of
medical
care
and
therapy
in
the
US
are
es-mated
at
$28
billion
per
year.
Lysosomal
Storage
Diseases
(LSD)
with
CNS
Involvement
• Niche
indica-ons,
but
lucra-ve
• Relevant
drugs
do
not
cross
BBB
• Clinical
need
unmet
by
current
drugs
•
Elaprase
treatment
for
MPSII
costs
~375,000
per
year
• Annual
US
sales
in
2012
were
$498
million
Infec-on
(Bacterial,
Viral,
Fungal)
• In
most
cases
clinical
need
is
well
met
by
current
drugs
• BePer
BBB
penetra-on
could
make
make
a
significant
difference
in
certain
infec-ons
Psychiatry
• Most
drugs
cross
the
BBB
and
the
clinical
need
is
generally
well
met
• Injec-ons
are
problema-c
for
most
chronic
indica-ons
Oncology
• Clinical
need
is
unmet
by
current
drugs
• Many
drugs
do
not
cross
the
BBB
• Large
market
opportunity
• Market
for
biological
therapies
for
cancer
is
expected
to
reach
$53.7
billion
in
2014.
Pain
&
Migraine
•
Latest
genera-on
drugs
have
limited
BBB
penetra-on
• In
2012
the
total
cost
for
pain
in
the
United
States
ranged
from
$560
to
$635
billion
Mul-ple
Opportuni-es
for
Transcend
Across
a
Range
of
Therapeu-c
Areas

13. TSX.V:
BTI
Current
&
Future
Brain
Opportuni-es
-­‐
Diseases
to
be
Treated
Crossing
the
BBB
Would
be
the
Most
Effec-ve
Method
to
Treat
These
Condi-ons;
Poten-al
Annual
Market
Value,
Greater
than
$50B
• Brain
cancers
10,000
new
cases
diagnosed
with
glioblastomas
annually
in
US
>200,000
new
cases
diagnosed
with
brain
metastasis
annually
in
US
• Chemotherapeu-cs
and
small
drugs
• MAbs
against
HER,
EGFR,
VEGF,
etc…
• siRNA
• Neurodegenera-ve
diseases
(AD,
PD,
MS,
ALS,
HD,…)
4M
cases
of
AD
in
2003
in
US,
exponen-al
growth
with
14M
of
AD
by
2025
• Neurotrophic
Factors
• Small
Drugs
• siRNAs
• Monoclonal
an-bodies
against
an--­‐No
Go
an-bodies
(MS),
an-
Ab
pep-des
and
an-
BACE-­‐1
(AD)
• Pep-des
• Obesity
• Neurotrophic
Factors
• Pep-des
• Rare
Gene-c
Diseases
(MPSI,
II,
III)
• Lysosomal
enzymes
such
as
IDU,
IDS
or
sulphamidases
• Infec-ous
Diseases
(AIDS,
meningi-s,
encephili-s…)
• An-bio-cs
• An--­‐HIV
• Psychiatric
Diseases
• Small
drugs
• Pain
Therapy
• Small
drugs
• Pep-des
13

14. TSX.V:
BTI
Market
Opportunity
for
Brain
Cancer
Treatment
• Brain
metastases
occur
in
20%-­‐40%
of
pa-ents
with
systemic
cancer,
30%-­‐40%
present
with
a
single
metastasis
1-­‐2
• Adjuvant
value
for
Oncology
(Metasta-c
Breast
Cancer)
–
Current
market
for
Transcend
is
greater
than
$6
billion
• 13,000
people
die
from
cancerous
brain
tumors
annually
in
the
U.S.3
• Global
brain
tumor
treatment
therapies
market
forecasted
to
grow
11%
annually
over
the
next
five
years
to
$2.1
billion
by
20174
• Small
molecule
therapeu-cs
can
be
designed
to
be
inac-ve
in
blood,
but
retain
their
full
ac-vity
once
released
in
the
intracellular
compartment
of
brain
tumor
cells
1) Cairncross
JG,
Kim
JH,
Posner
JB.
Radia-on
therapy
for
brain
metastases.
Ann
Neurol
1980;
7:
529–41.
2) Lohr
F,
Pirzkall
A,
Hof
H,
Fleckenstein
K,
Debus
J.
Adjuvant
treatment
of
brain
metastases.
Semin
Surg
Oncol
2001;
20:
50–56.
3) The
New
York
Times
4) GlobalData
“Brain
Tumor
–
Pipeline
Assessment
and
Market
Forecasts
to
2017”
released
Jan.
17,
2011.
$0.9B
$2.1B
2009
2010
2011
2012
2013F
2014F
2015F
2016F
2017F
($
Billions)
Global
Brain
Tumor
Therapies
Market

15. Applica-ons
of
Transcend
&
Transcendpep
Ac?ve
Program:
Delivery
of
Enzymes
to
Treat
LSD’s
Delivery
of
mAbs:
Alzheimer’s
Delivery
of
Small
Drugs
–
Cancer
Ac?ve
Program:
Cancer
Trastuzumab
Delivery
of
siRNA

16. TSX.V:
BTI
Ac-ve
Development
Program:
Lysosomal
Storage
Diseases
• Lysosomal
Storage
Diseases
(LSDs)
comprise
a
large
group
of
rare
inherited
metabolic
disorders
arising
from
an
enzyme
deficiency
• Approximately
50
LSDs
have
been
described
including
Tay
Sachs
Disease,
Fabry
Disease,
Gaucher’s
Disease,
Hunter
syndrome
and
mucopolysaccharidosis
(MPS)
• The
disorders
affects
children
many
of
whom
suffer
and
die
within
several
years
of
birth
Lysosomal
Storage
Disease
(LSD)

17. TSX.V:
BTI
Enzyme
Replacement
Therapy
(ERT)
• There
are
no
cures
for
LSDs.
• Most
effec-ve
therapeu-c
strategy
is
enzyme
replacement
therapy
(ERT)
in
which
intravenous
delivery
of
the
deficient
enzyme
is
used
in
an
aPempt
to
ameliorate
symptoms
in
pa-ents
with
certain
LSDs.
• Costs
of
ERT
are
extremely
high,
ranging
$90,000
to
$720,000
per
pa-ent
annually.
• Because
of
the
blood-­‐brain
barrier,
current
ERT
is
unable
to
restore
enzyme
func-on
in
the
brain
and
therefore
does
not
address
the
neurological
symptoms
associated
with
LSDs.

18. TSX.V:
BTI
Hurler
Syndrome
-­‐
MPS
I
Lysosomal
Storage
Disease
• Rare
inherited
gene-c
disorder
• MPS
I
is
caused
by
a
deficiency
of
α-­‐L-­‐iduronidase
(IDU)
• IDU
deficiency
results
in
accumula-on
of
GAGs
in
the
lysosome
resul-ng
in
cell
death
• ERT
can
treat
the
peripheral
effects
of
the
disease
but
the
BBB
prevents
CNS
treatment
resul-ng
in
progressive
mental
retarda-on

19. TSX.V:
BTI
Dose-­‐Dependent
Increase
in
Brain
Enzyme
Ac-vity
• Dose-­‐Dependent
Increase
in
Brain
Enzyme
Ac-vity
in
MPS
I
Knockout
Mice
With
Transcend-­‐IDU
Administered
IV
• Conjuga-on
to
Transcend
restores
IDU
brain
enzyme
ac-vity
towards
wild
type
levels
in
a
dose-­‐dependent
fashion
0
0.2
0.4
0.6
0.8
1
1.2
IDU)
Transcend-­‐IDU
Total
IDU
ac-vity
Capillaries
Parenchyma
MPS
I
Ac-vity

20. TSX.V:
BTI
Non-­‐Conjugated
Lysosomal
EnzymeAF647
in
Brain
Sec-ons
1
Unit
=
23.9
µm
Blue:
Nuclei
Green:
Capillaries
Red:
Lysosomal
EnzymeAF647

21. TSX.V:
BTI
MTf-­‐dpIDSAF647
1
Unit
=
23.9
µm
Transcend-­‐Lysosomal
EnzymeAF647
Conjugate
in
Brain
Sec-ons
Blue:
Nuclei
Cyan:
Capillaries
Pink:
Transcend-­‐
EnzymeAF647
Conjugate
1
Unit
=
23.9
µm
LAMP-­‐1
staining
and
lipofuscin
fluorescence
indicates
that
the
Transcend-­‐Enzyme
conjugates
are
localized
with
the
lysosomal
compartment

22. TSX.V:
BTI
Rela-ve
Increase
of
Lysosomal
Enzyme
in
Brain
0
5
10
15
20
25
Enzyme
Alone
Transcend-­‐Enzyme
Parenchyma
Fold
Increase
over
enzyme

23. TSX.V:
BTI
Enzyme
Replacement
Therapy
for
Lysosomal
Storage
Diseases
in
the
CNS
§ 40%
to
60%
of
the
Transcend-­‐Lysosomal
Enzymes
conjugates
(determined
from
AF647)
in
the
brain
was
located
in
the
parenchyma
with
the
remainder
in
the
capillaries
§ Conjuga-on
of
the
Enzymes
to
Transcend
resulted
in
a
8
to
10
fold
increase
in
the
volume
frac-on
of
the
Enzymes
in
the
brain
parenchyma
§ The
consequence
of
the
Transcend-­‐Enzyme
conjuga-ons
and
M6P
dephosphoryla-on
was
addi-ve
and
highly
significant
§ Greater
than
40%
of
lipofuscin
(lysosomes)
was
associated
with
the
Enzymes
when
administered
as
a
conjugate
of
Transcend
§ Less
than
18%
of
lipofuscin
was
associated
with
the
Enzymes
when
not
conjugated
to
Transcend
§ Confirms
that
Enzymes
conjugated
to
Transcend
co-­‐localizes
within
the
lysosome
within
the
brain
parenchyma
Summary

24. TSX.V:
BTI
Enzyme
Replacement
Therapy
for
Lysosomal
Storage
Diseases
in
the
CNS
• biOasis’s
Transcend
vector
can
deliver
lysosomal
enzymes
from
the
blood,
across
the
blood-­‐brain
barrier
and
into
brain
-ssue
• Conjuga-on
to
Transcend
restores
IDU
brain
enzyme
ac-vity
in
IDU-­‐deficient
mice
towards
wild
type
levels
in
a
dose-­‐dependent
fashion
• Conjuga-on
with
Transcend
results
in
a
marked
transport
of
lysosomal
enzymes
from
the
blood
into
CNS
lysosomes
• Transcend
offers
the
promise
of
an
enzyme
replacement
therapy
to
ameliorate
CNS
pathology
associated
with
Lysosomal
Storage
Diseases
Lysosomal
Membrane
Proteins
Summary
con’t…

25. TSX.V:
BTI
Development
Program:
Alzheimer's
Disease
Delivery
of
An--­‐Amyloid
Beta
An-body
Conjuga-on
of
An--­‐Aβ-­‐pep-de
an-body
to
Transcend
increases
transport
into
brain
parenchyma
by
~5-­‐fold
This
increase
of
transport
may
result
in
a
therapeu-c
concentra-on
in
brain
0.000#
0.001#
0.002#
0.003#
0.004#
0.005#
0.006#
0.007#
Transcend3an43AB#mAb# an43Ab#mab#
Volume'Frac,on'''
Parenchyma#
Image
Analysis
by
Laser
Scanning
Confocal
Microscopy

26. TSX.V:
BTI
Delivery
of
Doxorubicin
for
Treatment
of
Primary
&
Metasta-c
Brain
Cancers
• Doxorubicin
is
commonly
used
in
the
treatment
of
a
wide
range
of
cancers,
including
hematological
malignancies,
many
types
of
carcinoma,
and
sov
-ssue
sarcomas
• Doxorubicin
is
available
in
a
liposome-­‐encapsulated
form
as
Doxil,
which
used
primarily
for
the
treatment
of
ovarian
cancer
or
AIDS-­‐related
Kaposi's
sarcoma
• Doxorubicin
could
be
be
highly
effec-ve
for
trea-ng
brain
tumors
if
it
could
be
delivered
into
the
brain
• Doxorubicin
is
excluded
from
the
brain
because
it
is
recognized
by
the
mdr-­‐1
protein
at
the
BBB
• Also,
its
most
serious
adverse
effect
is
life-­‐
threatening
heart
damage
Doxorubicin
(Adriamycin®)

27. TSX.V:
BTI
Transcend-­‐ADR
Conjugate
Enhances
Doxorubicin
Transport
into
the
Brain
• Covalent
Linkage
• Stable
in
Plasma
—
Half-­‐life
of
8
hours
• Bioconjugates
inac-ve
in
blood
but
Doxo
retains
full
ac-vity
once
released
in
the
intracellular
compartment
of
brain
tumor
cells
• Significant
INCREASE
in
brain
uptake
with
the
Transcend
Vector
vs.
Doxo
on
its
own
0.00
1.00
2.00
3.00
Transcend-­‐Doxo
Doxo
%
INJECTED
DOSE
(G
TISSUE/G
BODY
MASS)*100%
Transcend
Significantly
Enhances
Doxorubicin
Transport
into
the
Brain

28. TSX.V:
BTI
Transcend
Significantly
Reduces
Doxorubicin
Transport
into
the
Heart
With
Doxo’s
most
serious
adverse
effect
being
life-­‐threatening
heart
damage,
Transcend
vs
Doxo
on
its
own
showed
a
significant
DECREASE
in
uptake
to
the
heart
0.0
5.0
10.0
15.0
20.0
Transcend-­‐Doxo
Doxo
%
INJECTED
DOSE
(gram
brain
-ssue/gram
body
mass)*100

29. TSX.V:
BTI
Transcend-­‐DOXO
Conjugate
Achieves
Therapeu-c
Levels
in
the
Brain
Increase
survival
of
treated
nude
mice
implanted
IC
with
ZR-­‐75-­‐1
mammary
tumor
cells.
Increase
survival
of
treated
nude
mice
implanted
IC
with
C6
glioma
cells
Injec-on
Schedule
• Study
Performed
at
the
Southern
Research
Ins-tute
–
Alabama
• Showed
the
Transcend
Vector
delivered
a
therapeu-c
dose
of
Doxo
in
the
Brain

30. TSX.V:
BTI
Ac-ve
Development
Program
Hercep-n®
(trastuzumab)
• This
humanized
monoclonal
an-body
interferes
with
the
HER2/neu
receptor
(regulates
cell
growth,
survival,
migra-on
and
differen-a-on)
• Greater
than
30%
of
breast
cancers
overexpress
HER2
(HER2+)
causing
breast
cells
to
reproduce
uncontrollably
• One-­‐year
course
of
Hercep-n
treatment
costs
~$70,000
and
annual
global
sales
are
~$6
billion
• Hercep-n
increases
pa-ent
survival
in
late-­‐
stage
metasta-c
breast
cancer,
but
~30%
develop
breast
cancer
metastasis
in
the
brain
• Hercep-n
does
not
cross
the
blood-­‐brain
barrier
Hercep-n®
is
a
registered
trademark
of
Roche/Genentech
Hercep-n:
How
it
works

31. TSX.V:
BTI
Hercep-n-­‐Transcend
(research
code
BT2111)
to
Treat
Brain
Metastases
of
Breast
Cancer
• Preclinical
studies
are
being
conducted
with
Transcend
conjugated
to
Hercep-n
using
heterobifunc-onal
protein
crosslinkers
followed
by
purifica-on
of
heterodimer
enriched
frac-on
• In
vivo
ac-vity
of
the
conjugate
was
assessed
in
a
number
of
HER2+
breast
cancer
cell
lines
• For
in
vivo
an
ex
vivo
studies
involving
microscopic
visualiza-on
and
measurement
of
distribu-on
of
the
conjugated
molecule
in
the
brain,
prior
to
conjuga-on,
Hercep-n
is
labeled
with
a
fluorescent
dye
or
with
radioac-ve
iodine
Hercep-n-­‐TranscendBT2111

32. TSX.V:
BTI
Hercep-n
&
Hercep-n-­‐TranscendBT2111
Halt
Tumor
Growth
BT474
HER2/neu
Over-­‐Expressing
Tumor
Xenogra{
Model
• 40
six
to
eight
week
old
female
athymic
nude
mice
inoculated
subcutaneously
with
1x107
BT474
cells
• Mice
dosed
subcutaneously
with
estradiol
twice
a
month
• Tumor
size
was
determined
using
the
formula
length
(mm)
x
width
(mm)
x
depth
(mm)
x
0.52
• Treatment
with
test
ar-cles
began
when
tumors
reached
a
size
of
50
to
100
mm3
• Test
ar-cles
were
administered
via
intraperitoneal
injec-on
twice
weekly
for
40
days
(5
weeks)
and
tumor
size
measured
BT2111
&
Hercep-n®
Halt
Growth
of
BT474
HER2/neu
Over-­‐Expressing
Tumors
25
50
75
100
125
150
175
200
225
Day
0
Day
10
Day
20
Day
30
Day
40
Day
50
Tumor
Size
(mm3)
PBS
Hercep-n
BT2111
BT2111
–
Benign
Toxicity
Profile
• Female
athymic
nude
mice
were
treated
with
BT2111
(18.5
mg/kg,
IP,
biweekly
for
five
weeks)
• No
test-­‐ar-cle
related
effects
on
body
weight
• No
test-­‐ar-cle
related
clinical
signs
of
toxicity
• No
test
ar-cle-­‐related
histopathology
findings
(selected
organs)

33. TSX.V:
BTI
Hercep-n-­‐TranscendBT2111
Localiza-on
in
Brain
Brain
Capillaries
Nuclei
BT2111:
Hercep-n®-­‐
Transcend
Confocal Image Performed by iCapture at St. Paul’s
Hospital Vancouver Canada
Confocal
Images
Two
Hours
Post
IV
Administra-on
Data
at
2
Hours
Post
IV
Administra-on
0.0E+00
5.0E-­‐04
1.0E-­‐03
1.5E-­‐03
MTf-­‐Hercep-n
2h
Hercep-n
2h
Volume
Frac-on
Fluorescence
Localized
to
Brain
Parenchyma
Work
performed
at
Na-onal
Research
Council
of
Canada
–
Research
Facility
Hercep-n-­‐TranscendBT2111
Localizes
in
Brain
Parenchyma

34. TSX.V:
BTI
Frozen
Brain
Sec-on
Analyzed
Using
Immunofluorescent
Staining
&
Autoradiography
Hercep-n-­‐TranscendBT2111
Distribu-on
in
Brain
and
Breast
Cancer
Tumors
Mouse
Model
of
Breast
Cancer
Metastasis
to
Brain
• Images
to
the
right
show
quan-fica-on
of
Hercep-n-­‐
TranscendBT2111
taken
up
in
brain
parenchyma
and
in
metastasis
• Demonstra-ng
poten-al
therapeu-c
concentra-on
• Histopathology
analysis
of
-ssue
samples
showed
no
Toxicity
in
Brain
and
other
organs
within
the
body
Time
Point
2hr
Post
IV
Injec-on
72.9ng/g
48.4ng/g
109.2ng/g
66.8ng/g
131.7ng/g
142.6ng/g
110.2ng/g
25.1ng/g
Preferen-al
uptake
of
radio
labeled
BT2111
into
tumors
compared
with
BDT
Calculated
concentra-ons
of
BT2111
within
brain
regions
Breast
cancer
metastasis
distributed
throughout
the
brain
Brain
-ssue
distal
to
tumors
(BDT)

35. TSX.V:
BTI
Hercep-n-­‐TranscendBT2111
and
Hercep-n
Uptake
into
Brain
&
Brain
Metastasis
of
Breast
Cancer
0.E+00
2.E-­‐06
4.E-­‐06
6.E-­‐06
8.E-­‐06
1.E-­‐05
1.E-­‐05
Trastuzumab
BT2111
Kin
(mL/s/g)
BDT
Tumor
Not
only
was
the
uptake
in
brain
of
Hercep-n-­‐TranscendBT2111
significantly
higher
than
Hercep-n
alone,
but
the
uptake
into
the
tumors
where
drama-cally
higher

36. TSX.V:
BTI
Brain
Metastasis
of
HER2+
Breast
Cancer
0
10
20
30
40
50
60
70
80
90
100
MTf
Trastuzumab
BT2111
Saline
Control
By
Number
of
Tumors
0.0
0.5
1.0
1.5
2.0
2.5
MTf
Trastuzumab
BT2111
Saline
Control
By
Mean
Tumor
Volume
n=20
in
each
group

37. TSX.V:
BTI
Hercep-n-­‐TranscendBT2111
Brain
Uptake
&
Efficacy
Summary
• Hercep-n-­‐TranscendBT2111
Uptake
into
Breast
Cancer
Metastasis
in
the
Brain
• Hercep-n-­‐TranscendBT2111
distributes
to
brain
and
brain
metastases
with
a
significant
uptake
into
the
tumors
demonstra-ng
blood
tumor
barrier
penetra-on
• Hercep-n-­‐TranscendBT2111
in
vivo
Efficacy
in
Breast
Cancer
Models
• Mouse
xenograv
Model
• Hercep-n-­‐TranscendBT2111
completely
prevents
breast
HER2+
cancer
tumor
growth
• Mouse
model
of
brain
metastasis
of
breast
cancer
• Hercep-n-­‐TranscendBT2111
reduced
the
number
of
HER2+
breast
cancer
tumors
in
brain
by
68%.
The
tumors
that
remained
aver
treatment
were
57%
smaller
than
those
in
the
Hercep-n
treated
animals

39. TSX.V:
BTI
Transcendpep-­‐mAbAF647
Transcendpep
are
a
number
of
small,
under
20
amino
acid
sequence
pep-des,
found
within
Transcend
(MTf)
which
we
discovered
aver
many
years
of
research
We
have
conjugated
Transcendpep
to
a
number
of
fluorescently
labeled
mAbs,
enzyme
and
siRNA
all
showing
equal
to
or
greater
transport
than
the
full
length
MTf-­‐
Transcend
protein
itself
This
confocal
image
prepared
by
the
Na-onal
Research
Counsel
of
Canada,
clearly
shows
the
mAb
(red)
has
been
transported
across
the
BBB
and
localizing
around
the
neurons
(blue)

40. TSX.V:
BTI
Transcendpep-­‐mAbAF647
-­‐1.0E-­‐03
1.0E-­‐17
1.0E-­‐03
2.0E-­‐03
3.0E-­‐03
4.0E-­‐03
5.0E-­‐03
mAb
MTfpep
MTfpep-­‐mAb
Volume
Frac-on
Capillaries
Parenchyma
Total
Mean
±
SE
Brain
Capillary
Parenchyma
And total Alexa 647

41. TSX.V:
BTI
Transcendpep-­‐mAbAF647
• mAb-­‐AF647
does
not
cross
effec-vely
the
BBB
as
determined
by
its
low
distribu-on
in
the
brain
parenchyma
• Transcendpep
(MTf
pep-des)
tagged
with
AF647
(MTfpep-­‐AF647)
efficiently
crosses
the
BBB
and
distributes
into
the
brain
parenchyma
• Conjuga-on
of
the
MTfpep
to
mAbs-­‐AF647
increases
the
an-body
transport
across
the
BBB
to
the
brain
parenchyma
(by
~5
fold)
as
efficiently
as
the
en-re
MTf-­‐Transcend
protein
itself

42. TSX.V:
BTI
siRNAAF680
Will
Not
Cross
the
BBB
Lectin-Texas Red
AF680Composite

43. TSX.V:
BTI
Transcendpep
is
Able
to
Deliver
siRNAAF680
Across
the
BBB
Lectin-Texas Red
AF680Composite

44. TSX.V:
BTI
Summary
–
Na3onal
Research
Counsel
of
Canada
• siRNAAF680:
Perinuclear
AF680
signal
was
not
detected
in
the
brain
parenchyma
of
any
mice
(n=7).
No
AF680
signal
was
observed
in
the
vasculature.
• siRNAAF680-­‐Transcendpep:
Perinuclear
AF680
signal
was
detected
in
the
brain
parenchyma
of
all
mice
(n=7).
Very
low
AF680
signal
was
observed
in
the
vasculature.
Transcendpep
is
able
to
deliver
siRNA
across
the
BBB
in
brain
parenchyma
cell’s
intracellular
compartment
Transcendpep-­‐siRNAAF680

45. TSX.V:
BTI
Transcend
has
A}racted
a
Number
of
Development
Programs
• Several
drug
development
programs
are
underway
with
leading
drug
companies
• Neurodegenera-ve
Diseases
(Alzheimer’s)
• Metabolic
Diseases
(Lysosomal
Storage
Diseases)
• Oncology
(Metasta-c
Breast
Cancer)
• Four
strategic
collabora-ons
are
underway
or
have
been
completed
with
world-­‐leading
pharmaceu-cal
companies
inves-gated
the
use
of
the
Transcend
Family
with
their
target
therapeu-c
compounds

46. TSX.V:
BTI
Business
Strategy
Our
overall
business
strategy
can
be
summarized
as
follows:
• Obtain
independent
3rd
party
valida-on
of
the
Transcend
Family
• Expand
and
protect
our
Intellectual
Property
por~olio
• Advance
development
of
our
Brain
Oncology
&
LDS
programs
thru
preclinical
studies
and
move
to
the
clinic
• Collaborate
through
research
licenses
with
reputable
Pharmaceu-cal
companies
that
are
interested
in
the
poten-al
of
u-lizing
the
Transcend
Family
as
a
pla~orm
to
deliver
their
targeted
therapeu-cs
across
the
BBB

47. TSX.V:
BTI
Key
Takeaways
• The
Transcend
Family
is
a
unique
brain
drug
delivery
pla~orm
with
large
market
opportuni-es
• An
array
of
biologic
and
small
molecule
therapeu-cs
can
be
linked
and
delivered
into
the
brain
with
the
Transcend
Family
• Transcend
Family
Conjugates
are
rapidly
transported
from
the
circula-on
into
brain
parenchyma
–
no
apparent
limita-on
in
size
or
class
of
therapeu-c
agent
• Proof
of
principle
demonstrated:
• Delivery
of
an-bodies
against
Aβ
pep-de
for
the
treatment
of
Alzheimer’s
disease
• Delivery
of
lysosomal
enzymes
into
brain
as
poten-al
therapies
for
Lysosomal
Storage
Disorders
• Delivery
of
monoclonal
an-bodies
into
the
brain
for
treatment
of
brain
cancers
The
Transcend
Family
may
address
major
unmet
medical
needs
in
the
area
of
central
nervous
system
diseases
&
disorders
BBB

48. TSX.V:
BTI
Publica-ons
Samples
PLoS
One:
A
Unique
Carrier
for
Delivery
of
Therapeu-c
Compounds
beyond
the
Blood-­‐Brain
Barrier
Journal
of
Neurochemistry:
hPp://onlinelibrary.wiley.com/doi/10.1046/j.1471-­‐4159.2002.01201.x/abstract
Nature
Gene
Therapy:
Direc-ng
adenovirus
across
the
blood–brain
barrier
via
melanotransferrin
(P97)
transcytosis
pathway
in
an
in
vitro
model
hPp://www.nature.com/gt/journal/v14/n6/abs/3302888a.html
PubMed
Iden-fica-on
of
a
Novel
Route
of
Iron
Transcytosis
across
the
Mammalian
Blood–Brain
Barrier
hPp://www.ncbi.nlm.nih.gov/pubmed/14745458
Journal
of
Neurochemistry,
924–933
High
transcytosis
of
melanotransferrin
(P97)
across
the
blood–brain
barrier
hPp://www.ncbi.nlm.nih.gov/pubmed/12421365

49. TSX.V:
BTI
Team
Rob Hutchison
Founder
Chairman & CEO
Christian Fibiger, PhD
Former CSO, Biovail Laboratories
Former head Neuroscience
Amgen & Eli Lilly
Wilf Jefferies, PhD
Founding Scientist
Ron Erickson
Visualant Inc
Chairman & CEO
Reinhard Gabathuler, PhD
Chief Scientist
Terry Pearson, PhD
Professor University of Victoria
Mei Mei Tian
Sr. Scientist
Michael Hutchison, LLB QC
Sr. Partner Smith Hutchison
Greg Gubitz, LLB
Former Head of Corporate
Development & General Counsel for
Biovail Corporation
Board
of
Directors

50. TSX.V:
BTI
biOasis
Technologies
Inc.
Suite
125-­‐10551
Shellbridge
Way
Richmond
BC
V6X
2W9
Canada
Rob
Hutchison
rob@bioasis.ca
1.778.383.3280
ext
101
Dr.
Reinhard
Gabathuler
Chief
Scien-st
gaba@bioasis.ca
Contact
Us