Edge Corporate Presentation October 2011

1.
Corporate
Presenta,on
October
2011

2. MISSION
Edge
was
founded
under
the
belief
that
site-­‐specific,
sustained-­‐release
delivery
of
medicines
directly
to
the
site
of
brain
injury
will
prevent
certain
delayed
and
life-­‐threatening
condi<ons,
improve
pa<ent
outcomes,
and
decrease
overall
cost
of
care

3. DELAYED
CEREBRAL
ISCHEMIA
(DCI)
Primary
injury,
oEen
caused
by
aneurysm
or
head
trauma,
is
rou<nely
addressed
PRIMARY
EVENT
DAY
1
DAY
3-­‐14
ISCHEMIA
/
NEURONAL
BRAIN
ARTERIES
VASOCONSTRICTION
DEATH
Secondary
injury
(DCI)
is
caused
by
a
complex
biochemical
cascade
leading
to
vasoconstric*on,
ischemia
and,
ul<mately,
neuronal
death
3
|
Source:
American
Heart
Associa<on

4. SUBARACHNOID
HEMORRHAGE
(SAH)
SAH
is
a
silent
epidemic
that
results
in
staggering
direct
and
indirect
costs
to
society.
• Average
age
50
years
old
• 90%
of
pa<ents
arrive
alive
to
the
hospital
• Poor
30-­‐day
prognosis
• Costs
exceed
$25B
annually
for
aneurysmal
SAH
Of patients arriving alive to the hospital…
2 die 2 permanent brain damage 1 resumes normal activity
4
|
4

5. CURRENT
STANDARD
OF
CARE
ACTIVE
AGENT,
POOR
DELIVERY
Oral
nimodipine
(Ac,ve
Systemic
Agent)
• Generic
calcium
channel
blocker
(FDA
approved
in
1989)
rou<nely
given
to
all
pa<ents
• Rinkel
et.
al.
(8
trials
reviewed)
showed
improved
outcome
and
reduced
cerebral
infarc<on
with
minimal
effect
on
angiographic
vasospasm
• Standard
oral
dose
of
nimodipine
is
60
mg
every
4
hours
x
21
days
However…
Dose
is
sub-­‐op,mal
(Poor
Delivery)
• Cerebrospinal
fluid
(CSF)
concentra<on
is
0.4
ng/ml
– CSF
concentra<on
is
at
least
10x
too
low
to
dilate
arteries
• Maximal
plasma
concentra<on
of
about
20
ng/ml
– Dose-­‐limi<ng
hypotension
in
>30%
of
pa<ents
• Hypotension
occurs
at
plasma
concentra<on
>30-­‐40
ng/ml
– Oral
nimodipine
gets
above
this,
yet
CSF
concentra<ons
too
low
5
|

6. EDGE
TECHNOLOGY
AN
ELEGANT
DELIVERY
SOLUTION
Site-­‐specific,
sustained
release
bioabsorbable
poly(D,L-­‐lac*de-­‐co-­‐glycolide)
(PLGA)-­‐
based
micropar*cles
• Handling
characteris<cs
– Minimizes
systemic
side
effects
– Circumvents
blood-­‐brain
barrier
– One-­‐<me
administra<on
• Administered
during/aEer
surgery
– Does
not
require
addi<onal
surgery
or
procedures
to
apply
– Simple
prep/administra<on
does
not
interfere
with
surgery
workflow
– NOT
an
emergency
care
administra<on
• Proven
commercially
feasible
technology
(scaled-­‐up
for
commercial
produc<on)
• Backed
by
strong
IP
poriolio
6
|

7. CONTINUOUS
MICROENCAPSULATION
PROCESS
THRU
FINISHED
PRODUCT
7
|

8. THE
“NIMO”
FRANCHISE
Agent Indication Pre-Clinical Development Phase 2
Formulation
In Vitro In Vivo Clinical
Development
Reduce DCI and improve 30-day
outcome in patients with aSAH
NimoGel* undergoing neurosurgical clipping
(intracisternal)
(EG-1961)
Moderate to severe head
trauma
Reduce DCI and improve 30-day
outcome in patients with aSAH
undergoing endovascular coiling.
NimoVent* (intraventricular)
(EG-1962)
Moderate to severe head
trauma
EG-1964 Chronic subdural hematoma
Post-craniotomy
Spontaneous intracerebral
EG-1960* hemorrhage
Moderate to severe head
trauma
*Denotes: Department of Defense Interest Potential

9. NIMOGEL
F TM
OR
SURGICAL
CLIPPING
• Biodegradable
polymer
encapsula<on
of
nimodipine
(FDA
505
(b)(2)
approval)
and
hyaluronic
acid
(HA)
carrier
• 14
days
release
• Applied
directly
to
the
injury
site
(intracisternally)
during
surgical
clipping
to
secure
the
bleeding
aneurysm
• Designed
to
provide
consistent
and
therapeu<c
concentra<ons
of
nimodipine
to
prevent
DCI
while
minimizing
side
effects
APPLICATION:
To
reduce
delayed
cerebral
ischemia
and
improve
30-­‐day
outcome
in
pa8ents
with
aneurysmal
SAH
undergoing
SURGICAL
neurosurgical
clipping.
CLIPPING
9
|

10. TM
NIMOVENT
F OR
ENDOVASCULAR
COILING
• Biodegradable
polymer
encapsula<on
of
nimodipine
(505
(b)(2)
approval)
and
buffer
• 14
days
release
• Designed
to
reduce
ischemia
deficits
and
improve
outcomes
in
pa<ents
who
undergo
endovascular
coiling
• NimoVent
delivery
is
minimally
invasive
– No
addi<onal
procedure
required
ENDOVASCULAR
– Delivered
in
the
intensive
care
unit
aEer
the
COILING
pa<ent
has
undergone
endovascular
coiling
through
an
exis<ng
intraventricular
catheter
inserted
to
measure
intracranial
pressure
(ICP)
APPLICATION:
To
reduce
delayed
cerebral
ischemia
and
improve
30-­‐day
outcome
in
pa8ents
with
aneurysmal
SAH
undergoing
endovascular
coiling.
10
|

11. DELIVERY
SYSTEM
PROOF
OF
CONCEPT
Site-­‐specific,
Sustained-­‐release
–
Human
Data
Therapeu*c
Doses
Of
Calcium
Channel
Blockers
Improve
Outcome
• Studied
in
252*
pa,ents
in
Japan
and
Germany
(Krischek
2007,
Barth
2007,
Kasuya
2002,
2005,
2011)
– Angiographic
vasospasm
decreased
from
73%
control
to
7%
nicardipine
– Mortality
decreased
from
38%
to
6%
– No
side
effects
• Pellets
not
commercializable,
difficult
to
administer,
cannot
be
injected
into
ventricles
(endovascular
coiling
/
closed
head
injury)
*
Subarachnoid
nicardipine
in
poly(D,L-­‐lac<de
co
glycolide)
(PLGA)
pellets
11
|

12. NIMOGEL
&
NIMOVENT
DELIVERY
PROFILE
• Nimodipine
micropar<cles
(NimoGel
&
NimoVent)
• Nimodipine
in
PLGA
micropar<cles
• Toothpaste-­‐like
gel
to
retain
NimoGel
in
subarachnoid
space,
liquid
NimoVent
allows
diffusion
from
ventricles
to
subarachnoid
space
• Easy
to
administer
for
both
clipped
and
coiled
pa<ents
• Ability
to
scale-­‐up,
easily
sterilized
via
gamma
irradia<on,
stable
12
|

13. EMERGING
TREATMENT
PARADIGM
NIMODIPINE:
A
MULTIPLE
PATHWAY
APPROACH
Subarachnoid
Hemorrhage
Transient Global Subarachnoid
Ischemia Blood
Cortical Oxidative Stress /
Angiographic Microthrombo-
Spreading Inflammation /
Vasospasm embolism
Ischemia Other?
Focal Cerebral Global Cerebral
Infarctions Atrophy
Delayed Cerebral
Ischemia (DCI)
Poor Outcome
13
|

14. PROOF
OF
PRINCIPLE:
STUDY
DESIGN
• Dog
double
hemorrhage
model
of
SAH
• 2
doses
of
NimoVent:
30mg
and
10mg
or
placebo
(vehicle)
formula<on
• Blood
was
injected
into
the
cisterna
magna
(Day
0
and
Day
2)
• Dogs
underwent
angiography
on
days
0,
7
and
14
• Endpoints:
angiographic
vasospasm,
behavior,
serum
and
CSF
nimodipine
concentra<ons,
pathology
Day
0
Day
7
14
|

15. PROOF
OF
PRINCIPLE
STUDY
THERAPEUTICS
LEVELS
TO
THE
BRAIN;
LOW
SYSTEMIC
LEVELS
Efficacy
Results:
Safety
Results:
• 30
mg
NimoVent
prevented
vasospasm
at
• Serum
concentra<ons
were
higher
in
30
mg
day
7
and
at
day
14
dose
compared
to
10
mg
dose
– CSF
concentra*ons
were
more
than
• Serum
(30
mg
and
10
mg
dose)
showed
highest
200
ng/ml
concentra<ons
on
day
2
(8
ng/ml
and
4
ng/ml)
• No
local
inflamma<on
or
other
signs
of
– Hypotension
occurs
at
plasma
neurotoxicity
were
observed
concentra*on
>
30-­‐40
ng/ml
Average
of
4
blinded
reviewers
%
change
from
baseline
(diameter
of
cerebral
basilar
artery)

16. PHASE
2
STUDY
 FDA
confirmed
505(b)(2)
path
for
NimoGel:
Relevance
is
NimoGel
can
refer
to
prior
toxicity
studies
for
nimodipine,
PLGA
and
HA
 Edge
has
clear
path
for
IND
and
scale-­‐up
needs
and
<melines
 FDA
clarified
expecta<ons
&
Edge
is
aligned
with
pre-­‐clinical
studies
for
IND
-­‐
no
change
in
the
general
plan
and
approach
proposed
by
Edge
 FDA
&
Edge
are
aligned
on
Phase
2
clinical
trial
design
– NimoGel
alone
can
be
compare
to
oral
nimodipine
(standard
of
care)
– First
<me
in
22
years
that
FDA
has
allowed
experimental
drug
vs.
oral
nimodipine
16
|

17. PHASE
2
STUDY
DESIGN
Phase
2a:
Dose
Finding
Study
[Con<nuous
Reassessment
Model
(CRM)]
•
n=
up
to
63
pa<ents
• 40mg,
120mg,
160mg,
up
to
1120mg
or
toxicity
• Endpoint
plasma
levels
>40ng/mL
causing
hypotension
• 10
centers
(2
pa<ents
/
month
per
center)
• 9
months
to
complete
(3
months
start-­‐up,
4
months
to
enroll,
3
months
to
analyze
data)
Phase
2b:
Toxicity
Study
• n=
88
pa<ents
• NimoGel
vs.
standard
of
care
(oral
nimodipine)
• Primary
endpoint:
toxicity
• Exploratory
endpoints:
infarc<on
or
neurological
deteriora<on
due
to
vasospasm,
need
for
rescue
therapy,
mortality,
ICU
LOS,
Hospital
LOS
 30-­‐day
endpoint,
90
day
follow-­‐up
• 15
centers
(2
pa<ents
/
month
per
center)
• 9
months
to
complete
(3
months
start-­‐up,
3
months
to
enroll,
3
months
to
analyze
data)
17
|

18. PHASE
3
STUDY
DESIGN
FDA
&
Edge
are
aligned
on
Phase
3
endpoints
Phase
3:
Efficacy
and
Safety
• n=
750
pa*ents
• NimoGel
vs.
standard
of
care
(oral
nimodipine)
• Primary
endpoint:
(composite
endpoint)
infarc<on
or
neurological
deteriora<on
due
to
vasospasm,
need
for
rescue
therapy,
mortality
• Secondary
endpoint:
posi<ve
trend
modified
Rankin
score
 30-­‐day
endpoint,
90
day
follow-­‐up
• Health
economic
secondary
endpoints:
ICU
LOS,
Hospital
LOS
• 100
centers
worldwide
(1.5
pa<ents
/
month
per
center)
• 15
months
to
complete
(3
months
start-­‐up,
9
months
to
enroll,
3
months
to
analyze
data)
18
|

19. DCI
MARKET
OPPORTUNITY
SPECIFIC
AND
ADDRESSABLE
DCI
is
a
great
burden
• All
SAH
pa<ents
are
at
risk
of
DCI
• >750,000
people/year
worldwide
are
at
risk
for
DCI
aEer
aneurysmal
SAH
 Aneurysmal
SAH
is
common
in
U.S.,
E.U.,
and
Japan
• Head
trauma
also
causes
SAH
and
are
at
risk
• Concentrated
customer
base;
easily
covered
by
25
–
50
person
specialty
salesforce
At
Risk
Addressable
Market
Concentrated
Customers
# of U.S. % Share of
Japan Percentile Hospitals patients
70,000 U.S.
100,000
1% 50 16%
E.U. 5% 250 66%
100,000
10% 500 85%
DCI
risk
auributed
to
all
SAH
(aneurysmal
SAH
&
head
trauma)

20. BROADER
MARKET
OPPORTUNITIES
30-Day
30-Day Mortality
Acute Neurological Incidence Incidence Average
Mortality Rate or
Condition U.S. World Age
Rate Brain
Damage
Ruptured Brain
Aneurysm – NimoGel & >40,000 >750,000 50 50% 75%
NimoVent
Chronic Subdural
>70,000 >1.5 Million 65 20% 40%
Hematoma – EG-1964
Intracerebral
100,000 >2 Million 60 45% 80%
Hemorrhage – EG-1960
Variable on Variable on Variable on
Craniotomy – EG-1960 >180,000 >2 Million
condition condition condition
Moderate & Severe Head
Trauma – NimoGel, >250,000 >3 Million 40 20% 50%
NimoVent, EG-1960
*
Source:
Leng,
L.,
Fink,
M.,
Iadecola,
C.
2010.
Spreading
Depolariza8on:
A
Possible
New
Culprit
in
the
Delayed
Cerebral
Ischemia
of
Subarachnoid
Hemorrhage.
Neurological
Review
20
|

21. DoD
APPLICATION
• A
study
evaluated
all
in-­‐pa<ents
with
blast-­‐
related
neurotrauma
from
Opera<on
Iraqi
Freedom
and
found
that
47%
had
blast-­‐related
vasospasm
• In
addi<on
to
the
vasospasm
caused
by
neurotrauma,
“blast
vasospasm”
is
a
recent
phenomenon
recently
documented
in
the
medical
literature
• DoD
has
maintained
an
ac<ve
research
program
in
reducing
injury
caused
by
hemorrhage
• DoD
has
recognized
the
poten<al
use
of
all
of
Edge’s
products:
– Combat
Casualty
Care
Unit
has
invited
Edge
to
submit
a
full-­‐proposal
for
NimoVent
($4.0MM)
– Awai<ng
an
invita<on
for
a
NimoGel
full-­‐proposal
($4.5MM)
– Submiued
pre-­‐proposal
to
DoD-­‐Telemedicine
&
Advanced
Technology
Research
Center
(TATRC)
– Awai<ng
an
invita<on
from
Veteran’s
Administra<on
(VA)
for
EG-­‐1964
21
|

22. WELL
PROTECTED
FRANCHISE
Layered
Intellectual
Property
Commercial
Barriers
“Nimo”
Franchise
• Orphan
drug
Polymorphs
=
Composi<on
• SurModics
of
Mauer
 License,
exclusive
&
Devmt.
of
“Nimo”
worldwide
Franchise
=
Composi<on
&
Process
Patents
 Produc<on
is
difficult
• Mfg.
polymers
&
SurModics
Process
Patent
micropar<cles
NIMO
Method
of
Use
–
• Investment
scale-­‐up
NimoGel
/
NimoVent
and
cGMP
• FormEZE
process
• Trade
secrets
22
|

23. KEY
PERSONNEL
Management
Board
&
Key
Advisors
Key
Scien,fic
Advisors
Brian
A.
Leuthner,
President
&
CEO,
Co-­‐founder
Sol
Barer,
PhD,
Board
Director
Neal
F.
Kassell,
MD,
University
of
Virginia
20+
years;
Pharma
&
Specialty
Pharma,
Founder,
Former
CEO
&
Execu<ve
Health
Sciences
Center
GlaxoWellcome,
Ortho
Biotech,
ESP
Pharma,
The
Chairman,
and
Chairman,
Celgene
Medicines
Company,
Fontus
Pharmaceu<cals
Corpora<on
Daniel
Hanggi,
MD,
Heinrich-­‐Heine-­‐
University,
Dusseldorf,
Germany
R.
Loch
Macdonald,
MD,
PhD,
CSO,
Co-­‐founder
Kurt
Con,,
Board
Director
Keenan
Endowed
Chair
of
Neurosurgery,
St.
Chairman,
The
Con<
Group,
Serial
Hidetoshi
Kasuya,
MD,
Tokyo
Women’s
Michael’s
Hospital,
Toronto,
Canada;
20-­‐years
Of
entrepreneur
Medical
University,
Tokyo
Research
Led
Us
To
NimoGel
&
NimoVent;
>400
James
Louglin,
Board
Director
Peter
D.
LeRoux,
MD,
FACS,
Hospital
of
the
Peer-­‐reviewed
Ar<cles
On
Secondary
Brain
Injury
Former
Chairman,
Pension
and
University
of
Pennsylvania
Priya
Jambhekar,
MS,
Execu,ve
Vice
President,
Investment
Commiuee
of
the
KPMG
Regulatory
and
Quality
Board,
Celgene
Director,
Heads
Audit
Stephan
A.
Mayer,
MD,
Columbia
Commiuee
20+
years;
Pharma
&
Specialty
Pharma
in
product
University
Medical
Center
development,
product
safety,
quality
assurance,
Geert
Cauwenburgh,
PhD,
Advisor
quality
compliance
and
U.S.
and
interna<onal
J.
Javier
Provencio,
MD,
Cleveland
Clinic
Former
CEO,
Barrier
Therapeu<cs,
regulatory
affairs;
BMS,
J&J,
Baxter,
and
Alkemes
Hospitals
Former
VP,
R&D
Johnson
&
Johnson
Bert
Marchio,
MBA
–
CFO
Arthur
Klausner,
Advisor
Peter
Vajkoczy,
MD,
Charite
17+
years;
Specialty
Pharma
in
senior
financial
Life
sciences
venture
capitalist;
Domain
Hospital,
Berlin,
Germany
leadership
posi<ons
in
both
the
public
and
private
Associates
and
Pappas
Ventures
sectors;
Informed
Medical
Communica<ons,
Paul
M.
Vespa,
MD,
David
Geffen
School
of
MedPointe,
and
Alpharma
Medicine
at
UCLA
Carl
J.
Soranno,
Esq.,
Execu,ve
VP,
Corporate
Bryce
Weir
OC,
MSc,
FRCSC,
FACS,
FRCS
Development,
Co-­‐founder
(Ed)
hon.,
Goldblau
Professor,
The
18+
years;
prac<ce
of
law;
11
years;
Financial
University
of
Chicago
Pritzker
School
of
career
on
Wall
Street
Medicine

24. MILESTONES
Corporate
development
and
capitaliza,on
to
date
– Raised
almost
$4M
in
financing
from
a
small
group
of
private
investors
and
non-­‐dilu<ve
sources
– Alliance
with
SurModics
(NASDAQ:
SRDX)
– Proof
of
concept
in
a
dog
model
– Successful
pre-­‐IND
mee<ng
(clear
endpoints)
– Manufactured
large-­‐scale
batch
of
NimoGel
and
NimoVent
Timeline
&
ac,vi,es
moving
forward
– cGMP
NimoGel
&
NimoVent
(4Q
2011)
– Clinical
trial
–
Inves<gator
ini<ated
trial
(FPI
1Q
2012)
– U.S.
IND
(1H
2012)
– Orphan
drug
designa<on
(1H
2012)
– Phase
2
Study
–
2012
– Phase
3
Study
–
2013/2015
24
|

25. SUMMARY
• Well-­‐defined,
addressable
unmet
worldwide
medical
need
• De-­‐risked
lead
assets
with
proof-­‐of-­‐concept
successfully
established
• Clear
and
abbreviated
clinical
and
regulatory
path
– FDA
confirmed
505(b)(2)
path
for
NimoGel
– Orphan
drug
designa<on
eligibility
– 90
day
trial
follow
up,
short
clinical
trial
dura<on
(Phase
2
for
NimoGel
and
NimoVent)
• High
legal,
regulatory,
R&D,
and
commercial
barriers
to
compe<<on
• Highly
concentrated
market
and
clear
pathway
to
2015/2016
launch
• Opportunity
for
new
indica<ons
and
addi<onal
first-­‐in-­‐class
products
25
|

26. LIMITED
INVESTMENT
/
LARGE
UPSIDE
Development
Timeline:
2.5
to
3
years
NimoGel
NimoVent
NimoVent
EG-­‐1964
EG-­‐1960
aSAH
aSAH
TBI
$15MM
Phase
3
Phase
3
Phase
2
-­‐
-­‐
$20MM
Phase
3
Phase
3
Phase
3
Phase
2
-­‐
$25MM
Phase
3
Phase
3
Phase
3
Phase
2
Phase
2
26
|

27. Corporate
Presenta,on
October
2011