Gray Bug "Ophthalmology Innovation Summit" Presentation presented at OIS@AAO 2014

1. MICHAEL
O’ROURKE
PRESIDENT
&
CEO
16t h
O c t o b er
2 0 1 4
Ophthalmology
InnovaHon
Summit

2. 2
Disclosure
GrayBug
and
Its
Investors
Have
a
Financial
Interest
in
This
Technology

3. 3
Developing
Injectable,
Ophthalmic
TherapeuHcs
for
MulH-­‐Billion
Dollar
Markets
Proprietary
Micro
and
NanoparHcle
Controlled
Release
Technologies
DRUG
DELIVERY
TECHNOLOGY
BEST
IN
CLASS
DRUGS
New
Best
In
Class
and
Longer-­‐LasHng
Products

4. 4
GrayBug
Value
ProposiHon
• Frequency
of
intra
vitreal
injecHons
is
a
major
unmet
medical
need
• GrayBug
can
deliver
4-­‐6
months,
or
longer
!
• Up
to
34%
drug
loading
demonstrated
COMPETITIVE
ADVANTAGE
• MicroparHcle
-­‐
Controlled
Release
-­‐
IP
• PLGA
-­‐
Reduces
-­‐
Eliminates
InflammaHon
NOVEL
TECHNOLOGY
• AnH
VEGF,
PDGF
• Single
Agent
LEAD
DRUG
• ExperHse
in
Ophthalmology,
Rx
and
Drug
Delivery
• Small
to
Large
Molecules
Delivery
• Based
in
The
Wilmer
Eye
InsHtute
EXPERIENCED
TEAM

5. 5
A
Leadership
Team
with
Pedigree
of
Excellence
and
Experience
Peter
Campochiaro,
MD
Founder
Eccles
Professor
of
Ophthalmology
and
Neuroscience,
Wilmer
Eye
InsHtute,
Johns
Hopkins
School
of
Medicine
Peter
McDonnell,
MD
Founder
William
Holland
Wilmer
Professor
and
Chair
of
Ophthalmology,
Director
of
the
Wilmer
Eye
InsHtute,
Johns
Hopkins
School
of
Medicine
Jus6n
Hanes,
PhD
Founder
and
CSO
Lewis
J.
Ort
Professor
of
Ophthalmology
&
Director
of
the
Center
for
Nanomedicine,
Wilmer
Eye
InsHtute,
Johns
Hopkins
School
of
Medicine
Michael
O’Rourke
President
and
CEO
Former
GM,
VP
Global
Strategy
Bausch
+
Lomb,
Chiron
Vision,
Alza
&
3M
Gerald
Cagle,
PhD
Board
Member
Former
CSO,
Senior
VP
R&D,
Alcon
Jeff
Cleland,
PhD
Board
Member
CEO,
VersarHs.
20
Years
of
Industry
Experience
in
R&D,
Including
Genentech
FOUNDERS
OPHTHALMOLOGY
&
INTRAOCULAR
THERAPY
ACADEMIC
OPHTHALMOLOGY
DRUG
DELIVERY
LONG
ACTING
PROTEINS
Vitrasert
BOARD

6. 6
Injectable
High
Capacity
Reservoir
and
LocalizaHon
of
MicroparHcles
Biodegradability
BiocompaHbility
Bioabsorbability
Polymer
Modified
to
Reduce
InflammaHon
ENCAPSULATED
DRUG
INTRAVITREAL
INJECTION
FREE
DRUG
RELEASED
AS
PARTICLES
ERODE
MicroparHcle
LocalizaHon
Designed
to
Aggregate
at
InjecHon
Site
and
Remain
Outside
Visual
Axis

7. 7
GrayBug
Solves
InflammaHon
Problem
of
PLGA
MicroparHcles
INFLAMMATION
SCORE
(MODIFIED
STANDARD
UVEITIS
SCALE)
GrayBug
PLGA
ParHcles
IdenHcal
to
Saline
Time
(Days)
0
2
4
6
8
10
0
1
7
14
30
Inflammatory
Standard
PLGA
Non-­‐Inflammatory
Saline
GrayBug
PLGA
• Results
from
InjecHon
into
Anterior
Chamber
of
NZ
White
Rabbit:
The
MOST
SensiHve
to
InflammaHon
• Similar
Results
Obtained
Following
Intravitreal
InjecHon

8. 8
INDICATION
PATHWAY
IDENTIFICATION
API
SELECTION
FORMULATION
DEVELOPMENT
IN
VIVO
EFFICACY PK/PD
NON-­‐GLP
TOXICOLOGY
LEAD
OPTIMIZATION
GLP
STUDIES
PROJECTED
IND
Wet
AMD
2015
Glaucoma
Corneal
Gram
RejecHon
Oncology
GB-­‐202†
GB-­‐301
GB-­‐102
GB-­‐101
GB-­‐203† (SR8165)
&
204†
GB-­‐201††
GrayBug
Pipeline
:
w-­‐AMD
Priority
†
NeuroprotecHon
††
IOP
lowering

9. 9
GB-­‐102:
Lead
Drug
for
AMD
delivery
• Single
Agent
• Extended
Release
-­‐
IVT
InjecHon
Every
4-­‐6
Months
• Uses
Small
Gauge
Needles
(27-­‐30G)
• Strong
Patent
ProtecHon
drug
• Blocks
VEGF
and
PDGF
• FDA
Approved
Drug
• Drug
loading
as
high
as
34%
(by
weight)
• Prolonged
suppression
of
CNV
• Efficacy
>
4.5x
longer
than
Ranibizumab
in
mice

10. 10
0 20 40 60 80 100 120
0
20
40
60
80
100
Drug
Release
(%)
Time
(
Days
)
0 20 40 60 80 100 120
0
20
40
60
80
100
Drug
Release
(%)
Time
(
Days
)
0 10 20 30 40 50 60 70
0
20
40
60
80
100
Drug
Release
(%)
Time
(
Days
)
30
days
40
days
100
days
120
days
0 10 20 30 40
0
20
40
60
80
100
Drug
Release
(%)
Time
(Days)
Tunable
GB-­‐102
Drug
Release
Profile
0 5 10 15 20 25 30 35
0
20
40
60
80
100
Drug
Release
(%)
Time
(
Days
)
ACCELERATED
IN
VITRO
DRUG
RELEASE
• Pilot
study
showed
at
1
month
vitreous
drug
level
in
rabbit
eyes
was
~
40
x
higher
than
the
IC50
against
VEGF-­‐R
and
PDGF-­‐R.
0 5 10 15 20 25 30
0
20
40
60
80
100
Drug
Release
(%)
Time
(
Days
)
21%
loading,
projected
to
last
~
12
months
70
days

11. 11
GB-­‐102:
Long-­‐Term
Suppression
of
NeovascularizaHon
Laser-­‐Induced
Model
of
CNV;
P.Campochiaro
MD,
J.Hanes
PhD
-­‐
Wilmer
Eye
Ins6tute
IMMEDIATE:
1
WEEK
Mean
Area
of
CNV
(mm2)
GB-­‐102
(10
ug)
Control
(PBS)
P<0.05
0.002
0
0.004
0.006
Control
GB102
SUSTAINED
EFFICACY:
9
WEEKS
P<0.05
Mean
Area
of
CNV
(mm2)
GB-­‐102
(10
ug)
Control
(PBS)
0
0.01
0.02
0.03
Control
GB102
Ranibizumab
lasts
only
2
weeks
in
mouse
models
Results
from
Mouse
Models:
Human
DuraHon
Typically
2-­‐3x
Longer

12. 12
GB-­‐202,
GB-­‐203,
GB-­‐204
Efficacy
in
Glaucoma
Donald
J.
Zack
MD,
Harry
Quigley
MD,
Jus6n
Hanes
PhD
-­‐
Wilmer
Eye
Ins6tute
RAT
LASER
MODEL
OF
ELEVATED
IOP
#
of
Op6c
Nerve
Axons
0
2000
4000
6000
8000
14000
10000
12000
Non-­‐
Lasered
Vehicle
GB203
GB202
GB204
RAT
OPTIC
NERVE
TRANSECTION
Vehicle
GB202
GB203
GB204
0
20
40
60
%
Survival
of
RGCs
Central
Middle
Peripheral

13. 13
Reduces/Eliminates
PLGA
InflammaHon
Research
ExperHse
RelaHonship
-­‐
Wilmer
Eye
InsHtute
RelaHonship
-­‐
Johns
Hopkins
Commercial
ExperHse
Small
to
Large
Molecules
4-­‐6
months
Delivery
or
Longer
Micro
and
NanoparHcles
High
Drug
Volume
-­‐
Remains
Outside
Visual
Axis
Robust
Animal
Models
Preclinical
PublicaHons/Data
Broad
IP
Porsolio
Many
Companies
Have
SOME
of
These
CharacterisHcs
…
…
GrayBug
HAS
THEM
ALL
Game
Changing
InnovaHon:
THE
POWER
OF
GRAYBUG
MulH
$
Billion
Markets
Reduces
Frequency
of
InjecHons

14. 14
What’s
in
a
Name
?
Grayson
“Gray”
Riley
“Bug”

15. Thank
You
michael@graybug.com