Kala Pharmaceuticals "Penetrating Mucosal Barriers to Maximize Ocular Therapeutic Outcome" presented at OIS@AAO 2014

1. Charles
McDermo.
Interim
President
and
CBO
Ophthalmology
Innova/on
Summit
-­‐
October
2014
Penetra'ng
mucosal
barriers
to
maximize
ocular
therapeu'c
outcome

2. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
2
Product/Indica9ons
Preclinical
PhI
PhII
PhIII
Launch
Post
Cataract
Surgery
Dry
Eye
Meibomian
Gland
Disease
Topical
Diabe/c
Macular
Edema
Topical
Wet
AMD
LE-­‐MPP
(0.25%
QID,
1%
BID)
Ph
III
LE-­‐MPP
(0.25%
QID)
PhII
LE-­‐MPP
(0.25%
QID)
PhII
RTKi*
LE-­‐MPP
(1.0%
QID)
POC
*
Lead
RTKi
cellular
IC50
Potency
~
KDR
0.2nM
/
PDGF
11nM
Kala’s
Internal
Eyecare
Pipeline
LE
MPP
=
Kala’s
Loteprednol
Etabonate
Mucus
Penetra'ng
Nano-­‐Par'cle
Formula'on

3. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
3
• Sterile,
aqueous
nanosuspension
of
LE
MPP
for
ophthalmic
dosing
• Scalable
cGMP
manufacturing
• All
excipients
FDA-­‐approved
for
ophthalmic
route
• Stable
(2
yrs
projected
shelf
life)
in
ready-­‐to-­‐use
form
(non-­‐viscous
eye
drops)
1%
LE
MPP
at
25°C
(representa9ve
batch)
Test
Representa9ve
batch
at
12
mo
Appearance
!
LE
Assay
!
LE
Related
Impuri/es
!
Preserva/ve
Assay
!
Par/cle
Size
!
pH
!
Osmolality
!
!
=
meets
specifica/ons
MPP
=
Scalable
CMC
and
Stable
Drug
Products

4. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
4
Rabbit
Study
of
Kala
LE
MPP
&
Conven9onal
LE
Formula9ons
Supports
Phase
II
Dry
Eye
Trial
In
a
rabbit
study,
LE-­‐MPP
outperformed
Lotemax®
suspension
and
similarly
sized
non-­‐MPP
nanopar9cles
at
the
same
dose
Single
topical
administra/on
of
equivalent
drug
doses
to
NZW
rabbit
eyes
at
t=0.
[n=6
eyes//me
point]
LE
MPP
0.5
%
LE
nanopar9cle
0.5
%
Lotemax®
suspension
0.5
%
Corneal
Drug
Levels
aCer
single
topical
dose
in
NZW
rabbits

5. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
5
LE
MPP
Delivery
to
Eyelid
Margins
in
Mini-­‐Pigs
Supports
Phase
II
MGD
Clinical
Trail
1%
LE-­‐MPP
dosed
QID
for
5
days
to
mini-­‐pigs
Peak
LE
concentra9ons
in
the
eyelid
margins
~20-­‐fold
higher
than
corneal
levels

6. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
6
Re'nal
Levels
ACer
Topical
Dosing
of
1%
LE-­‐MPP
in
Mini-­‐pigs
Pig
AUC0-­‐2
(Dosed/Non-­‐Dosed
eye)
Ra/os
Re/na
=
6
LE
MPP
Topical
Delivery
to
the
Re9na
in
Mini-­‐Pigs
Supports
DME
Trial
Higher
re9nal
levels
in
dosed
vs
non-­‐dosed
eye
in
mini-­‐pigs
supports
local
route
delivery
to
re9na
with
LE-­‐MPP
Schopf
et
al,
submi2ed
for
publica5on

7. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
7
RTKi-­‐MPP
Re9nal
Delivery
Following
Single
Topical
Dose
~1500-­‐fold
>
cellular
IC50
~500-­‐fold
>
cellular
IC50
2%
K0010-­‐MPP
single
topical
dose
Rabbit
Data
Re9nal
Drug
Level
MPP
delivered
re9nal
concentra9ons
well
above
IC50
over
24
hrs
aaer
single
topical
dose
of
2%
K0010
–
MPP
in
rabbits

8. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
8
Topical
Dosing
of
RTKi-­‐MPP
Equivalent
to
Intravitreal
Avas9n®
in
Rabbit
VEGF
Model
Study
Design
• 4
treatment
groups
‒ Avas9n®
IVT
at
day
1
‒ Vehicle
q4h
days
1
–
6
‒ 1%
K-­‐0010
q4h
days
1
–
6
‒ 1%
K-­‐0010
qd
days
3
–
6
• VEGF
challenge
on
day
3
• Fluorescein
angiography
on
day
6
to
grade
leakage
V
e
h
ic
le
A
v
a
s
tin
IV
T
1
%
K
0
0
1
0
-M
P
P
(q
4
h
r)
1
%
K
0
0
1
0
--M
P
P
(Q
D
)
0
1
2
3
4
LeakageScore
Sta9s9cally
Equivalent
In
this
rabbit
study,
K0010-­‐MPP
dosed
every
4
hours
or
once
daily
showed
efficacy
equivalent
to
Avas9n®
IVT

9. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
9
RTKI-­‐MPP
Topical
Delivery
to
Re9na
&
Choroid
in
Mini-­‐Pigs
C h o r o i d
H o u r s
0 1 2 3 4
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0 2 . 0 % M P P ( D o s e d E y e )
N o n - D o s e d E y e
Concentration(nM)
R e t i n a
H o u r s
0 1 2 3 4
0
5
1 0
1 5
2 0
Concentration(nM)
2 . 0 % M P P ( D o s e d E y e )
N o n - D o s e d E y e
Dosed
eye
higher
than
non-­‐dosed
eye
in
both
re9na
and
choroid
in
mini-­‐pigs,
sugges9ng
local
delivery
to
back
of
eye
Schopf
et
al,
submi2ed
for
publica5on
Fellow
Eye
Control:
Dosed
Eye
Drug
Levels
in
Re'na
&
Choroid
3
–
4
'mes
Non-­‐dosed
Eye

10. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
10
Lead
R&D
Programs:
Exclusive
Topical
Eyecare
Products
• LE
MPP
front
of
eye
and
back
of
eye
clinical
programs
• RTKi
VEGF/PDGF
pre-­‐clinical
re/na
program
Follow
On
R&D
Programs:
Respiratory,
GI,
and
Women’s
Health
• Preclinical
data
confirming
poten/al
of
Kala
MPP
technology
to
address
diseases
affec/ng
mucus
protected
organs
• Extending
use
of
the
plahorm
in
therapeu/c
areas
beyond
ophthalmology
MPP
Plajorm
Technology:
• Novel
exclusive
local
drug
delivery
technology
• Tunable
technology
that
may
be
engineered
to
apply
to
a
wide
range
of
molecules
• Kala
MPPs
are
scalable
and
manufacturable
in
a
pharmaceu/cally
acceptable
manner
Kala
MPP
Plajorm
Programs

11. KALA
PHARMACEUTICALS
|
Ophthalmology
Innova/on
Summit|
October
2014
|
Page
11
Partnering:
MPP
Plajorm
and
Kala
Clinical
Programs
MPP
Plajorm
Technology:
Partner
Compounds
Discovery
License
and
Supply
Agreements
• Feasibility
agreements
à
license
and
supply
agreements
• Term
sheets
à
license
and
supply
agreements
LE
MPP
Clinical
Programs:
Strategic
Partnership
• Data
room
is
open
to
all
interested
par/es.
• Consider
license
and
supply
agreements,
M&A,
asset
separa/ons,
regional
deals,
and
go
it
alone
strategies.