Cebix Presentation for Sofinnova Japan

1. 1
CONFIDENTIAL

2. Cebix
Mission
2
Cebix
will
develop
safe
and
effec?ve
therapies
for
the
treatment
of
long-­‐term
complica?ons
in
diabetes

3. Re?nopathy
(20%)
Nephropathy
Peripheral
Neuropathy
Autonomic
Neuropathy
Long-­‐term
complica?ons
of
Type
I
Diabetes
(35%)
(50%)
(25%)
3

4. 4
Type
I
Diabetes
Pro-­‐insulin/C-­‐pep?de
C-­‐pep?de
Insulin
Pro-­‐Insulin
4
C-­‐pep?de
is
the
second
hormone
•
Similar
to
Preglucagon
–
Glucagon
–
GLP-­‐1
and
GLP-­‐2

5. An agent for the treatment of mild to
moderate peripheral neuropathy in type 1
diabetes
The therapy of choice in the treatment of
this significant unmet medical need,
based on improvement of sensory
function
Initial Target Indication
5
Product Profile
C-­‐Pep?de
Replacement

6. C-­‐pep?de
influences
major
metabolic
pathways
Ca2+
MAPK
Na+,
K+-­‐
ATPase
eNOS
Na+
K+
Ca2+
Transcrip?on
factors
NO
NO
G-­‐protein
ATF-­‐1
CREB
ZEB
NFκB
PPARγ
6

7. 35
40
45
50
55
60
65
70
0
1
2
3
4
5
6
Onset
of
diabetes
1
week
2
months
5
months
m/s
Nerve
Conduc?on
Velocity
8
months
C-­‐pep?de
C-­‐pep?de
Sima
et
al
2001
Nerve
Func?on
Improved
Diabe?c
rat
model
CONFIDENTIAL
Non-­‐diabe?c
control
Diabe?c
no
treatment
Diabe?c
+
C-­‐pep?de

8. 8
C-­‐pep?de
Replacement:
Does
it
work
in
Type
1
Diabetes
pa?ents?

9. 9
Restores
sensory
nerve
conduc?on
Phase
2a
Ekberg
et
al,
Diabetes
2003
50
52
54
56
Baseline 6
wks 12
wks
SCV
(m/s)
C-­‐pep?de
n=26
Placebo
n=23
Healthy
Controls
p<0.05
9

10. C-­‐pep?de
Improves:
Nerve
Conduc?on,
Vibra?on
Percep?on
&
Clinical
Status
Phase
2
Ekberg
et
al,
Diab
Care
2007
Nerve
conduc:on:
%
pa8ents
>1
m/s
0
10
20
30
37
%
19
%
40
p<0.03
N=139
Placebo
n=
47
C-­‐pep?de
n=92
p<0.002
Median
differences
0.20
0.15
0.10
0.05
0
-­‐0.05
Foot
Leg
ns
Vibra:on
Percep:on:
Δ
VPT
(SDS)
0
0.5
1.0
1.5
Clinical
Status:
Neurological
Impairment
2.0
p<0.01
ns
Median
differences

11. Safety
profile
of
C-­‐pep?de
• 6
safety
pharmacology
studies
completed
• 5
toxicological
studies
(monkey
and
rat)
– Up
to
60x
higher
than
replacement
dose
• 19
clinical
studies
conducted
exposing
~300
pa?ents
– Replacement
of
endogenous
levels
intended:
0.4-­‐
6
nM
⇒ Benign
safety
profile,
consistent
with
replacement
therapy
CONFIDENTIAL
11

12. 12
Development
Path
Secured
 Unmet
medical
need
 Biology
-­‐
Func?on
and
Pathophysiology
 Safety
 Efficacy
 Dose
-­‐
Replacement
 Drug
manufacturing
1. Regulatory
Path
2. Intellectual
Property
3. Drug
delivery

13. Pre-­‐IND
Mee?ng
with
FDA
July
2010
• Regulatory
– FDA
Confirmed
qualifica?on
of
Subpart
H
• Allows
use
of
surrogate
end
point
for
Pivotal
Phase
2b
• Clinical
– Nerve
conduc?on
velocity
accepted
as
the
sole
primary
endpoint
for
approval
• Nonclinical
– IND-­‐enabling
tox
plan
endorsed
by
FDA
13

14. Intellectual
Property
• Seven
patents
issued:
– Formula?on
– Cardio
autonomic
effect
– Ac?ve
pentapep?de
• Three
submioed
to
US
Patent
Office
in
2009-­‐2010
– Effect
on
erec?le
dysfunc?on
– Effect
on
hypoglycemia
– Subject
of
maoer
on
long-­‐ac?ng
form
• Japan
strategy
– Will
file
PCT
within
12
months
of
original
filing
– Plan
to
use
the
Patent
Prosecu?on
Highway
(PPH)
14

15. Formula?on
Criteria
15
Injec?on
volume
≤
1
mL
1
2
3
4
5
6
7
Syringeability:
≤
27
gauge
<
20
seconds
<20%
drug
loss
in
burst
PK
profile
consistent
with
once
weekly
dosing

16. Selected
Formula?on
Technologies
16
PROMAXX
Atrigel
Pumps
Trans-­‐
dermal
patch
Octoplus
Eryto-­‐
pharm
Halozyme
Altus
Alkamer
Nektar
Enzon
Syringability
≤
27
gauge
Stable
for
>
1.5
years
at
4°C
PK
profile
consistent
with
once
weekly
dosing
No
more
than
20
percent
drug
loss
in
burst
Product
load
of
at
least
1
percent
of
volume
Camurus
Flamel
Durect
Alkermes
La?tude

17. PK
profile
17
100
1
10
C-­‐pep?de
conc
(ng/ml)
0
4
8
12
16
Time
(days)
T1/2
in
monkey
~
3
days
Extended
Half-­‐life
Product
Depot
Product

18. Path
Forward
Development
18
CONFIDENTIAL

19. Cebix
Development
Program
19
2011
2012
2013
2010
Formula?on
&
CMC
6-­‐mo
interim
data:
surrogate
marker
12-­‐mo
data:
clinical
end-­‐point
Pivotal
Phase
2b
NEUROPATHY
Human
PK
pre-­‐IND
mee?ng
IND
Submission
Partnering

20. World
Wide
Incidence
–
Type
1
CONFIDENTIAL
20

21. C-­‐pep?de
Replacement
Ini?al
Commercial
Opportunity
Type
I
diabe?cs
(auto-­‐immune)
in
US+
EU:
4
million
Severe
neuropathy
No
neuropathy
Type
I
Diabetes
Type
II
Diabetes
50%
400,000
pa:ents
25%
penetra?on
Mild-­‐to-­‐moderate
neuropathy
21
10%
40%
90%
10%

22. Diabetes
Market-­‐
Japan
22
50,000
pa?ents
Age
group:
under
20
Annual
incidence
rate:
1.3-­‐1.7/100.000
Diagnosed
Type
I
diabetes/
IDDM:
A
Amos
et
al
1997,
Diabe?c
Medicine
1997
Global
epidemiology,
in
The
epidemiology
of
diabetes
mellitus
2001
IDF:
Diabetes
Atlas
2000
All
diabetes:
8.7
million
pa?ents
Age
group:
older
than
20
400,000
pa?ents
5
%:
LADA,
SPIDDM,
type
1,5
Kobayashi
T
et
al
Ann
N
Y
Acad
Sci
958
:
117-­‐130,
2002

23. C-­‐pep?de
Replacement
• Large
unmet
need
• Experienced,
well
funded
team
• Convincing
biology
• Aorac?ve
risk-­‐benefit
profile
• Strong
proof-­‐of-­‐concept
in
mul?ple
indica?ons
• Once-­‐weekly
dosing
formula?on
established
• An?cipate
filing
IND
Q4
2010
23

24. Partnering
Objec?ve
• Cebix
is
seeking
to
partner
the
once-­‐weekly
C-­‐
pep?de
replacement
product
within
Japan
or
throughout
a
broader
region
up
to
and
including
Worldwide
opportuni?es
CONFIDENTIAL
24

25. Contacts
James
Callaway,
PhD
President
R
&
D
Email:
jim@cebix.com
Phone
(office):
+1-­‐858-­‐729-­‐6502
Phone
(mobile):
+1-­‐858-­‐967-­‐1471
Annica
Mårtensson,
PhD,
MBA
Director,
Pharm.
Development
&
Corp.
Strategy
Email:
annica@cebix.com
Phone
(office):
+1-­‐858-­‐729-­‐6503
Phone
(mobile):
+1-­‐858-­‐366-­‐2548
CONFIDENTIAL
25