cebix sofinnova japan presentation

1 CONFIDENTIAL

Cebix Mission

2

Cebix will develop safe and

effec?ve therapies for the

treatment of long-‐term complica?ons in diabetes

Re?nopathy (20%)

Nephropathy

Peripheral Neuropathy

Autonomic Neuropathy

Long-‐term complica?ons of Type I Diabetes

(35%)

(50%)

(25%)

3

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

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

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

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

C-‐pep?de Replacement:

Does it work in Type 1 Diabetes pa?ents?

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

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

Med

ian differen

ces

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

Med

ian differen

ces

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

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

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

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

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

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

PK profile

17

100

1

10

C-‐pe

p?de

con

c (ng/ml)

0 4 8 12 16

Time (days)

T1/2 in monkey ~ 3 days

Extended Half-‐life Product Depot Product

Path Forward

Development

18 CONFIDENTIAL

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

World Wide Incidence – Type 1

CONFIDENTIAL 20

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%

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

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

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

Contacts

James Callaway, PhD President R & D Email: [email protected] Phone (office): +1-‐858-‐729-‐6502 Phone (mobile): +1-‐858-‐967-‐1471

Annica Mårtensson, PhD, MBA Director, Pharm. Development & Corp. Strategy Email: [email protected] Phone (office): +1-‐858-‐729-‐6503 Phone (mobile): +1-‐858-‐366-‐2548

CONFIDENTIAL 25

cebix sofinnova japan presentation

Health & Medicine