Shifting Paradigms: Examining Pro-Thrombotic Activity from a Safety Perspective

CorDynamics conducts thrombosis experiments – using small and large animals

Mouse ferric chloride model of arterial thrombosis1) instrumentation to monitor carotid artery flow

- monitor artery flow prior to and after FeCl3

- FeCl3 migrates to lumen, results in endothelial injury

2) administer test article prior to FeCl3

-monitor for development of thrombus-use real-time monitor of blood flow, time to

occlusion

Validation- reduced concentrations of FeCl3, vessel vulnerability

present

MOUSE PROTHROMBOSIS MODEL

Effects of various concentrations FeCl3 on carotid artery blood flow

MOUSE PROTHROMBOSIS MODEL

-1 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 610.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Concetration-dependent effects of Ferric Chloride onCarotid Arterial Thrombosis in CD-1 Mice

Carotid Artery Flow

Vehicle (PBS, 3.5% FeCl3- Lot SZBE1900V) (n=5)Vehicle (PBS, 3.0% FeCl3- Lot SZBE1900V) (n=10)Vehicle (PBS, 2.8% FeCl3- Lot SZBE1900V) (n=10)Vehicle (PBS, 2.5% FeCl3- Lot SZBE1900V) (n=10)

Time (minutes)

mL/

min

FeCl3

Reducing FeCl3 reduces thrombosis – prothrombotic window opens

MOUSE PROTHROMBOSIS MODEL

3.5% FeCl3_x000d_Lot

SZBE1900V

3.0% FeCl3_x000d_Lot

SZBE1900V

2.8% FeCl3_x000d_Lot

SZBE1900V

2.5% FeCl3_x000d_Lot

SZBE1900V

ProThrombotic0

10

20

30

40

50

60

70

80

90

100

0

5

10

15

20

25

30

35

40

45

50

55

60

Concetration-dependent effects of Ferric Chloride onCarotid Arterial Thrombosis in CD-1 Mice

Occlusion time

Incidence of non-occlusion

Inci

denc

e of

non

–Occ

lusi

on (%

)

Occ

lusi

on T

ime

(min

)

4/10

1 outof 1 1

outof 1

2/10 6/100/7?