Hexabrix Review Missy Buchanan & Jean-Philippe Barraud ACC Guerbet LLC Team Mtg Orlando, FL March 28th, 2009

Hexabrix Review Agenda Review of Hexabrix Anti-thrombotic & Anti-platelet Properties Overview of Brochure Role Play Hexabrix Follow-up Questions

Anti-Thrombotic & Anti-Coagulant Properties So what happens?

Anti-Thrombotic & Anti-Coagulant Properties Blood Vessel Endothelium Subendothelium INJURY Collagen VWF Tissue Factor Vaso- constriction Platelet Adhesion & Secretion Coagulation Cascade Thrombin Platelet aggregation Fibrin Haemostatic plug Dr Isobel Ford

Anti-Thrombotic & Anti-Coagulant Properties So what’s the issue? This process can lead to occlusion of the vessels, such as coronary arteries, and subsequently to death

Anti-Thrombotic & Anti-Coagulant Properties So what role does Hexabrix play? 2 3 1 4

Anti-Thrombotic & Anti-Coagulant Properties So what role does Hexabrix play? 1 Hexabrix, does not activate resting platelets, unlike nonionic monomers. Doesn’t direct platelets to change shape, release pro-coagulant mediators or to adhere to anything. This prevents/delays formation of the platelet clot. 2 Hexabrix binds w/ Thrombin, preventing it from activating platelets; therefore preventing/delaying the formation of the platelet plug. 3 Hexabrix inhibits the generation of thrombin, reducing the amount of thrombin in the system; therefore Hexabrix inhibits the formation of fibrin. 4 These two together prevents/delays the formation of the fibrin mesh.

Anti-Thrombotic & Anti-Coagulant Properties So, which studies support these properties? (in vitro & animal) 1 Resting Platelet Activation S Heptinstall et al. British Journal of Heamtology. 1998 N Chronos et al. Circulation. 1993 L Melton et al. Acad Rad.1995 JM Idee & C Corot. Fundam Clin Pharmacol. 1999 2 Inhibition of Thrombin and Fibrin Li and Gabriel. Acad Rad. 1997 JJ Ing et al. Radiology. 1989. PM Kopko et al. Radiology. 1990 J Fareed et al. Radiology. 1990 C Corot et al. Blood Coag and Fibrinolysis. 1996 R Al Dieri et al. Journal of Thrombosis and Hemostasis. 2003 CP Markou et al. Thrombo and Heamost. 2001. 3 4

Anti-Thrombotic & Anti-Coagulant Properties So, the anti-platelet properties support the better clinical profile of Hx. (Clinical) Le Feuvre et al. Cathet Cardiovasc Interv. 2006 CL Grines et al. JACC. 1996.

Brochure Overview

Brochure Overview

Brochure Overview

Brochure Overview

Brochure Overview

Role Play Groups of 3 (count off) Roles: Customer, MCP & Observer Three rounds, take turns in each role

Role Play – Situation 1 Situation 1 Summary (5 min) Customer: Doc. Emmitt Brown, Interv. Card. Current Visipaque user Concerned about clotting during procedures MCP Objectives Explain the transition Detail Hexabrix anti-thrombotic & anti-platelet properties

Role Play – Situation 2 Situation 2 Summary (5 min) Customer: Dr. Biff Tannen, Interv. Card. Used Hexabrix in the past Switched due to price MCP Objectives Explain the transition Detail Hexabrix’s physicochemical characteristics

Role Play – Situation 3 Situation 3 Summary (5 min) Customer: Doc. Marty McFly, Interv. Card. Current Visipaque user Strong believer in NEPHRIC MCP Objectives Explain the transition Detail Hexabrix renal data

Follow-Up Questions For Discussion At what point in the procedure would you typically see vomiting? It can occur at anytime during a procedure Can the physician administer another CM immediately after Hexabrix administration? No. Should we be aware of diabetes drug interactions with CM? Yes, refer to package inserts for more details.