Clinical Experience with octaplas®/octaplasLG® Wolfgang Frenzel, M.D. International Medical Director Octapharma PPGmbH Vienna, Austria BPAC Meeting, Rockville, MD September 20, 2012

Clinical Experience with octaplas® Sources of Information Interventional clinical studies Non-interventional studies and retrospective data surveys Hemovigilance data Safety information from post-marketing reporting

Interventional Clinical Studies with octaplas® Reference Design Sponsor octaplas® Product Generation Indications No. of Patients (octaplas®) Focus Control No. of Patients Dosing General Outcome Inbal 1993 Prospective Octapharma Freeze-dried Hereditary and acquired coagulation disorders N=11 Pharmaco- kinetics, efficacy, safety None 6-12 mL/kg Half-lives similar to what is published for FFP Solheim 1993 Prospective Octapharma Open heart surgery N=20 Efficacy, safety FFP N=20 octaplas® mean 3.5 (range: 1-17) bags vs. FFP mean 4.1 (range: 2-16) bags No difference to FFP Williamson 1999 Prospective Octapharma Liquid, frozen Liver disease (LD): N=13 Liver transplantation (LTX): N=12 FFP LD: N=11 LTX: N=13 LD: octaplas® median 12 (range: 11-15) mL/kg vs. FFP median 13 (range: 11-17) mL/kg LTX: octaplas® median 12 (range: 11-15) mL/kg vs. FFP median 13 (range: 11-17) mL/kg

Interventional Clinical Studies with octaplas® Reference Design Sponsor octaplas® Product Generation Indications No. of Patients (octaplas®) Focus Control No. of Patients Dosing General Outcome Haubelt 2002 Prospective Octapharma Liquid, frozen Open heart surgery N=36 Efficacy, safety FFP N=31 octaplas® median 8.5 (range: 5.5- 14.2) mL/kg ; FFP median 8.5 (range: 5.5-12.2) mL/kg No difference to FFP Santagostino 2006 Prospective Non-Octapharma Inherited coagulation disorders N=17 Pharmaco- kinetics Efficacy, safety None Treatment courses median 18 (range: 6-29) mL/kg Recoveries & half- lives similar to what is published for FFP Demeyere 2010 Prospective Non-Octapharma Reversal of effect of oral anti-coagulants N=20 PCC N=18 octaplas®: 4-6 bags (200mL) per patient No difference in INR reversal but slower than PCC; more repeated doses than with PCC PCC Prothrombin Complex Concentrate INR International Normalized Ratio

Interventional Clinical Studies with octaplas® A comparative, open-label, randomized, cross-over Phase I trial in healthy volunteers to investigate the relative efficacy, safety and tolerability of octaplasLG® vs. octaplas® Primary objective: Efficacy (i.e. recovery of coagulation factors and haemostatic parameters) 60 subjects (per-protocol population N=43) Exposure: octaplas® 14.9 mL/kg; octaplasLG ® 15.3 mL/kg

Interventional Clinical Studies with octaplas® Set-up of Phase 1 Study

Interventional Clinical Studies with octaplas® Efficacy Results Phase 1 Study Fibrinogen FVIII FIX aPTT Protein S Plasmin inhibitor

Interventional Clinical Studies with octaplas® General Outcomes No difference between FFP and octaplas® in terms of efficacy No difference between FFP and octaplas® in terms of safety No difference between octaplas® and octaplasLG ® in terms of efficacy

Non-Interventional Studies and Retrospective Surveys Reference Design Sponsor octaplas® Product Generation Indications No. of Patients (octaplas®) Control No. of Patients Dosing General Outcome Hellstern 1993 Prospective Octapharma Liquid, frozen Disseminated Intravascular Coagulation N=30 None octaplas® mean 5.2 ± 1.1 mL/kg Satisfying efficacy Chekrizowa 2006 Retrospective Non-Octapharma Neonatal complications, obstetric emergencies, liver disease N=104 Neonates: mean 18.4 mL/kg; Obstetrics: mean 15 ± 8 mL/kg; liver disease: 38±42 mL/kg (children); 10.2±3.4 mL/kg (adults) Satisfying efficacy and tolerability; no unexpected clinical outcomes Scully 2007 Retrospective Non-Octapharma TTP N=21 CSP N=12 octaplas® 34.1 L per episode CSP 29.0 L No difference between products; octaplas® was better tolerated Edel 2010 Retrospective Non-Octapharma TTP N=8 (7 with severe ADAMTS13 deficiency) Daily 1-1.5 plasma volumes per exchange Platelet counts above 150 x 109/L achieved TTP Thrombotic Thrombocytopenic Purpura CSP Cryosupernatant Plasma

Observational Study conducted in Germany Non-Interventional, Prospective Study Observational Study conducted in Germany Sequence I: 65 patients on octaplas® Sequence II: 60 patients on octaplasLG® Under routine clinical conditions

Non-Interventional, Prospective Study Efficacy Results

Hemovigilance Data Bags of octaplas® 173,664 267,000 177,986 2,621 239,359 Total 860,630 United Kingdom: 3 hemovigilance reports covering 3 years Austria: 5 hemovigilance reports covering 5 years Norway: 4 hemovigilance reports covering 4 years Sweden: published experience from 1 site, covering 2 years Finland: publication; Finnish Red Cross, covering 7 years

Hemovigilance Data United Kingdom (SHOT Reports) 2009 FFP/MB 306.740 Year Bags AEs 95% CI FNHTR Allergic Allergic/ febrile Anaphylactic Hypotension TRALI Others 2009 FFP/MB 306.740 44 30.3-56.8 5 21 9 6 2 1 2009 octaplas® 52.963 0.2-7.2 2010 FFP/MB 292.884 45 32.0-59.1 4 26 3 2010 octaplas® 57.487 0.0-5.6 2011 FFP/MB 303.202 43 25 10 2011 octaplas® 63.214 0.6-8.8 Total '09-'11 FFP/MB 902.826 132 106.8-152.2 72 28 11 1 per ... NA 6.840 90.283 12.539 225.707 32.244 82.075 300.942 Total '09-'11 Octaplas 173.664 2.2-13.1 28.944 57.888 > 173'664 86.832 AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction MB Methylene Blue Plasma

Hemovigilance Data Austria (Hämovigilanz Jahresberichte) Year Bags AEs 95% CI FNHTR Allergic TRALI Others 2003 FFP 26.800 16 9.1-26.0 1 11 4 2003 octaplas® 57.700 7 2.8-14.4 3 2004 FFP 23.900 25 16.2-36.9 2 19 2004 octaplas® 55.000 0.0-5.6 2005 FFP 23.100 5.5-19.7 8 2005 octaplas® 50.100 0.0-3.7 2006 FFP 23.500 17 9.9-27.2 14 2006 octaplas® 52.400 0.2-7.2 2009 FFP 15.300 24 15.4-35.7 21 2009 octaplas 51.800 Total '03-'06+09 FFP 112.600 93 75.1-113.9 73 12 1 per ... NA 1.211 16.086 1.542 9.383 Total '03-'06+09 Octaplas 267.000 6.2-21.0 22.250 66.750 33.375 > 267'000 AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction

Lifethreatening /serious Hemovigilance Data Norway (TROLL Reports) – all octaplas® Year Bags AEs Lifethreatening /serious Less or non-serious TRALI Cardio-vascular Anaphylactoid Allergic FNHTR Others 2007 39.867 15 1 14 6 2 2008 47.690 13 4 3 2009 45.344 11 5 2010 45.085 Total '07-'10 177.986 45 43 19 9 1 per ... NA 3.955 88.993 4.139 > 177'986 29.664 9.368 16.181 19.776 AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction

Life threatening/ serious Hemovigilance Data Experience from Sweden (Vaara 2010) Year Bags AEs 95% CI Life threatening/ serious Less or non-serious FFP 1.135 19 11.5-29.5 5 14 octaplas® 2.621 0.0-3.7 Total FFP 1 per ... NA 60 227 81 Total Octaplas > 2'621

Hemovigilance Data Experience from Finland (Krusius 2012) Year Bags Serious AEs 95% CI TRALI FFP 90.372 22 13.8-33.3 5 1.6-11.7 octaplas® 239.359 14 0.6-8.8 0.0-3.7 Total '05-'11 FFP 1 per ... NA 4.108 18.074 Total '05-'11 Octaplas 17.097 > 239'359

Post-Authorization Safety (Pharmacovigilance) Data octaplas® Sales Figures 1992 to 2011 (trade sales & contract work) In total 7’553’122 bags, thereof 142’110 octaplasLG® in Germany

Post-Authorization Safety (Pharmacovigilance) Data Overview on Non-Serious Case Reports

Post-Authorization Safety (Pharmacovigilance) Data Overview on Serious Case Reports

Clinical Experience with octaplas® Summary of Available Clinical Information Interventional clinical studies: 7 studies, 177 patients Non-interventional studies and retrospective data surveys: 5 studies, 288 patients Hemovigilance data: covering 21 years documented in 14 reports of 5 countries, covering 860,000 bags of octaplas® Safety information from post-marketing reporting: from more than 7.6 million bags of octaplas® corresponding to about 2 million treatments since 1992