Slide 1: R&D Briefing
For personal use only R&D Briefing December 5, 2013
Slide 2: Legal Notice: Forward looking statements
Legal Notice Forward looking statements For personal use only The materials in this presentation speak only as of the date of these materials, and include forward looking statements about CSL’s financial results and estimates, business prospects and products in research, all of which involve substan
Slide 3: Agenda December 2013 R&D Briefing
Agenda December 2013 R&D Briefing • Welcome Mark Dehring For personal use only • Introduction & Highlights Andrew Cuthbertson • Protein Science Andrew Nash • Immunoglobulins & Specialty Products • Clinical Development Russell Basser • Commercial Opportunities Lutz Bonacker • Q&A Break • Coagulation/
Slide 4: Introduction and Highlights
For personal use only Introduction and Highlights
Slide 5: CSL Protein Therapeutics Technical Platform
CSL Protein Therapeutics Technical Platform For personal use only Breakthrough Medicines Immunoglobulins Specialty Products Haemophilia Products Plasma Recombinant Fractionation Technology Protein Science 5
Slide 6: CSL R&D Strategy
CSL R&D Strategy For personal use only • Maintain commitment Breakthrough to extracting maximum Medicines value from existing assets and supporting and improving current products Specialty Immunoglobulins Products • Develop new protein-based therapies for treating serious illnesses focusing Haemophi
Slide 7: Leveraging Global Capabilities
Leveraging Global Capabilities For personal use only 7
Slide 8: R&D Investment
8 For personal use only R&D Investment
Slide 9: Global R&D Portfolio December 2012
Global R&D Portfolio December 2012 Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH For personal use only Immunoglobulins Haemophilia Specialty Products Life Cycle Influenza Management Vaccine Hizentra ® CIDP Privigen
Slide 10: Progress through Stage Gates in 2013
Progress through Stage Gates in 2013 For personal use only Privigen® rvWF-FP rVIIa-FP rVIII-SC CIDP Hizentra® Anti-FXIIa Beriplex® Zemaira® EU Japan Japan Hizentra® Berinert® KcentraTM Bi-weekly s.c. Surgery US Voncento™ CSL112 EU FXIII Japan CSL362* Janssen KcentraTM Bleeding US IAT Berinert® EU pr
Slide 11: Protein Science
For personal use only Protein Science
Slide 12: CSL's Global Research Capability
CSL’s Global Research Capability • ~130 of 1000 scientists dedicated to research For personal use only • Hub & spoke model • Single coordinated project portfolio • Research excellence in therapeutic proteins • Plasma and recombinant manufacturing platforms 12
Slide 13: Bio21 - Research Hub
Bio21 - Research Hub • Located within world class university, medical research and hospital For personal use only precinct in Parkville • Technical expertise • protein engineering, molecular biology, cell biology, models of disease, genomics / bioinformatics • Improved access to • high quality staff
Slide 14: CSL Research Key Objectives
CSL Research Key Objectives For personal use only Deliver new development Scientific support Resolve critical opportunities to SG2 beyond SG2 scientific issues Assess new product Add value to the existing opportunities and CSL product portfolio: emerging threats - yield improvements - improved formu
Slide 15: Innovation in Key Areas of CSL's Business
Innovation in Key Areas of CSL’s Business For personal use only Immunoglobulins • PID - convenience Efficacy • Non-PID – efficacy / convenience Haemophilia Cost Drivers of Convenience • convenience / quality of life innovation in healthcare (CSL) Specialty Products • product specific but..... Supply
Slide 16: Plasma Proteins
Plasma Proteins • Capabilities from discovery to market For personal use only Plasma collection Plasma fractionation Completed Phase IIa - Strong increase in cholesterol efflux capacity Electron microscopy of CSL112 16
Slide 17: Recombinant Proteins
Recombinant Proteins • Capabilities from discovery to market For personal use only Manufacturing CLD Lab Phase III / launch manufacturing Protein Engineering Lab Patient Phase I / II manufacturing Animal models of disease 17
Slide 18: CSL654 (rIX-FP) – Discovery to Development
CSL654 (rIX-FP) – Discovery to Development For personal use only Factor IX fused to human CSL654 manufacturing CHO clones CSL654 T1/2 extension in Haem B albumin (CSL654) Bio21 patients compared to Benefix Marburg King of Prussia Mean values and fitted curves 1 CSL654 100 IU/kg (n=3) 0.50 BeneFIX® 1
Slide 19: Research Publications
Research Publications For personal use only 19
Slide 20: Plasma and Recombinant Synergies
Plasma and Recombinant Synergies Plasma therapeutics expertise / new recombinant therapies For personal use only • Recombinant coagulation factors • CSL654 / rIX-FP, CSL689 / rVIIa-FP, CSL627 / rVIII-SingleChain • CSL650 / rvWF-FP 20
Slide 21: CSL650 (rvWF-FP)
CSL650 (rvWF-FP) • vWF-FP expressed in CHO cells forms multimers and demonstrates For personal use only an extended half-life Rat PK study 4000 vWF:Ag [mIU/mL] pd vWF 3000 rvWF rvWF-FP 2000 Day 13 Day 18 Day 24 Day 29 Day 3 Day 7 SHP SHP 1000 0 0 120 240 360 480 1440 time [minutes] Animal Half-life
Slide 22: FXIIa Antagonists
FXIIa Antagonists For personal use only Auto-activation pathways Mitogenesis +FXIIa/β FXIIa Berinert PK → KAL Kalbitor βFXIIa Berinert Icatibant Fibroblast/ FXI → FXIa HK → BK→ BR2 C1qr,s → C1qr,s endothelial cell Vasodilation, Complement Hemostasis vascular permeability activation Thrombosis HAE Tr
Slide 23: FXIIa Antagonist mAb - HAE
FXIIa Antagonist mAb - HAE Percutaneous anaphylaxis, a mouse model of HAE For personal use only • anti-FXIIa mAb 3F7 inhibits edema * ** *** 120 *** Ctrl 100 80 % of PBS 60 40 20 3F7 0 0.5 0.5 0.2 0.1 0.05 mg BM4 3F7 23
Slide 24: FXIIa Antagonist mAb - Thrombosis
FXIIa Antagonist mAb - Thrombosis • Extracorporeal membrane oxygenation (ECMO) For personal use only • Heparin coated circuits and heparin infusion are required to prevent thrombosis • Bleeding is the most frequent complication • intracerebral hemorrhage (particularly new borns) • pulmonary hemorrha
Slide 25: FXIIa Antagonist mAb - Thrombosis
FXIIa Antagonist mAb - Thrombosis ECMO-rabbit model For personal use only • anti-FXIIa mAb 3F7 prevents fibrin deposition with no increased risk of bleeding 25
Slide 26: CSL362 for the Treatment of SLE
CSL362 for the Treatment of SLE CSL362 • Proposed role for pDC’s in SLE For personal use only CD123 / IL-3Ra TLR7/9 Complement-dependent cell cytotoxicity CSL362 targets activation and TLR7/9 CD8+ activation kills pDC’s pDC T cell Cytotoxicity Dying cell Dying cell IFNa RNA/DNA Immune complex Autoan
Slide 27: CSL362 for the Treatment of SLE (Lupus)
CSL362 for the Treatment of SLE (Lupus) • CSL362 prevents IFNa production in blood from normal donors and For personal use only SLE patients Healthy controls Healthy controls SLE SLEpatients patients Healthy SLE 1000 100 IFI44L IFNa concentration pg/ml (Log10) IFNa conc. (pg/ml) IFNa conc. (pg/ml) I
Slide 28: CSL Research and Protein Science
CSL Research and Protein Science • High quality research capability to For personal use only Efficacy generate new development opportunities and address key Cost Drivers of Convenience innovation in scientific issues healthcare (CSL) • Expertise to identify and progress Supply Safety opportunities u
Slide 29: Immunoglobulins
For personal use only Immunoglobulins
Slide 30: Immunoglobulins Key Focus
Immunoglobulins For personal use only Maintaining leadership position through focus on: • Patient convenience • Yield • Label Immunoglobulins • Formulation science • Specialty Igs Key Focus • Privigen® • Hizentra® 30
Slide 31: Privigen
Privigen® For personal use only The first and only 10% liquid intravenous immunoglobulin (IVIg) therapy that is proline stabilised with room temperature storage up to 36 months Strengthening Presence in Neurology Market • Phase III study showed treatment with Privigen® improved function in patients
Slide 32: Hizentra
Hizentra® For personal use only The first 20% high concentration low volume SCIG for convenient self administration providing steady-state Ig levels and an established long-term safety record with chronic administration Global Rollout • Launched in US since 2010 • Broad approvals in EU and Canada •
Slide 33: Hizentra Schedules
Hizentra® Schedules For personal use only US administration options expanded to include dosing once every two weeks (biweekly) in Sept 2013 • FDA and EU approval of biweekly dosing based on principles of pharmacometrics and pharmacokinetic modelling of clinical trial data from registration program S
Slide 34: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities
Slide 35: Global Immunoglobulin Market
Global Immunoglobulin Market For personal use only 2012/13 Sales • Market includes IVIG, SCIG and Hyperimmunes CSL • Growing, but competitive, market • CSL is well positioned: •X •X $US 7+ B •x 35
Slide 36: CSL's Immunoglobulin Portfolio
CSL’s Immunoglobulin Portfolio For personal use only 2012/13 Sales Specific IG • Globalise portfolio Hizentra® • Expand into neurology Privigen® • Increase convenience IVIG Other $US 2,081 M 36
Slide 37: Immunoglobulins: Progress Achieved
Immunoglobulins: Progress Achieved For personal use only • Hizentra® PID in Japan – first and only SCIG product in Globalise Japan • Privigen® currently registered in 61 countries portfolio • Hizentra® currently registered in 38 countries • Privigen® CIDP launched in Q2 2013 Expand into • Ongoing De
Slide 38: Benefits of SCIg: Steady-State, Convenience
Benefits of SCIg: Steady-State, Convenience 1600 For personal use only 1400 Total IgG (mg/dL) 1200 Intravenous Ig 1000 800 Subcutaneous Ig 600 400 0 2 4 6 8 10 12 14 16 18 20 22 Days Representative graph for illustration only SCIG: • True s.c administration profile • Steady-state IgG levels1 • Less
Slide 39: New Advances for Patients
New Advances for Patients For personal use only Biweekly 10g (50mL) Vial • Approval US: Sept 25, 2013 • Approval US: Jun 12, 2013 • Available US: Sept 25, 2013 • Available US: Oct 15, 2013 IVIg patients who: • Have considered SCIg but felt weekly infusions were too frequent Patients relying on careg
Slide 40: Specialty Products
For personal use only Specialty Products
Slide 41: Specialty Products Key Focus
Specialty Products Leveraging high quality, For personal use only broad product portfolio through: • New markets • Novel indications • Novel modes of Specialty administration Products Key Focus • Beriplex® / KcentraTM • Fibrinogen • Zemaira® • Berinert® 41
Slide 42: Kcentra (Beriplex)
KcentraTM (Beriplex®) For personal use only • Prothrombin Complex Concentrate = PCC • vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) Seeking approval for use of KcentraTM to reverse the effects of vitamin K antagonists (e.g. Warfarin) for: • Bleeding related to over-anticoagulation • P
Slide 43: Kcentra (Beriplex)
KcentraTM (Beriplex®) For personal use only • Kcentra approved by FDA in April for bleeding indication 43
Slide 44: Kcentra Surgical Study Design
KcentraTM Surgical Study Design For personal use only Kcentra + Vitamin K R A N D O Subjects on M VKA in need I of surgery S E Plasma + Vitamin K D 1:1 INR Haemostatic Safety Virus efficacy (SAEs) testing 30 min End of surgery 45 days 90 days end of infusion 44
Slide 45: Kcentra to reverse VKA prior to surgery
KcentraTM to reverse VKA prior to surgery For personal use only • All patients had reversal of blood thinning test (INR) to normal prior to surgery • Those given KcentraTM had less bleeding during subsequent surgery % of subjects Difference Kcentra – Kcentra Plasma plasma (%) (N = 87) (N = 81) “Effe
Slide 46: Kcentra Surgical Study Conclusions
KcentraTM Surgical Study Conclusions For personal use only KcentraTM was: • superior to plasma for control of bleeding • superior to plasma for rapid reduction in INR • as safe as plasma (safer with regard to some effects) FDA granted priority review • Action date 14 December 2013 46
Slide 47: Fibrinogen
Fibrinogen For personal use only The first and only treatment approved by the US FDA for acute bleeding episodes in patients with congenital fibrinogen deficiency Europe • Peri-/post-operative control of coagulopathic bleeding • REPLACE Phase III study • 200 subjects – recruitment commenced Jan 2012
Slide 48: Zemaira
Zemaira® For personal use only Zemaira is the first highly purified alpha-1 augmentation therapy approved by the FDA for chronic augmentation and maintenance therapy of adults with Alpha-1 and emphysema Seeking to broaden commercial reach through: • Launch in EU, Canada, Brazil • EU requires demonst
Slide 49: Alpha-1-antitrypsin Deficiency
Alpha-1-antitrypsin Deficiency For personal use only • Chronic obstructive pulmonary disease (COPD) or emphysema • Cirrhosis and liver failure less commonly • Under-diagnosed • Lung disease usually presents in 30-40’s 49
Slide 50: RAPID Study Design
RAPID Study Design For personal use only R EXTENSION STUDY Zemaira weekly iv A N D Zemaria weekly iv O M 180 subjects I Placebo S E D 1:1 baseline 12 months 24 months 36 months 48 months CT scan 50 2
Slide 51: RAPID Study Data
RAPID Study Data Physiologically Adjusted Lung Density (TLC) For personal use only Placebo Zemaira 0.0 -1.45 -1.0 Change From Baseline (g/L) -2.0 -2.90 -3.0 -2.19 -3.97 -4.0 -5.03 -5.0 -4.38 -6.0 -5.35 -7.0 -6.32 RAPID Trial RAPID Extension Trial -8.0 0 12 24 36 48 Month of Treatment Zemaira® slows
Slide 52: Berinert
Berinert® For personal use only Plasma derived, pasteurised & nanofiltered concentrate of C1 Esterase Inhibitor indicated for the treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) in adults and adolescents • US and European approved label expansion for self administration
Slide 53: Berinert subcutaneous prophylaxis study program
For personal use only Dose-ranging study • Assess safety, PK/PD • 18 HAE patients with infrequent attacks Phase II • Clinically relevant blood levels achieved Clinical efficacy study • Double-blind, placebo-controlled • 72 HAE patients with frequent attacks Phase III Long-term safety and efficacy •
Slide 54: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities
Slide 55: CSL's Specialty Products Portfolio
CSL’s Specialty Products Portfolio 2012/13 Sales For personal use only Wound Healing Other Specialty Products Tachocomb® Beriplast® Kybernin® Berinert® Zemaira® Streptase® Fibrogammin® Beriplex® Perioperative Bleeding $US719 M Riastap® • Increase clinical data set • Add indications • Expand regional
Slide 56: Blood Components vs. Concentrates
Blood Components vs. Concentrates For personal use only FFP Fibrinogen concentration at ≈2.3g / L Not virus inactivated Frozen, requires time (<50 minutes) to thaw Red Blood Cells Need to be matched to blood type Not virus inactivated Concentrated, virus inactivated, room temperature storage, Fibrin
Slide 57: Kcentra
KcentraTM For personal use only KcentraTM, Prothrombin Complex Concentrate (Human), is indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g. warfarin) therapy in adult patients with acute major bleeding 2013 Apr May Jun Jul Aug Sep Oct
Slide 58: Kcentra Awarded New Technology Add-On Payment
KcentraTM Awarded New Technology Add-On Payment For personal use only Centers for Medicare and Medical Community Support Medicaid Services (CMS) for Kcentra NTAP approved a new technology add-on payment (NTAP) for Kcentra “AABB strongly believes that Kcentra provides a significant improvement in car
Slide 59: Riastap
Riastap® For personal use only trial with global impact, Europe, Japan, Canada • Obtain US acquired bleeding label • Initiate acquired label expansion • Central role of fibrinogen in severe bleeding discussed in scientific literature1 • Early intervention with concentrates further recommended in gui
Slide 60: Zemaira and the RAPID results
Zemaira® and the RAPID results For personal use only The first and only proven disease-modifying A1-PI therapy shown to slow damage to lung tissue and delay the progression of emphysema RAPID data • Data rollout initiated at ATS • Will provide clinical differentiation supporting preferred formulary
Slide 61: Berinert
Berinert® For personal use only Berinert treats the fundamental cause of HAE symptoms by providing C1-Inhibitor deficient patients with the missing human protein1 Berinert has demonstrated that it provides fast relief of pain and swelling within 30 minutes2 • Obtain Prophylaxis indication • Increase
Slide 62: Berinert Key Features
Berinert® Key Features • Efficacy: Almost no For personal use only redosing required to treat attacks Product Advantages • Early onset of relief • Excellent Safety and tolerability • Control of product supply Manufact- - own plasma collection uring centers and manufacturing sites • s.c. prophylaxis
Slide 63: HAE Therapeutic Segments
HAE Therapeutic Segments Current Developments For personal use only Berinert (C1 Inhibitor) Acute HAE Therapeutic Bradykinin/Kallikrein antagonist Segments Steroids C1 Inhibitor i.v. Berinert s.c. Prophylaxis FXIIa MAb (longer half life) Kallikrein Inhibitors (longer half life) 63
Slide 64: Q&A
For personal use only Q&A
Slide 65: Break
For personal use only Break
Slide 66: R&D Briefing
For personal use only R&D Briefing December 5, 2013
Slide 67: Haemophilia Products
For personal use only Haemophilia Products
Slide 68: Haemophilia Key Focus
Haemophilia Supporting and enhancing plasma products and developing For personal use only novel recombinant portfolio with focus on: • Scientific and product innovation • Patient benefit Key Focus Haemophilia • Long acting rIX-FP Products • Long acting rVIIa-FP • rVIII-Single Chain • Research into l
Slide 69: Innovation to Drive Growth
Innovation to Drive Growth For personal use only Patient convenience primary Scientific Edge driver of innovation • Albumin fusion technology Improved half life, extended rAlbumin as fusion Precise engineering of specially dosing platform designed • rIX-FP, rVIIa-FP, rvWF-FP interval linker High vWF
Slide 70: rIX-FP (CSL654)
5 For personal use only rIX-FP (CSL654)
Slide 71: rIX-FP (CSL654) Global Clinical Program
rIX-FP (CSL654) Global Clinical Program For personal use only PUP study Phase I Phase I/II Phase II/III Phase III Paediatric PK PK PK safety Long-term safety Long-term safety 7d prophylaxis 7-14d prophylaxis Extension On-demand On-demand Surgical prophylaxis 6
Slide 72: Compared with in market rFIX
For personal use only Compared with in market rFIX • 5.3-fold longer half-life (92hrs) • ~ 45% higher incremental recovery • ~7-fold larger AUC • ~7-fold slower clearance 7
Slide 73: rIX-FP (CSL654) Efficacy in Phase I/II Study
rIX-FP (CSL654) Efficacy in Phase I/II Study For personal use only • Annualised spontaneous bleeding during the study vs previous 12 months (n=10) (n=3) (n=4) 8
Slide 74: rIX-FP (CSL654) Clinical Development
rIX-FP (CSL654) Clinical Development For personal use only • Excellent safety profile • Well tolerated • No inhibitors • No adverse events related to CSL654 • All patients now enrolled in Phase II/III and Paediatric studies • Dossier submission now planned early 2015 9
Slide 75: rVIIa-FP (CSL689)
10 For personal use only rVIIa-FP (CSL689)
Slide 76: rVIIa-FP half-life data
For personal use only Time • Half-life = 8.5 hrs (vs rFVIIa ~2-3hrs) • Well tolerated, no serious adverse events 11
Slide 77: rVIIa-FP (CSL689) Global Clinical Program
rVIIa-FP (CSL689) Global Clinical Program For personal use only • Pivotal Phase II/III trial in haemophilia A & B patients with inhibitors • Dose finding, safety & efficacy on-demand therapy • Ongoing discussions with regulatory agencies (FDA, PEI, PMDA) • Anticipate commencing in 2014 12
Slide 78: Potential of rVIIa-FP (CSL689)
Potential of rVIIa-FP (CSL689) For personal use only For patients with inhibitors • Single dose for treatment of bleeding • Prevention of bleeding in patients undergoing surgery • Prophylaxis Other indications • Congenital Factor VII deficiency • Acquired haemophilia • Glanzmann's thrombasthenia 13
Slide 79: rVIII-SingleChain (CSL627)
rVIII-SingleChain (CSL627) For personal use only 14
Slide 80: rVIII-SingleChain: approach for improved FVIII
rVIII-SingleChain: approach for improved FVIII FVIII’s physiological partner in plasma is von Willebrand For personal use only factor (vWF) • FVIII/vWF complex is important role in the physiological activity and clearance of FVIII • Aim - improve binding to vWF FVIII is an unstable molecule in the m
Slide 81: rVIII-SingleChain Phase I/III Study Design
rVIII-SingleChain Phase I/III Study Design Interim analysis For personal use only Part 1 Part 2 CSL627 & Octagog alfa CSL627 repeat-dose, on-demand or Extension study single-dose PK (n=30) prophylaxis (n=30) Part 3 CSL627 repeat-dose, on-demand or prophylaxis (n=78 evaluable subjects) Single-dose PK
Slide 82: CSL627 PK Supports Dosing Twice-Weekly
CSL627 PK Supports Dosing Twice-Weekly For personal use only Product Time to 2% Time to 1% (hr) (hr) rVIII-SingleChain 78.0 91.9 Octocog alpha 65.2 77.2 Data presented are mean values. n=22 17
Slide 83: CSL627 PK Evaluation: Area Under the Curve
CSL627 PK Evaluation: Area Under the Curve For personal use only 30 rVIII-SingleChain Octocog alpha Dose-normalised AUC (IU*hr/mL) 25 20 15 10 5 0 AUC0-last 1 AUC0-∞ *Dose-normalised baseline-corrected FVIII activity AUC0-last and AUC0-∞ in plasma following a single intravenous administration of rVI
Slide 84: rVIII-SingleChain Phase I/III Study Results to Date
rVIII-SingleChain Phase I/III Study For personal use only Results to Date • Very well tolerated • No inhibitors • All bleeding events effectively treated • Last patient now to be enrolled early 2014 • recruitment challenges • Dossier submission now planned early 2015 19
Slide 85: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities
Slide 86: Coagulation Sales
Coagulation Sales For personal use only 2012/13 Helixate® Pd Coag pd Coag $US1,090M • Broad portfolio presence • Growing pd portfolio • Helixate® as a strong foundation for recombinant pipeline 21
Slide 87: Coagulation: Key Market Segments and Products
Coagulation: Key Market Segments and Products For personal use only • Beriate ® • Helixate® NexGen/FS/81 • Factor X P® Hem A • rVIII-Single ~ $5.2B FX P Chain ~ $2M pd ITT management • Voncento® • rVIIa-FP Inhibitor bleed ~ $0.4B • Haemate P® treatment Target ~ $1B Segments • Mononine® • Voncento® V
Slide 88: Coagulation: Factors with Market Impact
Coagulation: Factors with Market Impact For personal use only Product Choice Treatment Options Diagnosis rIX-FP rVIIa-FP rVIII-SingleChain 23
Slide 89: Coagulation: Factors with Market Impact
Coagulation: Factors with Market Impact For personal use only Product Choice Treatment Options Diagnosis Identification of patients with bleeding disorders is still ongoing 1) 24 1) WFH Global Survey 2011
Slide 90: Coagulation: Factors with Market Impact
Coagulation: Factors with Market Impact For personal use only On Demand Treatment Prophylaxis Options • Episodic, fewer • Regular, more infusions infusions • Addresses bleed • Avoids bleeds WFH/ISTH recommendation: “Prophylaxis prevents bleeding and joint destruction and should be the goal of therap
Slide 91: Coagulation: Factors with Market Impact
Coagulation: Factors with Market Impact For personal use only Product Effective Choice Safe Low inhibitor risk Fewer needlesticks 26
Slide 92: rIX-FP (CSL654)
rIX-FP (CSL654) For personal use only Effective Safe Low inhibitor Fewer • Recombinant risk needlesticks • Bleeding events Albumin as • Specifically • T/2 at 92h effectively fusion partner designed • Supports treated • Well linker dosing every • Successful tolerated, • Recombinant 2+ weeks prophylax
Slide 93: rVIIa-FP (CSL689)
rVIIa-FP (CSL689) For personal use only Effective Safe Low inhibitor Fewer • Effective in • Recombinant risk needlesticks range of Albumin as • Specifically • T/2 at 8.5h animal fusion partner designed • Supports on models • Well tolerated flexible linker demand and locally and • Recombinant prophyl
Slide 94: rVIII-SingleChain (CSL627)
rVIII-SingleChain (CSL627) For personal use only Effective Safe Opportunity Fewer • Bleeding • Well for low needlesticks events tolerated inhibitor risk • Time to 1% effectively locally and • High binding FVIII level treated systemically affinity to supports 2x • Improved to date VWF per week molecu
Slide 95: Presenting Data: Active Scientific Presence
Presenting Data: Active Scientific Presence 40 For personal use only 35 30 25 20 15 10 5 0 Abstracts / Poster / Presentations Publications 30
Slide 96: Breakthrough Medicines
For personal use only Breakthrough Medicines
Slide 97: Breakthrough Medicines
Breakthrough Medicines For personal use only Leveraging clinical and technical insight in developing Breakthrough novel protein-based therapies Medicines • Significant unmet need • Multiple indications Key Focus • CSL112 (Apo AI) • CSL346 (anti-VEGF-B mAb) • FXII Antagonist 32
Slide 98: CSL112 (Apolipoprotein A-I)
CSL112 (Apolipoprotein A-I) For personal use only • CSL112 is natural apolipoprotein A-I (apoA-I) the chief protein component of HDL • Rapidly and robustly enhances capacity of plasma to promote cholesterol efflux • Potential to address significant gap in acute coronary syndrome • Cholesterol remova
Slide 99: CSL112 Mechanism of Action
CSL112 Mechanism of Action For personal use only HDL3 HDL2 Unesterified cholesterol CSL112 LCAT LCAT Cholesterol esters HDL-VS ApoA-I Phospholipid ABCA1 ABCG1 SRB1 • Global Phase IIb clinical program to initiate early 2014 34 Modified from Kingwell & Chapman. Circulation 2013;128:1112-21
Slide 100: Licensing and Collaborations
For personal use only Licensing and Collaborations
Slide 101: Licensing
Licensing For personal use only Optimising value of IP Portfolio and assets Breakthrough Breakthrough Medicines Medicines • Partner high opportunity products • GARDASIL® Specialty Immunoglobulins Specialty Immunoglobulins Products • Mavrilimumab (GM- Products CSFRa - Medi/AZ) Haemophilia • Periodont
Slide 102: GARDASIL
GARDASIL® • Impact of Australian HPV Vaccination Program For personal use only • 93% reduction in genital warts in females less than 21 years • 82% reduction in genital warts in heterosexual males less than 21 years • 48% less high grade pre-cancers in women vaccinated in catch-up program (12-17 yea
Slide 103: CSL362 (anti-IL-3Ra mAb)
CSL362 (anti-IL-3Ra mAb) • Initial indication: Acute myeloid leukaemia For personal use only • Enhanced recruitment of tumour killing NK cells • Phase I trial in progress • Other high quality opportunities in autoimmunity eg. SLE • Agreement with Janssen Biotech, Inc • Exclusive worldwide license to
Slide 104: ISCOMATRIX Adjuvant
ISCOMATRIX® Adjuvant Merck Research For personal use only FRNT Titre (Log10) Laboratories • Dengue Phase 1 fully enrolled • Long lived antibodies in pre exposed NHPs 100 Novavax VLP 45mcg 80 % Subjects seroconversion • H5N1 Low-dose IMX 60 5mcg • WVC 2013 Low-dose IMX 40 15mcg • H7N9 20 Med-dsoe Med
Slide 105: Summary
For personal use only Summary
Slide 106: Global R&D Portfolio December 2013
Global R&D Portfolio December 2013 Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH For personal use only Immunoglobulins Haemophilia Specialty Products Life Cycle Influenza Management Vaccine Hizentra ® Japan Hizentra
Slide 107: Expected Progress in next Months
Expected Progress in next 12 Months For personal use only rVIIa-FP Zemaira® EU KcentraTM CSL112 Surgery US Fibrinogen Anti-FXIIa Aortic US Beriplex® Japan Berinert® s.c. Fibrinogen Aortic Japan 42
Slide 108: Significant Target Launch Dates
Significant Target Launch Dates 2013 2014 2015 2016 2017 2018 For personal use only Voncento™ CSL654 CSL689 EU rIX-FP rVIIa-FP CSL627 rFVIII KcentraTM KcentraTM Fibrinogen EU Berinert® Bleeding Surgical Aortic Surgery SubCut Berinert® EU Zemaira® Beriplex® ST Prophylaxis EU Japan Privigen® CIDP Hize
Slide 109: 2013 Highlights
2013 Highlights For personal use only • Privigen® CIDP registration in EU Immunoglobulins • Hizentra® BiWeekly registration in US and EU • Hizentra® registration in Japan • KcentraTM registration for bleeding indication in US Specialty Products • Zemaira® efficacy data submitted in EU and US • Berin
Slide 110: Q&A
For personal use only Q&A
Slide 111: Further Information
Further Information Presentation Playback For personal use only A playback of the Research and Development presentations will be available for a period of two weeks following the R&D Briefing. Investors wishing to listen to these presentations should contact CSL Investor Relations to arrange access.