Slide 1: Investor R&D Briefing
For personal use only Investor R&D Briefing December 1, 2016 1
Slide 2: Global Legal Notice
Global Legal Notice For personal use only Forward looking statements The materials in this presentation speak only as of the date of these materials, and include forward looking statements about CSL Limited and its related bodies corporate (CSL) financial results and estimates, business prospects an
Slide 3: Agenda
Global Agenda For personal use only • Welcome Mark Dehring • Introduction & Highlights Andrew Cuthbertson • Research & Early Development Andrew Nash • Immunoglobulins & Specialty Products • Clinical Development Charmaine Gittleson • Commercial Opportunities Bob Repella • Q&A - Break - • Coagulation/
Slide 4: Introduction and Highlights
For personal use only Introduction and Highlights 4
Slide 5: Global Commitment to Research & Development
Global Commitment to Research & Development For personal use only 5
Slide 6: Past Launches from the R&D Portfolio
Global Past Launches from the R&D Portfolio For personal use only 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 VIVAGLOBIN® PRIVIGEN® Ig IsoLo® HIZENTRA® Ig RHOPHYLAC® RESPREEZA® (EU) ZEMAIRA® (US) BERINERT® (US) KCENTRA® (US) Specialty BERIPLEX® (EU) RIASTAP® (US) CORIFACT® (US) Coag./Heam
Slide 7: Leveraging Global Capabilities
Global Leveraging Global Capabilities For personal use only >1,400 scientists globally 7
Slide 8: R&D Portfolio – December 2015
Global R&D Portfolio – December 2015 For personal use only Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine HIZENTRA® CIDP C1-INH
Slide 9: Progress Through Stage Gates in 2016
Global Progress Through Stage Gates in 2016 For personal use only PRIVIGEN® PRIVIGEN® Japan IsoLo CSL640 Hizentra® IDELVION® rIX-FP subct IIM US CSL626 D’D3 IDELVION® LA rVIII AFSTYLA® EU Japan IDELVION® Haptoglobin/ CSL842 C1-INH Japan AFSTYLA® Hemopexin Transplant EU AFSTYLA® Next Gen Ig US Formul
Slide 10: R&D Portfolio – December 2016
Global R&D Portfolio – December 2016 For personal use only Commercial/ Research Pre-clinical Phase I Phase II Phase III Registration Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine HIZENTRA® CIDP C1-INH
Slide 11: CSL Behring R&D Strategy and Focus
For personal use only CSL Behring R&D Strategy and Focus 11
Slide 12: CSL Protein Therapeutics Technical Platform
Global CSL Protein Therapeutics Technical Platform For personal use only Breakthrough Medicines Immunoglobulins Specialty Products Haemophilia Products Plasma Recombinant Fractionation Technology Protein Science 12
Slide 13: Research & Early Development
For personal use only Research & Early Development 13
Slide 14: CSL's Global Research Capability
Global CSL’s Global Research Capability For personal use only • Coordinated global project portfolio Specialty Breakthrough Immunoglobulins Haemophilia Products Medicines • Hub (Bio21, Melbourne) & spoke model • Bio21 expansion to increase pre-clinical research • Research excellence in therapeutic p
Slide 15: Haemophilia Research Strategy
Haemophilia Research Strategy For personal use only • Major focus on patient Quality of Life Novel Strategies – Coag Factor • Extract maximum value and performance from existing assets Maximising Value Addressing • Develop new protein-based therapies and Performance and strategies for treating conge
Slide 16: Haemophilia FVIII Half-Life Extension
Haemophilia FVIII Half-Life Extension For personal use only • Short FVIII half-life, improved half life = improved prophylaxis • FVIII half-life regulated by VWF • Target VWF half-life while minimising thrombosis risk • CSL626 = VWF D’D3 fragment fused to human albumin Von Willebrand Factor D’ D3 Al
Slide 17: Haemophilia FVIII Half-Life Extension: CSL626 data
Haemophilia FVIII Half-Life Extension For personal use only CSL626 extends the half-life of co-administered AFSTYLA® in NHPs AFSTYLA® HAEMATE® P pd VWF + AFSTYLA® CSL626 dose 1 + AFSTYLA® CSL626 dose 2 + AFSTYLA® CSL626 dose 3 + AFSTYLA® CSL626 dose 1 • 4-5 fold increase in AFSTYLA® half-life • GLP
Slide 18: Immunoglobulins Research Strategy
Immunoglobulins Research Strategy For personal use only Optimising the • Formulation and purification Value of our processes Products • Opportunities for new technologies Anticipating / molecules Translating Ig Disruptive Mechanisms Innovation • Mechanism driven product design and indication selecti
Slide 19: Immunoglobulin Mimetics
Immunoglobulins Immunoglobulin Mimetics For personal use only Immunoglobulin functional domains Fab region •Immune deficiencies recombinant multimerised Fc Fc region •Autoimmune conditions Improved target binding 19
Slide 20: Immunoglobulin Mimetics: CSL777 proof-of-concept
Immunoglobulins Immunoglobulin Mimetics For personal use only CSL777 proof-of-concept in CAbIA model of arthritis 6 6 Mean clinical score (d7-14) 5 Clinical score 5 4 PBS 4 3 3 2 IVIG 2 * CSL777 1 1 0 0 6 7 8 9 10 11 12 13 14 PBS IVIG CSL777 Day of experiment • 200 mg/kg CSL777 or 2 g/kg IVIG, i.p.
Slide 21: Breakthrough Medicines Research Strategy
Breakthrough Medicines Research Strategy For personal use only Breakthrough Medicines • Leveraging clinical and technical insight in developing novel protein- Specialty based therapies Immunoglobulins Products o Significant unmet need o Multiple indications Haemophilia Products 21
Slide 22: Breakthrough Medicines Portfolio – Late Preclinical / Clinical
Breakthrough Medicines Portfolio – Late Preclinical / Clinical For personal use only • Portfolio of preclinical and early-mid stage clinical opportunities consistent with CSL commercial objectives • Delivery of high quality candidates for clinical development Research Pharm / tox Phase I Phase II CS
Slide 23: CSL324 – Chronic & Acute Inflammation
Breakthrough Medicines CSL324 – Chronic & Acute Inflammation For personal use only • Targeting the G-CSF receptor represents a novel approach to the treatment of neutrophil mediated pathologies • Efficacy in multiple animal models of inflammatory disease Bone G-CSF G-CSF inflamed Marrow tissues neut
Slide 24: CSL324 – Anti-G-CSFR mAb reverses arthritis
Breakthrough Medicines CSL324 – Chronic & Acute Inflammation For personal use only Anti-G-CSFR mAb reverses development of arthritis • Mouse CAbIA model ‡ P < 0.001 • GLP toxicology completed, CSL324 safe and well tolerated • Phase I commenced July 2016, Phase II H1 2018 Source: Campbell et al., J.
Slide 25: CSL312 – HAE and Thrombosis
Breakthrough Medicines CSL312 – HAE and Thrombosis For personal use only • Targeting FXIIa represents a novel approach to the treatment of hereditary angioedema and contact activated thrombosis • Efficacy in multiple animal models and translational studies Auto-activation FXIIa - FXI → FXIa PK → KAL
Slide 26: CSL312 – Prevents FXIIa mediated vascular leakage
Breakthrough Medicines CSL312 – HAE and Thrombosis For personal use only Anti-FXIIa antibody prevents FXIIa mediated vascular leakage • Mouse model incorporating a mutant (HAE type III) human FXIIa Tg (7mg/kg) Tg Off On On Mouse HAE wild Human HAE type III type FXII gene out FXII gene in + anti-FXII
Slide 27: CSL312 – Prevents thrombosis without bleeding risk
Breakthrough Medicines CSL312 – HAE and Thrombosis For personal use only Anti-FXIIa antibody prevents foreign surface activated thrombosis without increasing bleeding risk • Rabbit ECMO model Source: Larsson et al., Sci Transl Med, 2014 27
Slide 28: CSL346 – Diabetes / Diabetic Complications
Breakthrough Medicines CSL346 – Diabetes / Diabetic Complications For personal use only VEGF-B controls tissue uptake of fatty acids via regulation of endothelial fatty acids transport VEGF-B • Increased VEGF-B leads to lipid VEGFR-1 accumulation in tissues and NRP-1 lipotoxicity Fatty acids diabete
Slide 29: CSL346 – Prevents nephropathy in mice
Breakthrough Medicines CSL346 – Diabetes / Diabetic Complications For personal use only Anti-VEGF-B antibody prevents development of nephropathy in db/db//BLKS mice • GLP toxicology studies in progress • Phase I planned to commence in 2H, 2017 29
Slide 30: Strong Research Portfolio
Global Strong Research Portfolio For personal use only • Expanding capacity and capability across global research sites • Innovating in key areas of business strength Specialty Immunoglobulins Haemophilia Products • Developing new opportunities in important areas of unmet medical need o Three novel
Slide 31: Immunoglobulins
31 For personal use only Immunoglobulins
Slide 32: Immunoglobulins
Immunoglobulins For personal use only • Maintaining leadership position Breakthrough through focus on: Medicines o New Indications o Geographic expansion Specialty o Delivery options Immunoglobulins Products • Key Focus Haemophilia o HIZENTRA® Products o PRIVIGEN® 32
Slide 33: Progress in Neurology: CIDP
Immunoglobulins Progress in Neurology For personal use only Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) • Progressive weakness and impaired sensory function in the legs and arms • New cases per year ~1-2 per 100,000 people • Occurs at any age, in both genders, more common in young adult
Slide 34: PATH Program – Phase III Study
Immunoglobulins PATH Program – Phase III Study1 For personal use only N=276 N=245 N=207 N=172 • Largest placebo controlled study in CIDP • Data base locked • HIZENTRA® CIDP FDA submission mid 2017 and EMA submission 2H 2017 Source: 1. Von Schaik et al. Trials 016 Jul 25;17(1):345 34
Slide 35: PATH Supports Efficacy of PRIVIGEN in CIDP
Immunoglobulins PATH Supports Efficacy of PRIVIGEN® in CIDP For personal use only • 73% PATH subjects responded with improvement in INCAT score • PATH and PRIMA represent largest CIDP cohort studied • FDA submission sBLA November 2016 Source: 1. Leger, JM et al. J Peripher Nerv Syst 2013 Jun;18(2):1
Slide 36: Expanding on Successful CIDP Experience
Immunoglobulins Expanding on Successful CIDP Experience For personal use only Neurology • Auto-immune pathology Rheumatology Idiopathic • Muscle, skin and inner organ fibrosis Systemic Sclerosis Inflammatory • Evidence of efficacy of immunoglobulins Myopathies • Expand on our commitment to rare dise
Slide 37: IVIG and Haemolysis
Immunoglobulins IVIG and Haemolysis1 For personal use only • New generation IVIG products are associated with low, but relevant, risk of haemolysis Red blood cell haemolysis has been noted when IVIG > 2g/kg is administered to patients with blood groups A, B or AB • Due to isoagglutinins • Regulatory
Slide 38: PRIVIGEN Isoagglutinin Levels Lowered
PRIVIGEN® Isoagglutinin Levels Lowered to Immunoglobulins Reduce IVIG Associated Haemolysis Risk1 For personal use only Methods to Reduce Isoagglutinin Levels Immunoaffinity Donor screening chromatography (IAC) Cold ethanol fractioning The levels of Isoagglutinin levels in isoagglutinins can be PRIV
Slide 39: Reduction in PRIVIGEN Haemolysis
Immunoglobulins Reduction in PRIVIGEN® Haemolysis For personal use only CSL Behring proactively introduced an isoagglutinin reduction strategy that reflects our strong commitment to continue to deliver safe and effective therapies to patients • PRIVIGEN® IsoLo® approved in US, Europe, Canada, Austra
Slide 40: Commercial Market Overview
For personal use only Commercial Market Overview 40
Slide 41: Global Plasma-proteins Therapeutics Market
Global Plasma-proteins Therapeutics Market For personal use only Immunoglobulin Haemophilia $9.0B $10.8B Total Global Market Value: ~$27.0B Specialty Albumin $3.4B $3.8B Sources: Company 3Q 2016 reports/financial schedules, MRB global Coagulation Factors Concentrate Market 2015 & 2016, MRB WW Plasma
Slide 42: Key Segment Opportunities
Global Key Segment Opportunities For personal use only Deliver CIDP Ig Innovation Demonstrate Specialty HaegardaTM Leadership Drive Coag Growth 42
Slide 43: Immunoglobulins Commercial Opportunities and Activities
For personal use only Immunoglobulins Commercial Opportunities and Activities 43
Slide 44: Immunoglobulins Global Market
Immunoglobulins Global Market For personal use only • Global market volume growth Hyper projected at 5-7% in 2017 $0.9B SCIG • Demand driven by medical $1.2B education and brand promotion Total Global Market Value: • Growing patient acceptance of ~$9.0B subcutaneous delivery in developed and emergin
Slide 45: Immunoglobulins Reported Sales
Immunoglobulins For personal use only US $M US $2,457M 2,500 • Global revenue +7% SCIG • CIDP & SID indications in the EU 2,000 • Reliability of supply • Geographic and market expansion 1,500 • Introduction of PRIVIGEN® IsoLo® 1,000 IVIG • Global revenue +31% 500 • Significant increase in new patien
Slide 46: More proline in food than in HIZENTRA
Immunoglobulins More proline in food than in HIZENTRA® For personal use only 2 slices provolone 1 9oz piece sirloin 1 tub yoghurt 12g drumsticks (meat 5 serves broccoli 1 cup scrambled (meat and skin) 1 3oz can tuna 1 turkey wing 1 cup frozen 2 chicken (in water) and skin) spinach cheese steak eggs
Slide 47: Global Ig Franchise: Strategic Imperatives
Immunoglobulins Global Ig Franchise: Strategic Imperatives For personal use only GROW • Maximising current indications globally: continue geographic expansion; our Current accelerate subcutaneous growth; Franchise by: launch 5 & 10 ml PFS in 2017 BUILD • Focusing on CIDP: PRIVIGEN® today, HIZENTRA®
Slide 48: CSL Behring Ig Franchise Vision
Immunoglobulins CSL Behring Ig Franchise Vision For personal use only CSL Behring is the world renowned leader in Ig therapy delivering innovations that enhance patients’ lives 48
Slide 49: Specialty Products
49 For personal use only Specialty Products
Slide 50: Specialty
Specialty For personal use only • Leveraging high quality broad product portfolio through: Breakthrough Medicines o New markets o Novel indications Immunoglobulins o Novel modes of administration Specialty Products • Key Focus o HAEGARDATM/BERINERT® Haemophilia Products o BERIPLEX®/KCENTRA® o ZEMAIR
Slide 51: Clinical Presentation of Hereditary Angioedema (HAE)
Specialty Clinical Presentation of Hereditary Angioedema (HAE) For personal use only 51
Slide 52: QOL Negatively Impacted by HAE
Specialty QOL* Negatively Impacted by HAE For personal use only Work Productivity Activity Impairment (WPAI)1 •QOL – Quality of Life Source: 1. Lumry WR, et al. Allergy Asthma Proc 2010; 31(5):407–14. 52
Slide 53: Phase III Study Positive
Specialty Phase III Study Positive For personal use only Phase III COMPACT Study C1-INH (SC), CSL830, a low volume self-administered, subcutaneous C1-inhibitor preparation, is well tolerated and efficacious for preventing attacks in patients with HAE1 Source: 1. Zuraw et al. Oral Presentation Americ
Slide 54: HAEGARDA demonstrates efficacy in HAE Prophylaxis
Specialty HAEGARDATM demonstrates efficacy in HAE Prophylaxis For personal use only • Primary endpoint met: o 40 IU/kg reduced attack rate 88.6% (median, p<0.001) o 60 IU/kg reduced attack rate 95.1% (median, p<0.001) 5 p<0.001 p<0.001 4 HAE attacks 3 per month, LS mean 2 (95% CI) 1 3.6 1.2 4.0 0.5
Slide 55: HAEGARDA Reduces Attack Severity
Specialty HAEGARDATM Reduces Attack Severity For personal use only 55
Slide 56: Notable Responder Rate with HAEGARDA
Specialty Notable Responder Rate with HAEGARDATM For personal use only • FDA definition of a responder is a subject with ≥ 50% reduction of attacks Indirect Cross-study Comparison 100 % Responder relative to Placebo KEY: 90 ≥ 50% 80 70 ≥ 70% 60 ≥ 90% 50 40 COMPACT 30 lower bound 95% CI >33% 20 10 0
Slide 57: HAEGARDA Safe and Well-tolerated
Specialty HAEGARDATM Safe and Well-tolerated For personal use only Adverse Events in Study Safety Population 40 IU/kg CSL830 60 IU/kg CSL830 Combined placebo n (%) N=43 N=43 N=86 Patients reporting ≥1 AE 29 (67.4) 30 (69.8) 57 (66.3) Adverse drug reactions, number of patients (%) Injection site reac
Slide 58: Summary and Program Progress
Specialty Summary and Program Progress For personal use only • COMPACT trial demonstrated dose-dependent efficacy of HAEGARDA™ for the prevention of HAE attacks o Reduction in median attack rate: 89–95% o Response rate (≥50% relative attack reduction): 76–90% o 60 IU/kg consistently showed higher ef
Slide 59: Transplant – Overview of Unmet Need
Specialty Transplant – Overview of Unmet Need For personal use only • Increasing global demand for organ transplantation associated with limited supply1 AGR: 5.3% AGR: 1.7% AGR: 1.5% Source: 1. OPTN Database May 2016 (Note: Deceased donors may donate multiple organ) 59
Slide 60: CSL Therapies in Transplantation
Specialty CSL Therapies in Transplantation For personal use only Normal Kidney Transplant HLA reduction / Cellular Early AMR Late AMR Desensitisation / Rejection <12 mo >12 mo Improve viability Rejected Kidney Delayed or Primary Graft (Dys) Function Se ptember26 , 2001 60
Slide 61: Renal Transplantation
Specialty Renal Transplantation For personal use only • Lack of donors, organ unsuitability • Long-term graft survival still poor, graft loss after 1 year is 5% per year1 Kidney Wait List ~100,0002 Standard Kidney Cross Match + Sensitised Transplant Kidney Transplant (hi PRA) ~17,500/year* 300/year
Slide 62: C1 Inhibition in Refractory AMR
Specialty C1 Inhibition in Refractory AMR* For personal use only • Patients treated with BERINERT® demonstrated an improvement in renal function (GFR - glomerular filtration rate) * Refractory AMR (acute or late) patients who have not responded to 3 months standard of care • Source: Viglietti et al.
Slide 63: CSL Therapies in Transplantation
Specialty CSL Therapies in Transplantation For personal use only • Program will test ability to increase donor compatibility and improve long and short-term graft survival • First program of C1 inhibition in renal transplant in 2H 2017, pending regulatory interactions • Ongoing interactions with hig
Slide 64: Specialty Products Commercial Opportunities and Activities
For personal use only Specialty Products Commercial Opportunities and Activities 64
Slide 65: Specialty Global Market
Specialty Global Market For personal use only Other ~$0.3B Acquired • Orphan/rare diseases Bleed ~$0.7B • Unmet medical need Total Global • Often under or misdiagnosed Market Value: ~$3.4B HAE • Awareness and education ~$1.6B AATD ~$0.8B • Significant patient value Sources: Company annual reports/fi
Slide 66: CSL's Global Performance
Specialty CSL’s Global Performance For personal use only • KCENTRA®/BERIPLEX® usage growing across multiple specialties • BERINERT® geographic and market expansion continues • Launch of RESPREEZA® in EU • EU growth of HAEMOCOMPLETTAN® P CSL FY16 Sales $983M Key Brands: Acquired Bleeding AATD Other H
Slide 67: Reimbursement Status – RESPREEZA
Specialty Reimbursement Status – RESPREEZA® For personal use only Reimbursement Reimbursement • AATD market in Europe Achieved Pending approximately ~$200M Czech Rep Austria • Majority of treated patients are in France Belgium Germany and France Germany Denmark • RESPREEZA® differentiation: Greece F
Slide 68: HAEGARDA Value Proposition
Specialty HAEGARDATM Value Proposition For personal use only Most effective in preventing HAE attacks C1 Individualised Sub-Q Inhibitor Dosing Administration 68
Slide 69: Key Primary Market Research Findings – HAE
Specialty Key Primary Market Research Findings – HAE For personal use only HCP Patients • HAEGARDATM has two key • The core value proposition perceived advantages over current HAEGARDATM offers is greater options: efficacy (reduced number of attacks) with prophylaxis therapy 1. More efficacious in r
Slide 70: HAE Franchise
Specialty HAE Franchise For personal use only Revenue Potential of $0.75M – $1B p.a. HAEGARDATM BERINERT® Most effective in preventing HAE attacks Most effective in stopping HAE attacks C1 Individualised Sub-Q C1 Individualised IV Inhibitor Dosing Administration Inhibitor Dosing Infusion PK data to
Slide 71: Q&A
Q&A Or personal use only CSL Just getting started
Slide 72: Break
72 For personal use only Break
Slide 73: Investor R&D Briefing
For personal use only Investor R&D Briefing December 1, 2016 1
Slide 74: Haemophilia Products
For personal use only Haemophilia Products 2
Slide 75: Haemophilia
Haemophilia For personal use only • Supporting and enhancing plasma Breakthrough products and developing novel Medicines recombinant portfolio with focus on: o Scientific and product innovation o Patient benefit Immunoglobulins Specialty Products • Key Focus Haemophilia o IDELVION® (rIX-FP) Products
Slide 76: Global Approvals Ongoing
Haemophilia Global Approvals Ongoing For personal use only Achieved 2016 Anticipated 2017 Australia Canada Hong Kong EU Israel Japan New Zealand Switzerland Taiwan USA Australia EU (positive opinion Nov 2016) Canada Japan USA New Zealand Switzerland 4
Slide 77: Low AsBR on IDELVION Extended Regimens
Haemophilia Low AsBR on IDELVION® Extended Regimens For personal use only AsBR Extension 7-Day Regimen 10-Day Regimen 14-Day Regimen 21-Day Regimen Study (n=19) (n=7) (n=21) (n=10) Median (IQR) 0.85 (0,2.9) 0 (0,0) 0 (0,0) 0 (0,0) Estimated Mean 1.91 0.31 0.88 0.45 Adults AsBR (95% CI) (1.09-3.36)
Slide 78: rVIIa-FP (CSL689)
Haemophilia rVIIa-FP (CSL689) For personal use only rFVIIa Linker rAlbumin 6
Slide 79: Clinical Programs
Haemophilia Clinical Programs For personal use only Congenital Haemophilia A or B with Inhibitors (CHwI) Phase I (Healthy Volunteers) Phase II/III Phase III PK On-demand Prophylaxis Safety PK, Long-term safety Surgery COMPLETED ONGOING (PLANNED) Congenital Haemophilia Factor VII Deficiency Phase I (
Slide 80: CHwI Preliminary Efficacy Data
Haemophilia CHwI Preliminary Efficacy Data For personal use only • rVIIa-FP is efficacious and safe in treating bleeding events o 47 bleeds in 10 subjects o 77% of bleeds controlled with 1 infusion o 100% of bleeds controlled with 2 infusions o No thrombo-embolic adverse events experienced • NOVOSEV
Slide 81: Congenital Factor VII Deficiency
Haemophilia Congenital Factor VII Deficiency For personal use only • Phase I study confirms rVIIa-FP has measurable FVIIa levels up to 48 hrs • Supports testing once to twice weekly dosing in Phase II • Phase II to commence 2H 2017 rVIIa-FP 100 µg/kg N=3 rVIIa-FP 300 µg/kg N=3 pdFVII 30 IU/kg N=2 9
Slide 82: Haemophilia Commercial Opportunities and Activities
For personal use only Haemophilia Commercial Opportunities and Activities 10
Slide 83: Haemophilia Global Market
Haemophilia Global Market For personal use only • Trend toward recombinants in VWD $0.5B developed markets Hem B $1.4B • 75% of patients with bleeding disorders are under/un-treated Total Global • Launches of multiple longer-acting Inhibitor Market Value: Bleed products in Hem-A space Therapy ~$10.8
Slide 84: Haemophilia Global Portfolio
Haemophilia Global Portfolio For personal use only CSL FY16 Sales $1B Recombinant Plasma 12
Slide 85: Recombinant Coagulation Launches
Haemophilia Recombinant Coagulation Launches For personal use only Revenue Potential of $0.7 – $1B p.a. in 4-5 years US EU Japan • Unique albumin fusion protein • New SOC for haemophilia B Launched Launched Launched • Increased protection and convenience • Unique single chain design • Longer acting
Slide 86: Evolution of IDELVION Promotion
Haemophilia Evolution of IDELVION® Promotion For personal use only Steady-State: Single Dose: IDELVION® delivers steady-state mean FIX levels of IDELVION® maintains high trough levels (>5%) 21% with 7-day prophylaxis (patients <12 years) and for protection from bleeds between treatments 13% with 14-
Slide 87: Conversions to IDELVION
Haemophilia Conversions to IDELVION® For personal use only 3% 5% 10% BeneFix ® BENEFIX ALPROLIX Alprolix ® Mononine ® MONONINE 10% Alphanine ® ALPHANINE 52% Rixubis ® RIXUBIS Ixinity ® IXINITY 19% Source: My Source weekly reporting as of October 25. Based on data from U.S. Hub Services Provider 15
Slide 88: Conversions to AFSTYLA
Haemophilia Conversions to AFSTYLA® For personal use only 17% 22% Advate ® ADVATE Adynovate ® ADYNOVATE 6% Eloctate ® ELOCTATE Helixate FSFS® HELIXATE 6% 5% Kogenate FSFS® KOGENATE 5% Recombinate ® RECOMBINATE Unknown 39% Source: My Source weekly reporting as of October 25. Based on data from U.S. H
Slide 89: Breakthrough Medicines
For personal use only Breakthrough Medicines 17
Slide 90: Breakthrough Medicines
Breakthrough Medicines For personal use only • Leveraging clinical and technical insight in developing novel protein- based therapies Breakthrough Medicines o Significant unmet need o Multiple indications Specialty Immunoglobulins Products • Key Focus o CSL112 (Apo AI) Haemophilia o CSL324 (anti-G-C
Slide 91: Medical Need: Cardiovascular Disease
Breakthrough Medicines Medical Need: Cardiovascular Disease (CVD) For personal use only ACS patients experience a high rate of recurrent cardiovascular • In 2012, CVDs are the leading events in the sub-acute period cause of death globally (31%) o ~7.4 million were due to coronary heart disease o ~6.
Slide 92: Development of Atherosclerosis
Breakthrough Medicines Development of Atherosclerosis For personal use only Cholesterol Influx and Efflux Imbalance Cholesterol influx Cholesterol efflux ApoA-I LDL Lipid-poor preβHDL LDL retention and oxidative modification ABCA1 transporter Macrophage ABCA1=ATP-binding cassette transporter 1; HDL=
Slide 93: Cholesterol Efflux With CSL112
Breakthrough Medicines Cholesterol Efflux With CSL112 For personal use only Removal of Cholesterol From Unstable Plaque Upon infusion, CSL112 immediately produces a significant increase in circulating lipid-poor apoA-I particles… CSL112 particles ABCA1 transporters 21
Slide 94: Cholesterol Efflux With CSL112
Breakthrough Medicines Cholesterol Efflux With CSL112 For personal use only Removal of Cholesterol From Unstable Plaque …accompanied by a marked increase in ABCA1-dependent cholesterol efflux capacity CSL112 particles CSL112 particles ABCA1 transporter ABCA1 transporters Intracellular cholesterol CS
Slide 95: AEGIS-I
Breakthrough Medicines AEGIS-I For personal use only The Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Human ApoA-I, After Acute Myocardial Infarction: The ApoA-I Event reducinG in Ischemic Syndromes I Trial (AEGIS-I) Infusion of aopA-I (CSL112) in addition to standar
Slide 96: AEGIS-I Primary Endpoint Met
Breakthrough Medicines AEGIS-I Primary Endpoint Met For personal use only CSL112 2g CSL112 6g Placebo N=415 N=416 N=413 Liver Confirmed elevated markers of liver injury 4 (1.0%) 2 (0.5%) 0 (0.0%) Kidney Confirmed elevated markers of kidney injury 0 (0.0%) 3 (0.7%) 1 (0.2%) • Percentages are based on
Slide 97: Proof of Mechanism Demonstrated
Breakthrough Medicines Proof of Mechanism Demonstrated For personal use only • Cholesterol efflux capacity increased after Infusion of CSL112 in AMI patients 5 Fold Elevation at Peak After 1st Infusion 4.5 4 4.30 3.5 3.67 3 2.5 2 2.45 1.5 1.87 1 0.5 0.94 0.82 0 Total Cholesterol Efflux Capacity ABCA
Slide 98: AEGIS-I Exploratory Endpoint (MACE)
Breakthrough Medicines AEGIS-I Exploratory Endpoint (MACE) For personal use only • Major Cardiovascular Events (MACE) collected to inform Phase III o Comprised cardiovascular death, non-fatal myocardial infarction, stroke, hospitalisation for unstable angina • Low event rate was expected in this stu
Slide 99: AEGIS-I Summary
Breakthrough Medicines AEGIS-I Summary For personal use only • AEGIS-I study positive • Four weekly infusions of CSL112 following MI was feasible and did not have any safety concerns • CSL112 rapidly elevates cholesterol efflux in a dose dependent fashion in the acute MI setting • Based on the curre
Slide 100: Proposed Phase III Study Design
Breakthrough Medicines Proposed Phase III Study Design For personal use only A Phase III, Multicenter, Double-blind, Randomised, Placebo- controlled, Parallel-group Study to Investigate the Efficacy and Safety of CSL112 in Subjects with Acute Coronary Syndrome Double-blind, 1:1 randomisation 4 weekl
Slide 101: AEGIS Planning for Phase III
x Breakthrough Medicines AEGIS Planning for Phase III x For personal use only • Regulatory agency consultations have commenced • Results of safety study in moderate renal impaired ACS patients anticipated 2H 2017 • Study planned to start Dec 2017 / early 2018, pending outcome of above activities • S
Slide 102: Breakthrough Medicines Commercial Opportunities and Activities
For personal use only Breakthrough Medicines Commercial Opportunities and Activities 30
Slide 103: CSL112: Apo-A1 HDL
Breakthrough Medicines CSL112: Apo-A1 HDL For personal use only Unmet Medical Need: • Approximately 20% of patients that survive a heart attack will experience a recurrent CV event within one year • About half of these will occur in the first month post index event Potential Clinical Benefit: Signif
Slide 104: CSL112 Commercial Opportunity
Breakthrough Medicines CSL112 Commercial Opportunity For personal use only Uncontested sub-acute market space PLATO STUDY1 SWEDISH REGISTRY STUDY2 20 Vascular death, MI, or stroke (%) Chronic 12 15 Phase Vascular death, MI, or stroke (%) Chronic 10 Phase Statins 8 10 PCSK9i Statins PCSK9i CETPi 6 CE
Slide 105: CSL112 – Market Development Activities
Breakthrough Medicines CSL112 – Market Development Activities For personal use only Third-party Payers Payer perspective on key Phase 3 design variables Access and Reimbursement HEOR endpoints / HTA / Value demonstration Product Labeling Claims prioritisation and treatment guidelines placement 33
Slide 106: Seqirus R&D
34 For personal use only Seqirus R&D
Slide 107: Influenza Vaccine Platform
Seqirus Influenza Vaccine Platform For personal use only At-risk populations Standard risk Adjuvanted seasonal Seasonal TIV → QIV QIV Pandemic Egg based Cell culture Influenza Science TIV = trivalent influenza vaccine (3 strains) QIV = quadrivalent influenza vaccine (4 strains) 35
Slide 108: Influenza Changes Constantly
Influenza Changes Constantly For personal use only Antigenic drift Antigenic shift Small mutations New strain Epidemic Pandemic Yearly seasonal vaccine Occasional vaccine 3-4 circulating strains Single strain (2 “A”, 1 or 2 “B” strains) May vary season to season, SH vs NH 36
Slide 109: Programs at Time of Acquisition
Programs at Time of Acquisition For personal use only Registration Post Phase 3 & Launch Registration Fluad™ QIV 6m-5yrs Fluad™ TIV 65yrs+ Efficacy on-going Submitted USA Flucelvax® QIV 4yrs+ Submitted USA Afluria® QIV 5-17yrs Afluria® QIV 18yrs+ On-going Submitted USA, AUS 37
Slide 110: Delivery of all Milestones during Integration
Delivery of all Milestones during Integration For personal use only Registration Post Phase 3 & Launch Registration Fluad™ QIV 6m-5yrs Fluad™ TIV 65yrs+ Fluad™ TIV 65yrs+ Efficacy complete Submitted UK Approval USA Fluad™ QIV 65yrs+ Efficacy start Flucelvax® QIV 2yrs+ Flucelvax® QIV 4yrs+ Efficacy s
Slide 111: Differentiated Product Portfolio – Current and Future Indications
Differentiated Product Portfolio - Current and Future Indications Planned Future Age For personal use only Brand Age Indication Today Target Offer Indication 6 months to 2years 6 months to 5 years QIV 65 years + 65 years + 4 years + 2 years + QIV 18 years + 6 months + QIV 6 months + TIV 4 years + TI
Slide 112: FLUAD
For personal use only FLUAD™ Differentiated (MF-59 adjuvanted) influenza vaccine for vulnerable populations 40
Slide 113: Why FLUAD?
Why FLUAD™? For personal use only Age-related hospitalisations and TIV efficacy rates 100 Vaccine (TIV) Hospitalization rate4 70 • MF59 adjuvant strengthens and efficacy1-3 potentially broadens the 60 Influenza-related hospitalization rate 80 immune response Vaccine efficacy (%) 50 • >100 million do
Slide 114: FLUCELVAX
For personal use only FLUCELVAX® Developing a cell culture-derived QIV for the general population in global markets 42
Slide 115: Cell-culture offers potential benefits over egg-derived vaccine
Cell-culture offers potential benefits over egg-derived influenza vaccine For personal use only EGG-DERIVED • Process well established and understood • Long track record of safety and efficacy Virus • Efficient Seed Virus harvested, Filling, final propagation in Further purification strains concentr
Slide 116: AFLURIA
For personal use only AFLURIA® Developing an egg-derived QIV for the general population in global markets 44
Slide 117: Reduced fever rate with Afluria QIV in children
Reduced fever rate with Afluria® QIV in children Comparison with Historical Fever Rates For personal use only 5 - 8 years age group Afluria (NHF-04-05) Afluria (USF-06-29) Historical TIV Afluria (USF-07-36) Afluria TIV (Pooled*) Afluria TIV (USF-10-69) ↑ TDOC (H3N2+B) Fluzone (USF-07-36) Fluzone (US
Slide 118: Longer Term Directions for Influenza Vaccine Innovation
Longer Term Directions for Influenza Vaccine Innovation For personal use only Alternate routes of delivery Novel sources of antigens Universal vaccine 46
Slide 119: Milestones Expected for 2017
Milestones Expected for 2017 For personal use only Registration Post Phase 3 & Launch Registration Fluad™ QIV 6m-5yrs Fluad™ TIV 65yrs+ Submission USA Approval UK QIV Submission EU Afluria® QIV 6m-4yrs Afluria® QIV 6m-4yrs Safety & Immuno Submitted USA, AUS complete 47
Slide 120: Summary
48 For personal use only Summary
Slide 121: R&D Portfolio – December 2016
Global R&D Portfolio – December 2016 For personal use only Commercial/ Research Pre-clinical Phase I Phase II Phase III Registration Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine HIZENTRA® CIDP C1-INH
Slide 122: Expected Progress in next Months
Global Expected Progress in next 12 Months For personal use only HIZENTRA® PRIVIGEN® Ig Mimetic CSL689 CIDP US/EU CIDP US Congen Def CSL830 EU AFSTYLA® CSL842 C1-INH EU Transplant AFSTYLA® Japan CSL830 CSL346 CSL112 HAEGARDATM US Anti-VEGFB apoA-I KCENTRA® Japan FLUAD® QIV 6m-5yrs US QIV EU AFLURIA®
Slide 123: Significant Target Launch Dates
Global Significant Target Launch Dates For personal use only 2016 2017 2018 2019 2020 2021 PRIVIGEN® PRIVIGEN® HIZENTRA® HIZENTRA® IsoLo CIDP US CIDP US/EU CIDP Japan PRIVIGEN® Japan PID/SID IDELVION® US AFSTYLA® CSL689 rVIIa-FP EU/Japan Prophylaxis IDELVION® EU CSL689 rVIIa-FP IDELVION® Japan On De
Slide 124: 2016 Highlights
Global 2016 Highlights For personal use only • PRIVIGEN® IsoLo® approved in major markets Immunoglobulins • HIZENTRA® CIDP Phase III study (PATH) completed • PATH supports efficacy of PRIVIGEN® in CIDP • C1-INH subcut (CSL830) Phase III (COMPACT) completed Specialty Products • COMPACT demonstrates e
Slide 125: Q&A
53 For personal use only Q&A R&D Briefing
Slide 126: Further Information
Global Further Information For personal use only Presentation Playback A webcast of the presentation can be accessed in the investors section of the CSL website. Contact: maria.pikos@csl.com.au Investor Relations: Mark Dehring Head of Investor Relations CSL Limited Phone: +613 9389 3407 Email: mark.