Slide 1: Annual Research and Development Investor Briefing
For personal use only For immediate release 4 December 2019 ANNUAL RESEARCH AND DEVELOPMENT INVESTOR BRIEFING Melbourne, Australia – CSL (ASX:CSL; USOTC:CSLLY) Please find attached the presentation and an accompanying media release ahead of CSL’s Annual Research and Development Investor Briefing bei
Slide 2: R&D Investor Briefing December 4, 2019
For personal use only R&D Investor Briefing December 4, 2019
Slide 3: Legal Notice: Forward looking statements
After struggling for years to get an accurate diagnosis, hereditary Legal Notice angioedema (HAE) patient Kathrin Schoen For personal use only is working to ensure Forward looking statements the next generation of The materials in this presentation speak only as of the date of these materials, and i
Slide 4: Introduction
Introduction For personal use only William Mezzanotte, M.D. Executive Vice President, Head of Research and Development CSL Behring 3 | Driven by Our Promise™
Slide 5: Agenda
Agenda For personal use only Welcome Mark Dehring Introduction Bill Mezzanotte Research, Gene and Cell Therapy Andrew Nash Clinical Development Part 1 Diana Lanchoney Commercial Part 1 Bill Campbell Panel Q&A Session Break Commercial Part 2 Bill Campbell Seqirus Russell Basser Clinical Development P
Slide 6: Global Research and Development Footprint
Global Research and Development Footprint For personal use only 5 | Driven by Our Promise™
Slide 7: Global Collaborations for Innovation Access
Global Collaborations for Innovation Access For personal use only 6 | Driven by Our Promise™
Slide 8: Commitment to Research and Development
Commitment to Research and Development For personal use only New Product Development activities focus on innovative new therapies for life-threatening diseases Market Development strategies seek to bring therapies to new markets and new indications Life Cycle Management ensures continuous improvemen
Slide 9: Active R&D Support for Growth in Plasma Business
Active R&D Support for Growth in Plasma Business For personal use only Technical Process Operations Improvement New Plasma Product New Formulations Products Development & Indications New Devices 8 | Driven by Our Promise™
Slide 10: Focus Through Our Therapeutic Areas and Platforms
Focus Through Our Therapeutic Areas and Platforms For personal use only Therapeutic Influenza Vaccines Areas Immunology and Haematology Respiratory Cardiovascular Transplant (Seasonal and Neurology and Thrombosis and Metabolic Pandemic) Plasma Recombinant Cell and Adjuvanted Platforms Fractionation
Slide 11: R&D Portfolio – December 2018
R&D Portfolio – December 2018 For personal use only PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION POST-REGISTRATION CSL730 CSL830 CSL200 (CAL-H)SCD CSL312 Anti-FXIIa HAE PRIVIGEN® PID Japan PRIVIGEN® CIDP Japan rFc Multimer C1-INH Subcut EU CSL324 HIZENTRA® CIDP CSL889 Hemopexin SCD Mavrilimu
Slide 12: Key Past Launches from R&D Portfolio
Key Past Launches from R&D Portfolio For personal use only 2013 2014 2015 2016 2017 2018 2019 PRIVIGEN® CIDP (US) HIZENTRA® PRIVIGEN® Immun & Ig IsoLo® HIZENTRA® CIDP (Japan) Neuro CIDP (EU) CIDP HAEGARDA® (US) PRIVIGEN® CIDP (Japan) VONCENTO® (EU) IDELVION® Haem & Throm KCENTRA® (US) AFSTYLA® Respi
Slide 13: Notable Regional Regulatory Approvals Dec 2018 – Nov 19
Notable Regional Regulatory Approvals 1 Dec 2018 – 20 Nov 2019 For personal use only Ongoing Activities CSL842 (AMR*) CSL842 (for treatment solid Expanded Label for CSL964 (prevention GvHD**) organ transplant) Enhanced Administration CSL964 (treatment GvHD**) Parameters Expanded Label for Dosing Eve
Slide 14: Clinical Portfolio Progression in 2019
Clinical Portfolio Progression in 2019 For personal use only PRE-CLINICAL/PHASE I PHASE II PHASE III REGISTRATION POST-REGISTRATION CSL200 PRIVIGEN® PID PRIVIGEN® CIDP PRIVIGEN® SSc HIZENTRA® DM (CAL-H) SCD Japan Japan CSL312 Anti-FXIIa CSL964 AFLURIA® QIV 6M-4yrs HIZENTRA® CIDP HIZENTRA® SSc Thromb
Slide 15: Key Partnerships and Collaborations
Key Partnerships and Collaborations For personal use only PRE-CLINICAL PHASE I PHASE II PHASE III P. gingivalis/POD CSL730 rFc Multimer Mavrilimumab GM-CSFR Clazakizumab Anti-IL-6 CSL334 / ASLAN004 IL-13R CSL964 GvHD Treatment 14 | Driven by Our Promise™
Slide 16: R&D Portfolio – December 2019
R&D Portfolio – December 2019 For personal use only POST- RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION REGISTRATION CSL730 CSL312 Anti-FXIIa CSL830 Discovery Projects Improved Fibrinogen HIZENTRA® DM PRIVIGEN® PID Japan rFc Multimer HAE C1-INH Subcut EU CSL787 CSL324 CSL112 FLUAD® Q
Slide 17: Research, Gene and Cell Therapy
Research, Gene and Cell Therapy For personal use only Dr. Andrew Nash Senior Vice President, Research CSL Behring 16 | Driven by Our Promise™
Slide 18: CSL Research
CSL Research For personal use only • Capabilities and facilities Immunology and Haematology Cardiovascular Respiratory Transplant Neurology and Thrombosis and Metabolic • New product opportunities – Plasma – Haptoglobin for the treatment of Subarachnoid Haemorrhage (SAH) • Innosuisse grant awarded t
Slide 19: CSL Research: New Facilities
CSL Research New Facilities For personal use only Bio21 Institute, Melbourne SITEM*, Bern Gene therapy, Pasadena • ~ 4100m2 of lab and office space • 2000m2 of lab and office space • Expanding gene therapy expertise • Parkville precinct • Bern University and Hospital campus – Research, QA, cell proc
Slide 20: CSL Research: External Innovation Strategy
CSL Research External Innovation Strategy For personal use only CSL – Walter and Eliza Hall Institute (WEHI) Bioinformatics Alliance Strategic Partnerships CSL biologics discovery platform (universities, MRIs, hospitals) Research Acceleration Initiatives Global Funding & AUS, EU and US Research site
Slide 21: Haptoglobin for the Treatment of Subarachnoid Haemorrhage (SAH)
Haptoglobin for the Treatment of Subarachnoid Haemorrhage (SAH) Pathophysiology of SAH For personal use only • Acute indication – rupture of an aneurysm in the brain, followed by bleeding and haemolyis within the subarachnoid space • Survivors of initial bleeding are at risk for Delayed Ischemic Neu
Slide 22: Haptoglobin and SAH
Haptoglobin and SAH Link Between CSF Hb Levels and DIND For personal use only Cumulative Hb exposure (µM/days) Concentration oxyHb (µM) DIND No DIND Days after bleeding Days after bleeding Hb levels in CSF correlate with DIND 39 year old, right-handed female with thunderclap SAH patients (n=18) deve
Slide 23: How the Body Deals with Toxic Free Haemoglobin and Heme
How the Body Deals with Toxic Free Haemoglobin (Hb) and Heme For personal use only Damage Haemolysis haemoglobin heme iron • Nitric Oxide (NO) scavenging • Tissue damage Protection haptoglobin (Hp) hemopexin (Hx) transferrin Treatment Plasma proteins • Opportunities to treat chronic and acute haemol
Slide 24: Haptoglobin Prevents Vasospasms Induced by Haemorrhagic CSF
Haptoglobin for the Treatment of SAH Haptoglobin Prevents Vasospasms Induced by Haemorrhagic CSF – ex vivo Functional Assay For personal use only Sheep Model of SAH CSF From Sheep SAH Model CSF Samples From SAH Patients Hb, Hb+Hp Sample Buffer Hb Pre-haemorrhagic CSF Haemorrhagic CSF Hb-Hp Haemorrha
Slide 25: Haptoglobin Prevents Penetration of Hb into Brain Tissue
Haptoglobin for the Treatment of SAH Haptoglobin Prevents Penetration of Hb into Brain Tissue For personal use only Labeled Hb ± haptoglobin was injected into CSF 2 hours before analysis Source: J Clin Invest. 2019. https://doi.org/10.1172/JCI130630 24 | Driven by Our Promise™
Slide 26: Haptoglobin for the Treatment of SAH: Summary
Haptoglobin for the Treatment of SAH For personal use only Summary Haemoglobin • Concentrations in CSF correlate with DIND in SAH patients • Rapidly penetrates from CSF into the brain parenchyma • Induces angiographic vasospasms in 100% of animals Haptoglobin • Blocks tissue penetration of cell-free
Slide 27: CSL311 for the Treatment of Airways Inflammation
CSL311 for the Treatment of Airways Inflammation Airways Inflammation For personal use only Targeting multiple inflammatory mediators with a single therapeutic GM-CSF IL-3 & IL-5 GM-CSF IL-3 & Bone IL-5 marrow Myeloid cell lineages 26 | Driven by Our Promise™
Slide 28: CSL311 Targets Multiple Cytokines via a Shared Receptor
CSL311 for the Treatment of Airways Inflammation CSL311 Targets Multiple Cytokines via a Shared Receptor For personal use only CSL311 GM-CSF IL-3 & Shared IL-5 βc receptor GM-CSF, IL-3 or IL-5 Survival, Proliferation, Differentiation, Activation Rα-chain Inflammation Source: Panousis et al., Mabs 8:
Slide 29: In Vivo Efficacy in a Mouse Model of Human Airways Inflammation
CSL311 for the Treatment of Airways Inflammation In Vivo Efficacy in a Mouse Model of Human Airways Inflammation For personal use only Xenografting human nasal polyps into immunodeficient mice Polyp Inflammation Mucus CSL311 1 x / week for 4 GM-CSF Xenograft weeks, 5 mg/kg IL-3 or IL-5 Graft size, c
Slide 30: In Vivo Efficacy – Mouse Model of Human Airways Inflammation
CSL311 for the Treatment of Airways Inflammation In Vivo Efficacy – Mouse Model of Human Airways Inflammation For personal use only CSL311 restrains human nasal polyp CSL311 treatment reduces mucous glad numbers xenograft progression in vivo and mucus production in nasal polyps in vivo Source: Yip e
Slide 31: CSL311 for the Treatment of Airways Inflammation: Summary
CSL311 for the Treatment of Airways Inflammation For personal use only Summary • CSL311 is a potent antagonist of IL-3, IL-5 and GM-CSF in vitro • CSL311 inhibits the activity of multiple cell types involved in inflammation • CSL311 demonstrates efficacy in an in vivo translational model of airways
Slide 32: In Vivo vs Ex Vivo Gene Therapy
CSL Gene Therapy In Vivo vs Ex Vivo Gene Therapy For personal use only Direct delivery Cell-based delivery Treatment or Treatment or missing gene missing gene The treatment gene is added to a vector The patients own stem The treatment such as an adeno cells are removed from gene is added to a associ
Slide 33: Cell and Gene Therapy Research and Product Development
Cell and Gene Therapy Research and Product Development For personal use only • 2+ years post-acquisition of Calimmune • First clinical program recruiting patients • Integration into CSL R&D complete • Pipeline of early stage gene therapy projects Expertise/Know-how In Vivo Selection Tool Cell Proces
Slide 34: CSL200 for the Treatment of Sickle Cell Disease
CSL200 for the Treatment of Sickle Cell Disease (SCD) For personal use only Sickle Cell Disease • Group of disorders caused by abnormal beta-globin gene resulting in sickled red cells • High unmet need CSL200 Cytegrity™ Select+™ SIN-LV γ-globin construct (sGbGM) lenti-backbone technology 7SK shRNA β
Slide 35: Gene Therapy for Wiskott-Aldrich Syndrome (WAS)
Gene Therapy for Wiskott-Aldrich Syndrome (WAS) For personal use only • WAS is a rare X-linked PID (~ 1:100,000 live births) Primary Immune Deficiencies* – Mutations in the gene that encodes the WAS protein (WASp) • WAS is exclusively expressed in blood cells and plays a key role in organizing the a
Slide 36: Gene Therapy for Wiskott-Aldrich Syndrome (WAS)
Gene Therapy for Wiskott-Aldrich Syndrome (WAS) For personal use only Design and generation of lentiviral candidates based on our Cytegrity stable producer cell line backbone is in progress In vivo WAS protein Safety selection expression element Select+ Promoter WAS transgene Insulator Lentiviral ve
Slide 37: Immunoglobulin Therapy Mechanism of Action Summary
Immunoglobulin Therapy For personal use only Mechanism of Action Summary Pathogen Reduction of Complement FcγR Expression Immune Cells Cytokine Neutralisation Pathologic Ig Scavenging Modulation Modulation Modulation Ig Therapy IgG Fc Multimers FcRn Binding Agents No Activity Possible Activity Activ
Slide 38: CSL Research
CSL Research For personal use only • Expanding capacity and capability across global research sites • Continued investment in external innovation activities • Leveraging our three strategic platforms across five therapeutic areas • Continuing to innovate in areas of business strength • Developing ne
Slide 39: Clinical Development – Part 1
Clinical Development – Part 1 For personal use only Dr. Diana Lanchoney Vice President, Clinical Pharmacology and Translational Development CSL Behring 38 | Driven by Our Promise™
Slide 40: CSL Pipeline Progressing into Multiple New Disease Areas
CSL Pipeline Progressing into Multiple New Disease Areas Using All Three Product Development Platforms For personal use only • Sickle Cell Anemia – CSL200 (lentiviral stem cell gene therapy), CSL889 (Hemopexin) • Contact Mediated Thrombosis – Garadacimab (CSL312 Anti-Factor XIIa) • Respiratory Disea
Slide 41: Overview of Sickle Cell Disease (SCD)
Overview of Sickle Cell Disease (SCD) For personal use only • Missense mutation of the β-globin gene • Worldwide incidence ~300,000/year (US ~155,000) • Sickle red blood cells are fragile, prone to endothelial adhesion • Many downstream consequences – Avg. life expectancy 40 - 60yrs • Vaso-occlusive
Slide 42: Sickle Cell Anemia: CSL Programs Poised to Evolve the Paradigm
Sickle Cell Anemia CSL Programs Poised to Evolve the Paradigm For personal use only Long Term Disease Lentiviral stem cell gene Management therapy: CSL200 Prophylaxis for VOC Sickle Cell Anemia Treatment for VOC Hemopexin: CSL889 Supportive Care for VOC 41 | Driven by Our Promise™
Slide 43: CSL889 Hemopexin
CSL889 Hemopexin Addresses the Toxic Effects of Free Heme For personal use only Chronic Intravascular Haemolysis Vasculature CSL889 • Hemopexin, scavenger of Plasma heme (Hpx) heme with highest affinity metHb, Fe3+ Haemolysis • Depleted in SCD Cell free “river of heme” Hpx:heme haemoglobin Clearance
Slide 44: Garadacimab (CSL312 Anti-Factor XIIa) Multiple Potential Indications
Garadacimab (CSL312 Anti-Factor XIIa) Multiple Potential Indications For personal use only Auto-activation +FXIIa/β FXIIa FXII FXII C1 Inh PK → KAL* βFXIIa C1 Inh Fibroblast/ FXI → FXIa HK → BK→ BR2 C1qr,s → C1qr,s endothelial cell Vasodilation, Complement Haemostasis Mitogenesis vascular permeabili
Slide 45: Garadacimab Thrombosis Development Program Overview
Garadacimab (CSL312) Thrombosis Development Program Overview Mechanism to Prevent Contact-Activated Thrombosis Without Bleeding Risk For personal use only Phase I Contact Activation (FIH study) Associated Thrombosis SAD in healthy subjects • Safety • Pharmacokinetics (PK) Peripherally Inserted • Bio
Slide 46: CSL311 Anti-Beta Common
CSL311 Anti-Beta Common A Broad Mechanism of Action With Potential to Address the Entire Spectrum of Severe Asthma For personal use only Asthma: ~300 million globally Severe asthma: 2-10% Source: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.201508-514MG 45 | Driven by Our Promise™
Slide 47: CSL311 Phase I Clinical Strategy
CSL311 Phase I Clinical Strategy Informs Early POC Expansion For personal use only 2019-20 2020-21 2021+ Single Ascending Dose (SAD) Multiple Ascending Dose (MAD) Proof of Concept (POC) mild asthma mild asthma severe asthma exacerbation 1001a 1001b endpoint dose range finding chronic tox studies SC
Slide 48: CSL346 VEGF-B Antagonist
CSL346 VEGF-B Antagonist For personal use only • CSL346 is a novel humanised monoclonal antibody (IgG4) that binds VEGF-B • Strong renoprotective effects in diabetic kidney disease (DKD) animal models CSL346 Muscle • Phase II proof of concept study to start in early 2020 CSL346 Liver Adipose tissue
Slide 49: Diabetes and Diabetic Kidney Disease
Diabetes and Diabetic Kidney Disease For personal use only Increasing Prevalence 1994 2000 2015 Diabetes accounts for 30-50% of all chronic kidney disease 1 in 3 70% ~300,000 diabetics develop among them develop albuminuria People with DKD developed end stage DKD over time (ACR ≥30 mg/g; ie, incipie
Slide 50: CSL324 G-CSF Receptor Antagonist
CSL324 G-CSF Receptor Antagonist For personal use only G-CSF, neutrophils and inflammatory disease • Neutrophils are the most abundant white blood cells (WBC), ~109 cells / kg body weight leave the bone marrow daily • Excessive neutrophil production and G-CSF persistence within tissues leads to chro
Slide 51: CSL324 Begins Phase Ib Study in Neutrophilic Dermatoses
CSL324 G-CSF Receptor Antagonist Begins Phase Ib Study in Neutrophilic Dermatoses For personal use only • Hidradenitis Suppurativa (HS) and Other Neutrophilic Dermatoses (ND) • Hidradenitis Suppurativa – 1% prevalence – A disease of hair follicles, immune dysregulation – Chronic inflammation, discha
Slide 52: Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) For personal use only • Characterised by immunologic abnormalities, complex Disease pathophysiology Features • Heterogeneous disease Symptoms • Nearly every organ system may be affected Diagnosis • Diagnosis based on clinical symptoms and laboratory testing • Women
Slide 53: Strong Rationale for CSL362 Anti-IL-3Ra in SLE
Strong Rationale for CSL362 Anti-IL-3Ra (CD123) in SLE For personal use only • Type 1 IFNs known to play a pivotal role Immune complex containing host derived nucleic acid CSL362 in pathogenesis of SLE • pDCs are the major producer of Type 1 CD123 CD16 NK Cell IFNs Stimulates TLR7 and 9 pDC • CSL362
Slide 54: Systemic Sclerosis (SSc)
Systemic Sclerosis (SSc) For personal use only • Most life-threatening rheumatic disease: 10-year cumulative survival is 62.5% • Limited approved disease modifying agents • Most treatments aimed at improving symptoms and managing complications • Prevalence 7 - 43/100,000 (US/EU) Source: Nature Revie
Slide 55: IMPRESS: PRIVIGEN Phase II Study
IMPRESS PRIVIGEN® (IVIG) PhII, Efficacy and Safety Study For personal use only Week 48 Week 72 End of DB Treatment End of OL Treatment Screening Double-Blind Treatment Period Open Label Treatment Period Up to 4 weeks 48 Weeks 24 Weeks End of Study (Safety F/U) Subjects PRIVIGEN ® with PRIVIGEN ® dcS
Slide 56: SURPASS: HIZENTRA Phase II Study
SURPASS HIZENTRA® (SCIG) PhII, Safety and Bioavailability Study in Systemic Sclerosis For personal use only Treatment Period A Treatment Period B Randomization Screening HIZENTRA® PRIVIGEN® Arm 1 (n=10) Patients with dcSSc PRIVIGEN® HIZENTRA® Arm 2 (n=10) 16 weeks 16 weeks Full PK Profile 55 | Drive
Slide 57: Dermatomyositis (DM)
Dermatomyositis (DM) For personal use only • Rare (2 - 9/100,000), serious, and life- threatening – 5-year mortality rate 10-30% • Rash, muscle weakness, dysphagia, and systemic manifestations (heart, lung, gut, cancer) and specific autoantibodies • Female predominant, typical onset in adults late 4
Slide 58: RECLAIIM: HIZENTRA DM Treatment Study Design
RECLAIIM HIZENTRA® DM Treatment Study Design For personal use only Weeks 1 to 53 Safety Follow-Up Randomization HIZENTRA® HIZENTRA® Screening Placebo HIZENTRA® Up to 2 Weeks 1 to 25 Weeks 25 to 53 months 126 patients, Primary endpoint: 1:1 randomisation TIS responder status 57 | Driven by Our Promis
Slide 59: Garadacimab Phase II Hereditary Angioedema Study
Garadacimab Phase II Hereditary Angioedema (HAE) Study Completed Double Blind Period For personal use only Run-in period Treatment Period 1 Extension ~13 4–8 weeks weeks ~13 weeks ≥44 weeks Placebo q4W SC 1:1:1:1 First 32 patients Low dose Garadacimab q4W SC Screened Garadacimab SC subjects with Med
Slide 60: CSL Pipeline Progressing into Multiple New Disease Areas
CSL Pipeline Progressing into Multiple New Disease Areas Using All Three Product Development Platforms For personal use only • Sickle Cell Anaemia – CSL200 (lentiviral stem cell gene therapy), CSL889 (Hemopexin) • Contact-Mediated Thrombosis – CSL312 Garadacimab (Anti-Factor XIIa) • Respiratory Dise
Slide 61: Commercial – Part 1
Commercial – Part 1 For personal use only Mr. Bill Campbell Executive Vice President and Chief Commercial Officer CSL Behring 60 | Driven by Our Promise™
Slide 62: Global Commercial Operations at a Glance
Global Commercial Operations at a Glance For personal use only ~1,800 35 Affiliate Offices US$7.2 Commercial employees Conducting business in 100+ Countries Billion in annual revenue 4 Commercial Regions 5 Therapeutic Areas 61 | Driven by Our Promise™
Slide 63: FY'19 Highlights
FY’19 Highlights For personal use only Strong Balanced Executing to Ig Growth well Expanding China GSP Implemented Business Regional Plan on New Above Market Market License TA Structure / Performance Growth: Launches Presence Establishment Model 9% – 17% through New Affiliates 62 | Driven by Our Pro
Slide 64: Strong Demand Across the Portfolio
Strong Demand Across the Portfolio For personal use only • Strong underlying market growth Ig • Disciplined approach to market expansion • Growth driven by volume and mix improvements • Market leadership with IDELVION® in key markets Coagulation • Additional launch opportunities for AFSTYLA® / IDELV
Slide 65: Immunoglobulin Market
Immunoglobulin Market For personal use only Market Dynamics Global IG Volume by Indication 8% Growth • Increasing awareness and diagnosis • Growth in PID and CIDP Other 21% PID • Expanding usage for SID 28% • Potential new indications MG 5% ITP • Continued market supply tightness 6% SID CIDP 16% 24%
Slide 66: CSL Portfolio: Immunoglobulin
CSL Portfolio: Immunoglobulin For personal use only Positioned for Continued Growth • Market Leading Products Albumin Immunoglobulin • Substantial volume and share growth • Balanced growth across all regions $3,543M • IV and SC for CIDP Haemophilia +16% • History of Innovation Specialty Source: Data
Slide 67: PRIVIGEN: Expanding Global Market Leadership
PRIVIGEN® Expanding Global Market Leadership: 87 countries For personal use only #1 Prescribed IVIG Worldwide Proven effective and well tolerated in 12+ years Used in >100,000 patients with chronic disease in the last year Approved for use in multiple indications Indications: EU: PID, SID, ITP, GBS,
Slide 68: PRIVIGEN Performance Through Q2'19
PRIVIGEN® Performance Through Q2’19 For personal use only 30% 28% 27% 26% Share of IVIG Market (Volume) Total 7MM 24% 24% 25% 23% 23% 24% 24% 23% 20% 15% 10% 5% 0% Q1'17 Q2'17 Q3'17 Q4'17 Q1'18 Q2'18 Q3'18 Q4'18 Q1'19 Q2'19 PRIVIGEN® Privigen Competitor A Competitor B Competitor C Competitor D Sourc
Slide 69: HIZENTRA: Expanding Global Market Leadership
HIZENTRA® Expanding Global Market Leadership: 57 Countries For personal use only Innovator, Market Leader, Most Prescribed SCIG Worldwide Proven efficacy and tolerability since 2010 100,000 patient-years of experience More than 6,000,000 exposures worldwide* PID PID + CIDP Source: Data on file *Hize
Slide 70: HIZENTRA Undisputed Market Leader in SCIG
HIZENTRA® Undisputed Market Leader in SCIG For personal use only 80% Share of SCIG Market (Volume) (US, 5EU, JP) 70% 62% 61% 60% 61% 58% 57% 57% 57% 58% 60% 57% 50% 40% 30% 20% 10% 0% Q1'17 Q2'17 Q3'17 Q4'17 Q1'18 Q2'18 Q3'18 Q4'18 Q1'19 Q2'19 Total SCIG (grams) Hizentra HIZENTRA® Competitor A Compe
Slide 71: HIZENTRA Addresses Unmet Needs in CIDP
HIZENTRA® Addresses Unmet Needs in CIDP For personal use only Approved March ‘18 US & EU Approved March ‘19 Japan Experience IV-related 5x as many patients said Interest & Awareness HIZENTRA® Remains High Have venous systemic adverse they felt fewer side effects does not require access issues reacti
Slide 72: CSL Behring on Track to Become Market Leader in CIDP
CSL Behring on Track to Become Market Leader in CIDP For personal use only 40 35 % Patient Share (US, 5EU, JP) 30 25 20 15 10 5 0 Q1 17 Q2 17 Q3 17 Q4 17 Q1 18 Q2 18 Q3 18 Q4 18 Q1 19 Q2 19 CSL Behring Competitor A Competitor B Competitor C Competitor D Source: Data on file 71 | Driven by Our Promis
Slide 73: Market Leadership in Ig Therapy
Market Leadership in Ig Therapy For personal use only Past 1979 2006 2007 2010 2013 2013 2015 1st IVIG 1st SCIG Next generation IVIG 1st 20% SCIG 1st SCIG in Japan CIDP in EU 1st flexible dosing Sandoglobulin® Vivaglobin® PRIVIGEN® HIZENTRA® HIZENTRA® PRIVIGEN® HIZENTRA® Present 2017 2018 2018 2019
Slide 74: Panel Q&A Session
Panel Q&A Session For personal use only 73 | Driven by Our Promise™
Slide 75: Break
Break – 15 minutes For personal use only 74 | Driven by Our Promise™
Slide 76: Commercial – Part 2
Commercial – Part 2 For personal use only Mr. Bill Campbell Executive Vice President and Chief Commercial Officer CSL Behring 75 | Driven by Our Promise™
Slide 77: Haemophilia Market
Haemophilia Market For personal use only Market Dynamics • New therapies continue to increase Inhibitor 16% competitiveness in Hem A segment vWD 4% • Patient education about Prophylaxis in Hem B Hem B Total value Hem A driving utilization of long acting products 14% $11.7B 66% • VWD is underserved d
Slide 78: Haemophilia Portfolio
Haemophilia Portfolio For personal use only • 40% growth* • 85% growth* • Leadership position in VWD: 59%^ market share globally • Continued patient switching • Long lasting and reliable bleed protection • Additional countries to launch • Successful product transition • 21 day dosing HELIXATE® phase
Slide 79: IDELVION Prophylaxis Market Leadership
IDELVION® Prophylaxis Market Leadership For personal use only 45% 39% 40% 38% 40% 37% 35% 35% 30% 33% 29% Patient Share 25% 25% 20% 21% 17% 15% 10% 5% 0% Q1 17 Q2 17 Q3 17 Q4 17 Q1 18 Q2 18 Q3 18 Q4 18 Q1 19 Q2 19 IDELVION® Idelvion Competitor A Competitor B All Other Based on 5 major markets (US, J
Slide 80: Positioning AFSTYLA in a Competitive Market
Positioning AFSTYLA® in a Competitive Market For personal use only • Unique single-chain molecular structure provides increased binding Higher binding affinity to vWF • Enhanced binding affinity protects AFSTYLA® from degradation, extending time in circulation • FDA-approved for 2x or 3x weekly dosi
Slide 81: CSL Portfolio: Specialty Products
CSL Portfolio: Specialty Products For personal use only Immunoglobulin Albumin $1,572M Haemophilia +6% Specialty M = US$ millions 80 | Driven by Our Promise™
Slide 82: Continued Growth Opportunity for KCENTRA
Continued Growth Opportunity for KCENTRA® For personal use only US clinical practice guidelines recommend KCENTRA® over FFP to reverse the effects of Warfarin* Anticoagulation Market US1 Warfarin Market US (Patients)1 Warfarin Reversal Market US2 Warfarin Product A Product B Other 1,800,000 100% 1,6
Slide 83: KCENTRA Growth in US Since Launch
KCENTRA® Growth in US Since Launch For personal use only KCENTRA® • KCENTRA® remains the first and only FDA 250 approved 4F-PCC for reversing patients on warfarin 200 • KCENTRA® is supported by multiple clinical guidelines as the preferred reversal agent 150 Units (Millions) • KCENTRA® growth driven
Slide 84: HAEGARDA: #1 prescribed therapy in the US
HAEGARDA® For personal use only #1 prescribed therapy in the US for the prevention of HAE attacks Address C1-INH deficiency with HAEGARDA® C1-INH has been used in HAE > 35 years HAEGARDA® reduced HAE attacks by 95%* Rescue medication use was reduced by >99%†‡1 *Median reduction in number of attacks
Slide 85: HAE Prophylaxis Market
HAE Prophylaxis Market For personal use only 2000 1825 Total Prophylaxis Patients (US) 1800 1600 1509 • HAEGARDA® is the market leader in HAE 1400 1292 prophylaxis in the US 1200 1000 • Rapid uptake at launch 800 600 • Significant brand loyalty 400 200 • Additional capacity to support new launches 0
Slide 86: Why HAEGARDA?
Why HAEGARDA® ? For personal use only HAEGARDA® Patients Rely On C1-INH Physicians Highly Satisfied with HAEGARDA®, For Efficacy And Safety Delivering On Its Promise of Efficacy With a Known MOA “I’ve been on HAEGARDA for one year, and I haven’t had “People ask about Takhzyro but they’re an attack.
Slide 87: Commercial Summary
Commercial Summary For personal use only Strong Performance in FY19 New Products Market Leading Contributing Brands significantly to Growth Balanced Regional Substantial Volume & Contribution Share Growth 86 | Driven by Our Promise™
Slide 88: Seqirus R&D
Seqirus R&D For personal use only Dr. Russell Basser Senior Vice President, Research and Development Seqirus 87 | Driven by Our Promise™
Slide 89: Seqirus Influenza Vaccines
Seqirus Influenza Vaccines For personal use only High-risk Standard risk populations Seasonal Adjuvanted TIV / QIV seasonal TIV / QIV Pandemic Egg Based Cell Based Influenza Science 88 | Driven by Our Promise™
Slide 90: Milestones in 2019
Milestones in 2019 For personal use only AFLURIA® QUADRIVALENT • AUS approval for 6M – 4yrs FLUCELVAX® QUADRIVALENT • European approval for 9yrs and older • Paediatric efficacy study (2 - 17yrs) – met all clinical endpoints • Canadian approval for 9yrs and older FLUAD® TRIVALENT • Strong effectivene
Slide 91: Influenza Vaccine Innovation Through Cell-based Manufacturing
Influenza Vaccine Innovation Through Cell-based Manufacturing For personal use only Eggs • Most influenza vaccines • Egg supply – long lead times • Low flexibility Egg-Derived Virus Seed Circulating Virus Cell-Derived Cell Culture Virus Seed • Closed reactor • High yield and volume • Potential for r
Slide 92: Science of Influenza Virus Mutation and Rationale for Non-egg Vaccines
Science of Influenza Virus Mutation and the Rationale for Non-egg Vaccines For personal use only Yearly seasonal vaccine Circulating virus 4 strains – currently 2 x “A” – H3N2, H1N1 2 x “B” – B/Victoria, B/Yamagata Manufacturing change Environmental drift Environmental shift → altered strain → alter
Slide 93: 2018-19 was a Moderate Influenza Season in US
2018-19 was a Moderate Influenza Season in US (and elsewhere) For personal use only Estimated Cases of Influenza and Related Hospitalizations, U.S 2010-19 Seasons 50000000 Hospitalisations Cases 1000000 45000000 900000 40000000 800000 Number of influenza illnesses Number of hospitalizations 35000000
Slide 94: Influenza Vaccine Effectiveness Varies by Year and Age
Influenza Vaccine Effectiveness Varies by Year and Age For personal use only 2018-19 affected by strain mismatch due to “drift” in US Vaccines least effective in older adults 100 2018-19 VE by age (%) 100 % vaccine effectiveness 90 80 80 60 70 49 % vaccine effectiveness 60 40 60 56 25 52 47 49 48 20
Slide 95: Bringing Together MF59 Adjuvant and Cell-based Vaccine - aQIVc
Bringing the Benefits of MF59 Adjuvant and Cell-based Vaccine Together - aQIVc For personal use only Egg Seed Cell Seed MF59 adjuvant Circulating strain Increases “breadth” of immunity Increases antibody response Antigenic distance 94 | Driven by Our Promise™
Slide 96: Potential Benefits of Cell-based Vaccine
Potential Benefits* of Cell-based Vaccine For personal use only • Evidence of egg adaptation strongly supported by non-clinical data# • Studies of Real World Evidence from 2017-18 season show benefit of cell-based vs egg-based vaccine in a season dominated by H3N2 strain (~2 of every 4 years) – 36%
Slide 97: Real World Evidence and the Impact of FLUAD
Real World Evidence and the Important Impact of FLUAD® For personal use only • Recent data comparing FLUAD® to non-adjuvanted egg-based vaccines in people 65 years and above • US nursing home observational study* in 52,000 residents in 2016-17 – 6% reduction in all-cause hospitalisation • Public Hea
Slide 98: Strengthening the Power of RWE at Seqirus
Strengthening the Power of RWE at Seqirus From Electronic Medical Record to Integrated Understanding For personal use only • Real world evidence (RWE) is data regarding potential benefits or risks of a 2020 and Beyond vaccine from sources other than traditional randomised clinical trials • Influence
Slide 99: Focus on Influenza – Process and Seed Innovation
Focus on Influenza – Ongoing Process and Seed Innovation For personal use only Process Improvement Seed Innovation “Upstream” growth and isolation of virus Viral Reassorting Mixed Infection Cell Reassorting Selection Wave Infection Filtration Selection of Bioreactors Bioreactors Virus virus Amplific
Slide 100: Shift to Differentiated Products Expected to Drive Future Value Growth
Shift to Differentiated Products is Expected to Drive Future Value Growth For personal use only • Global influenza vaccine market volumes between 500-600 million doses – 150 million doses distributed in US* in 2018-2019 season – Slow future growth, largely due to ageing population • Seasonal global
Slide 101: Anticipated Milestones in 2020
Anticipated Milestones in 2020 For personal use only FLUCELVAX® FLUAD® Pre-Pandemic aQIVc QUADRIVALENT QUADRIVALENT aH5N1c • Commence • AUS approval • US approval for • US approval clinical program 9yrs+ 65yrs+ • Clinical study • EU approval for data 65yrs+ for 6M - 4yrs 100 | Driven by Our Promise™
Slide 102: Clinical Development – Part 2
Clinical Development – Part 2 For personal use only William Mezzanotte, M.D. Executive Vice President, Head of Research and Development CSL Behring 101 | Driven by Our Promise™
Slide 103: Investigating Alpha-1 Antitrypsin in Graft vs Host Disease
Investigating the Benefit of Alpha-1 Antitrypsin in Graft vs Host Disease (GvHD) For personal use only Alpha-1 Antitrypsin (CSL964) for GvHD Prevention Part 1 Part 2 Cohorts 1-3 Cohorts 4 Dose Levels 1-3 Selected Dose Cohort 1 completed Open Label Placebo-controlled Bone Marrow Transplant Clinical T
Slide 104: Antibody-Mediated Rejection in Renal Allografts
Antibody-Mediated Rejection (AMR) in Renal Allografts For personal use only • Development of Donor Specific Antibodies (DSAs) • Late in the post-transplant period • Progressive decline in kidney function • Loss of graft • No approved therapies – Pilot data for C1 inhibitor and anti-IL-6 Source: Am J
Slide 105: AMR: Complement Dependent and Independent Pathways
AMR: Complement Dependent and Independent Pathways For personal use only C1 inhibitor – Complement-dependent antibody- ARMOR study mediated activity cytotoxicity Donor-Specific Antibodies (DSA) & Antibody-Mediated Complement-independent antibody- Rejection (AMR) mediated cellular toxicity • Direct e
Slide 106: CSL112 ApoA-1
CSL112 ApoA-1 For personal use only • Study enrolment is active in >45 countries and progressing well CSL112 – PMDA approval for Japan to join trial particles • Independent Data Monitoring Committee – no safety concerns ABCA1 transporter Intracellular cholesterol • First futility analysis in 2020 1°
Slide 107: Summary
Summary For personal use only William Mezzanotte, M.D. Executive Vice President, Head of Research and Development CSL Behring
Slide 108: R&D Portfolio – December 2019
R&D Portfolio – December 2019 For personal use only POST- RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION REGISTRATION CSL730 CSL312 Anti-FXIIa CSL830 Discovery Projects Improved Fibrinogen HIZENTRA® DM PRIVIGEN® PID Japan rFc Multimer HAE C1-INH Subcut EU CSL787 CSL324 CSL112 FLUAD® Q
Slide 109: Expected Progress in Next 12 Months
Expected Progress in Next 12 Months For personal use only PRE-CLINICAL PHASE I PHASE II PHASE III POST-REGISTRATION CSL362 CSL346 HAEGARDA® PRIVIGEN® PID recC1-INH Anti-IL-3Ra Anti-VEGF-B Japan Japan CSL787 aQIVc (MF59 plus Garadacimab IDELVION® Novel Complement Inhibitor Nebulised Ig FLUCELVAX® ant
Slide 110: Significant Target Launch Dates
Significant Target Launch Dates For personal use only 2019 2020 2021-2025 HIZENTRA® CIDP Japan PRIVIGEN® PID Japan Garadacimab (Anti-FXIIa) HAE Clazakizumab AMR PRIVIGEN® CIDP Japan IDELVION® 21 Day Dosing HIZENTRA® DM IVIG Kidney AMR FLUAD® QIV 65yrs+ AFLURIA® QIV 6m+ (AUS) HAEGARDA® Japan CSL842 C
Slide 111: 2019 Highlights
2019 Highlights For personal use only • HIZENTRA® and PRIVIGEN® approved for treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Japan Immunology • HIZENTRA® granted Orphan Drug Exclusivity for CIDP and Neurology • HIZENTRA® Dermatomyositis (DM) Phase III Study initiated • Garad
Slide 112: Panel Q&A Session
Panel Q&A Session For personal use only 111 | Driven by Our Promise™
Slide 113: News Release: CSL Continues to Advance R&D Capabilities
News Release For immediate release CSL Continues to Advance R&D Capabilities Unique portfolio mix of plasma, cell and gene therapy, recombinant proteins and For personal use only antibody assets highlighted at Research & Development Briefing Sydney, Australia, 4 December 2019 – CSL Limited (ASX:CSL;
Slide 114: News Release: CSL311 monoclonal antibody
News Release For immediate release The potential therapy, which currently holds the working title “CSL311,” is a monoclonal antibody that targets multiple inflammatory agents involved in various diseases. For personal use only CSL311 is the first monoclonal antibody to simultaneously target three ce