Csl Limited · ASX:CSL
Csl — Investor Day (December 2018)
116 slides from Csl's investor day presentation, Dec 5, 2018
Slide 1: Annual Research & Development Investor Briefing
For personal use only For immediate release 5 December 2018 Annual Research & Development Investor Briefing Please find attached the presentation and an accompanying media release ahead of the Company’s Annual Research & Development Investor Briefing being held today commencing at 9am ADST. The brie
Slide 2: R&D Investor Briefing
For personal use only R&D Investor Briefing December 05, 2018 ™ 1 | Driven by Our Promise
Slide 3: Legal Notice
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 and produ
Slide 4: Agenda
Agenda For personal use only • Welcome Mark Dehring • Introduction and Highlights Andrew Cuthbertson • Seqirus Gregg Sylvester • Research & Early Development Andrew Nash • Commercial Market Overview, Ig & Haemophilia Bill Campbell • Q&A – Break – • Clinical Development Overview Bill Mezzanotte • Com
Slide 5: Introduction and Highlights
For personal use only Introduction and Highlights Professor Andrew Cuthbertson AO Chief Scientific Officer 4 | Driven by Our Promise™
Slide 6: 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 improveme
Slide 7: Key Past Launches from R&D Portfolio
Key Past Launches from R&D Portfolio For personal use only 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 PRIVIGEN® HIZENTRA® PRIVIGEN® CIDP (US) HIZENTRA® Ig PRIVIGEN® CIDP (EU) Ig IsoLo® CIDP Specialty BERINERT® (US) KCENTRA® (US) RESPREEZA® (EU) RIASTAP® CORIFACT® HAEGARDA® (US) VONCENTO®
Slide 8: Leveraging Global Capabilities
Leveraging Global Capabilities For personal use only Integration via project management processes 7 | Driven by Our Promise™
Slide 9: R&D Portfolio - December 2017
R&D Portfolio - December 2017 For personal use only COMMERCIAL / RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION PHASE IV Clinical C1-INH New PRIVIGEN® PRIVIGEN® Japan HIZENTRA® CIDP Applications Indications CIDP US Fibrinogen New KCENTRA® HIZENTRA® IIM Formulations Japan Haptoglobin/
Slide 10: Progress Through Stage Gates in 2018
Progress Through Stage Gates in 2018 For personal use only New Product Phase I Registration & Post Product Research Development & Phase II Phase III (FIH) Launch Registration Opportunity GLP Toxicology 1 2 3 4 5 6 7 Enter Enter Product Enter Phase I Enter Phase II Enter Phase Enter Enter Post Resear
Slide 11: R&D Portfolio - December 2018
R&D Portfolio - December 2018 For personal use only COMMERCIAL / RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION PHASE IV Emerging CSL787 CSL730 CSL312 Anti-FXIIa Clazakizumab* IDELVION® Technologies Nebulised Ig rFc Multimer in HAE Transplant CSL311 CSL324 Novel Strategies Mavri GM-CS
Slide 12: Seqirus R&D
For personal use only Seqirus R&D Dr Gregg Sylvester Vice President Medical Affairs 11 | Driven by Our Promise™
Slide 13: Seqirus Influenza Vaccines
Seqirus Influenza Vaccines For personal use only At-risk Standard risk populations seasonal Adjuvanted TIV / QIV seasonal TIV / QIV Pandemic Cell Based Egg Based Influenza Science 12 | Driven by Our Promise™
Slide 14: Influenza Viruses Mutate in Various Ways
Influenza Viruses Mutate in Various Ways For personal use only Circulating virus Yearly seasonal vaccine Environmental shift Immunological drift • Environmental 4 strains • Manufacturing 2 x “A” – H3N2, H1N1 2 x “B” – B/Victoria, B/Yamagata New virus Strain altered Usually vary season to season → pa
Slide 15: Seqirus Technologies aim to Enhance Influenza Vaccines
Seqirus Technologies aim to Enhance Influenza Vaccines For personal use only Cell Seed Egg Seed Antigenic distance Circulating strain MF59 Adjuvant Antigenic distance 14 | Driven by Our Promise™
Slide 16: Milestones in 2018
Milestones in 2018 For personal use only • AFLURIA QIV • US approval for 6M-4yrs • FLUCELVAX QIV • US approval of major process improvement (“FCC3.0”) • European positive opinion • Positive effectiveness data compared with egg-based vaccines in US 2017-18 season • FLUAD • Completion of US registrati
Slide 17: Successful completion of AFLURIA QIV program
Successful completion of AFLURIA QIV program For personal use only 6 to 35 months age group 36 to 59 months age group NHF0405 USF0629 USF0736 AFLURIA TIV Pooled Fluzone USF0736 Fluzone AFLURIA 0 5 10 15 20 25 30 35 40 45 50 5 10 15 20 25 30 35 40 45 50 Percentage of subjects with fever above 38ºC 16
Slide 18: Improvements in FLUCELVAX manufacturing output
Improvements in FLUCELVAX manufacturing output For personal use only Number of doses of FLUCELVAX manufactured by calendar year 30 FCC3.0 dossier filing • MDV launch 25 • FCC3.0 PPQ 20 million doses 15 FCC3.0 • QIV PFS approval Licensed for 2 lines • Latex free 10 • TIV PFS • 4yr+ indication • 18yr+
Slide 19: Vaccine Seed Adapts to Grow in Eggs
Vaccine Seed Adapts to Grow in Eggs For personal use only Adaptation Required in Generation of Egg Seed Seasonal strain \ Selection based on • seasonal HA and NA High growth donor strain • high growth properties No Adaptation Required in Generation of Cell Seed Seasonal strain High yielding viruses
Slide 20: Virus adaptation to grow in eggs
Science describes specific adaptation required for virus to grow in eggs, especially (but not only) H3N2 For personal use only HEMAGGLUTININ Receptor Dominant binding Antigenic site Region HA1 HA2 19 | Driven by Our Promise™
Slide 21: H3N2-dominant seasons and health burden
H3N2-dominant seasons occur often and can be associated with a substantial health burden For personal use only Deaths 37,000 12,000 43,000 38,000 51,000 25,000 51,000 Source: US data from CDC, available at www.cdc.gov/flu/about/disease/2015-16.htm 20 | Driven by Our Promise™
Slide 22: US 2017-18 Season was Severe and Dominated by H3N2
US 2017-18 Season was Severe and Dominated by H3N2 For personal use only First season a cell-based seed was included in FLUCELVAX → H3N2 chosen Source: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD); https://www.cdc.gov/flu/weekly/index.
Slide 23: Big Data to Assess Real World Health Impact of a Vaccine
Big Data to Assess Real World Health Impact of a Vaccine For personal use only • Randomised clinical trials provide an estimate of efficacy in a controlled setting in a well- defined population • Real world vaccine effectiveness (VE) evaluation addresses the health impact of a vaccine in the general
Slide 24: Relative VE of cell- vs egg-based vaccines in 2017-18 US Season
Relative VE of cell- vs egg-based vaccines in 2017-18 US Season For personal use only • Seqirus data (ALLSCRIPTS)* • → 36% (95% CI 26.1, 44.9) reduction in ‟influenza-like illness” • FDA data (Centers for Medicare & Medicaid Services)^ • → 11% (95% CI 7.5, 13.7) reduction in hospital/ER “encounters”
Slide 25: Francis Crick Institute (WHO) year data
Francis Crick Institute (WHO) 15 year data Cell- vs egg-based “reference virus” similarity to wild-type H3N2 For personal use only Virus collection date % Samples antigenically similar (HI assay) 100 Cell-propagated virus; n = < 50 Cell-propagated virus; n = 50 – 99 Cell-propagated virus; n = ≥ 100
Slide 26: MF59 Adjuvant
MF59 Adjuvant For personal use only Span 85 • Oil-in-water adjuvant Tween 80 • Seasonal vaccine (FLUAD) – increased and broader Squalene immunogenicity, focussed on people 65yrs and older • Pandemic vaccine – dose sparing • aH5N1c dose 1/12 of that required without adjuvant • >130 million doses admi
Slide 27: FLUAD is Gaining Wider Usage for People 65yrs and Older
FLUAD is Gaining Wider Usage for People 65yrs and Older For personal use only • Approved in Europe 1997, USA 2015 • Preferential recommendation for population 65years and older in UK & AUS • Meta-analysis* of published studies (real world data) describes effectiveness of FLUAD in prevention of lab-c
Slide 28: Real World Data to Investigate the Potential Benefits of FLUAD
Real World Data to Investigate the Potential Benefits of FLUAD For personal use only • FDA/CMS (insurance claims) data 2017/18 season • FLUAD showed 3% reduction in hospital/ER encounters in mismatch season* • Cluster Randomised Trial in Nursing Homes during 2016/17 season (interim analysis) • FLUAD
Slide 29: Seqirus Technologies aim to Enhance Influenza Vaccines
Seqirus Technologies aim to Enhance Influenza Vaccines For personal use only Cell Seed Egg Seed Antigenic distance Circulating strain MF59 Adjuvant Antigenic distance 28 | Driven by Our Promise™
Slide 30: Anticipated Milestones in 2019
Anticipated Milestones in 2019 For personal use only • AFLURIA QIV • AUS approval for 6M-4yrs • FLUCELVAX QIV • European approval for 9yrs+ • AUS submission • FLUAD QIV • US approval for 65yrs+ • EU/UK and AUS submissions • PrePandemic aH5N1c • US submission 29 | Driven by Our Promise™
Slide 31: CSL Behring Research and Early Development Portfolios
For personal use only CSL Behring Research and Early Development Portfolios Dr Andrew Nash Senior Vice President, Research 30 | Driven by Our Promise™
Slide 32: Research Organisation and Portfolio
Research Organisation and Portfolio For personal use only • Coordinated global project portfolio Specialty Breakthrough Immunoglobulins Haemophilia Transplant Products Medicines • Bio21(Parkville), Bern and Marburg • Bio21 expansion completed • Research capabilities: plasma and recombinant proteins,
Slide 33: Research Organisation and Portfolio: Bern relocation
Research Organisation and Portfolio For personal use only • Relocation of CSL Research Bern Swiss Institute of Translational and Entrepreneurial Medicine (SITEM) • Bern University and Hospital Campus • Translational medicine, Phase I Unit • Cell and Gene Therapy Bern relocation / expansion – complet
Slide 34: Early Development Portfolio
Early Development Portfolio 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 Product Dev / Tox Phase I Phase II CSL312 (anti-FXIIa) CSL324 (ant
Slide 35: Immunoglobulin Therapy
Immunoglobulin Therapy For personal use only Ig Fab region • Immune deficiencies • Autoimmune conditions recombinant Fc multimer – CSL730 FcRn targeting Ig Fc region Potentially reproduces all • Autoimmune conditions Fc mediated Ig activity FcγR targeting From Lunemann et al., Nat Rev Immunol 2015 3
Slide 36: Immunoglobulin Therapy: Targeting FcRn
Immunoglobulin Therapy For personal use only Targeting FcRn – IG vs. anti-FcRn agents • IV & SC IG therapy in autoimmune disease • Increase in total circulating IgG • Pathogenic auto-antibody IgG out-competed IVIG therapy for access to FcRn • Long term safety established FcRn recycling controls circ
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: CSL730 – Recombinant Fc Multimer
CSL730 – Recombinant Fc Multimer For personal use only CSL730 is effective in a mouse model of ITP • Non-clinical safety toxicity data supports commencement of FIH studies • Phase I study (healthy volunteers) commenced Q1 2018 CSL730 dose 37 | Driven by Our Promise™
Slide 39: Immunoglobulin Therapy – Expanding Benefit
Immunoglobulin Therapy – Expanding Benefit For personal use only Nebulised Ig – respiratory tract infections • Concept: Prevention of viral and bacterial infections of the respiratory tract by inhaling polyclonal immunoglobulins • Technical feasibility demonstrated Potential indications for NebIg: •
Slide 40: Inhaled IgG prevents bacterial and viral infection
Immunoglobulin Therapy – Expanding Benefit For personal use only Inhaled IgG prevents bacterial and viral infection Mouse model of S. pneumoniae infection In vitro model of influenza virus infection 100 Tissue integrity Mucociliary clearance infected infected Percent survival 50 Vehicle IgG 0 0 5 10
Slide 41: CSL312 – HAE and Thrombosis
CSL312 – HAE and Thrombosis For personal use only Auto-activation • Targeting FXIIa FXIIa - represents a novel approach to the treatment of HAE & FXI → FXIa PK → KAL βFXIIa contact activated thrombosis → thrombin HK → BK→ BR2 C1qr,s → C1qr,s Vasodilation, Complement • Efficacy in multiple Haemostasi
Slide 42: CSL312 – First in Human Phase I study
CSL312 – HAE and Thrombosis For personal use only First in Human (healthy volunteers) Phase I study Pharmacokinetics (SAD) CSL312 serum conc.(mg/ml) • Phase II study in HAE patients in progress • Study in contact activated thrombosis to commence in 2019 Time (h) • Safe and well tolerated • Linear ph
Slide 43: CSL324 – Neutrophil Mediated Inflammation
CSL324 – Neutrophil Mediated Inflammation For personal use only G-CSF / Neutrophils / Inflammation COPD exacerbations • Neutrophils – contribute to protective CF exacerbations mechanism against infections Reperfusion injury / ARDS • Neutrophil numbers and activity under Delayed graft function contro
Slide 44: CSL324 – First in Human Phase I study
CSL324 – Neutrophil Mediated Inflammation For personal use only First in Human (healthy volunteers) Phase I study Pharmacokinetics (SAD) 10 CSL334 serum conc.(mg/ml) 0.8 mg/kg 1.0 0.3 mg/kg 0.1 mg/kg 0.1 Nominal time • Safe and well tolerated • Linear PK with target saturation and expected pharmacod
Slide 45: CSL324 – Phase Ib in neutrophilic dermatoses
CSL324 – Neutrophil Mediated Inflammation For personal use only Phase Ib study in neutrophilic dermatoses commencing Q2 2019 Hidradenitis Suppurativa (Acne Inversa) Palmoplantar pustulosis • Chronic, inflammatory, recurrent, debilitating skin • Characterised by a chronic eruption of sterile disease
Slide 46: CSL324 – Kidney graft reperfusion injury
CSL324 – Neutrophil Mediated Inflammation For personal use only Kidney graft reperfusion injury • G-CSFR blockade protects against renal Ischemia Reperfusion Injury (IRI) in a mouse model G-CSFR blockade prevents neutrophil infiltration Control Ab (500 ug) VR81 (100 ug) Ly-6G Left renal ischemia (22
Slide 47: CSL324 – Kidney graft reperfusion injury
CSL324 – Neutrophil Mediated Inflammation For personal use only Kidney graft reperfusion injury • G-CSFR blockade protects against renal IRI in a mouse model G-CSFR blockade preserves kidney function VR81 = surrogate anti-mG-CSFR Opportunity for CSL324 in solid organ transplantation 46 | Driven by O
Slide 48: Research and Early Development
Research and Early Development For personal use only • Expanding capacity and capability across global Research sites • New projects leveraging Calimmune gene and cell therapy technologies • Continuing to innovate in areas of business strength Specialty Immunoglobulins Haemophilia Products • Develop
Slide 49: Commercial Market Overview
Commercial Market For personal use only Overview Mr Bill Campbell Executive Vice President & Chief Commercial Officer 48 | Driven by Our Promise™
Slide 50: Targeted Protein Therapeutic Market
Targeted Protein Therapeutic Market For personal use only Albumin $4.1B Immunoglobulin $11.1B Total Global Market Value: Haemophilia ~$30.5B $11.4B Specialty $3.6B Source: Adivo, Global Market Research, Analyst Reports, Company Annual Reports, Haemophilia mkt includes Inhibitor mkt 49 | Driven by Ou
Slide 51: CSL Portfolio
CSL Portfolio For personal use only Albumin Immunoglobulin CSL Total FY18 $6,678M $3,145M +11% Haemophilia $1,490M +24% $1,113M +5% $921M +7% Specialty Growth at constant currency 50 | Driven by Our Promise™
Slide 52: New Product Launches
New Product Launches For personal use only CIDP CIDP March ‘16 May ‘16 June ‘17 Feb. ’18 March ‘18 (US only) Launch date denotes first country to launch globally 5 major launches in 24 months Some of the most successful launches in the industry Significant contribution to the business now…in future
Slide 53: Immunoglobulin Market
Immunoglobulin Market For personal use only Global IG volume by indication 9% Growth PID 28% Growth Drivers Other 21% • Enhanced diagnosis in PID, CIDP • Immunotherapy driving SID growth MG • Increasing per capita use in emerging markets 4% ITP • Continued market supply tightness 6% CIDP 24% SID 17%
Slide 54: CSL Portfolio: Immunoglobulin
CSL Portfolio: Immunoglobulin For personal use only Immunoglobulin Albumin FY18 $3,145M +11% • Above market volume growth • Expansion in PID, SID, CIDP Haemophilia • Balanced growth across all regions • Continued life-cycle investments Specialty Disciplined execution 53 | Driven by Our Promise™
Slide 55: Immunoglobulins: Category Leadership
Immunoglobulins: Category Leadership For personal use only • Maximise PID / SID opportunity GROW • Leverage broad portfolio the current business • Enhance product offerings • Replicate our approach to build market leading segments EXPAND • Build on PRIVIGEN® experience in CIDP our presence in neurol
Slide 56: Privigen and Hizentra
For personal use only Privigen is a ready-to-use Proven effective and well More than 10% IVIG approved in tolerated with 100,000 80+ countries 10+ years patient-years of experience3 & 6 million exposures worldwide3 worldwide1 of patient experience Approved for use in Used in Proven efficacy and tole
Slide 57: Hizentra: Innovator, Market Leader
: Innovator, Market Leader For personal use only Patients on SCIG Therapy: US 1 Patients on SCIG Therapy: 7 Major Markets 1 16,000 25,000 14,000 20,000 12,000 10,000 15,000 8,000 10,000 6,000 4,000 5,000 2,000 0 0 Q1'16 Q2'16 Q3'16 Q4'16 Q1'17 Q2'17 Q3'17 Q4'17 Q1'18 Q2'18 Q1'16 Q2'16 Q3'16 Q4'16 Q1
Slide 58: Hizentra addresses unmet needs in CIDP therapy
addresses unmet needs in CIDP therapy For personal use only CIDP Update • Early in launch cycle • Leading indicators are positive 5x as many patients Experience IV- Have venous HIZENTRA® said they felt fewer related systemic access issues does not require side effects with venous access • Market sha
Slide 59: Market Leading Therapies
For personal use only • Positioned for continued growth • Expanding market presence • Diverse disease opportunities • Balanced geographic footprint • Continued life cycle investment • Plasma collections running ahead of the market • Early days…but very positive in CIDP Market Leading Therapies 58 |
Slide 60: Haemophilia Market
Haemophilia Market For personal use only Inhibitor 20% • Highly competitive Haem A segment VWD • Rapid transition of Haem B to long acting products 4% Total value • 75% of patients with bleeding disorders are under or $11.4B untreated Hem B Hem A 14% 62% • New technologies / advancements hold great
Slide 61: CSL Portfolio: Haemophilia
CSL Portfolio: Haemophilia For personal use only FY18 $1,113M +5% Haem A Albumin Immunoglobulin • AFSYTLA® • Launched in 12 countries • Plasma-derived portfolio Haem B • IDELVION® Haemophilia • Transformational Product • Strong growth • Market leadership von Willebrand Disease Specialty • HUMATE-P®,
Slide 62: Positioning in a Competitive Market
Positioning in a Competitive Market For personal use only Higher binding • Unique single-chain molecular structure provides increased binding affinity to vWF • Enhanced binding affinity protects AFSTYLA® from degradation, extending time in circulation • FDA-approved for 2x or 3x weekly dosing 2x wee
Slide 63: Clinical Profile is Uniquely Differentiated
Clinical Profile is Uniquely Differentiated For personal use only 0 • Zero median annualized spontaneous Median AsBR bleeding rate (AsBR) in prophylaxis Up to 14 day dosing* • Greater freedom from infusions 21% Factor IX • High and sustained factor levels at steady state trough levels† steady-state
Slide 64: Performance in Key Markets
Performance in Key Markets For personal use only Switzerland Germany 100% 100% 80% 80% 60% 58% 58% 60% 40% 40% 20% 20% 0% 0% Q3 16 Q4 16 Q1 17 Q2 17 Q3 17 Q4 17 Q1 18 Q2 18 Q1 16 Q2 16 Q3 16 Q4 16 Q1 17 Q2 17 Q3 17 Q4 17 Q1 18 Q2 18 Japan US 60% 50% 50% 40% 40% 37% 30% 30% 30% 20% 20% 10% 10% 0% 0%
Slide 65: Q&A
For personal use only Q&A 64 | Driven by Our Promise™
Slide 66: Clinical Development
For personal use only Clinical Development Dr Bill Mezzanotte EVP & Head R&D 65 | Driven by Our Promise™
Slide 67: Immunoglobulins
Immunoglobulins For personal use only • Maintaining leadership position Breakthrough through focus on: Medicines Transplant • New Indications • Geographic expansion • Delivery options Specialty Immunoglobulins Products • Key Focus: • HIZENTRA® Haemophilia • PRIVIGEN® Products 66 | Driven by Our Prom
Slide 68: Milestones in Ig Development for CIDP
Milestones in Ig Development for CIDP For personal use only PRIMA study shows PATH study confirms HIZENTRA® and efficacy of PRIVIGEN® efficacy of PRIVIGEN® PRIVIGEN® for CIDP for CIDP for CIDP PMDA Approval 2019 PRIVIGEN® for CIDP PRIVIGEN® for CIDP: approved in EU FDA approval Sept 13 2012 2013 201
Slide 69: Impact of Ig (IV & SC) in Rare Diseases
Impact of Ig (IV & SC) in Rare Diseases For personal use only Primary Immuno- deficiency Secondary Additional Immuno- Diseases deficiency Ig Immune & Chronic Inflammatory Inflammatory Myositis IIM and SSc CIDP Demyelinating Polyneuropathy and Systemic Sclerosis • Health Authority (FDA, EMEA, PMDA) i
Slide 70: Haemophilia Products
Haemophilia Products For personal use only • Supporting and enhancing plasma Breakthrough products and developing novel Transplant Medicines recombinant portfolio with focus on: • Scientific and product innovation • Patient benefit Specialty Immunoglobulins • Key Focus: Products • IDELVION® (rIX-FP)
Slide 71: IDELVION Delivering in the Real World
IDELVION® Delivering in the Real World Annualised Bleed Rates in switched patients For personal use only FIX product All FIX rFIX-Fc IDELVION Prophylaxis-to- prophylaxis patients 7.4 ± 9.1 (n=34) 8.9 ± 9.6 (n=12) 1.5 ± 4.5 (n=34) • Further increased dosing mean ± SD flexibility anticipated • 21-day
Slide 72: Specialty Products
Specialty Products For personal use only • Leveraging high quality broad product Breakthrough portfolio through: Medicines Transplant • New markets • Novel indications • Novel modes of administration Specialty Immunoglobulins Products • Key Focus: • HAEGARDA®/BERINERT® Haemophilia • KCENTRA®/BERIPLE
Slide 73: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) For personal use only • Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling • All body sites are associated with impairment and patients are impacted during and between attacks • Most severe are laryngeal attacks which can requir
Slide 74: Demonstrating Unique Benefit of HAEGARDA
Demonstrating Unique Benefit of HAEGARDA® For personal use only BASELINE Median Attack Rate Reduction: 95% 4 HAE attack/month (median) Mean Age 39.6 ± 14.9 3 Female % 67 2 Mean # HAE attacks 3 prior months 9.8 ± 6.6 1 % use of HAE Prophylaxis 3 prior 42% 0 months Placebo 60 IU/kg Longhurst et al NEJ
Slide 75: Demonstrating Unique Benefit of HAEGARDA
Demonstrating Unique Benefit of HAEGARDA® For personal use only CSL830 Reduces Severity of Attacks Persistent Efficacy of 60 IU/Kg 100 100 8.9 90 80 75 28.9 % of Study Patients Severe 70 68.9 Moderate 60 50 17.8 50 Attack-Free Mild 4.4 40 No Rescue Use Unknown severity 30 25 No attack 40.0 22.2 20 2
Slide 76: CSL312 Anti-FXIIa in HAE
CSL312 Anti-FXIIa in HAE For personal use only Placebo Run-in Low dose Extension Patients with HAE Medium dose High dose • Phase II study initiated in October 75 | Driven by Our Promise™
Slide 77: Transplant
Transplant For personal use only • Developing CSL and other novel therapies with potential to improve transplant Breakthrough outcomes: Medicines Transplant • Significant unmet need • Key Focus: Specialty • C1 inhibitor (C1-INH) Immunoglobulins Products • Alpha1 anti-trypsin (AAT) • Anti-IL-6 / claz
Slide 78: Solid Organ Transplant (SOT): Unmet Medical Need
Solid Organ Transplant (SOT): Unmet Medical Need For personal use only Before Transplantation During Transplantation After Transplantation Patient & Donor Donor Organs Patient Patient Organ Availability and Organ Viability and Ischemia-Reperfusion Transplant Patient-Donor Matching Donor Management I
Slide 79: Improving Graft Survival in Kidney Transplantation
Improving Graft Survival in Kidney Transplantation For personal use only Transplants by Organ Type Ischemia-Reperfusion (US - 2015) Transplant Rejection Injury and Consequences Other 3% Delayed Graft Function (DGF) Antibody Mediated Rejection Lungs 7% Heart • Delayed graft function (DGF - any 9% use
Slide 80: Donor-specific Antibodies underpin Antibody Mediated Rejection
Donor-specific Antibodies (DSAs) underpin Antibody Mediated Rejection in Kidney Transplantation For personal use only Complement-binding DSAs • Associated with more severe inflammation and graft injury • C1-INH offers therapeutic option Non-complement-binding DSAs • Antibody-mediated cellular toxici
Slide 81: Long Term C1 INH Administration Stabilises Graft Function
Long Term C1 INH Administration Stabilises Graft Function in AMR Patients Unresponsive to Standard of Care For personal use only Renal Function at the time of initial AMR Dx. In a pilot study 6 patients with AMR, unresponsive to standard Renal Function at the end of care, were treated with C1 of fir
Slide 82: CSL842 Phase III
CSL842 Phase III Randomised, Placebo-controlled Withdrawal For personal use only Part 1: 12 Weeks Part 2: 26 Weeks 3.5 Years C1 INH IVIg + C1 INH open label Placebo Responders Randomised 1° endpoint 2° endpoint Study actively recruiting and on track Loss of Response** Graft Survival **occurrence of
Slide 83: Vitaeris and CSL Strategic Collaboration in AMR
Vitaeris and CSL Strategic Collaboration in AMR For personal use only • Clazakizumab (anti-IL6) in clinical development • Successful FDA Type C meeting • Anticipated dosing in chronic AMR patients in 2019 • IL-6 may play a role in • DSA production and DSA mediated allograft injury • Cell-mediated re
Slide 84: Beyond Solid Organ Transplant: HSCT and GvHD
Beyond Solid Organ Transplant: Hematopoietic Stem Cell Transplant (HSCT) and Graft versus Host Disease For personal use only Annual HSCTs in the US GvHD is a common cause of morbidity and mortality in HSCT • Survival is 30% for Grade III and 10% for Grade IV ~50-60% of Allogeneic HSCT develop acute
Slide 85: Potential Immunomodulation of AAT in Acute GVHD
Potential Immunomodulation of Alpha-1 Antitrypsin (AAT) in Acute GVHD AAT For personal use only Cyclosporine or Tacrolimus + MTX DAMPs Activation and proliferation of Teff cells PAMPs APC Naïve T cell TNF-α, IL-1β Acute GVHD AAT IL-6, IL-32 Teff End-organ damage: Skin, liver, gut Promotion AAT AAT I
Slide 86: Treatment of Steroid-Refractory GvHD with AAT
Treatment of Steroid-Refractory GvHD with AAT For personal use only CSL964 AAT GvHD Prevention Mangenau et al Blood 2018 • Planned evaluations in prophylaxis of GvHD with AAT Alpha-1 Antitrypsin (AAT) • Study start up activities • 40 Patients with Steroid refractory aGVHD commenced • Open label AAT
Slide 87: Breakthrough Medicines
Breakthrough Medicines For personal use only • Leveraging clinical and technical Breakthrough Transplant insight in developing novel protein- Medicines based therapies: • Significant unmet need • Multiple indications Specialty • Key Focus: Immunoglobulins Products • CSL112 (ApoA-I) • CSL312 (anti-FX
Slide 88: CSL112 Hypothesis
CSL112 Hypothesis For personal use only CSL112 will • be safe and well tolerated • enhance cholesterol efflux CSL112 capacity (CEC) particles • acutely stabilise atherosclerotic plaques and prevent subsequent major adverse cardiovascular events (MACE) in the early, highest risk period (unique ABCA1
Slide 89: CSL112 Phase III Study Design
CSL112 Phase III Study Design For personal use only 1° Endpoint: MACE MACE Follow Up D90 D180 D365 17400 AMI subjects ≥ 18 Placebo (n=8700) years of age, With Acute Screening Randomisation 6g CSL112 (n=8700) Coronary Syndrome 1000 Centers - >40 Countries • Enriched Study Population: Multi-vessel cor
Slide 90: CSL112 Program Timeline
CSL112 Program Timeline For personal use only 2016 2017 2018 2019 2020 2021 2022 2023 CSL112 CMC - Supply AEGIS-I Phase III (AEGIS II) Outcomes Study BLA MOD RI Phase II Futility #1 Mar ‘20 Futility #2 MAA Oct ‘20 Interim Efficacy Apr‘21 • Actively recruiting and on track • To date, patient activity
Slide 91: Commercial Overview: Specialty, Transplant, CSL112
For personal use only Commercial Overview Specialty, Transplant, CSL112 Mr Bill Campbell Executive Vice President & Chief Commercial Officer 90 | Driven by Our Promise™
Slide 92: CSL Portfolio: Specialty
CSL Portfolio: Specialty For personal use only FY18 1,490M +24% Albumin Immunoglobulin Haemophilia Specialty 91 | Driven by Our Promise™
Slide 93: Continued Growth Opportunity for KCENTRA
Continued Growth Opportunity for For personal use only Anticoagulation Market US1 Warfarin Market US1 100% 90% Other , 3% 80% KCENTRA®, 40% Xarelto, 24% 70% 60% 50% Warfarin, 39% 40% Eliquis, 34% FFP & 30% Others, 60% 20% 10% 0% Column1 US clinical practice guidelines recommend KCENTRA® over FFP to
Slide 94: Growth Since Launch
Growth Since Launch For personal use only End User Demand (IU) 250 200 150 Millions 100 50 0 FY 13/14 FY 14/15 FY 15/16 FY 16/17 FY 17/18 93 | Driven by Our Promise™
Slide 95: Specialty Products – HAEGARDA
Specialty Products – For personal use only • Transformational HAE therapy • New patients weekly • Strong patient, physician and prescriber engagement • Natural C1 replacement #1 prescribed therapy in the US for prevention of HAE attacks 94 | Driven by Our Promise™
Slide 96: Established efficacy
For personal use only Established efficacy • 95% reduction in HAE attacks • Rescue medication reduced by >99% • HAEGARDA® studied in patients with 3.8 attacks per month C-INH for C1-INH deficiency • HAEGARDA® replaces missing or dysfunctional C1-INH, regulating the normal production of bradykinin •
Slide 97: Why HAEGARDA: KOL and patient quotes
Why For personal use only Key KOL Quote Additional HCP Quotes “With efficacy it is as good as it gets with HAEGARDA®. However if Lanadelumab can prove the same level of efficacy, HAEGARDA® “From our collective experience, we gave efficacy 5. I have can still clearly differentiate by its MOA, replaci
Slide 98: Cardiovascular Disease (CVD): High Unmet Medical Need
Cardiovascular Disease (CVD) High Unmet Medical Need For personal use only • CVD remains leading cause of death globally • In the US & Europe, 2 million MI’s occur each year • Survivors remain at high risk for early recurrent CV events • Among high-risk populations: • 14% recurrence in year one • of
Slide 99: CSL112 – Our Vision and Strategy
CSL112 – Our Vision and Strategy For personal use only Vision Establish CSL112 as a leading hospital initiated solution to prevent early recurrent CV events in post-AMI pathway of care Strategy • Define the unmet need within the 90d period • Establish the role of Apo A-I and Cholesterol Efflux • Pos
Slide 100: CSL112 – Our Journey
CSL112 – Our Journey For personal use only • Expanding patient focus to heart disease, the leading cause of death W/W • Refining high-risk AMI target population and validating with real world data • Developing insights relative to the post-MI pathway of care • Engaging with hospitals and payors to d
Slide 101: Transplant Opportunity
Transplant Opportunity For personal use only • Two fundamental types of transplant: • Solid organ transplant (SOT) • Hematopoietic stem cell transplant (HSCT) • Transplant is amongst the most transformative and curative therapies in all of medicine • Utility is currently restricted due to • Treatmen
Slide 102: Transplant Strategy
Transplant Strategy For personal use only 1. Reduce Complications (e.g. AMR) IVIG, C1-INH, anti-IL6 SOT 2. Improve Organ Function AAT, C1-INH 3. Organ Availability and Viability 2018 2023 2028 2033 Unmet Needs & Leadership Opportunities 1. Reduce Complications (e.g. GVHD) AAT 2. Adjunct T-Cell Thera
Slide 103: Transplant Fit for CSL
Transplant Fit for CSL For personal use only • Significant unmet patient needs • Multiple opportunities with current assets with proof-of-concept evidence • Limited competition and concentrated call points • Building on our strong foundation of plasma assets • Potential to expand use of Hematopoieti
Slide 104: Summary
For personal use only Summary 103 | Driven by Our Promise™
Slide 105: R&D Portfolio - December 2018
R&D Portfolio - December 2018 For personal use only COMMERCIAL / RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION PHASE IV Emerging CSL787 CSL730 CSL312 Anti-FXIIa Clazakizumab* IDELVION® Technologies Nebulised Ig rFc Multimer in HAE Transplant CSL311 CSL324 Novel Strategies Mavri GM-CS
Slide 106: Current CSL Behring Therapeutics Platform
Current CSL Behring Therapeutics Platform For personal use only Breakthrough Medicines Transplant Immunoglobulins Specialty Products Haemophilia Products Plasma Recombinant Fractionation Technology Gene Therapy Protein Science 105 | Driven by Our Promise™
Slide 107: Future CSL Behring Therapeutic Area Framework
Future CSL Behring Therapeutic Area Framework For personal use only Immunology and Neurology Haematology and Thrombosis Transplant Respiratory Cardiovascular and Metabolic Plasma Recombinant Gene and Cell Fractionation Technology Therapy 106 | Driven by Our Promise™
Slide 108: R&D Portfolio - December 2018
R&D Portfolio - December 2018 For personal use only COMMERCIAL / RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION PHASE IV CSL787 CSL730 CSL312 Anti-FXIIa Clazakizumab* Discovery Projects IDELVION® Nebulised Ig rFc Multimer in HAE Transplant CSL311 CSL324 Discovery Projects Mavri GM-CSF
Slide 109: Expected Progress in Next Months
Expected Progress in Next 12 Months For personal use only New Product Product Dev. & Registration Post Research Phase I (FIH) Phase II Phase III Opportunity GLP Toxicology & Launch Registration 1 2 3 4 5 6 7 Enter Enter Product Enter Register Enter Post Enter Phase I Enter Phase II Enter Phase III R
Slide 110: Significant Target Launch Dates
Significant Target Launch Dates For personal use only 2018 2019 2020 2021-2024 HIZENTRA® CIDP US/EU HIZENTRA® CIDP Japan PRIVIGEN® PID Japan CSL312 (Anti-FXIIa) HAE PRIVIGEN® CIDP US PRIVIGEN® CIDP Japan IDELVION® 21 Day Dosing Hizentra® IIM CSL830 C1-INH Subcut EU Improved Fibrinogen Kcentra Japan
Slide 111: 2018 Highlights
2018 Highlights For personal use only • Completion of CSL324 (anti-G-CSF) Phase I study Immunology & • Initiation of CSL312 (anti-FXIIa) HAE Phase II study • Initiation of CSL730 (rec FC multimer) Phase I study Neurology • PRIVIGEN® CIDP and HIZENTRA® CIDP approved in the US Haematology & • Ongoing
Slide 112: Q&A
For personal use only Q&A 111 | Driven by Our Promise™
Slide 113: Next Generation Cell-based Influenza Vaccine Shows Greater Effectiveness
For immediate release 5 December 2018 Next Generation Cell-based Influenza Vaccine Shows Significantly Greater Effectiveness Compared to For personal use only Standard Egg-based Options in the 2017-18 US Influenza Season CSL spotlights developments in cell-based vaccine technology at Australian Rese
Slide 114: Media release continued
For immediate release 5 December 2018 “The real‐world data, along with other emerging evidence, indicates that cell‐based influenza vaccines may result in better influenza‐related outcomes compared to standard egg‐based vaccine options in some seasons, particularly those seasons characterised by egg
Slide 115: About the Study
For immediate release 5 December 2018 About the Study: Data from a large U.S. electronic medical record (EMR) provider for primary care practices were obtained between August 1, 2017 and March 31, 2018. This was a retrospective cohort study with the objective of determining the relative vaccine effe
Slide 116: References
For immediate release 5 December 2018 REFERENCES: For personal use only 1 Centers for Disease Control and Prevention (CDC). (2018). Estimated influenza illnesses, medical visits, hospitalizations, and deaths in the United States — 2017–2018 influenza season. Retrieved from: https://www.cdc.gov/flu/a