Csl Limited · ASX:CSL
Csl — Investor Day (December 2017)
96 slides from Csl's investor day presentation, Dec 5, 2017
Slide 1: R&D Investor Briefing
For personal use only R&D Investor Briefing December 5, 2017
Slide 2: 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 3: Introduction and Highlights
For personal use only Introduction and Highlights Professor Andrew Cuthbertson AO R&D Director and Chief Scientist
Slide 4: Agenda
Agenda For personal use only • Welcome Mark Dehring • Introduction and Highlights Andrew Cuthbertson • Research Andrew Nash • Early Development Charmaine Gittleson • Immunoglobulins, Haemophilia and Specialty Products – Clinical Development Bill Mezzanotte – Commercial Opportunities Bill Campbell •
Slide 5: Global Commitment to Research and Development
Global Commitment to Research and Development For personal use only Research and Development Investment 645 614 New Product Development (US$ Millions) activities focus on innovative new therapies for life-threatening diseases 466 463 Market Development strategies 427 seek to bring therapies to new m
Slide 6: Key Past Launches from R&D Portfolio
Global Key Past Launches from R&D Portfolio For personal use only 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 VIVAGLOBIN® PRIVIGEN® HIZENTRA® PRIVIGEN® Ig IsoLo® Ig RHOPHYLAC® CIDP (EU) Specialty ZEMAIRA® (US) BERINERT® (US) KCENTRA® (US) RESPREEZA® (EU) BERIPLEX® (EU) RIASTAP® CORIF
Slide 7: Leveraging Global Capabilities
Global Global Leveraging Global Capabilities For personal use only PASADENA, US WUHAN, CHINA CSL Behring Seqirus >1,500 scientists globally 7
Slide 8: 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 Immunoglobulins Life Cycle Haemophilia Management# Specialty Products Influenza Vaccine PCC New C1-INH New PRIVIGEN® VONCENTO® HIZENTRA® CIDP Indications Ind
Slide 9: CSL Behring Protein Therapeutics Platform
Global CSL Behring Protein Therapeutics Platform For personal use only Breakthrough Medicines Immunoglobulins Specialty Products Haemophilia Products Plasma Recombinant Fractionation Technology Protein Science 9
Slide 10: Evolving Therapeutics Platform
Global Evolving Therapeutics Platform For personal use only Breakthrough Medicines Transplant Immunoglobulins Specialty Products Haemophilia Products Plasma Recombinant Fractionation Technology Gene Therapy Protein Science 10
Slide 11: Progress Through Stage Gates in 2017
Global Progress Through Stage Gates in 2017 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 Pha
Slide 12: R&D Portfolio – December 2017
Global R&D Portfolio – December 2017 For personal use only COMMERCIAL / RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION PHASE IV C1-INH New PRIVIGEN® Clinical Applications PRIVIGEN® Japan HIZENTRA® CIDP Indications CIDP US Fibrinogen New KCENTRA® HIZENTRA® IIM Formulations Japan Haptog
Slide 13: Research Portfolio and Technologies
For personal use only Research Portfolio and Technologies Dr Andrew Nash Senior Vice President, Research 13
Slide 14: Research Organisation & Portfolio
Research Organisation & Portfolio For personal use only • Coordinated global project portfolio Specialty Breakthrough Immunoglobulins Haemophilia Transplant Products Medicines • Hub (Bio21, Parkville) & spoke model • Bio21 expansion to be completed Feb 2018 • Research capabilities: plasma & recombin
Slide 15: Recombinant Fc Multimer – CSL730
Recombinant Fc Multimer – CSL730 For personal use only Fab region • Immune deficiencies recombinant multimerised Fc Fc region • Autoimmune conditions Improved target binding 15
Slide 16: Recombinant Fc Multimer – CSL730: CSL / Momenta Collaboration
Recombinant Fc Multimer – CSL730 For personal use only CSL / Momenta Collaboration • First‐in‐class recombinant Fc multimer targeting Fcγ receptors • Exclusive Research Collaboration and License Agreement – Development and commercialisation of the Fc multimer M230/CSL730 – Research & development of
Slide 17: Recombinant Fc Multimer – CSL730
Recombinant Fc Multimer – CSL730 For personal use only • Non-clinical safety toxicity data supports commencement of FIH CSL730 therapeutic efficacy in ITP model studies • Phase I study (healthy volunteers) planned to commence Q1 2018 • Phase Ib proof of mechanism study anticipated for 2019 CSL730 do
Slide 18: Calimmune Technology
Calimmune Technology For personal use only • Acquisition of California based biotechnology company – Performance based milestones • Gene / cell based therapy, rare genetic disorders – ex vivo Lenti virus transduction of hematopoietic stem cells (HSC’s) • Calimmune differentiating technology: Cytegri
Slide 19: Calimmune – CAL-H Program
Calimmune – CAL-H Program For personal use only Sickle Cell Disease • Group of disorders caused by abnormal beta-globin gene resulting in sickled red cells • Average life expectancy in the developed world is 40 – 60yrs • High unmet need • Total SCD patients: 155,000 (US + 5EU) Cytegrity™ Select+™ SI
Slide 20: Calimmune – CAL-H Program
Calimmune – CAL-H Program For personal use only CAL-H Select+ Cytegrity lenti vector Post cell infusion monitoring / Patient referral / transfer 6-TG dosing (Select+), outpatient strategy HSC Clinical program planned to commence in 2019 • Range of further opportunities beyond SCD 20
Slide 21: Early Development Portfolio
For personal use only Early Development Portfolio Dr Charmaine Gittleson Chief Medical Officer 21
Slide 22: 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 23: CSL312 – HAE and Thrombosis
CSL312 – HAE and Thrombosis For personal use only Auto-activation FXIIa • Targeting FXIIa - represents a novel approach to the treatment of hereditary FXI → FXIa PK → KAL* βFXIIa angioedema and contact activated thrombosis → thrombin HK → BK→ BR2 C1qr,s → C1qr,s • Efficacy in multiple Haemostasis Va
Slide 24: CSL312 – HAE and Thrombosis
CSL312 – HAE and Thrombosis For personal use only Phase II (2018/19) Phase I Patients with HAE (dosing complete Nov 2017) Safe, well tolerated GO Normal Healthy Volunteers • Safety/PK/PD Phase Ib (~2019) First in Human Phase I study Proof of mechanism in thrombosis – Single doses administered – Conf
Slide 25: CSL324 Anti-G-CSF Receptor Antibody
CSL324 Anti-G-CSF Receptor Antibody For personal use only • White blood cells (neutrophils) – contribute to protective mechanism against infections • Neutrophil numbers and activity under control of Granulocyte Colony Stimulating Factor (G-CSF) • Excessive activated neutrophils, in absence of infect
Slide 26: CSL324 Anti-G-CSF Receptor Antibody
CSL324 Anti-G-CSF Receptor Antibody For personal use only Phase I Phase Ib (completing Jan 2018) (2018/19) Safe, well tolerated GO Normal Healthy Volunteers Patients with neutrophil driven disease • Safety/PK/PD • Proof of mechanism First in Human Phase I study – Single and multiple doses administer
Slide 27: CSL346 Anti-VEGF-B Antibody
CSL346 Anti-VEGF-B Antibody For personal use only • Free fatty acids (FFA) in diet support normal energy requirements in skeletal muscle, heart and kidney Tissue Blood vessel wall • VEGF-B controls FFA movement into tissues VEGFR -1 NRP-1 • Excess fatty acid uptake causes: – Reduced glucose utilisat
Slide 28: CSL346 Anti-VEGF-B Antibody
CSL346 Anti-VEGF-B Antibody For personal use only Phase I Phase Ib Normal Healthy Volunteers Safe, well tolerated Patients with metabolic disorders GO • Safety/PK/PD • Proof of mechanism • Started November 2017 • Study anticipated for 2019 28
Slide 29: CSL311 – Anti-Beta Common
CSL311 – Anti-Beta Common For personal use only • Central receptor (Beta Common) involved in stimulating immune modulating cells • Increased activation in Auto-immunity, Allergy and Inflammation • Blocking Beta Common (CSL311) and down regulating cells may ameliorate disease • CSL311 blocks activity
Slide 30: Immunoglobulins, Haemophilia and Specialty Products
For personal use only Immunoglobulins, Haemophilia and Specialty Products Dr Bill Mezzanotte Senior Vice President, Clinical Development
Slide 31: Immunoglobulins
Immunoglobulins Immunoglobulins For personal use only • Maintaining leadership position Breakthrough Transplant through focus on: Medicines – New Indications – Geographic expansion – Delivery options Specialty Immunoglobulins Products • Key Focus: Haemophilia Products – HIZENTRA® – PRIVIGEN® 31
Slide 32: Impact of Ig (IV & SC) in Rare Diseases
Immunoglobulins Impact of Ig (IV & SC) in Rare Diseases For personal use only Primary Immuno- deficiency Systemic Secondary Sclerosis & Immuno- other diseases? deficiency Ig Immune & Chronic Inflammatory IIM CIDP Inflammatory Myositis Demyelinating Polyneuropathy 32
Slide 33: Impact of Ig (IV & SC) in Rare Diseases
Immunoglobulins Impact of Ig (IV & SC) in Rare Diseases For personal use only Primary Immuno- deficiency Systemic Secondary Sclerosis & Immuno- other diseases? deficiency Ig Immune & Chronic Inflammatory IIM CIDP Inflammatory Myositis Demyelinating Polyneuropathy 33
Slide 34: PATH: SCIg (HIZENTRA) Provides Effective Prophylaxis for CIDP Patients
Immunoglobulins PATH: SCIg (HIZENTRA®) Provides Effective Prophylaxis for CIDP Patients For personal use only • PATH study the largest controlled CIDP study ever performed • Investigated multiple doses • Disease control demonstrated in patients previously treated with IVIG van Schaik et al; Lancet N
Slide 35: IV and SC Ig are Effective Treatments for CIDP
Immunoglobulins IV and SC Ig are Effective Treatments for CIDP For personal use only • In the PRIMA trial – 61% of patients responded to PRIVIGEN®; 50% after the first dose – Almost 50% of IVIG-naïve patients responded to PRIVIGEN® • In the PATH study – 81% patients on high dose and 67% on low dose
Slide 36: Milestones in Ig Development for CIDP
Immunoglobulins Milestones in Ig Development for CIDP For personal use only PRIMA study PATH study shows efficacy of confirms efficacy of PRIVIGEN® for CIDP PRIVIGEN® for CIDP PRIVIGEN® for CIDP PRIVIGEN® for CIDP: approved in EU FDA approval Sept 13 2012 2013 2014 2015 2016 2017 2018 HIZENTRA® for
Slide 37: Impact of Ig (IV & SC) in Rare Diseases
Immunoglobulins Impact of Ig (IV & SC) in Rare Diseases For personal use only Primary Immuno- deficiency Systemic Secondary Sclerosis & Immuno- other diseases? deficiency Ig Immune & Chronic Inflammatory IIM CIDP Inflammatory Myositis Demyelinating Polyneuropathy • Proposed Ig IIM with Unique Study
Slide 38: Specialty Products
Specialty Specialty Products For personal use only • Leveraging high quality broad Breakthrough Transplant product portfolio through: Medicines – New markets – Novel indications – Novel modes of administration Specialty Immunoglobulins Products • Key Focus: Haemophilia – HAEGARDA®/BERINERT® Products
Slide 39: Hereditary Angioedema (HAE)
Specialty 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
Slide 40: Demonstrating the Unique Benefit of HAEGARDA
Specialty Demonstrating the Unique Benefit of HAEGARDA® For personal use only Median Attack Rate Reduction: 95% CSL830 Reduces Severity of Attacks 4 100 HAE attack/month (median) 8.9 3 75 28.9 Severe 68.9 Moderate 2 50 17.8 4.4 Mild Unknown severity 1 25 40.0 22.2 No attack 6.7 2.2 0 0 Placebo 60 IU
Slide 41: Commercial Market Overview
For personal use only Commercial Market Overview Mr Bill Campbell Executive Vice President & Chief Commercial Officer
Slide 42: Targeted Protein Therapeutic Market
Global Targeted Protein Therapeutic Market For personal use only Haemophilia Immunoglobulin $10.8B $9.3B Total Global Market Value: ~$27.6B Specialty Albumin $3.6B Sources: Company annual reports/financial schedules, MRB $3.9B global Coagulation Factors Concentrate Market 2016, MRB WW Plasma Fractio
Slide 43: CSL Portfolio
Global CSL Portfolio For personal use only CSL Total FY17 $5,811M $2,774M Immunoglobulin $1,174M Specialty $1,023M Albumin $840M Haemophilia 43
Slide 44: Commercial / R&D Partnership
Global Commercial / R&D Partnership For personal use only • Integrated strategy teams Multiple high value product launches: • Coordinated New Product 2013 KCENTRA® Development / Market 2016 IDELVION® & AFSTYLA® preparation 2017 HAEGARDA® • Disciplined launch preparation & execution 2018 HIZENTRA® CI
Slide 45: CSL's Global Performance
Immunoglobulins CSL’s Global Performance For personal use only • CSL FY17 Sales $2,774 M • Significant growth opportunity – Per capita use varies widely IVIG – Core areas PID / SID – Neurology – New indications SCIG • Continued acceptance, growth & patient Hyper benefits of SCIG 45
Slide 46: Immunoglobulins: Category Leadership
Immunoglobulins Immunoglobulins: Category Leadership For personal use only GROW • Maximise PID / SID opportunity • Leverage broad portfolio the current business • Enhance product offerings EXPAND • Replicate our approach to build market leading segments • Build on PRIVIGEN® experience in CIDP our pr
Slide 47: HIZENTRA: Innovator, Market Leader
Immunoglobulins HIZENTRA®: Innovator, Market Leader For personal use only 90,000 patient-years, 7 years and Convenient Individualised Most prescribed 4.8M exposures 51 countries self-administration therapy SCIG worldwide worldwide 47
Slide 48: CIDP – Growing Area of Focus
Immunoglobulins CIDP – Growing Area of Focus For personal use only Global IG volume by indication CIDP • ~23% of all IG usage globally Other • Growing market segment • Many unmet needs remain PID SID Sources: Data on File – US, 5EU, Japan. 48
Slide 49: HIZENTRA addresses unmet needs in CIDP therapy
Immunoglobulins HIZENTRA® addresses unmet needs in CIDP therapy For personal use only Unmet Needs IVIG improves CIDP symptoms but many patients experience “wear off” Steady state IG levels for continuous control with IVIG therapy IVIG therapy difficult for patients with Hizentra therapy does not req
Slide 50: Haemophilia Global Market
Haemophilia Global Market For personal use only VWD $0.5B Haem B • Highly competitive Haem A market space $1.4B • Rapid transition of Haem B category Total Global • Major advancements in patient care Inhibitor Market Value: Bleed Therapy ~$10.7B • 75% of patients with bleeding disorders $2.1B Haem A
Slide 51: Coagulation Portfolio
Haemophilia Coagulation Portfolio For personal use only Haemophilia A Haemophilia B VWD Other 51
Slide 52: Transforming Care of Haemophilia B Patients
Haemophilia Transforming Care of Haemophilia B Patients For personal use only #1 “Switch to” brand providing highest factor levels for the longest period of time 1st Haemophilia Long-lasting Excellent therapy with up protection with efficacy to 14-day dosing high trough levels UP TO 14 DAYS ZERO 14-
Slide 53: Product of Choice for Physicians
Haemophilia Product of Choice for Physicians ” For personal use only “All my IDELVION® patients were on “This is not something I would associate with prophylaxis previously with BeneFIX… another FIX. It’s higher than Alprolix, and, from they were very interested in having a physician’s perspective t
Slide 54: Transition to New Products in Haemophilia B
Haemophilia Transition to New Products in Haemophilia B For personal use only Patient switches % • Demand exceptionally strong – Capturing ~2/3 of patient switches • Ongoing launch – Launched in 12 countries – First hemophilia product in Japan – France, Spain, Greece, Poland, Portugal, Israel, Canad
Slide 55: Accelerating AFSTYLA Adoption
Haemophilia Accelerating AFSTYLA® Adoption For personal use only Proven long-lasting bleed protection with a unique single-chain design Long-lasting Higher binding Excellent Individualised protection with affinity to vWF efficacy dosing high trough levels 3X HIGHER ABOVE 1.9% ZERO 2X WEEKLY COMPARED
Slide 56: Specialty: CSL's Global Performance
Specialty CSL’s Global Performance For personal use only • Specialty portfolio growth FY17 +20% – KCENTRA® / BERIPLEX® +35%; BERINERT® +31% • HAEGARDA® US launch & rapid acceptance • Often under or misdiagnosed Acquired Bleeding CSL FY17 Sales $1,174 M Other HAE AATD 56
Slide 57: Continued Growth Opportunities for Kcentra
Specialty Continued Growth Opportunities for Kcentra® For personal use only US Anti-Coagulation Market US Demand (IU) PRADAXA SAVAYSA 170 Japan 4% 0% 180 160 • Launch Sep 2017 140 119 120 • Fast formulary XARELTO 25% COUMADIN/ 100 94 acceptance WARFARIN 80 46% – Over 300 60 hospitals ELIQUIS 40 25%
Slide 58: Specialty Products – HAEGARDA
Specialty Specialty Products – HAEGARDA® For personal use only • Product launched July 2017 • 7 year orphan exclusivity • 95% reduction in HAE attacks • >99% reduction in the need for rescue medication • First and only subcutaneous formulation • Strong patient, physician and provider Other engagemen
Slide 59: Patient testimonials on HAEGARDA
Specialty ” For personal use only “This is the longest period in my life having “I haven’t had a single attack since gone without a single attack since my very starting the HAEGARDA® study in 2015!” first one at age 13.” “I choose not to suffer, and “I feel like I am finally a HAEGARDA® gives me tha
Slide 60: Transplant and Breakthrough Medicines (CSL112)
For personal use only Transplant and Breakthrough Medicines (CSL112) Dr Bill Mezzanotte Senior Vice President, Clinical Development
Slide 61: Transplant
Transplant Transplant For personal use only • Developing CSL and other novel Breakthrough therapies with potential to improve Transplant Medicines transplant outcomes: – Significant unmet need Specialty • Key Focus: Immunoglobulins – C1 inhibitor (C1-INH) / BERINERT® Products – Alpha1 anti-trypsin (
Slide 62: Solid Organ Transplant (SOT): Unmet Medical Need
Transplant 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 M
Slide 63: Solid Organ Transplant (SOT): Unmet Medical Need
Transplant 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 M
Slide 64: Antibody Mediated Rejection (AMR) in Kidney Transplantation
Transplant Antibody Mediated Rejection (AMR) in Kidney Transplantation For personal use only The kidney is the most commonly transplanted solid organ • AMR occurs in up to 5-10% of transplants acutely and up to 30% chronically • AMR is marked by declining renal function and is associated with lower
Slide 65: Long Term C1 INH Administration Stabilises Graft Function in AMR Patients
Long Term C1 INH Administration Stabilises Graft Function in AMR Patients Unresponsive to Standard of Care For personal use only In a pilot study 6 patients with AMR, unresponsive to standard of care, were treated with C1 INH and had improved renal function (estimated Glomerular Filtration Rate, eGF
Slide 66: CSL842 C1-INH to prevent recurrent AMR: Randomised Withdrawal
Transplant CSL842 C1-INH to prevent recurrent AMR: 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 Loss of Response** Graft Survival **occurrence of any o
Slide 67: Complement Dependent & Independent Pathways Involved in AMR
Transplant Complement Dependent & Independent Pathways Involved in AMR For personal use only Potential Benefits of Complement-dependent Anti-IL6 therapy in AMR: Donor-Specific cytotoxicity • Reducing DSA production Antibodies (DSA) & • Reducing DSA mediated injury Antibody Mediated Complement-indepe
Slide 68: Vitaeris and CSL Strategic Collaboration
Transplant Vitaeris and CSL Strategic Collaboration For personal use only • Vitaeris Inc. • clazakizumab (anti-IL6 mAb) in clinical development • Successful FDA Type C Meeting • Anticipated dosing in AMR patients in 2018 • CSL – Vitaeris Strategic Collaboration • Collaboration and purchase option ag
Slide 69: Unmet Medical Need in Graft versus Host Disease (GvHD)
Transplant Unmet Medical Need in Graft versus Host Disease (GvHD) For personal use only • Incidence and mortality – Hematopoietic Stem Cell Transplant (HSCT) is a common effective therapy for many life- threatening malignant and non-malignant diseases • Autologous – Patient’s own cells • Allogenic –
Slide 70: Treatment of Steroid-Refractory GvHD with AAT
Transplant Clinical Data: Treatment of Steroid-Refractory GvHD with AAT For personal use only • ZEMAIRA® (AAT) - Mangenau, ASBMT 2016 – 40 Patients with Steroid refractory aGVHD – Open label AAT - 60mg/kg twice weekly x 4 weeks – Overall response rate (ORR) - 65% • 35% Complete Response – Sustained
Slide 71: Transplant
Transplant Transplant For personal use only • Developing CSL and other novel Breakthrough therapies with potential to improve Transplant Medicines transplant outcomes: – Significant unmet need Specialty • Key Focus: Immunoglobulins – C1 inhibitor (C1-INH) / BERINERT® Products – Alpha1 anti-trypsin (
Slide 72: Breakthrough Medicines
Breakthrough Medicines Breakthrough Medicines For personal use only • Leveraging clinical and technical insight in developing novel protein-based Breakthrough therapies: Transplant – Significant unmet need Medicines – Multiple indications • Key Focus: Specialty Immunoglobulins – CSL112 (ApoA-I) Prod
Slide 73: Cardiovascular Disease (CVD) - High Unmet Medical Need
Breakthrough Medicines Cardiovascular Disease (CVD) - High Unmet Medical Need For personal use only • CVD remains leading cause of death globally • In the US alone, 800,000 acute MIs occur each year • Survivors remain at high risk for early recurrent CV events • Among high-risk populations: – 14% re
Slide 74: Cholesterol Efflux With CSL112 (apolipoprotein A-I)
Breakthrough Medicines Cholesterol Efflux With CSL112 (apolipoprotein A-I) For personal use only Apolipoprotein A-I (ApoA-I) is the primary component of HDL (“good cholesterol”) and responsible for cholesterol efflux capacity (CEC) • HDL levels & CEC are inversely CSL112 correlated with atherosclero
Slide 75: CSL112 Hypothesis
Breakthrough Medicines CSL112 Hypothesis For personal use only • CSL112 will be safe and well tolerated • CSL112 will enhance cholesterol efflux capacity (CEC) CSL112 particles • CSL112 will acutely stabilise atherosclerotic plaques and prevent subsequent major adverse cardiovascular events (MACE) i
Slide 76: CSL112: Clinical Path to Phase III – Safety & Mechanism of Action
Breakthrough Medicines CSL112: Clinical Path to Phase III – Safety & Mechanism of Action For personal use only Phase I Single Ascending Dose (SAD) Phase I Multiple Ascending Dose (MAD) • Normal Healthy Volunteers • Normal Healthy Volunteers • N=57; Single Site: AUS • N=36; Single Site: AUS STATUS: C
Slide 77: No Safety Concerns in Patients with Moderate Renal Impairment
Breakthrough Medicines No Safety Concerns in Patients with Moderate Renal Impairment For personal use only Number of subjects Number of subjects with data with events, n (%) n’ Renal SAEs CSL112 6g (N=52) 52 1 (1.9%) 1 Placebo (N=28) 28 4 (14.3%) 5 Acute Kidney Injury (AKI) Events CSL112 6g (N=52) 5
Slide 78: CSL112 raises Cholesterol Efflux in Patients with Moderate Renal Impairment
Breakthrough Medicines CSL112 raises Cholesterol Efflux to a similar extent in Patients with and without Moderate Renal Impairment For personal use only Total Cholesterol Efflux Capacity • At the end of infusion time points, the relative increases in CEC and ABCA1 dependent CEC were similar in both
Slide 79: Phase III (AEGIS-II): Study Design
Breakthrough Medicines Phase III (AEGIS-II): Study Design For personal use only 1° Endpoint : MACE Follow Up MACE D90 D180 D365 6 g CSL112 (n=8700) 17400 AMI subjects ≥ 18 years of age, Screening Randomisation With Acute Coronary Syndrome Placebo (n=8700) 1000 Centers - >40 Countries • Enriched Stud
Slide 80: Phase III (AEGIS-II)
Breakthrough Medicines Phase III (AEGIS-II) For personal use only Designed with Health Authority Input Designed with International Trialists 21
Slide 81: CSL112 Program Timeline
Breakthrough Medicines 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 22
Slide 82: Breakthrough Medicines Commercial Opportunities
For personal use only Breakthrough Medicines Commercial Opportunities Mr Bill Campbell Executive Vice President & Chief Commercial Officer
Slide 83: CSL112 to Address High Unmet Medical Need
Breakthrough Medicines CSL112 to Address High Unmet Medical Need For personal use only • CVD remains leading cause of death globally • In the US alone, 800,000 acute MIs occur apoA-I each year • Survivors remain at high risk for early recurrent CV events: • Among high-risk populations: Macrophage AC
Slide 84: AEGIS-II Population – High Early Recurrent Event Rate
Breakthrough Medicines AEGIS-II Population – High Early Recurrent Event Rate For personal use only Patients with vascular death, MI or stroke % 16% 14% 14% 12% Statins 12% 10% Chronic PCSK9i’s 10% 8% 8% 6% Sub-Acute CSL “Uncontested sub-acute 112 market space” 4% 2% Acute 0% 0 30 60 90 120 150 180 2
Slide 85: Significant Opportunity in Sub Acute Space
Breakthrough Medicines Significant Opportunity in Sub Acute Space For personal use only • Acute MI Discharges per year (US & EU5) 1.2M • High Risk Patients and other exclusion 380-520K (AEGIS II population) • Hospital coverage & utilisation 230-320k • CSL112 patient population 200-270k 26
Slide 86: CSL112 Strategic Commercial Activities
Breakthrough Medicines CSL112 Strategic Commercial Activities For personal use only Phase III Plan Integrating clinical, regulatory and payer input Real World Evidence Validating with customised database Value Proposition & Pricing Engaging hospitals and payers Education & Prelaunch Developing the m
Slide 87: Seqirus R&D
For personal use only Seqirus R&D Professor Andrew Cuthbertson AO R&D Director and Chief Scientist 28
Slide 88: Highlights of 2017
Highlights of 2017 For personal use only • FLUAD™ – Approved in UK, strong recommendation for people 65yr and older – Holly Springs approved by FDA as a MF59 manufacturing and FLUAD fill-finish site • aQIV – Submission for paediatric indication USA (end December) • AFLURIA® QIV – 5 years+ • Approved
Slide 89: Planned Milestones During 2018
Planned Milestones During 2018 For personal use only Phase III Registration & Launch Post Registration Fluad™ QIV 65yrs+ Fluad™ QIV 6m-23m Fluad™ TIV 65yrs+ Safety & Immuno complete Approval USA Approval AUS Afluria® QIV 5yrs+ Approval AUS, CAN Afluria® QIV 5yrs+ Afluria® QIV 6m-4yrs Submitted Canad
Slide 90: Summary
31 For personal use only Summary
Slide 91: R&D Portfolio – December 2017
Global R&D Portfolio – December 2017 For personal use only COMMERCIAL / RESEARCH PRE-CLINICAL PHASE I PHASE II PHASE III REGISTRATION PHASE IV C1-INH New PRIVIGEN® Clinical Applications PRIVIGEN® Japan HIZENTRA® CIDP Indications CIDP US Fibrinogen New KCENTRA® HIZENTRA® IIM Formulations Japan Haptog
Slide 92: 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 93: Significant Target Launch Dates
Significant Target Launch Dates For personal use only 2017 2018 2019 2020-2023 PRIVIGEN® CIDP US HIZENTRA® CIDP US/EU PRIVIGEN® CIDP Japan Hizentra® IIM PRIVIGEN® PID/SID Japan HIZENTRA® CIDP Japan AFSTYLA® EU/Japan pdFVIII Ruide CSL830 HAEGARDA® US CSL830 EU KCENTRA® Japan CSL112 ApoA-I AFLURIA® QI
Slide 94: 2017 Highlights
2017 Highlights For personal use only • PRIVIGEN® CIDP approved in US Immunoglobulins • HIZENTRA® CIDP accepted for review by US FDA and EMA • Momenta collaboration to develop CSL730 (rFC Multimer) • HAEGARDA® results in 95% reduction in HAE attacks and >99% reduction in rescue mediation Specialty P
Slide 95: Q&A
36 For personal use only Q&A
Slide 96: Further Information
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.dehring