Csl Limited · ASX:CSL
Csl — Investor Day (December 2014)
110 slides from Csl's investor day presentation, Dec 3, 2014
Slide 1: R&D Briefing
For personal use only R&D Briefing December 3, 2014
Slide 2: Legal Notice
Legal Notice Forward looking statements The materials in this presentation speak only as of the date of these materials, and include forward looking statements about CSL For personal use only Limited and its related bodies corporate (CSL) financial results and estimates, business prospects and produ
Slide 3: Agenda December 2014 R&D Briefing
Agenda December 2014 R&D Briefing • Welcome Mark Dehring For personal use only • Introduction & Highlights Andrew Cuthbertson • Protein Science Research Andrew Nash • Immunoglobulins & Specialty Products • Clinical Development Charmaine Gittleson • Commercial Opportunities Bob Repella • Q&A Break •
Slide 4: Introduction and Highlights
For personal use only Introduction and Highlights
Slide 5: CSL Protein Therapeutics Technical Platform
CSL Protein Therapeutics Technical Platform For personal use only Breakthrough Medicines Immunoglobulins Specialty Products Haemophilia Products Plasma Recombinant Fractionation Technology Protein Science 5
Slide 6: CSL R&D Strategy
CSL R&D Strategy For personal use only • Maintain commitment Breakthrough to extracting maximum Medicines value from existing assets and supporting and improving current products Specialty Immunoglobulins Products • Develop new protein-based therapies for treating serious illnesses focusing Haemophi
Slide 7: Leveraging Global Capabilities
Leveraging Global Capabilities For personal use only • >1,100 scientists globally 7
Slide 8: Building Global Recombinant Capabilities
Building Global Recombinant Capabilities For personal use only Lengnau rCOAG Manufacturing Facility Broadmeadows Biotech Manufacturing Facility 8
Slide 9: R&D Investment
9 For personal use only R&D Investment
Slide 10: Global R&D Portfolio December 2013
Global R&D Portfolio December 2013 Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH For personal use only Immunoglobulins Haemophilia Specialty Products Life Cycle Influenza Management# Vaccine Hizentra® Japan Hizentra
Slide 11: Progress through Stage Gates in 2014
For personal use only Progress through Stage Gates in 2014 Hizentra® EU Flex Dosing CSL689 CSL654 rVIIa-FP Def rIX-FP Beriplex ® KcentraTM Japan Surgery US CSL312 CSL112 Zemaira® EU Anti-FXIIa Apo AI CSL334* Beriplex® Quad Flu ASLAN NOACs*Daiichi Vaccine 18+ Trivalent Flu 5-9 yrs 11
Slide 12: Global R&D Portfolio December 2014
Global R&D Portfolio December 2014 Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH For personal use only Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine Hizentra® Japan Hizentra
Slide 13: Protein Science Research
For personal use only Protein Science Research
Slide 14: CSL's Global Research Capability
CSL’s Global Research Capability For personal use only • Hub & spoke model • Single coordinated project portfolio • Research excellence in therapeutic proteins • Plasma and recombinant manufacturing platforms 14
Slide 15: Bio21 - Research Hub
Bio21 - Research Hub • Located within world class university, medical research and hospital For personal use only precinct in Parkville, Melbourne • Technical expertise • protein engineering, molecular biology, cell biology, models of disease, genomics / bioinformatics • Improved access to • high qu
Slide 16: CSL Research Project Portfolio
CSL Research Project Portfolio Some examples from the CSL Research Project Portfolio For personal use only Haemophilia Specialty Breakthrough Priority Immunoglobulins Products Medicines Beriplex NOACs CSL312 HAE/Throm High Ig Formulations FVIII half-life ext. Reversal CSL362 SLE* P.ging vaccine / mA
Slide 17: Plasma and Recombinant Proteins
Plasma and Recombinant Proteins • Capabilities from discovery to market For personal use only Manufacturing CLD Lab Phase III / launch manufacturing Target Patient Protein Engineering Lab Phase I / II manufacturing Animal models of disease Market 17
Slide 18: CSL654 (rIX-FP) – Discovery to Development
CSL654 (rIX-FP) – Discovery to Development For personal use only Factor IX fused to human CSL654 manufacturing CHO clones CSL654 T1/2 extension in Haem B albumin (CSL654) patients compared to Benefix Mean values and fitted curves 1 CSL654 100 IU/kg (n=3) 0.50 BeneFIX® 100 IU/kg (n=2) Faxtor IX antig
Slide 19: CSL312 (FXIIa antagonist mAb)
CSL312 (FXIIa antagonist mAb) Contact activation Hereditary Angioedema (HAE I, II, III) For personal use only (intrinsic) pathway Damaged surface HAE attack FXII FXIIa X C1-INH Current therapeutic strategy FXI PK FXIa KAL • On demand treatment with: - plasma derived C1-Inhibitor (Berinert) - small m
Slide 20: CSL312 (FXIIa antagonist mAb)
CSL312 (FXIIa antagonist mAb) Generation & characterisation of a human FXIIa antagonist mAb For personal use only • screening of human Ab (Fab) phage display library • mAb 3F7 shows complete inhibition of FXIIa • affinity matured 3F7 (= CSL312) shows further specificity improvements 20
Slide 21: CSL312 – Hereditary Angioedema
CSL312 – Hereditary Angioedema CSL312 inhibits vascular leakage in ACEI treated C1-INH null mice For personal use only * 0.5 ** *** ACEI 0.4 OD @ 620 nm 0.3 0.2 0.1 Basal 0.0 ACEI - + - + ns WT KO ns 0.6 3F7/ACEI *** *** OD @ 620 nm 0.4 0.2 BM4/ACEI 0.0 al EI EI EI KO mice as C C C A A A B 7/ 4/ Col
Slide 22: CSL312 – Hereditary Angioedema
CSL312 – Hereditary Angioedema CSL312 inhibits Factor XIIa activity in human plasma For personal use only Healthy Donors (n=10) HAE Type I (n=2 pts) 3 4 Factor XIIa activity (OD 405) Factor XIIa activity (OD 405) HAE #1 + Dex 3 2 HAE #2 + Dex 2 1 1 HAE #1 - Dex HAE #2 - Dex 0 0 0 10 30 5 4 04 12 37
Slide 23: Haptoglobin (Hp) / Hemopexin (Hx)
Haptoglobin (Hp) / Hemopexin (Hx) Red blood cell lysis and inflammation / tissue damage For personal use only • In pathological settings RBC lyse to release haemoglobin (Hb) • Haemoglobin is further oxidised leading to the release of heme • Free Hb and heme are toxic and contribute to disease pathol
Slide 24: Haptoglobin (Hp) / Hemopexin (Hx)
Haptoglobin (Hp) / Hemopexin (Hx) Sickle Cell Disease For personal use only • Mutation in b-Hb gene, aggregation of b-Hb, sickle-shaped RBC • Obstruct microvasculature, prone to lysis and release of Hb / heme Diverse manifestations • Acute chest syndrome, severe pain, pulmonary hypertension, stroke,
Slide 25: Hx therapy normalises blood pressure in SCD mice
Haptoglobin (Hp) / Hemopexin (Hx) Hx therapy normalises blood pressure in SCD mice For personal use only • Transgenic mice that express human a-globlin and b-globin incorporating the sickle mutation (HbS), no expression of mouse Hb genes • 0.7mg Hx, 2x per week for 4 weeks from 1 month of age Vinchi
Slide 26: CSL Research on Hp / Hx
CSL Research on Hp / Hx For personal use only • Swiss government funding since 2011 • Collaborators: University of Zurich, University of Torino, FDA CBER • Processes for purification of Hp and Hpx from plasma developed • Initial pre-clinical proof-of-concept data generated in vitro and in vivo • Pla
Slide 27: Immunoglobulins
For personal use only Immunoglobulins
Slide 28: Immunoglobulins
Immunoglobulins For personal use only Maintaining leadership position through focus on: • Patient convenience • Yield • Label Immunoglobulins • Formulation science • Specialty Igs Key Focus • Hizentra® • Privigen® 28
Slide 29: Privigen and Hizentra
For personal use only The first and only 10% liquid intravenous immunoglobulin (IVIg) therapy that is proline stabilised with room temperature storage up to 36 months The first 20% high concentration low volume SCIG for convenient self administration providing steady-state Ig levels and an establish
Slide 30: Benefits of Hizentra: Steady-State Kinetics
Benefits of Hizentra®: Steady-State Kinetics Headache will typically For personal use only occur here (Ig-peak-levels in plasma) Total IgG mg/100 mL Wear-off effect & potential infections will occur here (Ig- trough-level) Pharmacokinetic Profile of IVIG vs. SCIG • SCIG weekly dosing results in stea
Slide 31: Hizentra Schedules Beyond Biweekly
Hizentra® Schedules Beyond Biweekly Individualised dosing strategies for patient protection For personal use only * • More optionality, better management of dosing holiday • Approved by EMA 31 • Under FDA review Data on file CSL Behring *Hizentra® pharmacometric modeling and simulation
Slide 32: Strengthening Presence in Neurology
Strengthening Presence in Neurology For personal use only Chronic Inflammatory Demyelinating Polyneuropathy • Increased use of Privigen® across Europe and Canada in patients with CIDP • Hizentra® CIDP orphan designation in the US • Ongoing progress in Hizentra® Path study 32
Slide 33: Path Phase III Study Design
Path Phase III Study Design For personal use only IgG dependency Test 33
Slide 34: Path Study Progress
Path Study Progress For personal use only • 60 patients completed • 114 / 174 randomised • Expect to close recruitment in late 2015 • Last patient completing late 2016 • FDA and EMA submissions Q3/4 2017 34
Slide 35: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities
Slide 36: Global Immunoglobulin Market
Global Immunoglobulin Market For personal use only 2013/14 Sales (USD) • Ig volume continues to grow globally CSL • Increased competition particularly in SCIg • CSL is well positioned ~ $8b 36 Sources: Company annual reports / earnings releases, CSL Estimates of Target Markets
Slide 37: CSL's Immunoglobulin Portfolio
CSL’s Immunoglobulin Portfolio For personal use only 2013/14 Sales (USD) • Increased presence in neurology in Europe Hyper IG • Maximise patient SCIG convenience IVIG • Geographical expansion $2,320m 37
Slide 38: Immunoglobulins: Progress Achieved
Immunoglobulins: Progress Achieved For personal use only Increased • Privigen® CIDP launched in Europe and Canada presence in • Ongoing development of Hizentra® in CIDP • Additional indications under evaluation neurology Maximise • Individualised therapy from daily to bi-weekly patient • Further act
Slide 39: Individualised Therapy
Individualised Therapy For personal use only Patient Enhanced Weekly Options Preference Outcomes Advantages of individualised therapy with Hizentra® • Dosing flexibility provides more freedom to patients, allowing them to manage their condition based upon their specific needs and lifestyle • All dos
Slide 40: Specialty Products
For personal use only Specialty Products
Slide 41: Specialty Products
Specialty Products Leveraging high quality, For personal use only broad product portfolio through: • New markets • Novel indications • Novel modes of Specialty administration Products Key Focus • Beriplex® / Kcentra™ • Berinert® • Zemaira® • Fibrinogen 41
Slide 42: Kcentra (Beriplex)
Kcentra™ (Beriplex®) For personal use only • Prothrombin Complex Concentrate = PCC • vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) Kcentra™ launched in April in the US as a first in class therapy to reverse the effects of vitamin K antagonists (e.g. Warfarin) for: • Bleeding related t
Slide 43: Kcentra (Beriplex)
Kcentra™ (Beriplex®) • Potential clinical application for new oral anticoagulant reversal? For personal use only Reversal Effects of Beriplex ® on Edoxaban* in Healthy Volunteers Key: BD=bleeding duration ETP=endogenous thrombin potential PT=prothrombin time • 50IU/kg Beriplex® dose reversed the ant
Slide 44: Berinert
For personal use only Berinert® Plasma derived, pasteurised & nanofiltered concentrate of C1 Esterase Inhibitor indicated for the treatment of acute abdominal, laryngeal or facial attacks of hereditary angioedema (HAE) in adults and adolescents • Post marketing safety studies completed • No antibody
Slide 45: CSL830 (Subcutaneous C1-INH)
CSL830 (Subcutaneous C1-INH) For personal use only Plasma derived, pasteurised & nanofiltered highly concentrated C1 Esterase Inhibitor indicated for subcutaneous administration in the prophylaxis of hereditary angioedema (HAE) in adults and adolescents • Patients with frequent attacks (50 to <100/y
Slide 46: Vulnerable Period (time <40% C1-INH activity)
Vulnerable Period (time <40% C1-INH activity) SC CSL830 maintains trough levels above “protective” C1 levels For personal use only (a) 1000 IU IV pdC1-INH (b) 3000 IU SC CSL830 150 Peak Trough Ratio Peak Trough Ratio 63.9 29.4 2.2 60.3 42.9 1.4 C1-INH functional activity (%) 100 50 0 0 5 10 15 20 25
Slide 47: CSL830 Clinical Program
CSL830 Clinical Program For personal use only Phase II Phase III Phase IIIb Dose-ranging study Clinical efficacy study Long-term safety • Safety • Efficacy • PK/PD • PK • 18 HAE patients • Safety with infrequent attacks Completed Ongoing Commencing Dec 14 47 www.clinicaltrials.gov
Slide 48: CSL830 Phase II COMPACT Study Results
CSL830 Phase II COMPACT Study Results Primary Endpoint For personal use only Protective Level 48 Modified from Zuraw et al; EEACI 2014
Slide 49: CSL830 Phase III Study Design
CSL830 Phase III Study Design For personal use only *Pbo = Placebo 49 Modified from Zuraw et al; EEACI 2014
Slide 50: CSL830 COMPACT Program Progress
CSL830 COMPACT Program Progress For personal use only • 84/100 patients randomised • Last Patient visit Q4 2015 • Long term Safety study to commence Dec 2014 • Submission to FDA Q2/3 2016 50
Slide 51: Zemaira
Zemaira® For personal use only Zemaira is the first highly purified alpha-1 augmentation therapy approved by the FDA for chronic augmentation and maintenance therapy of adults with alpha-1 and emphysema Seeking to broaden use through approval in EMA in 2015 • Completed RAPID trial in 2013 • Under re
Slide 52: Zemaira Biochemical Efficacy
Zemaira® Biochemical Efficacy For personal use only Study CE1226_2002 RAPID Study Equivalence to Prolastin® 30 30 Zemaira® Placebo Serum API (µM) ±SD Serum API (µM) ±SD 20 20 11 µM 11 µM 10 10 CE1226 60 mg/kg Prolastin 60 mg/kg 0 0 1 2 3 4 5 6 7 8 9 10 11 BL 3 6 9 12 15 18 21 24 Weeks Months 52 www.
Slide 53: Zemaira Continues to Slow the Rate of Lung Density Decline
Zemaira® Continues to Slow the Rate of Lung Density Decline Over 4 Years For personal use only Estimated Rate of Decline in Physiologically Adjusted P15 at TLC RAPID Study RAPID Extension (Dec 2013) 0 N=97 N=97 -1 Annual Rate of Decline -1.37 g/L/Year Estimated Decline -2 from Baseline -3 Annual Rat
Slide 54: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities
Slide 55: Select Specialty Products – Global Markets
Select Specialty Products – Global Markets For personal use only HAE • Rare diseases ~$900m • Unmet medical need • High value PCC Target Alpha-1 • Increasing awareness ~$300m segments ~$750m Fibrinogen ~$250m ~$2.2b 55 Sources: Company annual reports / earnings releases, CSL Estimates of Target Mark
Slide 56: CSL's Specialty Products Portfolio
CSL’s Specialty Products Portfolio 2013/14 Sales (USD) For personal use only Other Specialty Peri-Operative Products Bleeding • Increase demand • Geographical expansion • Education and diagnosis $848m 56
Slide 57: Kcentra
Kcentra™ For personal use only Kcentra™, Prothrombin Complex Concentrate (Human), is the first non- activated 4-factor PCC approved in the U.S. for the urgent reversal of vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with acute major bleeding or needing an urgent surgery or ot
Slide 58: Berinert
Berinert® For personal use only Berinert treats the fundamental cause of HAE symptoms by providing C1- Inhibitor deficient patients with the missing human protein1 Berinert has demonstrated that it provides fast relief of pain and swelling within 30 minutes2 Geographical expansion Patient care and c
Slide 59: Berinert Key Features
Berinert® Key Features For personal use only Improved patient •Low volume formulation convenience New method of use • subQ prophylaxis New • Explore new indications Indications (e.g. Transplantation) 59
Slide 60: Zemaira
Zemaira® For personal use only Indicated in the US for chronic augmentation and maintenance therapy in adults with alpha-1 deficiency and clinical evidence of emphysema Has been shown to slow the progression of emphysema as measured by CT lung density DNA1 is the first and only test to confirm known
Slide 61: Q&A
For personal use only Q&A
Slide 62: Break
For personal use only Break
Slide 63: R&D Briefing
For personal use only R&D Briefing December 3, 2014
Slide 64: Haemophilia Products
For personal use only Haemophilia Products
Slide 65: Haemophilia
Haemophilia Supporting and enhancing plasma products and developing For personal use only novel recombinant portfolio with focus on: • Scientific and product innovation • Patient benefit Key Focus Haemophilia • Long acting rIX-FP Products • Long acting rVIIa-FP • rVIII-Single Chain • Research into l
Slide 66: Innovation to Drive Growth
Innovation to Drive Growth For personal use only Patient benefit primary driver of innovation Scientific Edge • Albumin fusion technology Precise Improved engineering half life, rAlbumin of extended as fusion specially • rIX-FP, rVIIa-FP, rvWF-FP dosing interval platform designed linker • Factor VII
Slide 67: PROLONG-9FP Clinical Development Program: rIX-FP
PROLONG-9FP Clinical Development Program: rIX-FP For personal use only www.clinicaltrials.gov 67
Slide 68: Compared with in market rFIX
For personal use only Compared with in market rFIX • 5.3-fold longer half-life (92hrs) • ~ 45% higher incremental recovery • ~7-fold larger AUC • ~7-fold slower clearance 68
Slide 69: PROLONG-9FP Clinical Development Program: rIX-FP
PROLONG-9FP Clinical Development Program: rIX-FP For personal use only Phase III Phase I Phase I/II Phase II/III • Pediatric • PK • PK • PK • Safety • Long-term • Long-term safety safety • Weekly • 7,10 and14-day Extension prophylaxis prophylaxis • On-demand • On-demand PUP treatment treatment Surge
Slide 70: PROLONG-9FP Clinical Results Summary
PROLONG-9FP Clinical Results Summary For personal use only • Excellent safety profile • Well tolerated • No inhibitors • No adverse events related to CSL654 • Meets all criteria for registration • Effectively treats bleeding episodes • Offers benefit for prophylaxis • Effective in 7-day, 10-day and
Slide 71: FIX Activity: rIX-FP vs. rFIXFc
FIX Activity: rIX-FP vs. rFIXFc rIX-FP shows higher activity at the 240 hour time point For personal use only Paired comparison: Mean (SD) Plasma FIX activity-time Profiles 100100 after 50 IU/kg in 12 yo and older Plasma FIX activity (IU/dL)* (IU/dL, % ) Plasma FIX activity (IU/dL) rIX-FP (n=12) (IU
Slide 72: rIX-FP (CSL654) Clinical Development
rIX-FP (CSL654) Clinical Development For personal use only • All patients now in extension study • Dossier submission for adult and paediatric indications • FDA Dec 2014 • EMA Q2 2015 72
Slide 73: rVIIa-FP (CSL689)
rVIIa-FP (CSL689) For personal use only rFVIIa Linker rAlbumin 73
Slide 74: For personal use only
For personal use only • Half-life = 8.5 hrs (vs rFVIIa ~2-3hrs) 74
Slide 75: rVIIa-FP Clinical Development Program
rVIIa-FP Clinical Development Program For personal use only Congenital Factor VII Deficiency Phase II/III Phase I Prophylaxis Extension PK On-demand safety Pediatrics • Phase I PK/PD study in congenital FVII deficiency patients • PK and safety in patients • To commence December 2014 75
Slide 76: rVIIa-FP Clinical Development Program
rVIIa-FP Clinical Development Program For personal use only Congenital Haemophilia with Inhibitors Phase II/III Phase I PK Phase III PK Long-term safety Prophylaxis safety On-demand Surgery Pediatrics • Pivotal Phase II/III trial in haemophilia A & B patients with inhibitors • Dose finding, safety &
Slide 77: rVIII-SingleChain (CSL627)
rVIII-SingleChain (CSL627) For personal use only Me++ A1 A2 A3 C1 C2 rVIII-SingleChain 77
Slide 78: AFFINITY Clinical Development Program: rVIII-SingleChain
AFFINITY Clinical Development Program: rVIII-SingleChain For personal use only Phase I/III 1001 Phase III • PK • Pediatric • Long-term safety • On-demand treatment • Long-term prophylaxis • Surgical prophylaxis Extension Completed Ongoing Ongoing www.clinicaltrials.gov 78
Slide 79: CSL627 PK Evaluation: Area Under the Curve
CSL627 PK Evaluation: Area Under the Curve For personal use only 30 rVIII-SingleChain Advate Dose-normalised AUC (IU*hr/mL) 25 20 15 10 5 0 AUC0-last 1 AUC0-∞ *Dose-normalised baseline-corrected FVIII activity AUC0-last and AUC0-∞ in plasma following a single intravenous administration of rVIII-Sing
Slide 80: CSL627 PK Evaluation: Clearance and t1/2
CSL627 PK Evaluation: Clearance and t1/2 For personal use only *Dose-normalised baseline-corrected FVIII activity Clearance and half-life in plasma following a single intravenous administration of rVIII-SingleChain or Octocog alpha. FVIII activity determined by chromogenic assay and normalised by in
Slide 81: CSL627 PK Supports Dosing Twice-Weekly
CSL627 PK Supports Dosing Twice-Weekly For personal use only Product Time Time to 2% to 1% (hr) (hr) rVIII- 78.0 91.9 SingleChain Octocog 65.2 77.2 alpha Data presented are mean values. n=22 81 CSL Behring. Data on file.
Slide 82: rVIII-SingleChain Phase I/III Study
rVIII-SingleChain Phase I/III Study For personal use only • Very well tolerated • No inhibitors • All bleeding events effectively treated • All surgeries successfully treated • Pivotal study primary endpoint reached • US dossier submission first half 2015 • EMA dossier submission Q4 2015 82
Slide 83: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities
Slide 84: Coagulation: Key Market Segments (USD)
Coagulation: Key Market Segments (USD) For personal use only • Beriate ® • Helixate® Hem A ~$5.4b1 • rVIII-Single Chain • Haemate P® • rVIIa-FP Inhibitor bleed Hem B treatment Target ~$0.9b1 ~$1.4b1 segments • Mononine® • Berinin® • rIX-FP • Voncento® VWD • Haemate P® ~$0.5b1 • rvWF-FP 84 Sources: C
Slide 85: Global Haemophilia Market (USD)
Global Haemophilia Market (USD) For personal use only • Trend toward recombinants in major markets • New longer-acting Plasma derived competition Recombinant • Pd highly competitive tender markets $8.2b 85 Sources: Company annual reports / earnings releases, CSL Estimates of Target Markets
Slide 86: CSL Coagulation Sales 2013/14 (USD)
CSL Coagulation Sales 2013/14 (USD) For personal use only • Broad portfolio presence • Growth in developed and pd Coag pdCoag emerging markets Helixate® • Helixate® strong foundation for recombinant pipeline $1,064m 86
Slide 87: rVIII-SingleChain (CSL627)
rVIII-SingleChain (CSL627) For personal use only Single chain design with most of B-domain deleted Covalent link between heavy and light chains Single Chain Design Potential Differentiated Profile • Binds strongly to vWF • Effective bleeding control • Greater molecular integrity and • Favorable tole
Slide 88: rIX-FP (CSL654)
rIX-FP (CSL654) For personal use only Unique recombinant albumin fusion protein molecule Enhanced pharmacokinetic profile including five-fold half-life extension, seven fold increase in AUC* and higher trough levels Attributes of Albumin Potential Differentiated Profile • Natural protein • Effective
Slide 89: Coagulation: Growth Drivers
Coagulation: Growth Drivers For personal use only Increased • Estimated 1 in 1,000 people have inherited blood disorders diagnosis • 75% inadequate or no care; disorder not diagnosed Awareness of • Publications and presentations benefits of • Benefits of long/longer acting products prophylaxis Growt
Slide 90: Breakthrough Medicines
For personal use only Breakthrough Medicines
Slide 91: Breakthrough Medicines
Breakthrough Medicines For personal use only Leveraging clinical and technical insight in developing Breakthrough novel protein-based therapies Medicines • Significant unmet need • Multiple indications Key Focus • CSL112 (Apo AI) • CSL346 (anti-VEGF-B mAb) • FXII Antagonist 91
Slide 92: CSL112 (Apolipoprotein A-I)
CSL112 (Apolipoprotein A-I) For personal use only • Reduction of early recurrent cardiovascular events represents a substantial unmet medical need • Recurrent CV events occur early, are associated with high mortality and are inadequately addressed by available therapies Figure adapted from PLATO Tri
Slide 93: CSL112
CSL112 For personal use only • Novel Mechanism of Action for Early Reduction of Recurrent CV Events • Produces an immediate and robust increase in the efflux of cholesterol from cells, including lipid-rich macrophages in coronary arteries • Expected to rapidly stabilise plaque and reduce the inciden
Slide 94: CSL112 AHA Presentations
CSL112 AHA Presentations Nov 18, 2014 For personal use only Further elucidation of mechanisms by which CSL112 may rapidly stabilise plaque at risk of rupture Mechanism of HDL Remodeling Induced by CSL112 • Prebeta-1 HDL levels correlate strongly with ABCA1 mediated cholesterol efflux • Infusion of C
Slide 95: CSL112
CSL112 AHA announcement of Phase 2b start For personal use only Randomisation N = 1200 Four Weekly Infusions High dose (6 gms) Low Dose (2 gms) Placebo N = 400 N = 400 N = 400 Administrated in acute MI setting Primary endpoint: liver and renal safety To be followed by Phase 3 morbidity/mortality tri
Slide 96: Licensing and Collaborations
For personal use only Licensing and Collaborations
Slide 97: Licensing
Licensing For personal use only Optimising value of IP Portfolio and assets Breakthrough Breakthrough Medicines Medicines • Partner high opportunity products • GARDASIL® Specialty Immunoglobulins Specialty Immunoglobulins Products • Mavrilimumab (GM- Products CSFRa - Medi/AZ) Haemophilia • Periodont
Slide 98: GARDASIL
GARDASIL® • Impact of Australia’s HPV Vaccination Program For personal use only Genital warts • 93% reduction in genital warts in females less than 21 years • 82% reduction in genital warts in heterosexual males less than 21 years • Rates of treatment for genital warts in private hospitals have also
Slide 99: GARDASIL
GARDASIL® • Long term protection For personal use only • Follow up studies up to 8 years demonstrate no break through disease • V503: 9-Valent HPV Vaccine • Merck’s 2nd generation HPV vaccine • Phase III data: prevented 97% cervical, vaginal and vulvar pre- cancers caused by additional 5 types • US
Slide 100: Mavrilimumab (GM-CSFRa mAb)
Mavrilimumab (GM-CSFRa mAb) For personal use only Phase IIb (EARTH EXPLORER 1) study: • 326 patients with moderate-to-severe RA and an inadequate response to at least one disease-modifying anti-rheumatic drug • Dosing (30, 100, 150mg) every 2 weeks for 24 weeks • Co-primary endpoints • Mean change f
Slide 101: Mavrilimumab
Mavrilimumab Phase IIb study met DAS28-CRP co-primary endpoint: For personal use only • At Week 12, a statistically significant difference in DAS28-CRP was seen for all doses of mavrilimumab versus placebo • Sustained at Week 24 versus placebo • A significantly greater percentage of mavrilimumab-tre
Slide 102: Mavrilimumab
Mavrilimumab For personal use only Phase IIb study conclusions: • Study met both co-primary endpoints at all mavrilimumab doses • All secondary endpoints (including ACR50, ACR70 response) achieved statistical significance for the 150 mg dose • Rapid (after one week of initiation of treatment) and su
Slide 103: CSL362 (anti-IL-3Ra mAb)
CSL362 (anti-IL-3Ra mAb) For personal use only • Initial indication: Acute myeloid leukaemia • Enhanced recruitment of tumour killing NK cells • Phase I study in progress • Other high quality opportunities in autoimmunity eg. SLE • Partnership with Janssen Biotech, Inc 103
Slide 104: Summary
For personal use only Summary
Slide 105: Global R&D Portfolio December 2014
Global R&D Portfolio December 2014 Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH For personal use only Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine Hizentra® Japan Hizentra
Slide 106: Expected Progress in next Months
Expected Progress in next 12 Months For personal use only Privigen Privigen Hizentra US MG Japan Flex Dosing Haptoglobin/ rVIIa-FP rIX-FP Hemopexin Inhibitors US Approval rIX-FP EMA Dossier CSL12 Anti-FXIIa rVIII-SC BLA Dossier CSL324 G-CSFR CSL830 Zemaira® EU C1-INH s.c. CSL334* CSL362* Beriplex® A
Slide 107: Significant Target Launch Dates
Significant Target Launch Dates 2014 2015 2016 2017 2018 2019 For personal use only Voncento™ Voncento™ CSL654 CSL654 CSL689 rVIIa-FP Haem A EU V WD EU rIX-FP US rIX-FP Japan Congen Def CSL654 CSL627 rFVIII rIX-FP EU EU/Japan CSL627 rFVIII-SC US KcentraTM Zemaira® CSL830 C1-INH Surgical EU SubCut Be
Slide 108: 2014 Highlights
2014 Highlights For personal use only • Hizentra® flexible dosing registration in EU Immunoglobulins • Hizentra® CIDP orphan drug designation • Ongoing global Privigen CIDP registrations • KcentraTM registration for surgical indication in US Specialty Products • Berinert® s.c. Pivotal Phase III rapi
Slide 109: Q&A
For personal use only Q&A
Slide 110: Further Information
Further Information Presentation Playback For personal use only A playback of the Research and Development presentations will be available for a period of two weeks following the R&D Briefing. Investors wishing to listen to these presentations should contact CSL Investor Relations to arrange access.