Csl Limited · ASX:CSL
Csl — Investor Day (December 2010)
88 slides from Csl's investor day presentation, Dec 7, 2010
Slide 1: R&D Briefing December 7, 2010
For personal use only R&D Briefing December 7, 2010
Slide 2: Agenda December 2010 R&D Briefing
Agenda December 2010 R&D Briefing For personal use only 8.30am: Sign in and coffee • Welcome Mark Dehring • Introduction and Highlights Andrew Cuthbertson • Immunoglobulins Andrew Cuthbertson • Specialty Products Russell Basser • Q&A • 20 Minute Break • Rec Coagulation Program Simon Green • Breakthr
Slide 3: Introduction and Highlights
For personal use only Introduction and Highlights
Slide 4: CSL R&D Strategy
CSL R&D Strategy • Maintain commitment to extracting maximum For personal use only value from existing assets and supporting and improving Breakthrough Specialty current products Medicines Products • Develop new protein- Immuno- based therapies for Haemophilia globulins Products treating serious ill
Slide 5: Immunoglobulins Strategy
Immunoglobulins Strategy Supporting and For personal use only enhancing current portfolio and developing new products • Yield Breakthrough Specialty Medicines Products • Label • Formulation science Immuno- • Patient convenience Haemophilia globulins Products
Slide 6: Specialty Products Strategy
Specialty Products Strategy Expanding use through For personal use only new markets, novel indications and/or modes of administration e.g. Breakthrough Specialty • Berinert Medicines Products • Beriplex • Fibrinogen Immuno- Haemophilia globulins Products
Slide 7: Haemophilia Strategy
Haemophilia Strategy Supporting and For personal use only enhancing portfolio and developing new products • Plasma products Breakthrough Specialty • Long acting rIX & Medicines Products rVIIa • Patient convenience Immuno- Haemophilia • Coagulation research globulins Products
Slide 8: Breakthrough Medicines Strategy
Breakthrough Medicines Strategy Developing new protein- For personal use only based therapies • Significant unmet need • Multiple indications, e.g. Breakthrough Specialty Medicines Products • Reconstituted HDL • Anti IL-3Ra mAb Immuno- Haemophilia • Anti G-CSFR mAb globulins Products
Slide 9: Global R&D: Integrated R&D Facilities
Global R&D: Integrated R&D Facilities For personal use only
Slide 10: Leveraging Global Capabilities
Leveraging Global Capabilities For personal use only CSL Behring CSL Limited CSL Biotherapies Organisation by site Marburg Bern K3 KoP Japan Parkville Parkville/ Organisation by function Broadmeadows Global project management to ensure leverage of best capabilities
Slide 11: Stage Gate Decision System
Stage Gate Decision System For personal use only New Preclinical GLP Tox & Registration Product Research Product Phase I Phase II Phase III Launch Opportunity Development (FIH) Phase IV 1 2 3 4 5 6 Enter Enter Enter GLP Enter Enter Register Preclinical Research Tox & Phase I Phase II Phase III Launc
Slide 12: Progress through Stage Gates in 2010
Progress through Stage Gates in 2010 For personal use only New Preclinical GLP Tox & Registration Product Research Product Phase I Phase II Phase III Launch Opportunity Development (FIH) Phase IV 1 2 3 4 5 6 Enter Enter Enter GLP Enter Enter Register Preclinical Research Tox & Phase I Phase II Phase
Slide 13: R&D Investment
R&D Investment For personal use only * Foreign currency impact using FY2009 exchange rates
Slide 14: Global R&D Pipeline December 2009
Global R&D Pipeline For personal use only December 2009 Humate® P Zemaira® US Privigen® Fibrinogen Fibrinogen Rhophylac® US Hizentra®EU Privigen® CIDP EU Hizentra®US New Indications Aortic Surgery Berinert® US PCC Zemaira® EU Beriplex® EU New Indications Riastap® US Beriplex ® US Riastap® EU Afluria
Slide 15: Global R&D Pipeline December 2010
Global R&D Pipeline December 2010 For personal use only Humate® P Zemaira® US Privigen® Rhophylac® US Afluria® Fibrinogen Fibrinogen Privigen®CIDP EU Hizentra® EU Hizentra® US New Indications Aortic Surgery Zemaira® EU Beriplex® EU Berinert® US PCC Beriplex ® US Riastap® US New Indications Riastap®
Slide 16: Expected Progress in next months
Expected Progress in next 12 months For personal use only New Preclinical GLP Tox & Registration Product Research Product Phase I Phase II Phase III Launch Opportunity Development (FIH) Phase IV 1 2 3 4 5 6 Enter Enter Enter GLP Enter Enter Register Preclinical Research Tox & Phase I Phase II Phase
Slide 17: Immunoglobulins
For personal use only Immunoglobulins
Slide 18: Immunoglobulins Strategy
Immunoglobulins Strategy Supporting and For personal use only enhancing current portfolio and developing new products • Yield Breakthrough Specialty Medicines Products • Label • Formulation science Immuno- Haemophilia • Patient convenience globulins Products
Slide 19: Privigen
Privigen® For personal use only • Only room temperature stable IVIG (36 months) • IgLab Module2 comes on-line 2011 (submitted to the FDA 25 Nov) • Privigen approved and launched in US, Europe, Australia, Canada and other countries, with additional registrations underway • European Phase III study in
Slide 20: Hizentra
Hizentra® • First 20% SCIg launched in US For personal use only • FDA approval March 2010 • Expected to be the first 20% SCIg launched in Europe, Canada, Switzerland, Japan and other geographies • Review in progess: EMA, Switzerland, Canada • Launches expected in 2011 • Japan Phase III study initiat
Slide 21: Specialty Products
For personal use only Specialty Products
Slide 22: Specialty Products Strategy
Specialty Products Strategy Expanding use through For personal use only new markets, novel indications and/or modes of administration e.g. Breakthrough Specialty • Berinert Medicines Products • Beriplex • Fibrinogen Immuno- Haemophilia globulins Products
Slide 23: Improving Treatment for Hereditary Angioedema: Berinert Program
For personal use only Improving Treatment for Hereditary Angioedema Berinert® Program
Slide 24: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) For personal use only • C1-esterase inhibitor is the primary control protein of activation of mediators of vascular permeability • HAE results from deficiency or dysfunction due to gene mutation • i.e. life-long condition
Slide 25: What Happens to Patients?
What Happens to Patients? For personal use only • Recurrent episodes of swelling, sometime with a rash • Unpredictable and occur anywhere in the body • Life-threatening if laryngeal swelling • Attacks caused by stress, infection, menstruation, some drugs, unknown causes
Slide 26: HAE Treatment Guidelines
HAE Treatment Guidelines For personal use only 1. Bowen , et al, Ann Allergy Asthma Immunol. 2008 2. Gompels et al, Clin Exp Immunol. 2005
Slide 27: Berinert - Effective Treatment for HAE
Berinert® - Effective Treatment for HAE For personal use only • Long clinical use in Europe • Orphan drug status for treatment in US in 2009 • Currently given via intravenous administration • A&E or self-administration • High quality manufacturing process • Strong safety record
Slide 28: Berinert Development Program
Berinert® Development Program For personal use only • Improving Convenience • Developing a high concentration, low volume formulation • More rapid and easier subcutaneous administration • Improving Options • Program to gain indication for prevention for sufferers with frequent attacks • Launch when
Slide 29: Treating the Bleeding Patient
For personal use only Treating the Bleeding Patient
Slide 30: Acquired Bleeding Disorders
Acquired Bleeding Disorders • Coagulation factor deficiencies can occur because of multiple factors For personal use only • Current treatment options • Donated blood products – platelets, fresh frozen plasma (FFP), cryoprecipitate • Specific products such as those in CSL portfolio • Problems with do
Slide 31: Beriplex to reverse anti-coagulation with Vitamin K antagonists
For personal use only Beriplex® to reverse anti-coagulation with Vitamin K antagonists (e.g. warfarin)
Slide 32: Challenges with Anti-Coagulation
Challenges with Anti-Coagulation For personal use only • Vitamin K antagonists are the most commonly prescribed oral anti-coagulants to prevent clotting for people who are at risk, i.e. previously had a clot, artificial heart valves, etc • Potential problems • Over anti-coagulation can be a conseque
Slide 33: What is Beriplex?
What is Beriplex®? For personal use only • Highly purified preparation containing vitamin K- dependent coagulation factors • FII, FVII, FIX, FX • 2 viral inactivation steps • Specific antidote to vit K antagonists (anti-coagulants) • provides rapid normalisation of clotting • Used in Europe for >10
Slide 34: Program to licence Beriplex in US
Program to licence Beriplex® in US For personal use only • Seeking approval for use of Beriplex® to reverse the effects of vitamin K antagonists for • Bleeding related to over-anticoagulation • Patients needing surgery • 2 large randomised, controlled clinical trials • Bleeding study completed and a
Slide 35: Fibrinogen Concentrate for Major Cardio-Aortic Surgery
For personal use only Fibrinogen Concentrate for Major Cardio-Aortic Surgery
Slide 36: Aortic Aneurysm – a Potentially Lethal Problem
Aortic Aneurysm – a Potentially Lethal Problem For personal use only
Slide 37: Fibrinogen in Aortic Surgery
Fibrinogen in Aortic Surgery For personal use only • Patients go on cardiopulmonary bypass and coagulation factors are consumed bleeding • Concept – a quickly administered, fast acting, low volume medicine to microvascular bleeding that will substantially reduce the need for donated (allogeneic) b
Slide 38: Pilot Experience in Hannover
Pilot Experience in Hannover For personal use only
Slide 39: Proof-of-Concept Study in Aortic Repair
Proof-of-Concept Study in Aortic Repair For personal use only • Prospective, randomized, double-blind, placebo- controlled, single-center study
Slide 40: Standardised Approach
Standardised Approach For personal use only Standard transfusion protocol
Slide 41: Fibrinogen Reduced Amount of Blood Transfused
Fibrinogen Reduced Amount of Blood Transfused For personal use only 50 p < 0.0001 Units of allogeneic blood products 40 30 20 10 0 Fibrinogen Placebo N = 29 N = 31
Slide 42: Fibrinogen Reduced Proportion of Patients Requiring Transfusion
Fibrinogen Reduced Proportion of Patients Requiring Transfusion For personal use only Administration of Proportion of subjects donated blood Fibrinogen Placebo products (N = 29) (N = 31) No 45% 0% Yes 55% 100% p<0.0001
Slide 43: Fibrinogen in Aortic Surgery Program
Fibrinogen in Aortic Surgery Program For personal use only • Next 12 months • Confirm findings in multi-centre trials in Europe to commence in 2011 • Longer term Outlook • Obtain extended approvals in EU • Obtain indication approval in US
Slide 44: Q&A
For personal use only Q&A
Slide 45: Break
For personal use only Break
Slide 46: Haemophilia
For personal use only Haemophilia
Slide 47: Haemophilia Strategy
Haemophilia Strategy Supporting and For personal use only enhancing portfolio and developing new products • Plasma products Breakthrough Specialty • Long acting rIX & Medicines Products rVIIa • Patient convenience Immuno- Haemophilia • Coagulation research globulins Products
Slide 48: Recombinant Coagulation Factors with extended half-life
For personal use only Recombinant Coagulation Factors with extended half-life
Slide 49: Half-life Improvement for Coagulation Products
Half-life Improvement for Coagulation Products Products with improved half-life will be beneficial to patients For personal use only • Less frequent injections • Improved compliance • May enable prophylaxis Albumin as a Carrier Protein • Albumin has a naturally long half-life (~20 days) • Proof of p
Slide 50: Albumin fusion extends the half life of rFIX
Albumin fusion extends the half life of rFIX Pharmacokinetics in Rabbits For personal use only rIX-FP: average curves rIX-Albumin Fusion Protein 2048 Pharmacokinetics in Monkeys 3 Dimensional Model 1024 Factor IX (IU/L) above background 512 100 U/kg 256 • Pre clinical toxicology completed 128 50 U/k
Slide 51: Albumin fusion extends the half life of rVIIa
Albumin fusion extends the half life of rVIIa For personal use only Pharmacokinetics in Rats Haemostatic Efficacy in FVIII Deficient Mice NovoSeven 0.9 mg/kg rVIIa-FP 0.9 mg/kg • Pilot scale manufacturing process developed • Proceeding to pre clinical toxicology, Q1 2011
Slide 52: Manufacturing for Rec Coagulation Products
Manufacturing for Rec Coagulation Products For personal use only Phase I / II CSL Process Development Parkville GMP Manufacture Melbourne Australia Technical Phase III & Launch Transfer Contract Manufacturing CSL’s purification expertise CMO CSL Behring, Marburg Intermediate Transportation Cell Cult
Slide 53: Large Scale Biotech Facility
Large Scale Biotech Facility For personal use only 2009 2010 2011 2012 2013 2014 2015 2016 2017 Design Construction Operations • Support large scale manufacturing for CSL’s R&D portfolio Broadmeadows, Melbourne, Australia • Highly flexible to accommodate range of biotechnology manufacturing processe
Slide 54: Utilising Marburg's Coagulation Expertise
Utilising Marburg’s Coagulation Expertise For personal use only • Facility for purification and formulation of recombinant coagulation proteins • Renovation of existing FDA compliant recombinant facility • Utilise existing knowhow of plasma coagulation factors • Opened November 2010
Slide 55: Breakthrough Medicines
For personal use only Breakthrough Medicines
Slide 56: Breakthrough Medicines Strategy
Breakthrough Medicines Strategy Developing new protein- For personal use only based therapies • Significant unmet need • Multiple indications, e.g. Breakthrough Specialty Medicines Products • Reconstituted HDL • Anti IL-3Ra mAb Immuno- Haemophilia • Anti G-CSFR mAb globulins Products
Slide 57: Reconstituted HDL (CSL112)
Reconstituted HDL (CSL112) For personal use only • Compelling opportunity • Significant investment and risk in late stage development • Phase I study progressing well • Phase IIa to commence in 2011
Slide 58: Optionality of rMAb Programs
Optionality of rMAb Programs For personal use only • Establish paradigm • Opportunity for multiple medical indications Autoimmune Arthritis Other Blood Malignancies Respiratory Relapsed CF exacerbations Refractory AML CSL362 CSL324 IL-3Ra G-CSF AML, MRD Vasculitis *Possible clinical indications only
Slide 59: CSL362 Acute Myeloid Leukemia
For personal use only CSL362 Acute Myeloid Leukemia
Slide 60: CSL362 - AML
CSL362 - AML AML For personal use only • most common acute leukaemia in adults • incidence increases with age • untreated AML fatal: 3 - 4 mo KA Thornton, M Levis. NEJM 2007. 357:1639 • chemotherapy 50-75% CR 100 ~70% will relapse Study Years 1989-1997, n=553 80 Median Survival = 3.2 months 5-Year
Slide 61: CSL362 - AML: CD123 target
CSL362 - AML CD123 is a target expressed on AML blasts and leukemic stem cells For personal use only Transforming mutations AML Blasts and LSC 100 CD34+38+ Express CD123 80 10000 % of Max 60 HSC LSC (CD123+) 1000 40 CD38 20 CD38 100 0 1 10 100 1000 10000 CD123 Normal blood 10 100 CD34+38- 80 cell fo
Slide 62: CSL362 - AML
CSL362 - AML CSL362 – a second generation mAb targeting CD123 (IL-3Ra) For personal use only • retains (cf. CSL360) the ability to potently inhibit IL-3 activity • humanised for reduced immunogenicity • optimised for enhanced tumour killing activity • in-licensed proprietary technologies FcRIII NK
Slide 63: CSL362 - AML: killing activity in vitro I
CSL362 - AML CSL362 shows potent killing activity in vitro I • blood basophils and pDC For personal use only no mAb CSL362 (10mg/mL) Down regulation of CD16 on activated NK cells 10 4 10 4 NK cells (CD3-, CD56+) 100 10 3 10 3 80 basophils 1.94 4.44e-4 60 IgE FITC IgE FITC IgE 10 2 10 2 40 1 1 10 10
Slide 64: CSL362 - AML: killing activity in vivo I
CSL362 - AML CSL362 shows potent killing activity in vivo I For personal use only • basophils and pDC in non-human primates Basophil depletion Time course analysis of cell depletion CSL362: 10mg/kg 3 NHP’s / grp, CSL362: 10mg/kg 104 Day -2 0.523 103 Basophils FITC-A % maximum cell number 2 10 101 10
Slide 65: CSL362 - AML: killing activity in vitro II
CSL362 - AML CSL362 shows potent killing activity in vitro II For personal use only • tumour cell lines and primary AML cells CD123+ve CTLEN Primary AML, RMH048 100 90 80 % Specific lysis 70 CSL362 60 50 CSL362 40 30 CSL360 20 10 CSL360 0 -10 0.0001 0.001 0.01 0.1 1 10 0.0001 0.001 0.01 0.1 1 10 Ant
Slide 66: CSL362 - AML: killing activity in vivo II
CSL362 - AML CSL362 shows potent killing activity in vivo II For personal use only • primary AML cells in NOD/SCID mice AML sample mAbs, 300mg, 3x/wk, CSL360 4 weeks CSL362v1 4 weeks CSL362v2 P= 0.0007 comparing CSL360 and CSL362 V1 4 weeks P= 0.0002 comparing CSL360 and CSL362 (LGD between these gr
Slide 67: CSL362 - AML: killing activity in vitro III
CSL362 - AML CSL362 shows potent killing activity in vitro III For personal use only • primary patient AML blasts with autologous remission NK cells No Antibody CSL362 4 4 10 10 6.35 1.31 3 3 10 10 PE 2 2 CD33 PE CD33 PE CD33 10 10 1 1 10 10 0 0 10 10 0 1 2 3 4 0 1 2 3 4 10 10 10 10 10 10 10 10 10 1
Slide 68: CSL362 – AML
CSL362 – AML FIH, Phase I/IIa study of CSL362 in AML patients AML For personal use only (24,300) - remission / early relapse Primary objectives: Best Induction Supportive • safety and tolerability of escalating doses Care • PK; immunogenicity Fail 1st line Achieve CR Secondary objectives: therapy (1
Slide 69: CSL362 – Longer Term Potential for SLE
CSL362 – Longer Term Potential for SLE pDC and basophils support the progression of SLE For personal use only • SLE is characterised by an IFNa signature and pDC are the major source of IFNa in SLE CSL360 CSL362 • mAb added for 18 hr to deplete pDCs, CpG (5 uM) added for 24 hr to stimulate IFN-a pro
Slide 70: CSL324 Acute and Chronic Inflammation
For personal use only CSL 324 Acute and Chronic Inflammation
Slide 71: CSL324 – Acute and Chronic Inflammation
CSL324 – Acute and Chronic Inflammation Neutrophils and inflammatory disease For personal use only • most abundant WBC, ~109 cells / kg body weight leave the bone marrow (BM) per day • key effectors of the innate response to infection but... COPD exacerbations • excessive production and persistence
Slide 72: The role of G-CSF in mouse models of inflammatory disease
CSL324 – Acute and Chronic Inflammation For personal use only The role of G-CSF in mouse models of inflammatory disease • anti-G-CSF mAb inhibits disease progression in mouse models of arthritis Anti-collagen Ab – induced arthritis Collagen-induced arthritis 12 control Control 10 anti-G-CSF aG-CSF G
Slide 73: G-CSF in a mouse model of COPD
o o S G G k is is k ti- ti- Sm Sm + + an an CSL324 – Acute and Chronic Inflammation Sm Dil S m Fl u il + u+ D + Fl + k+ k k+ k Sm Sm Total Macrophages in For personal use only The role of G-CSF in mouse models of inflammatory disease BALF • anti-G-CSF mAb inhibits disease progression in a mouse mode
Slide 74: Identification and characterisation of a lead candidate mAb
CSL324 – Acute and Chronic Inflammation Identification and characterisation of a lead candidate mAb For personal use only • options available included: • humanisation of in-licensed mouse mAbs against the huG-CSGR • de novo generation of fully human mAbs utilising Dyax phage display technology (G-CS
Slide 75: CSL324 is a potent inhibitor of G-CSF action in vitro
CSL324 – Acute and Chronic Inflammation For personal use only CSL324 is a potent inhibitor of G-CSF action in vitro • inhibition in of G-CSF mediated neutrophil production from HSC mAb IC50 (nM) C1.2 0.016 RO5F6 ND Each point represents the mean +/- range of duplicate measurements
Slide 76: CSL324 is a potent inhibitor of G-CSF action in vivo
CSL324 – Acute and Chronic Inflammation For personal use only CSL324 is a potent inhibitor of G-CSF action in vivo • inhibition of PEG-G-CSF induced neutrophilia in NHP’s • 2 groups (3 animals per group) • s.c PEG-GCSF on Day 1 • single i.v infusion of CSL324 12 hrs later
Slide 77: Concluding comments
CSL324 – Acute and Chronic Inflammation For personal use only Concluding comments • CSL324: • fully human monoclonal antibody directed against the G-CSFR • a potent antagonist of G-CSF activity in in vitro and in vivo assays systems • does not induce acute neutropenia in NHP’s (role of G-CSF in home
Slide 78: Licensing
For personal use only Licensing
Slide 79: ISCOMATRIX Adjuvant
For personal use only ISCOMATRIX® Adjuvant
Slide 80: Business Plan: Pillars for Success
Business Plan: Pillars for Success For personal use only Value • Increased • Flexible capacity interest from with long term major partners Broad Exclusive supply Licenses Manufacture • ~30 fields
Slide 81: Merck Sharp & Dohme Corp.
For personal use only Merck Sharp & Dohme Corp. • Merck Sharp & Dohme Corp. continues to show confidence in ISCOMATRIX® adjuvant for vaccine development programs • Additional Licences • Broader research interest
Slide 82: High Quality Scientific Research
High Quality Scientific Research For personal use only Internal research Partners (Merck, Genentech) High quality academics (WEHI) Mechanisms FDA Investigator led clinical studies (NCI) Biomarkers
Slide 83: Partnered Projects
For personal use only Partnered Projects
Slide 84: Partnered Projects
Partnered Projects For personal use only CAM3001 (GM-CSFRa) • Medimmume/AstraZeneca commenced Phase II study in Rheumatoid Arthritis Feb 2010 Periodontal disease vaccine • Research agreement with Sanofi pasteur • Option to an exclusive worldwide license
Slide 85: GARDASIL
For personal use only GARDASIL®
Slide 86: Summary
For personal use only Summary
Slide 87: Global R&D Pipeline December 2010
Global R&D Pipeline December 2010 For personal use only Humate® P Zemaira® US Privigen® Rhophylac® US Afluria® Fibrinogen Fibrinogen Privigen®CIDP EU Hizentra® EU Hizentra® US New Indications Aortic Surgery Zemaira® EU Beriplex® EU Berinert® US PCC Beriplex ® US Riastap® US New Indications Riastap®
Slide 88: Q&A
For personal use only Q&A