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Slide 2: Agenda
Agenda December 2006 R&D Briefing Welcome Mark Dehring Introduction and highlights Andrew Cuthbertson - Strategy, portfolio overview and budget mix ISCOMATRIX® Adjuvant Andrew Cuthbertson Influenza vaccine portfolio Andrea Douglas Q&A Tea break Plasma Products Simon Green Recombinant Monoclonal Anti
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Slide 4: R&D Highlights - Growth Strategy
R&D Highlights - Growth Strategy * Novel Biotech” products * Improv d products « Market Development _ ae Research & Development pharmaceutical Leverage core capabilities Strong portfolio of IP Deliver phased growth New products - unmet medical needs
Slide 5: R&D Highlights — Investment
R&D Highlights — Investment $Am neal $161m 150 + $141m 120) Market Development 90 - 60 - Life Cycle 30 - Management 0 . FY2005 FY2006 Plus 10% for 2007 oe 300 AU 290 NH 550 total staff
Slide 6: R&D Portfolio
R&D Portfolio — 1 Project Ig 12% liquid (US) Ig Chrom10% IV Ig Chrom SC Humate® vWD surg Zemaira® Beriplex® Berinert® Anti-D ITP rHDL - ACS | Pre-Clin Phase | | | | | | | | | | i | | | | | | i Phase ll Phase Ill Registration Phase IV CSL
Slide 7: R&D Portfolio
R&D Portfolio — 2 Project |Research | Pre-Glin Phase! | Phase fl | Phase lll _ Registration Flu Pandemic Flu Flu-IMX NY-ESO-1 (GSK) nV Therapy Mx HCOV-IMX (Novartis) Various-IM& (Merck) ie Various-IMX (Wyeth) CSL
Slide 8: R&D Portfolio
R&D Portfolio — 3 Project TLA 1L-13Rat (Merck) GM-CSFRa (CATIAZ) Blorn4 G-CSF VEGF-B Other antibodies Other rec proteins TED | i ' |Research | Pre-Clin | Phase! t i i | Phase ll | Phase I! | Registration CSL
Slide 9: Highlights
HIGHLIGHTS * Merck Gardasil® registrations and rollout - Australian Government funding *ISCOMATRIX® adjuvant commercialization «influenza vaccine projects *igs and specialty plasma products ¢3 rMAbs going into the clinic «Zenyth integration
Slide 10: Merck's HPV GARDASIL
Merck’s HPV GARDASIL® GARDASIL. fduadrivalent Human Papillomavirus (Types 6, 11,16, 18) Recombinant Vaccine] « http:/Awww.merck.com/newsroom/webcast/ * Accelerated approval in US, EU and 18 other markets for 9-26 * Broad indication for cervical cancer, genital warts and related HPV diseases * Unanim
Slide 11: Merck's HPV GARDASIL
@ Merck’s HPV GARDASIL® GARDASIL, | (Types 6,11,16, 18) Recomblaant Vaccinel * Expectation of Gardasil launches in more than 65 markets by end 07 * Product and disease awareness continues to increase. In US 50% of targeted customers now identify HPV as cause of cervical cancer vs 5% previously * Pla
Slide 12: GARDASIL: ongoing clinical programs
GARDASIL®: canton. Selected ongoing clinical programs — tpucwislmeinnvcen * Efficacy study in mid-adult women - Anticipated FDA submission 4Q07 * Efficacy program in males - Anticipated FDA submission 2008 « Cross-protection studies * Concomitant use studies with other adolescent vaccines
Slide 13: GARDASIL: Competitive Differentiation
GARDASIL®: Competitive Differentiation First and only HPV vaccine on the market Proven cervical cancer protection Broadest cancer protection — cervical cancer, precancerous or dysplastic lesions, and genital warts caused by HPV types 6, 11, 16 and 18 Proven 4 years+ duration of protection and immune
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Slide 15: ISCOMATRIX adjuvant meets all criteria for inclusion in new human vaccines
ISCOMATRIX® adjuvant meets all criteria for inclusion in new human vaccines mmunomodulator and antigen delivery Safe and immunogenic in humans Long lasting antibody and T cell responses Dose sparing capability “Industrialised”
Slide 16: Multiple value drivers for ISCOMATRIX adjuvant
Multiple value drivers for ISCOMATRIX® adjuvant « Licenses -Upfronts -Milestones -Royalties =Patents "Know-how * Worldwide supplier «Internal vaccine development programs
Slide 17: Wyeth to use ISCOMATRIX adjuvant
Wyeth to use ISCOMATRIX® adjuvant * License and option agreement * Number of fields * Upfronts and milestones >US$90m * Product royalties * Exclusive supply
Slide 18: ISCOMATRIX adjuvant underpins Merck's vaccine development programs
ISCOMATRIX® adjuvant underpins Merck’s vaccine development programs * Aug05 Licence and Option Agreement *Dec06 additional options added ¢ Upfront payment and milestones * Royalties on products ¢ Distribution rights * Exclusive supply * Two clinical programs have been initiated
Slide 19: ISCOMATRIX adjuvant manufactured at commercial scale at Kankakee
ISCOMATRD©® adjuvant being manufactured at commercial scale at Kankakee * Facilities and expertise *|ISCOPREP® saponin -pilot scale -commercial scale * ISCOMATRIX® adjuvant -commercial scale "process being tech transferred
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Slide 21: Global Influenza Vaccine Business
Global Influenza Vaccine Business *« Manufactured influenza vaccine since 1968 * Leading provider and sole manufacturer of flu vaccine in Southern Hemisphere Bujfer preparation area in CSL’s new state-of-the-art influenza vaccine centre *CSL flu vaccines are licensed and sold in 16 countries worldwi
Slide 22: Influenza Vaccine Strategy
influenza Vaccine Strategy Increase FDA GMP manufacturing capacity to meet global demand Continue at the forefront of Increased share of Pandemic Vaccine key global markets development Improved Influenza Vaccines using CSL technological expertise and know-how
Slide 23: Influenza Vaccine Strategy
influenza Vaccine Strategy Increase FDA GMP manufacturing capacity to meet global’ demand Continue at the forefront of increased share of Pandemic Vaccine key global markets development Improved Influenza Vaccines using CSL technological expertise and know-how
Slide 24: Influenza Vaccine Manufacturing Capacity
influenza Vaccine Manufacturing Capacity * Modern egg processing facility completed in 2004 * $80m investment to double vaccine capacity -Duplication of existing facility Egg harvesting machine in CSL’s new State-of-the-art influenza vaccine centre -NH capacity of ~40m doses
Slide 25: Influenza Vaccine Strategy
influenza Vaccine Strategy Increase FDA GMP manufacturing capacity to meet global’ demand Continue at the forefront of Increased share of Pandemic Vaccine key global markets development Improved Influenza Vaccines using CSL technological expertise and know-how
Slide 26: Global Influenza Vaccine Program
Global Influenza Vaccine Program ¢ Expand flu business - Enter the U.S., China and new markets in Europe - Meet regulatory and clinical requirements for each new market — Increase share of key global markets ¢ Utilise resources and capability of CSL Biotherapies to market and distribute vaccine CSL
Slide 27: United States
United States ¢ IND filed April 2006 - Pivotal Clinical Trial completed - 1359 subjects recruited - Immunogenicity criteria met *« BLA submission end Q1 2007 * Launch 2007/08 winter season (contingent upon regulatory approval) CSL
Slide 28: Influenza Vaccine Strategy
influenza Vaccine Strategy Increase FDA GMP manufacturing capacity to meet global demand Continue at the forefront of Increased share of Pandemic Vaccine key global markets development Improved Influenza Vaccines using CSL technological expertise and know-how
Slide 29: Annual Flu-Related Deaths - US
Annual Flu-Related Deaths - US Elderly have 13-fold higher : risk of death from flu / than ages 50-64 50-64 Age Group >65 Source: CDC (ameaecc.eay) tnt SOP CSL
Slide 30: Current Flu Vaccines Less Effective in Elderly
Current Flu Vaccines Less Effective in Elderly Vaccine efficacy (%) 18-59* Age >60** *Source: CDC Gwww.edegoy) **Source: Govaert, JAMA, 1994 “ces
Slide 31: Influenza ISCOMATRIX Vaccine
influenza ISCOMATRIX ® Vaccine Global presence & Proprietary expertise ISCOMATRIX® adjuvant & expertise « Reduction of incidence of influenza-associated illness and mortality in people aged 65yrs and older * Commence clinical program Q3 2007 CSL
Slide 32: Influenza Vaccine Strategy
influenza Vaccine Strategy Increase FDA GMP manufacturing capacity to meet global demand Continue at the forefront of Increased share of Pandemic Vaccine key global markets development Improved Influenza Vaccines using CSL technological expertise and know-how
Slide 33: Pandemic Vaccine Development
Pandemic Vaccine Development ° Testing human immune response to avian influenza vaccine ° Using Aluminium adjuvant with long and safe history of use * First Trial - Excellent safety and tolerability - Two doses of vaccine and an adjuvant required to achieve a satisfactory immune response a Transmiss
Slide 34: Pandemic Vaccine Development cont.
Pandemic Vaccine Development cont. ¢ Further trials to support registration of ‘prototype’ vaccine - Higher doses of antigen - Broader population base * Drivers for approach - Generate understanding of immunogenicity and safety of range of antigen doses - Develop body of data to guide policy decisio
Slide 35: H5N1 Challenge in Ferrets using an ISCOMATRIX H5N1 Vaccine
H5N1 Challenge in Ferrets using an ISCOMATRIX® H5N1 Vaccine* [-] Control (no vaccine) TM AIPO, H5N1 vaccine (i ISCOMATRIX® H5N1 vaccine % surviving H5N1 challenge 0 7.6 15 3.75 7.6 15 HA Content (jg) * NHMRC Avian Influenza Pandemic Research Grant Participants: UniMelb, CSIRO, WHO CC |
Slide 36: ISCOMATRIX H5N1 Vaccine
ISCOMATRIX® H5N1 Vaccine * Potential for: - Antigen Sparing ~ Increased duration of immune response - Cross reactivity with other H5N1 clades * Clinical Development - Commence clinical program 2007 ~ Assess range of antigen doses
Slide 37: Influenza Vaccine Program
Influenza Vaccine Program ¢ Expansion of business into key global markets ¢ Evaluation of improved influenza vaccines * Development of pandemic influenza vaccines
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Slide 39: Plasma R&D Centres of Excellence
Plasma R&D Centres of Excellence Marburg GER Haemophilia Wound Healing Specialty Products Broadmeadows AUS Product Support ‘Féchnical Innovation Bern CH Immunoglobulins King of Prussia USA US, Clinical,. Regulatory: & Pharmacovigilance Kankakee USA Alpha-1 Proteinase inh. Tokyo JPN UPN Clinical & re
Slide 40: Immunoglobulins
immunoglobulins Clinical |. Regulatory | Approved | Phase Ill Review CSL
Slide 41: Liquid IVIG
Liquid IVIG Chromatographic 10% * Clinical program based on PID and ITP * BLA submitted Sept 06. Accepted for filing, Nov 06 + Global registration program to start in Jan, 2007 2 Mii re a E 6g 130 mi | Sendoglobulin® liquid 1120 mim! anlusionsibauag Sandoglobulin® Liquid 12% * Successfully marketed
Slide 42: Liquid Sub Cutaneous IgG
Liquid Sub Cutaneous IgG Vivaglobin® * 16% liquid formulation * Successfully marketed in 20 EU countries, USA and Canada for PID « First subcutaneous product licensed in the USA * Excellent feedback from patients — home therapy Chromatographic SC * High yielding process * Phase III clinical trials c
Slide 43: Hyperimmune Immunoglobulins
Hyperimmune Immunoglobulins Rhophylac® * Indicated for Haemolytic Disease of the Newborn * Approved in 26 countries. 11 more countries in progress + New indication: Chronic Immune Thrombocytopenic Purpura (ITP) * BLA efficacy supplement for ITP accepted for filing by FDA, Aug 06 CytoGam® * Cytomegal
Slide 44: Haemophilia — Humate P / Haemate P
Haemophilia — Humate® P / Haemate® P Needieless transfer device Mix-2-Viails successtully launched (Helixate, Beriate & Berinin) Volume Reduction Approved in 22 countries indication for vWD & Surgery 2006
Slide 45: Opportunities for Growth
Opportunities for Growth Fibrin= ogen New markets Wound New indications Healing Speciality products Core products Revenue per liter Litres PEQ CSL
Slide 46: Specialty Products — New Markets
Specialty Products — New Markets Beriplex® P/N * Indicated for acquired bleeding deficiency (ie. Warfarin reversal) + Expansion of European market ae + Phase Ill clinical trial complete + Regulatory process initiated Berinert ® P * Ci esterase inhibitor indicated hereditary angioedema « Expansion in
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Slide 49: Therapeutic Leukaemia Antibody (TLA)
Therapeutic Leukaemia Antibody (TLA) + Acute Myeloid Leukemia * IP from Australian academic + Anaemia, infection, bleeding collaborator « US incidence 10,500 + Target is differentially expressed * 18% 5 year survival, often only between leukaemia and normal blood cells months « Correlation with poor
Slide 50: TLA Therapeutic Concept
TLA Therapeutic Concept H&G Mutatlon(s} Normal growth | and differentlation Normal blood cells. “Current Oprionin Cel Bology CSL
Slide 51: In vivo Leukaemia Assays
In vivo Leukaemia Assays Engrafted human AML cells 1 407 40 CDIS FITC 10 AML Engraftment: AML stem cells initiate human leukemia when transplanted into irradiated NOD/SCID mice. Quantitative assay for AML stem cells.
Slide 52: Status: Therapeutic Leukaemia Antibody
Status: Therapeutic Leukaemia Antibody * Effective in models of leukaemia « Antibody modified for human therapeutic use * CHO cell line scale up completed * Safety determined in primate toxicity studies * IND filing completed * Phase | clinical safety trial in AML patients aimed for 2007
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Slide 54: GM-CSFR — Rheumatoid Arthritis
GM-CSFR — Rheumatoid Arthritis Rheumatoid Arthritis (RA) * Chronic inflammatory disease of the joints «2.4 million treatable RA patients in the US (2006) + First line therapies include DMARDS such as methotrexate - 33-49% achieve ACR50 * Biological DMARDS - anti-TNF’s (Enbrel, Remicade, Humira) - 50
Slide 55: GM-CSFR — Rheumatoid Arthritis
GM-CSFR — Rheumatoid Arthritis GM-CSF and rheumatoid arthritis In animal models of RA * GM-CSF antibodies inhibit disease E - inflammation and cartilage destruction 5 - TNFa and IL-18 levels : + Animals genetically modified to lack GM-CSF 3 are resistant to the development of RA ‘ 3 « GM-CSF adminis
Slide 56: GM-CSFR — Rheumatoid Arthritis
GM-CSFR — Rheumatoid Arthritis A GM-CSFR antibody for the treatment of RA + Zenyth holds granted target related IP * Partnered with Cambridge Antibody Technology (Dec 01) * CSL and CAT to share costs of drug development * CAT Phage Display technology to generate human antibodies * An optimised lead
Slide 57: GM-CSFR — Rheumatoid Arthritis
GM-CSFR — Rheumatoid Arthritis CAM-3001 is a potent inhibitor of the response to GM-CSF in non-human primates WBC counts 405 PBS == 1mg/kg =~ 10mg/kg J 304 —=30mg/kg = Gal < = 20+ Qo m = 104 0. T T T Ai2 -2hr /+0.5hr +4hr D2 «D3 «|D4 DG Leukocyte Increase in numbers of margination circulating leukoc
Slide 58: GM-CSFR — Rheumatoid Arthritis
GM-CSFR — Rheumatoid Arthritis CAM-3001 — a GM-CSFR antibody for the treatment of RA * Antibody generation and optimisation completed * Cell-line development / manufacturing in progress * In vivo confirmation of antagonist activity completed * Formal preclinical toxicology in progress * Phase | clin
Slide 59: IL-13R — Asthma
IL-13R — Asthma Asthma * Chronic inflammatory disease of the lungs * Affects 20 million people in the US (2005), 5000 deaths annually * First line therapies include B,-agonists and inhaled corticosteroids « New therapies - leukotriene receptor antagonists (Singulair) - biologicals (Xolair) « Market
Slide 60: IL-13R — Asthma
IL-13R — Asthma IL-13 and asthma In animal models of asthma * IL-13 antagonists inhibit disease - eosinophilic inflammation - airways hyperresponsiveness - mucus hypersecretion * Animals genetically modified to lack IL-13 are resistant to the development of asthma- like pathology From Wills-Karp et
Slide 61: IL-13R — Asthma
IL-13R — Asthma An IL-13R antibody for the treatment of asthma + Zenyth holds target related IP (WEHI, CRC-CGF) * Licensed to Merck and Co., Inc in June 2003 « Zenyth / Medarex license agreement, May 2003 * An optimised lead antibody has been generated and progressed into development « Further precl
Slide 62: IL-13R — Asthma
IL-13R — Asthma Antibodies directed against IL-13Ra1 are potent inhibitors of IL-13 activity IL-13 activity assay 4.2 a a rs a & = 1 a a a < Ss 2 oe o Qo & 08 2 —e Mouse antibody 6 Boa —e- Therapeutic antibody candidate 1 Zo —— Therapeutic antibody candidate 2 02 *® Control Ab ¢ SE LE RELL LA 1000 1
Slide 63: IL-13R — Asthma
IL-13R — Asthma An IL-13R antibody for the treatment of asthma « Antibody generated and optimised * Cell-line development / manufacturing underway * Preclinical development in progress
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Slide 65: R&D Portfolio
R&D Portfolio Research Pre-clinical | Phase | | Phase li Phase lil Registration | Phase IV 1 Ll =m Life Cycle =m Management | i H H i =m t H 1 t t t i Market Development New Product Developrnient