CSL Ltd. — Investor Presentation 2006

Dec 13, 2006

RADISTANTO

December 14, 2006

Agenda December 2006 R&D Briefing

• Welcome
• Introduction and highlights
• Strategy, portfolio overview and budget mix
• ISCOMATRIX^® Adjuvant
• Influenza vaccine portfolio

• $\cdot$ Q&A

• Tea break

• Plasma Products
• Recombinant Monoclonal Antibodies
• $-$ Introduction
• Therapeutic Leukaemia Antibody
• Zenyth portfolio
• Summary highlights, Q&A and wrap up

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Mark Dehring Andrew Cuthbertson Andrew Cuthbertson Andrea Douglas

Simon Green

Andrew Cuthbertson

Andrew Nash

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ANDREW OUTHBERTSON

. . . . . . . . . . . . . . . . . . .

R&D Highlights - Investment

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R&D Portfolio - 1

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R&D Portfollo - 2

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......................................

R&D Portfolio - 3

Project	Research	Pre-Clin	Phase I	Phase II	Phase III	Registration
TLA		en 1979. Ngjarje
IL-13Ra1 (Merck)		e de la facta de la facta de la facta de la facta de la facta de la facta de la facta de la facta de la facta La facta de la facta de la facta de la facta de la facta de la facta de la facta de la facta de la facta de la
GM-CSFRa (CATIAZ)
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VEGF-8
Other antibodies
Other rec proteins
TED	Millige

HGHLIGHTS

• 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

Merck's HPV GARDASIL®

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• http://www.merck.com/newsroom/webcast/ $\bullet$
• Accelerated approval in US, EU and 18 other markets for 9-26 $\bullet$
• Broad indication for cervical cancer, genital warts and related HPV $\bullet$ diseases
• Unanimous ACIP recommendation in the US $\bullet$
• Broad vaccination endorsement by professional societies $\bullet$
• US State efforts to achieve high immunization rates $\bullet$
• Reimbursed by plans covering 94% managed care lives $\bullet$
• States/cities covering 80% of public sector under Vaccines for $\bullet$ Children program
• Widespread scientific presentations/publications of clinical evidence $\bullet$

Merck's HPV GARDASIL®

• 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
• Plan to capitalize on lead to market for other populations in addition to launch market (females 9-26)
• Estimates of market sizes:
  • Launch market females (9-26) 118M;
  • Females (9-45) 264M;

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• Females (9-45) plus Males (9-24) cumulative cohort with sequenced roll out 374M.

GARDASIL®: Selected ongoing clinical programs

• 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

GARDASIL®: Competitive Differentiation

• First and only HPV vaccine on the market
• Proven cervical cancer protection

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• 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 memory

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ISCOMATRIX® adjuvant meets all criteria for inclusion in new human vaccines

• Immunomodulator and antigen delivery
• Safe and immunogenic in humans
• Long lasting antibody and T cell responses
• Dose sparing capability
• "Industrialised"

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Multiple value drivers for ISCOMATRIX® adjuvant

· Licenses

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• -Upfronts
• -Milestones
• -Royalties
• $\blacksquare$ Patents
• Know-how
• Worldwide supplier
• · Internal vaccine development programs

Wyeth to use ISCOMATRIX® adjuvant

• License and option agreement
• Number of fields
• Upfronts and milestones >US\$90m
• Product royalties
• Exclusive supply

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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

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• Two clinical programs have been initiated

ISCOMATRIX® adjuvant being manufactured at commercial scale at Kankakee

• Facilities and expertise
• ISCOPREP® saponin
• -pilot scale

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• -commercial scale
• ISCOMATRIX^® adjuvant
• -commercial scale
  • "process being tech transferred

Initianza Vaccine Program

14 December 2006

Global Influenza Vaccine Business

• Manufactured influenza vaccine since 1968
• Leading provider and sole manufacturer of flu vaccine in Southern Hemisphere

Buffer preparation area in CSL's new state-of-the-art influenza vaccine centre

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• CSL flu vaccines are licensed and sold in 16 countries worldwide

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Influenza Vaccine Strategy

Continue at the forefront of Pandemic Vaccine development

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Increase FDA GMP manufacturing capacity to meet global demand

Increased share of key global markets

Improved Influenza Vaccines using CSL technological expertise and know-how

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Influenza Vaccine Strategy

Continue at the forefront of Pandemic Vaccine development

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Increase FDA GMP manufacturing Cabality to meal global demand

Increased share of key global markets

Improved Influenza Vaccines using CSL technological expertise and know-how

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Influenza Vaccine Manufacturing Capacity

• Modern egg processing facility completed in 2004
• \$80m investment to double vaccine capacity
• -Duplication of existing facility
• -NH capacity of ~40m doses

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Egg harvesting machine in CSL's new state-of-the-art influenza vaccine centre

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Influenza Vaccine Strategy

Continue at the forefront of Pandemic Vaccine development

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Increase FDA GMP manufacturing Cabacity to meet global demand

Indreased share of key global markets

Improved Influenza Vaccines using CSL technological expertise and know-how

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Global Influenza Vaccine Program

• Expand flu business

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• 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

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United States

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• IND filed April 2006
• Pivotal Clinical Trial completed
• 1359 subjects recruited
• Immunogenicity criteria met

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• BLA submission end Q1 2007
• Launch 2007/08 winter season (contingent upon regulatory approval)

Influenza Vaccine Strategy

Continue at the forefront of Pandemic Vaccine development

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Increase FDA GMP manufacturing capacity to meet global demand

Increased share of key global markets

Improved Influenza Vaccines USING CSL technological expertise and know-how

CSĽ

Annual Flu-Related Deaths - US

Current Flu Vaccines Less Effective in Elderly

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Influenza ISCOMATRIX^® Vaccine

Global presence & expertise

Proprietary ISCOMATRIX® adjuvant & expertise

• Reduction of incidence of influenza-associated illness and mortality in people aged 65yrs and older
• Commence clinical program Q3 2007

Influenza Vaccine Strategy

Continue at the forefront of Pandemic Vaccine development

ostoniaisistististikk^oi

Increase FDA GMP manufacturing capacity to meet global demand

Increased share of key global markets

Improved Influenza Vaccines using CSL technological expertise and know-how

CSĽ

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

Transmission electron micrograph of 2 H5N1 virions. Source: CDC Public Health Image Library.

Pandemic Vaccine Development cont.

• Further trials to support registration of 'prototype' vaccine
• Higher doses of antigen
• Broader population base
• Drivers for approach

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• Generate understanding of immunogenicity and safety of range of antigen doses
• Develop body of data to guide policy decisions

H5N1 Challenge in Ferrets using an ISCOMATRIX® H5N1 Vaccine*

Participants: UniMelb, CSIRO, WHO CC for Influenza, CSL Limited

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ISCOMATRIX^® H5N1 Vaccine

• Potential for:

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• Antigen Sparing
• Increased duration of immune response
• Cross reactivity with other H5N1 clades
• Clinical Development
• Commence clinical program 2007
• Assess range of antigen doses

Influenza Vaccine Program

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• Expansion of business into key global markets
• Evaluation of improved influenza vaccines
• Development of pandemic influenza vaccines

Dr. Simon Green General Manager CSL Behring, GmbH Marburg, Germany

Plasma R&D Centres of Excellence

Marburg GER

Haemophilia Wound Healing Specialty Products

Broadmeadows AUS

Product Support Technical Innovation

Bern CH

Immunoglobulins rHDL.

Kankakee USA

Alpha-1 Proteinase Inh.

King of Prussia USA

US Clinical, Regulatory & Pharmacovigilance

Tokyo JPN

JPN Clinical & Requisition

Immunoglobulins

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

Sandoglobulin^® Liquid 12%

• Successfully marketed in 11 European countries
• Registrations received in Canada & Australia
• BLA review process ongoing
• US focus likely to shift the high yielding chromatographic liquid

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 commenced

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®

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• Cytomegalovirus (CMV) immune globulin
• Acquired from Medimmune, Dec 06
• Prophylaxis against CMV disease associated with transplantation of the kidney, lung, liver, pancreas and heart.

Haemophilia - Humate® P / Haemate® P

Needleless transfer device

Mix-2-Vials successfully launched (Helixate, Beriate & Berinin)

Volume Reduction

Approved in 22 countries

Indication for vWD & Surgery

Humate® P

Interim label claim approved

BLA efficacy supplement submitted, Jun 06

2006

2007

2008

Opportunities for Growth

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Specialty Products - New Markets

Beriplex^® P/N

• Indicated for acquired bleeding deficiency (ie. Warfarin reversal)
• Expansion of European market
• Phase III clinical trial complete
• Regulatory process initiated

Berinert^® P

• C1 esterase inhibitor indicated hereditary angioedema
• Expansion into both USA and EU markets
• Phase III clinical trial ongoing

Zemaira $\mathcal{R}$

• Indicated for Alpha1 Proteinase Inhibitory Deficiency
• FDA Phase IV post approval commitment
• Clinical data to support European registration

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Therapeutic Leukaemia Antibody (TLA)

• · Acute Myeloid Leukemia
• Anaemia, infection, bleeding
• US incidence 10,500
• 18% 5 year survival, often only months
• First line therapy chemo +/- BMT
• 80% relapse / refractory
• Limited treatment options

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• IP from Australian academic collaborator
• Target is differentially expressed between leukaemia and normal blood cells
• Correlation with poor outcome
• Target common to all types of AML
• Parent antibody effective in disease models
• Human compatible antibody ready for AML patient clinical trial in 2007

TLA Therapeutic Concept

Engraftment: AML stem cells initiate human leukemia when transplanted into irradiated NOD/SCID mice. Quantitative assay for AML stem cells.

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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

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• Phase I clinical safety trial in AML patients aimed for 2007

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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

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• anti-TNF's (Enbrel, Remicade, Humira)
• $-50\%$ achieve ACR50
• Market opportunity anti-TNF inadequate responders

GM-CSF and rheumatoid arthritis

In animal models of RA

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• GM-CSF antibodies inhibit disease
• inflammation and cartilage destruction
• TNF $\alpha$ and IL-1 $\beta$ levels
• Animals genetically modified to lack GM-CSF are resistant to the development of RA
• GM-CSF administration exacerbates RA

A GM-CSFR antibody for the treatment of RA

• Zenyth holds granted target related IP

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• 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 antibody has progressed into manufacturing and preclinical development (CAM-3001)

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CAM-3001 is a potent inhibitor of the response to GM-CSF in non-human primates

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

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• Phase I clinical studies planned to commence mid-2007

Asthma

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• Chronic inflammatory disease of the lungs
• Affects 20 million people in the US (2005), 5000 deaths annually
• First line therapies include $\beta_2$ -agonists and inhaled corticosteroids
• New therapies
• leukotriene receptor antagonists (Singulair)
• biologicals (Xolair)
• Market opportunity severe persistent asthma (5-10%)

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 asthmalike pathology
• IL-13 administration induces asthma-like pathology

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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 preclinical and clinical milestone payments plus royalties
• Future drug development costs to be met by Merck

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Antibodies directed against IL-13R $\alpha$ 1 are potent inhibitors of IL-13 activity

An IL-13R antibody for the treatment of asthma

• Antibody generated and optimised
• Cell-line development / manufacturing underway

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• Preclinical development in progress

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SUMARY AREA

ANDREW OUTHBERTSON

R&D Portfolio

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