CSL Ltd. — Board/Management Information 2007

Dec 12, 2007

R&D Briefing

December 13, 2007

Agenda December 2007 R&D Briefing

Welcome Introduction and highlights

Mark Dehring Andrew Cuthbertson

• Strategy, portfolio and budget mix ISCOMATRIX[®] Adjuvant

Influenza vaccine portfolio Plasma Products Q&A

Simon Green

Tea break

Recombinant Protein Portfolio Pre-clinical Projects • CSL360 for acute myeloid leukemia Research Projects

• Long acting coagulation factors Summary highlights, Q&A and wrap up

Andrew Cuthbertson Russell Basser Andrew Cuthbertson Simon Green Andrew Cuthbertson

R&D Integral to Company Strategy

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R&D Core Capabilities

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Plasma Therapeutics
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ISCOMATRIX [®] Adjuvant
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Vaccines
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Recombinant Proteins
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Global R&D: Integrated R&D Facilities

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650 employees worldwide
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R&D Investment Growth in new product and market development

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FY2008
~$220m
$191
FY2005 FY2006 FY2007
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Global Research & Development Pipeline December 067

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CSL718 Humate ® P
SCIG 20%
Privigen® Zemaira ® US
IVIG 10%
GARDASIL®
Berinert ® Rhophylac ® ITP
US
Zemaira® EU Beriplex ® EU
Afluria ® China
Afluria ® US
Afluria/Enzira® EU
Rec coag factors Vaccines– Merck CSL111
Vaccines– Merck reconstituted HDL
Novel plasma
proteins Partnered Vaccine
CSL412 Programs
Vaccines– Merck ISCOMATRIX® Flu
Vaccines – WyethVaccines– Wyeth CSL444
Pandemic
Beta common ISCOMATRIX® Flu
(Bion1/2)
CAM3001 CSL401
GM-CSFR - Pandemic Flu
CAT/AZ
Discovery projects
MK6105 IL-13R
Merck
CSL360 for AML
Core Capabilities Plasma Therapeutics Vaccines ISCOMATRIX® Adjuvant Recombinant Proteins
Partnered Projects
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GARDASIL®

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Driving Continued Growth Through Life Cycle Management
Second
Generation
HPV Vaccine
Stage Four
�
9-26 Year Old Males
Stage Three
�Adult Women Through Age 45
Stage Two
�
Vaginal Cancer, Vulvar Cancer
�Immune Memory
�
Cross Protection
Stage One – Core Phase III Program in 9-26 Year Old Females
�
Cervical Cancer
�
Genital Warts
�
CIN 1-III, VIN/VAIN II, III
Time
From Merck & Co presentation Dec 11, 2007
Cumulative Market Penetration
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ISCOMATRIX[®] Adjuvant Technology

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ISCOMATRIX[®] Adjuvant

• Proprietary biological adjuvant for use in vaccines

• Complex of ISCOPREP[®] saponin, cholesterol and phospholipid

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ISCOMATRIX[®] Adjuvant has an Integrated Mechanism of Action

• Delivery

• ~40nm particle

• Accelerated and long-lived antigen presentation

• Immunomodulation

• ISCOPREP[®] saponin

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• Cytokines/chemokines

• Recruit and activate immune cells

Manufacture of ISCOMATRIX[®] Adjuvant Optimised and at Industrial Scale

• Developed robust processes focussed on key characteristics

• Kankakee, USA

• ISCOPREP[®] Saponin

• Pilot scale

• Commercial scale

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• ISCOMATRIX[®] Adjuvant

• Commercial scale

• Routine GMP manufacture

Merck & Co. Inc. Continues to Show Confidence in ISCOMATRIX[®] Adjuvant for Vaccine Development Programs

• Aug05/Dec06 agreements

• Dec07 – 2 new licences added

• Upfront payment and milestones

• Royalties on products

• Distribution rights for Australia

• Exclusive supply of ISCOMATRIX[®] adjuvant

• Clinical programs continuing

Influenza Vaccine Program

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Influenza

• Manufacturing influenza vaccine since 1968

• Largest supplier in the Southern Hemisphere

• Doubling capacity to 40 million doses per season

• Bulk antigen supplied for vaccines sold in 24 countries

• Registered in 18 countries

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Global Influenza Vaccine Program

• Expand influenza business

• Licensure in Germany and Ireland

  • On track to launch in 2008

• Regulatory dossier submitted to enable launch in China in 2008

• Competitive advantages

• Global pre-filled syringe capacity

• Thiomersal free vaccine

United States

• US licensure

• BLA approval for Afluria[®] on 28 Sept 07

• Product launched October 07

• Post-marketing clinical commitments

• Clinical Endpoint Study (Aus/NZ 2008)

• At-risk Population Study (US 2008)

• Paediatric Population (Aus/US 2009)

Influenza ISCOMATRIX[®] Vaccine

+

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Global presence & expertise

Proprietary ISCOMATRIX[®] adjuvant & expertise

• Reduction of incidence of influenza-associated illness and mortality in people aged 65yrs and older

• Phase IIa clinical study well advanced. Results in 1H 08.

Pandemic Vaccine Development

• Testing human immune response to avian influenza vaccine

• 2 x 30μg doses of vaccine and AlPO4 required

• Persistence of antibody & strong booster response at 6 months

  • 18-64 and >65yrs

• Safety and tolerability similar to seasonal flu vaccine

• Core Pandemic Dossier submitted to TGA April 07

• Paediatric data expected early 2008

• Registration of prototype vaccine expected April 08

Plasma Products Portfolio

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Profitable Litre Objective for Margin Expansion

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New markets
Wound
Healing New indications
Beriplex [®] P
Fibrin-
ogen Specialty Berinert [®] P
Zemaira [®]
products
FIX Haemocomplettan [®] P
Beriplex
API
Inhibitors Privigen [®]
SCIG
Factor VIIIs
Rhophylac
Cytogam
Immunoglobulins Humate P [®]
Albumin
Litres PEQ
Margin growth
Revenue per litre
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Immunology - Liquid IVIG

Highlights

• US Approval in July 07

• EMEA submission, Jan 07

Compelling Features

• Excellent stability profile - 24 month, room temperature

• Improved production yield over time

Annual Capacity

• 3 million grams currently available

• Additional 10 million gram capacity available 1H cal. 2009

• Further capacity proposed for 2011

Immunology – Liquid SCIG

Vivaglobin®

• 16% liquid formulation

• Successfully marketed in 20 EU countries, USA and Canada for PID

• First subcutaneous product licensed in the USA

IgPro20: 2[nd] Generation Product

• 20% liquid formulation

• High yielding chromatography process

• Phase III clinical trial status

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• USA: recruitment complete. 50% infusions done

• Europe: recruitment initiated

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• Indicated for Haemolytic Disease of the Newborn

• Marketing authorisation received in the USA in April 07 for a new clinical indication “ITP”

Haemophilia

Humate P[®]

• Indicated for patients with FVIII and vWD deficiency

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Improvement of patient convenience

• Needless transfer device

• Reduction of infusion volume by 50%

• 24 month shelf life at room temperature

Clinical

• -Surgical label for vWD approved by FDA April 07

Specialty Products – Market Expansion

Beriplex[®] P/N – Market expansion

• Indicated for acquired bleeding deficiency

• Expansion into 12 new EU European markets

• Positive results from phase III clinical trial.

• Regulatory submission June 07. Approval Q1, 08

• Expansion into US market

• IND submission June 07

• Initiation of clinical program, 2008

Berinert[®] P

• C1 esterase inhibitor indicated hereditary angioedema

• Positive phase III clinical trial results announced Dec 07

Specialty Products – Market Expansion

Zemaira[®]

• Indicated for Alpha1 Proteinase Inhibitory Deficiency

• FDA Phase IV post approval commitment

• Clinical data to support European registration

Haemocomplettan[®] P (Fibrinogen)

• Indicated for congenital fibrinogen deficiency

• Market expansion in Europe and USA

• IND submission Nov 06

• Orphan drug application submitted June 07

• Clinical program underway. Recruitment 50% completed

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Q&A

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Break

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Recombinant Protein Portfolio Pre-clinical / early clinical projects Research Projects

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Pre-clinical / Early Clinical Projects

• “Cytokine” rMAbs

• Partnered projects IL13R and GM-CSFR

• CSL 360 (TLA) for leukemia: type of product we can develop

• Celltrion agreement

IL-13R – Asthma

• Market opportunity –

severe persistent asthma (5-10%)

• IL-13 antagonists inhibit disease

• eosinophilic inflammation

• airway hyperresponsiveness

• mucus hypersecretion

• Licensed to Merck

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normal lung
untreated
anti-IL-13 treated
From Wills-Karp et al .
1998
Science 282:2258
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GM-CSFR – Rheumatoid Arthritis

• CAM-3001 licensed to MedImmune (AZ)

• Phase I clinical study commenced Dec 2007

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CSL360 for acute myeloid leukemia

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What is Acute Myeloid Leukemia?

• Cancer of immature blood cells

• Patients die of insufficient normal blood cells - infection, bleeding

• US Incidence - 10,500 per year

• Outcome depends on number of factors

• < 50yrs old: 5yr survival 30-40%

• 60yrs old: 1yr survival 10-20%

• No major changes in treatment for last 20 years

• Based on aggressive chemotherapy

• Sometimes bone marrow transplantation

• Otherwise palliative (maintaining best quality of life)

15 years of Scientific Evolution: the Development of Normal Blood & Leukemia is Alike

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LSC
CD34 [+] , CD38 [–]
CD123 [+] CD123 [–]
Huntly, Nature (2003)
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Targeting Cancer Stem Cells in Leukemia

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CSL360 is an Antibody that Neutralises the Activity of CD123

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Evidence that CSL360 Might be an Effective New Treatment (1)

Experiment 1 Control Richard Lock, ASH 2007, Abstract #161

Evidence that CSL360 Might be an Effective New Treatment (2)

Experiment 2 Control Richard Lock, ASH 2007, Abstract #161

Future of CSL360

• Phase I clinical study ongoing in Australia

• Phase II studies planned in AML if CSL360 safe and biologically active in patients

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Research Projects

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Examples of CSL Research

• Recombinant coagulation factors

• Anti-cytokine rMAbs

• Alzheimer’s Disease

• Adjuvant technology

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Recombinant Coagulation Factors with Albumin Fusion Technology

Half-life Improvement for Coagulation Products

Products with improved half-life will be beneficial to patients

• Less frequent injections

• Improved compliance

• May enable prophylaxis

Numerous technologies to extend half-life of proteins

• Sustained delivery

• Chemical modification

• Genetic mutation

• Fusion with carrier proteins (Fc fusion, Albumin)

Albumin as a Carrier Protein

• Albumin has a naturally long half-life (~20 days)

• Highly abundant protein

• Molecular structure is known

• Proof of principle data for fusion proteins

Coagulation factor Albumin + short half-life long half-life

Albumin fusion = Albumin half-life extension

rFVIIa - Albumin Fusion Protein

• Albumin fused to the C-terminus of FVII

• Flexible glycine-serine linker

• Expression in mammalian cell culture

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FVIIa linker Albumin
•
Proof of principle research data presented by
Schulte et al, at the American Society of Hematology
49 [th] Annual Meeting and Exposition. Dec 2007.
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Improved Half-life for rFVIIa - Albumin Fusion

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Pharmacokinetic data in rats
100
10
1
0,1
0 2 4 6 8 10 12 14 16 18 20 22 24
Time [hours]
Albumin
rFVIIa-FP
NovoSevenrFVIIa wt
% of initial dose
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• 6 to 9 fold improvement in half-life
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Novozymes Biopharma & CSL Behring

• CSL Behring has exclusive rights to the Albumin Fusion Technology from Novozymes Biopharma for selected plasma coagulation factors. Patent protection until 2021

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• CSL research program has generated “own” IP for various product candidates and molecular constructs. Patent applications filed.

Alzheimer’s Disease

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Brain Changes in Alzheimer‘s Disease

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• Shrinkage
cortex & hippocampus
• Large ventricles
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Global Research & Development Pipeline December 07

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CSL718 Humate ® P
SCIG 20%
Zemaira ® US
Privigen®
IVIG 10%
GARDASIL®
Berinert ® Rhophylac ® ITP
US
Zemaira® EU Beriplex ® EU
Afluria ® China
Afluria ® US
Afluria/Enzira® EU
Rec coag factors Rec coag factors Vaccines– Merck
Vaccines– Merck
Novel plasma
Vaccines– Wyeth
proteins Partnered Vaccine
CSL111
Programs
Vaccines– Merck reconstituted HDL
Vaccines – Wyeth CSL444 CSL412
Pandemic ISCOMATRIX® Flu
Beta common ISCOMATRIX® Flu
(Bion1/2)
CAM3001 CSL401
GM-CSFR - Pandemic Flu
CAT/AZ
Discovery projects
MK6105 IL-13R
Merck
CSL360 for AML
Core Capabilities Plasma Therapeutics Vaccines ISCOMATRIX® Adjuvant Recombinant Proteins
Partnered Projects
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Q&A

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