R&D Briefing

December, 2005

Agenda 2006 R&D Briefing

Welcome 鐖
Introduction and Biotech Project Update 鏭
Strategy, portfolio and budget mix
HPV $\frac{1}{2}$
$-$ rHDL: ACS
Pandemic influenza vaccine development 錣
Tea break 錣
Plasma Products 譢
ISCOMATRIX^® Adjuvant 錣
Recombinant Monoclonal Antibodies 錣
Introduction
Therapeutic Leukaemia Antibody
Q&A and wrap up

Mark Dehring Andrew Cuthbertson

Jeff Davies Debbie Drane

Andrew Cuthbertson

David Gearing

Andrew Cuthbertson

The Phased Development of CSL Limited

Rindisernaceuticals for l

Developing the Right R&D Portfolio

Investment strategy
Staff and structure
Budget mix

Insightful R&D Investment

CSL HPV Franchise

Merck's HPV vaccine Gardasil
submitted to FDA for US approval December 1st, 2005
submitted MAA in Europe

submitted TGA in Australia

Breakthrough vaccine prevents cervical cancer, the second leading cause of death in women worldwide

■ CSL's HPV therapeutic entering Phase 2 trial

Cervical Cancer: A Serious Global Burden

Slides from Merck's Annual Business Briefing: Dec 15, 2005

Globally 630 million people, including 20 million Americans, are 鑿 currently infected with human papillomavirus (HPV)
Infection with certain types of HPV is the cause of cervical cancer 鑿
HPV infection also causes other cancers, genital warts and cervical 饠 dysplasia
HPV causes a high level of personal and financial burden 飈
HPV-related disease, including screening, follow-up and treatment costs about \$5 billion per year in the U.S.

Significant Physician and Consumer Interest in HPV Vaccine

Strong Physician Intent to Vaccinate...

and Consumer Vaccine Acceptance

Market research conducted by CDC in September 2005 and presented at October 2005 ACIP meeting

Boehner CW, et al. Viral Sexually Transmitted Disease Acceptability Among College Students. Sexually Transmitted Diseases 2003, Kahn JA, et al. Attitudes about human papillomavirus vaccine in young women. International Journal of STD & AIDS 2003; 14:300 - 306, Parent Quantitative Market Research Project: November 2003

Ringframaceuticals for L

۱ITA

Gardasil^® is Expected to be the First HPV Vaccine to Market with Broadest Coverage

Represents a significant medical breakthrough in cancer prevention 鐖
The only investigational cancer vaccine for the prevention of cervical 鐖 cancer, cervical dysplasia and genital warts
Broadest coverage will be provided through a quadrivalent vaccine 譏
Expected to be the first cervical cancer vaccine worldwide 飈
Submitted to FDA for U.S. approval on December 1, 2005; 鑿 submissions in other markets will closely follow

Large Potential Vaccination Cohort

Leverage first mover advantage to capture large appropriate catch-up cohort
Future growth will be fueled by indications for additional populations

Per capita $GNI$ \$9,385; developing markets to be addressed via partnerships

Phase III Studies for Gardasil^® with 25,000 Participants Demonstrated 100% Efficacy

Gardasil® prevented 100% of HPV 16/18/6/11-related CIN, AIS or EGL in women not yet infected with HPV 16/18 and/or 6/11 at enrollment

Endpoint	YEMIE OF KA	PERSI O OFFICIES	Efficacy (%)
CIN 1, 2/3, AIS related to HPV 16/18/6/11	[6]	$\sim$ $\sim$	100
CIN $2/3$ or AIS related to HPV 16/18	61	$\sim$	100
EGL related to HPV 6/11		250)	100

Participants in 33 countries in all regions of the world

Prepared to Maximize Launch of Gardasil^®

Gardasil^® represents a major breakthrough in cancer prevention 錣
Benefits a large vaccination cohort and addresses an important unmet 錣 medical need
High global burden raises significant physician and consumer interest in a 錣 vaccine
Merck is poised to rapidly convert widespread interest and excitement into 錣 appropriate routine vaccination globally
Implementation of strategy will contribute to public health and to Merck's 鐖 performance
Potential future indications will drive continued growth

Therapy of Existing Lesions Enlarges CSL's HPV Franchise

CSL HPV Therapeutic

Not based on VLPs
Wholly owned project
E6E7 plus ISCOMATRIX^® adjuvant
Issued U.S. patent
On target for phase 2 study in AIN therapy to commence Q2 2006

CSL Pandemic Influenza Vaccine Development

Current Pandemic Clinical Trial

EXECUTE: Testing human immune response to avian flu vaccine candidate

Testing effective doses which can be used practically to protect Australian population
one or two doses
$-7.5$ and 15 mcg antigen
effect traditional immune stimulant

Decision Tree Following February Pandemic Vaccine Clinical Data

Best case

• Middle ground

■ Worst case

Research Evaluation: ISCOMATRIX^® - potent immunostimulant

Dose-sparing
More effective
Plant capacity $+$ dose-sparing $=$ more rapid response to pandemic threat

Reconstituted High Density Lipoprotein Clinical Studies

rHDL: Acute Coronary Syndromes

ACS (ERASE Study)
sites actively recruiting study progressing well
aiming for initial data to be available Q3 2006

Plasma Products R&D

Jeff Davies General Manager, CSL Bioplasma

Plasma R&D Centres of Excellence

Marburg, Germany 纙
Coaquiation, speciality products, wound healing
Bern, Switzerland 纙
Immunoglobulins, reconstituted HDL
Melbourne, Australia 丝
Product support, new separation and filtration technologies
Kankakee & King of Prussia, USA ▓
Alpha-1 Proteinase inhibitor, fractionation, US clinical trials

Opportunities for Growth

Plasma Volume

Benefits of Integration for Key Products

Improved Operational Efficiencies

Improved Product Features

Strengthening our IgG Portfolio

Sandoglobulin ® (Lyophilized, IV) Carimune ®

Vivaglobin ® (16%, Sub-cutaneous)

Sandoglobulin ® Liquid $(12\%, IV)$

Chromatographi $(10\%, IV)$

Strengthening our IgG Portfolio

Requisions review timeframe may take conciderable time and is difficult to predict

Rinditermereuticels for L

Coagulation Portfolio: Humate/Haemate P

Plasma Products

ZLB Behring Products

Haemate/Humate-P

CSL Bioplasma Products

Biostate

PTX-HT

Thrombotrol-VF

MonoFIX-VF

Maximising Profitable Litres

Haemocomplettan (fibrinogen) 羉
congenital deficiency
$-$ new markets/indications

$2₂$

Haemocomplettan^® P

Active ingredient: Human Fibrinogen

Fibrogammin (FXIII) n.
Ngj
$-$ congenital deficiency
$-$ new markets/indications

250 U F XIII Fibrogammin® P

Active ingredient: Human plasma coagulation factor XIII

Berinert P (C1 Esterase Inhibitor)

Clinical trial design for treatment of acute episodes 纙 approved by the FDA and trial commenced
Competitive advantage 鑼
half life
multifactorial action
well tolerated

Alpha-1-Proteinase Inhibitor Deficiency

Expanded market in USA
Investigating expanded use internationally
Clinical trial (Phase IV) commenced
Kankakee output to increase in 2006

Integration Complete and Projects Well Advanced

Immunoglobulin manufacturing delivering on yield 纙 projections (synergy case)
Immunoglobulin portfolio improvements advanced
Coaquiation product improvements delivered
Specialty product R&D programs advanced

ISCOMATRIX^® Adjuvant

Debbie Drane Program Leader

Vaccines and Adjuvants

Vaccines
traditional
$-$ recombinant antigens
$-$ therapeutic
Adjuvants
many in research
few in development

Virus particle

Adjuvant Mechanisms: "Help" Immune Response

ISCOMATRIX^® adjuvant has multiple functions

ISCOMATRIX® Adjuvant: Uniquely Positioned

Technology	Immuno- stimulatory	Delivery	7.15	(QHI)
ISCOMATRIX® adjuvant mande de distantivate de de de de de de de de de de de	๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛	milistis die de de de de de de de de de de de la de de de de de de de de de de de de de	Codedededededededededededede	ાઈ કરોની કરી કરતી કરતી કરતી કરી કરી કરી કરી કરી કરી કરી કરી કરી કર
Aluminium ๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛ ๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛
MF59
,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, MPL				的复数复数英国的复数英国的复数英国的变形变形变形变形变形变形变形变形变形变形变形变形变形变形变形变形变形变形变形
๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛๛ Virosomes
,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, CpG
QS21

ISCOMATRIX^® Adjuvant Meets All Criteria

Nooks" like virus

Antibody and CTL responses in animal models and humans
Long lasting responses
Dose sparing capability
Good safety profile in humans
Industrialised

Development of Industrialised Manufacturing Processes

Optimised proprietary processes
$-$ ISCOPREP^® saponin (critical component)
ISCOMATRIX^® adjuvant
Processes consistent, robust, scalable
Product stable and characterised an di Salaman.
Kabupatèn Sulawan Kabupatèn Kabupatèn Kabupatèn Kabupatèn Kabupatèn Kabupatèn Kabupatèn Kabupatèn Kabupatèn K
Pilot facilities in Melbourne

Commercialisation Strategy Drives Long Term Value

Internal projects
Example 20 Increase by application to major vaccine manufacturers
TP
patents, know how, trademarks
Worldwide supplier of ISCOMATRIX^® adjuvant

ISCOMATRIX^® Adjuvant: Attractive Package for Partners

Rinoftermaceuticals for I

ISCOMATRIX^® Adjuvant: Commercialised

Unique position
• IP protected
Major partners 獵
Commercial manufacture 繈
Kankakee (Chicago)
- ^■ facilities
- * process expertise

TLA Recombinant Antibody

David Gearing PhD Director, Research

Recombinant Antibodies

Significant part of biotech sector
Many profitable drugs en de la population de la population de la population de la population de la population de la population de la
La population de la population de la population de la population de la population de la population de la popul
Good success rate
Proteins

Selected Recombinant Antibodies

ReoPro^® 蘯
Synagis^® 灐
OrthocloneOKT3^® 纝
Zenapax^® 灐
Remicade^® 灐
Humira^® 灐
Xolair^® 蘯
Raptiva® 灐
Rituxan^® 灐
Herceptin^® 灐
Mylotarg^® 灐
Campath- $1H^\circledR$ 灐
Avastin^® 灐
Erbitux^® 灐
Zevalin^® 灐
Bexxar^® 灐

Haemostasis Infection Immunological Immunological Immunological Immunological Immunological Immunological Oncological Oncological Oncological Oncological Oncological Oncological Oncological Oncological