CSL Ltd. — Investor Presentation 2003

Dec 15, 2003

CSL Limited R&D BRIEFING DECEMBER 16, 2003

De Andrew Guthbertson Assoc. Professor Russell Basser Professor Stephen Davis

CSL Limited R&D BRIEEING DECEMBER 16, 2003 TIMETABLE

(845am) REGISTRATION

• (9am) WELCOME AND HOUSEKEEPING
• (905am) INTRODUCTION
• (SRSHIT) STROKE/QRA nerang
• (1010am) BREAK
  • (1030an) HPV

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• (1040am) ISCOMATRIX® Acquvant
• (1135cm) BRIEF UPDATES
• (12 noon) Q&A
• (1215pm) LUNCH

INTRODUCTION

• o We make high value human proteins - plasma/recombinant E life-dycle management/new products
• O Innovation for future growth o Focussed R&D spend Unique competitive advantages a. Team is high calibre

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R&D INVESTMENT STRATEGY

o Key competitive advantages - specialist focus s effective scale

• AU academic partner of choice - CSL reputation attracting talent

Empact of AB - global capability - centres of excellence E Synengies antigipated

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R&D BREADTH AND DEPTH

Four Technology/IP Platforms

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De la provincia de la provincia de la provincia de la provincia de la provincia de la provincia de la provinci

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• Plasma fractionation
• ISCOMATRIX® adjuvant
  • Recombinant antigens Reconforment antibolies

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COMMERCIALLY DRIVEN R&D INVESTMENT PROCESS

PharmaPlan

Strategy & Investment

New Opportunities

Idanificciion Evaluation

Lesine

Project Management

Oparchions Material STATE

Project Review

Parformance

Commercial

sin new emmoni

Analytical Deal Making

R&D PORTFOLIOR BALANCE AND DIVERSITY

HPV Prophylaxis

IP Protected Candidates

• PHDL
• HOV
• STERY TREADY ALEYS

Leverage with funding $\cdot$ HD Adita Darua

Line Extensions

• · IVIG Rhophylac/rAntiD
• 2 Blosfiera
• Thio-free flu

More speculative 5 ESO1 · CRCs

A ANAISS

Malaria

HHDL FOR STROKE

POTENTIAL ADDITIONAL HIGH-VALUE PRODUCT FROM PLASMA

PHDL = RECONSTITUTED HIGH-DENSITY LIPOPROTEIN

LIDLE YOOD CHOLESTEROL"

MOL = GEYAT KATZA hoproid'n partide, chemically and biologically resembling native HDL

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MANUFACTURED FROM DISCARDED FRACTION OF PLASMA

Francisco Company de la company de la company de la company de la company de la company de la compa

plasma

dsard fracture

ADOALDTOTEIN

GEOT!

PHDL IS VERY SAFE & BIOLOGICALLY ACTIVE IN HUMANS

Clinical trials in over 150 people - Very well tolerated

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– No szatols or unorzetetzel stelz-z frzers Potent biological activity demonstrated

Professor Stephen Davis
Royal Melbourne Hospital

WHAT IS STROKE?

O Death of brain tissue o Caused by sudden disruption of blood flow - obstruction due to dot (Ischaenia) 35% - bleeding (hemorrhage) 15% Consequence $\sim$ decity - disability

WHO HAS A STROKE?

o Disease of aging - 70% occur in people more than 65 years old

• Risk factors are the same as for heart disease anangan
  Kabupatèn - Algh blood pressure
• smoking - diabetes - family history - high cholesterol - 611243

THE BURDEN OF STROKE

o 3rd most common cause of death Leading cause of disability - 750,000 strokes per year in USA - 40% people do not regain independence - 20% need institutional care

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Cost in USA = US\$45.4 billion per year

CURRENT MANAGEMENT OF ACUTE STROKE

o "Clot buster" (tPA) - indicated for patients who present within 3 hours of onset of symptoms - currently relevant for 5-10% of patients Blood thinning (aspirin) Care in Stroke Unit Early rehabilitation

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DEATH OF BRAIN TISSUE AFTER STROKE

dead core

minures

penumbra

ROURS

days & weeks

· CORE dies immediately O PENUMBRA IS Stirrotheling green inche des slowly

Dirnagl, Trends Neursei 1999

WHAT HAPPENS IN THE PENUMBRA?

o altered blood flow precipitates processes that ultimately lead to cell death

REDUCING TISSUE DEATH IN THE PENUMBRA

Potential benefits

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• increase independence
• E reduce need for rehabilitation, nursing home

Many drugs tested in clinical trials - none registered - all failed to show barath

WHY HAVE BRAIN PROTECTING DRUGS FAILED TO SHOW BENEFIT?

• O Too little preclinical evidence of activity
• Poor trial design

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Side effects Biological activity too specific

WHY USE AHDL FOR TREATMENT OF ACUTE STROKE?

PHDL REDUCES STROKE DAMAGE IN RATS

Work in 2 laborationies - Howells (Melbourne), Patterno $(N$ doles) 260% reduction in volume of dead brain

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– correlation with physical activity - long lasting protection

With permission: D Howells et al, 2002

PHDL BLOCKS MULTIPLE PROCESSES

INNOVATIVE DESIGN FOR PROOF-OF-CONCEPT CLINICAL TRIAL

• o Novel statistical design to reduce number of pattients required
• $\bullet$ Use of MR imaging to assess size of "infarct" (decd brain)

• reflects likelihood of clinical benefit to partents

• increases confidence of benefit prior to large (expensive) phase 3 trials ÷ validation work close to completion

Ischaemic Penumbra

PWI>DWI mismatch

PROMISE OF 2HDL VALIDATED BY LEADING EXPERTS

o External review of data from - Prof Fisher (Boston) - Prof Buchan (Galgary) - Prof Donnan (Austin Hosp.)

• Prof DOVIS (RMH)

$\rightarrow$ High quality work -> As good or better than any preclinical data they have seen!

PEDL IN STROKE 2004/05

Ongoing preclinical experiments Safety trial in patients with stroke 2004 (Australia) Planning proof-of-concept trial World class Clinical Advisory Board - to provide trial & strategic guidance - Prof Davis, Donnan, Fisher - Prof Lees (Glasgow) - expert in trial design

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MERCK HPV VACCINE

MERCK HUMAN PAPILLOMA VIRUS VACCINE LARGE PHASE ITT PROGRAM ENROLMENT COMPLETE

Phase ULL quadrivalent vaccine program

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• PIPV 16 and 18 associated with most cervical cancer deaths
• HPV 6 and 11 associated with most genital warts cases
• Enrolment in pivotal efficacy trials complete (n=17,800) ana.
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Phase II Proof-of-Concept study with HPV 16 vaccine showed 100% efficacy

Confident that competing IP claims will not delay our HPV Drogram

Submission anticipated 2- 2005

CSL HPV UPDATE

o US patent issued on HPV16 L1 protein o Additional HPV patent granted in Europe Secures US and European royalty revenue to CSL o Exclusive domestic distribution rights

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ISCOMATRIX® ADJUVANT

POTENT STIMULATOR OF THE IWWUNE SYSTEM

WHATTIS ISCOMATRIX® ADJUVANIP

O An adjuvant is part of a vaccine that heightens the immune response to the antigen

ISCOMATRIX® adjuvant is CSL's proprietary Technology

WHY IS ISCOMATRIX® ADJUVANT VALUABLE?

6 Broad IP protection GMP manufacture (quality and scale) 7 O * Broad antibody and cellular responses - Therepy of chronic infections and cancer Reclueed close of chiligen peculiped . Alternate routes of delivery

Enables commercial development of novel Velectines

Terminal

INGREASING OPPORTUNITIES FOR ISCOMATRIX^® ADJUVANT

Dose sparing antigen

Prophylocitic

LIM FILI (MPC)

Broad immune responses antibody and T cell

Prophylactic

HeV (Chiron) Dangue (HBI) Malaria (NEH) FEW (MPC) HPV (MPC) Stabh (MPG) Wasi Nila (HBD)

$HPV$ Therapy $(CSL)$ ESO1 (LICR) HCV (Chiron) HBV (Goley) Cancer (MPC)

Therapetric

Nasal delivery antibody

Prophylectic

EN FILI (MPO)

ITSCOMATRIX® HCV VACCINE

A COMPELLING DEVELOPMENT FOR THE TREATMENT OF HEPATITISG

WHAT IS HEPATITIS C?

o Mike Houghton, George Kuo & Qui-Lim Choo (Chiron) identified the causative agent for Hepartitis C 85% of infected people become chronic en de la provincia de la construcción de la construcción de la construcción de la construcción de la construcc
Construcción de la construcción de la construcción de la construcción de la construcción de la construcción de carriers Tine-bomb - problems evolve over 20: years - carriers have reduced quality of life - liver cirrhosis (25%) ÷ liver cancer

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BURDEN OF HEPATITIS 6 INFECTION

170 million people infected worldwide

• 3 million infected

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USA

– 40,000 new cases per yr

CURRENT MANAGEMENT OF HEPATITIS C

• No treatment if normal liver function If evidence of liver damage - interferon & AbxWirin
• clearance of virus in 40% parients
• substantial stace of feats

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• expensive Liver failure - transplantation (No vaccine to prevent infection)

NEW APPROACHES TO TREATMENT

o Efforts to control infection

• Improvements to current drugs
• Small molecules to block enzymes related to replication
• Gene blockers
• Innune modulators

O Efforts to cure infection - ISCOMATRIX® HCV Vaccine

CSL-CHIRON COLLABORATION

GSL proprietary ISCOMATRIX® adjuvant $\mathsf{O}^{\mathbb{Z}_2}$ * potent stimulation of broad immune response, especially T cells - optimised process of manufacture - registrable

6 Chiron Hepatitis C proteins - direct the immune response

MOBILISING THE IMMUNE SYSTEM WITH A THERAPEUTIC VACCINE

Induce T cell and antibody response to Hep C Clear virus => prevent further liver damage

Options for therapy

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• improve effectiveness of current treatment
• where current treatment is intolerable or doesn't work
• acceptable to chronic carriers

ISCOMATRIX® HCV Vaccine incluces Long Lasting Immunity in Monkeys

Polakos et al. J Immunol 2001

ISCOMATRIX® HCV Vaccine Reduces Viral Infection in Chimps

ISCOMATRIX®HGVVACCINETS SAFE & PRODUCES A POTENT IMMUNE RESPONSE IN HUMANS

• Clinical trial in 30 volunteers 2003 (Adelaide) Very well tolerated
• Potent antibody and cellular responses

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Presented at International Symposium on Viral Hepartitis and Liver Disease in Sydney, April 2003

ISCOMATRIX^® HCV VACCINE 2004/05

O Clinical study in patients with chronic infection, 2004

Further development of chiligens for manufacture

Advisory Board planned for 2004

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ISCOMATRIX® HPV THERAPY FOR ANAL DYSPLASTA & RELATED DISEASES

A PRODUCT FULLY OWNED AND DEVELOPED BY CSI.

WHAT IS THE CSL PRODUCT?

ISCOMATRIX® adjvuvant + human papillomavirus (HPV) fusion protein O Treatment for HPV-related diseases

• precchcerous growths (dysplasta)

WEIPIS

• OTACC

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Essued U.S. patents on all components

ANAL DYSPLASIA - THE DISEASE

Caused by persistent HPV infection - sexually transmitted S Prendfondit - kads to graf cancer Occurs especially in homosexuals and HIV+ D20DI2 180,000 new cases per yr in USA No proven trectment

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LSCOMA TRIX® HPV THERAPY PLANS

Completed clinical trial to define optimal dose & schedule 2003 Clinical study in HEV+ patients to start 2004 Advisory Bogrd meeting planned for 2004

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ISCOMATRIX® ESO1 THERAPY FOR MELANOMA & OTHER CANCERS

A COLLABORATION WITH THE LUDWIG INSTITUTE FOR CANGER RESEARCH

WHAT IS THE CSL PRODUCT?

O ISCOMATRIX^® adjuvant + ESO1 cancer profein

ESOIL Is found on many cancers $-$ inalgnoma $~35\%$ of cases – also: bladder, lung, breast, prostate, others

generalist
Stadt Stadt

WHAT IS THE BURDEN OF MELANOMA?

USA

Personal

• 51,000 new cases per year $-7,300$ deciths Australia

• 8,500 new cases per year - 1000 deaths

ISCOMATRIX® ESOL THERAPY PLANS

O Initial clinical trial results presented at 3 international neethes

Metastatic melanoma clinical study $\overline{\mathbb{C}}$ commenced q4 2003

UPDATE ON REOPEMLAC / PATID

Rhophylac

• mother-baby blood mismatch (HDN) - Immune destruction of platelets (LTP)
• CAGED
• next generation, recombinant product - best data in early human trials
• discussing regulatory strategy
• ongoing development

UPDATE ON HEMOSTATIC DRESSING

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• 6 Key relationship with American Red Gross
• O Development time-line clisrupted by Energency Program"
• Units produced for US literatur.
  Santa Baraton miltiary
• Promising use in Iraq 2003 2000
• 3 Future development will depend on US military funding

REVTEW

6 R&D capacity - experience, integrity, skill-base o Strategically aligned & commercially focussed - rHDL from plasma for stroke commercialisation of ISCOMATREX® products Quality commencial and academic partnerships - HPV vaccine with Merck - HCV development with Chiron - cancer program with Ludwig Institute Benefits of AB acquisition 1999

Key Projects: Value Maintenance

EXTENSION

IVICE

GLINICAL INDICATION

Emmunodeficiencies

Rhophylac HDN

Heemolytic Disease of the Newborn

Rhophylac ITP Blostate: vWD EVIG-GSL/ZLB

Immune Thrombocytopenic Purpura

Von Willebrand Disease (AUS)

Trimunodeficiencies

PIW. GUPA TERES ES BE GU Mena PA ITEI PATHT 2004

DEVELOPMENT

PHASE

PAT 2004

Key Projects - Value Drivers

GLINICAL INDICATION

PRODUCT CANDIDATE

HPV, Merck VLP vaccine ESOLITIMY® THE LIBRACE TWXO HPV E6E7 IMX® HAV TMX® Hemostatic Dressing Topical Eye Delivery Radishiliae FDL

Gentral warts, cancer

Melanoma TATION

ZTAN Herritits

Savare Trauna

Eye disease, ARMD

Sitoka

Party PATE CAR 24 T/TF PAWOO PAU Prediction Przedinica

PHASE

PATOL

DEVELOPMENT