NAT for Blood Banks by Chiron Novartis - A Global Commitment Tony Woo, PhD 29 April 2008

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Agenda

Chiron/Novartis Background

NAT Impact on Global Blood Safety

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19911981 1983 1985 1987 1989 1993 1995 1997 1999

Chiron founded

Hepatitis B antigen

developed

HIV genome cloned and sequenced

Hepatitis C genome

cloned and sequenced

Hepatitis B diagnostic developed

Proleukin® approved in

Europe (kidney cancer)

First bloodtest for

Hepatitis C

Betaseron® (multiple sclerosis)

NAT adopted by Australian Red Cross

Regranex® for skin ulcers

2000

Proleukin® approved

in US

Nucleic acid probe for

Hepatitis B & C

developed

Gen-Probe partnership formed

2001

TOBI® European

launch

Menjugate vaccine

approved in U.K.

Chiron History

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Novartis acquired Chiron on April 19, 2006

New business unit

NovartisVaccines and Diagnostics

A new division of Novartis

New business unit

Blood Testing business today

Potential addition of Molecular Diagnostics in the future

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Novartis Pharmaceutica

ls

Novartis Pharmaceutica

ls

Novartis Vaccines and Diagnostics

Novartis Vaccines and Diagnostics

Sandoz(Generics)

Sandoz(Generics)

Novartis Consumer

Health

Novartis Consumer

Health

Novartis Family of Companies

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Novartis

One of the worlds largest companies

Sales $US32.2 billion

96,000 employees in >140 countries

Fortune Magazine ranks Novartis as

one of the worlds most admired companies.

• 47th worldwide, 2nd in healthcare (J&J # 1)

Has held >40% equity in Chiron for many years

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Expanding Global Reach

SuresnesEmeryville

Hong Kong

Emeryville, US Hong Kong, ChinaSuresnes, France

Novartis DiagnosticsRegional Headquarters

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Asia Pacific

Regional headquarter• Technical Support, Scientific Affairs, Quality Assurance, Supply

Chain…

Distributors• Malaysia

- Science Valley Sdn. Bhd.

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Chiron Status Worldwide

Chiron is the market leader worldwide• Market share increasing annually

• Greater than 90% market share in the USA and growing

• 10% increase in market share since 2004

• Of countries who have chosen to centralize NAT – Chiron has been consistently selected

Key success factors• Focus and commitment

• Right product at right time

• Full automation

• Assay performance

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Donation Trends

WW Donation Volume 2007(Millions)

Total = 84.2MM*

13.28.8

3.8

4.17.7

7.4

3.25.9

7.2 22.923.2

26.9

34.1

0

5

10

15

20

25

30

35

40

Americas E ME A AP AC

C hiron/Gen-P robe Roche Homebrew Open

NAT Market Share by Donation Volume

*Note: 2007 donation volume calculated from WHO report of 81.1MM in 2002 that has been grown by 1% based on population weighted growth of medium and high development index countries Sources: WHO Global Database on Blood Safety and Chiron Regions

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Asia Pacific Market

9 out of 10 NAT countries use Chiron – 7 of 9 exclusively• Malaysia

• Australia

• New Zealand

• Singapore

• Hong Kong

• India

• Indonesia

Global Blood Safety

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The Goal: Zero-Risk Blood Supply

Despite progressive improvement, there is still concern about residual risk of transmission of blood-borne viruses

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Most transfusion recipients are battling serious disease and have weakened immune systems

Screening limitations Gaps in current defenses exist, due to the window period and

limited screening sensitivity

Known pathogensRoutine testing covers only

a limited number

Bacteria The most frequent

transfusion-transmitted infection

LeukocytesResidual cells and cytokines

can cause harmful post-transfusion reactions

New and emerging pathogensA risk that current safety

measures cannot eliminate

Current Blood Safety Risks to Patients

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Background/Epidemiology for HBV, HCV, and HIV

Global data:

2 billion people worldwide have serologic evidence of past or present HBV infection

360 million carriers are chronically infected with HBV

600,000 people or more die each year from HBV-related chronic liver disease

~ 170 million people are infected with HCV (WHO)

~ 40 million people are infected with HIV (Dec. 2006; UNAIDS)

Ref.: Shepard et al., 2006, Epidemiol Rev, 28:112-125.

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Seroprevalence in Malaysia

Population: approximately 26.6 million (2000 census)

Prevalence of HIV: 0.5% (WHO 2006 data)

Prevalence of HBV: > 8% (Shepard et al., 2006, Epidemiol Rev, 28:112-125.)

Prevalence of HCV: 1.5% (www.msgh.org.my/resources/managementhepatitisc2.htm)

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Serology +ve Rate

Malaysia (2005)

HK1 ARC2 (2006)

HBsAg 0.63 % 0.45 % 0.012 %

anti-HCV 0.11% 0.018 % 0.037 %

anti-HIV 1/2 0.03 % 0.003 % 0.003 %

National Blood Centre, Malaysia

1 Dr. Lin presentation in CSBT

2 S. Stramer, ARC

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Suitability

Altruistic Goal

Recruited without pressure

No risk factors

Pre-donation information

Assessment

The 4 Layers of Blood Safety

Self deferral

Private health screen

Focused health questioning

Signed consent

Simple examination

ABO/Rh/Syphilis

ABO and RH typingIrregular antibody screeningSyphilis reagin testingComparison with past records

EIA + NAT

Immuno-tests: -HBsAg -HIV-Ab -HCV-Ab -[HBCoreAb]NAT Tests: -HIV -HCV -HBV -WNV

Recruitment Health History

Conventional Testing

Infection Testing

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Increased safety of blood supply

All volunteer donors

HBsAg test

AIDS high-risk exclusions

Anti-HIV test

ALT/HBcAb testsAnti-HCV test

Improved HCV tests

1965 1970 1975 1980 1985 1990 1995 2000

Year

% R

ec

ipie

nts

In

fec

ted

Tobler and Busch, Clin Chem 1997.

25

20

15

10

5

0

NAT Implementation

MALAYSIA

PDNYour hospital?

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Nucleic Acid Testing (NAT)

Advantages of NAT

Important technological advance in blood screening

Highly sensitive & specific

• targets specific viral nucleic acid sequences

Direct detection of viral RNA or DNA

Shortens the Window Period from infection to detection

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Comparison of key NAT and EIA Performance Features

NAT EIA

High sensitivity Medium to high sensitivity

Target amplification Signal amplification

Earlier detection

HIV-1: 12 - 14 daysHCV: 32 days

HBV: 17-18 days

Seroconversion window

High specificity Cross-reactivity

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Classic Development of HIV & HCV Markers

10 20 30 40 50 60 70 80 900

Viral RNA,Ag, or Ab

level

HIV-1RNA HIV-1 Ab

10 20 30 40 50 60 70 80 900Days after infection

Viral RNAor Ablevel

HCV RNAHCV Ab

HIV-1 p24 Ag

Schreiber et al. N Engl J Med. 1996;334:1685.McDonough et al. Infusionsther Transfusionsmed 1998;25:164.

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Window Period Closure

Compared to serological tests, NAT has the ability to further reduce the window period from infection to detection of the virus

Sources: (1) Busch et al. Transfusion. 2005;45(2):254-264.

(2) Kleinman and Busch. J Clin Virol. 2006;36:S23-S29.

(3) Data on file at Chiron, Novartis Vaccines and Diagnostics, Inc.

Reducing the window period of detection reduces the associated morbidity and mortality rate

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HIV

HCV

HBV

InternalControl

Signal

Signal

Signal

SignalValid

Reaction

HybridizationProtection

Assay (HPA)

Dual KineticAssay (DKA)

Transcription-Mediated

Amplification (TMA)

Reactive:VirusNot

Specified

Unboundprobes

destroyed

Lyse VirusesAnd CaptureNucleic Acids

AmplifyNucleic Acids

Bind DetectionProbes and Destroy

Unbound Probes

Add DetectionReagents andRead Signal

1 2 3 4

TMA Technology

Magnetic Micro particles

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PROCLEIX® ULTRIO®

Assay (HIV-1, HCV, HBV)

PROCLEIX® System (Hardware & Software)

PROCLEIX®

WNV Assay

PROCLEIX® OPTIVATM

System

PROCLEIX® TIGRIS®

System

PROCLEIX®

PROCLEIX®

NAT TRACKER®

Software

PROCLEIX®

HIV-1/HCV Assay

PROCLEIX® Family of Products

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Procleix Assays

PROCLEIX® HIV-1/HCV Assay

• CE Marked, FDA approved

PROCLEIX® ULTRIO Assay (HIV-1, HCV, HBV)

• CE Marked, FDA approved, registered in Malaysia

PROCLEIX® WNV Assay

• FDA approved

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Ultrio Multiplex Assay Analytical Sensitivity

Virus 95% Limit of Detection

HIV-1 20.27 c/mL

(17.69 – 25.43)

HCV2.78 IU/mL

(2.44 – 3. 27)

HBV7.46 IU/mL

(6.43 - 8.97)

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Ultrio Assay Specificity

Assay Specificity After Initial Testing

Specificity After Repeat Testing

Ultrio (Multiplex) 99.60% 100%

dHIV-1 100% 100%

dHCV 99.73% 100%

dHBV 100% 100%

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PROCLEIX® System

FEP

RAS

Target Capture System

Luminometer HC+

Level of Automation

Low High

PROCLEIX® TIGRIS® Analyzer

PROCLEIX® TIGRIS® System

Procleix® Instrument Platforms

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Procleix Instruments

Target Capture Reagent Addition and Amplification Detection

Read-OutAutomated Sample Pippetting

Room Requirement: Pre & Post amplification

Throughput: 100 samples per 51/2 hours

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A fully Automated System

TIGRIS performs all steps – target capture, amplification, detection and results reporting – automatically.

Its compact footprint takes up less space than conventional NAT systems.

Minimal manual labor required.

Fully integrated process controls protect the integrity of every sample.

1000 samples in 14 hours (1st result @ hour 5 + 100/hr)

Can perform both IDT & pooled samples, & EQC in one run

TIGRIS SystemState of the art. Hands down

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CE Mark/FDA Approval on PROCLEIX® Products

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Countries Using PROCLEIX®

> Europe- Belgium- Demark- Egypt - France- Germany- Ireland- Italy- Lithuania- Poland- Portugal- Slovenia- Slovakia- Spain- Switzerland- UK

>AP- Australia- Korea- New Zealand- Hong Kong- Malaysia- Singapore- Thailand- Indonesia- India

>ROW- Greece- Israel- South Africa- Turkey

>Americas- US- Brazil- Curacao

~ 30% of the entire global blood supply is screened with Procleix products

Within AP, 9 out of 10 NAT countries are using Chiron NAT and 7 out of 9 exclusively

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Asia Pacific Yield DataPROCLEIX® Assays

Country N HIV-1 HCV HBV

Australia (7/00-10/06) 6,635,313 2 10 NT

Singapore (10/00-9/06) 483,943 0 11 10*

Korea (2/05 – 5/06) 733,140 2 3 NT

Malaysia (06) 50,000 0 6 22

India (04/06-10/06) 10,720 0 2** 2

Thailand (03-10/06) 695,760 16 3 17***

New Zealand (11/01-10/06) 660,078 0 0 NT

Hong Kong (7/02-01/08) 986,870 2 1 43****

Total 9,472,684 22 36 94

* Since November 2004 ** 1 HCV/HBV co-inf but HBsAg + *** Started Jan 2006 N= 364,067 ****Started Arp 2007

PROCLEIX Only Results, Source: Chiron User Meetings (2005 – 2006)

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Looking Forward

With NAT, we are closer to zero risk blood supply