QIAGEN- Development Programs in HPV Testing A Special Focus

-1- 

QIAGEN- 

Development Programs in HPV Testing 

A Special Focus 

QIAGEN Analyst and Investor Day, February 14, 2008 

Dr. James Godsey 

Senior Vice President R&D North America 

Sample & Assay Technologies

Forward Looking Statements 

Safe Harbor Statement: Certain of the statements contained in this presentation may be 

considered forward-looking statements within the meaning of Section 27A of the U.S. Securities 

Act of 1933, as amended, and Section 21E of the U.S. Securities Exchange Act of 1934, as 

amended. To the extent that any of the statements contained herein relating to QIAGEN's 

products and markets and operating results are forward-looking, such statements are based on 

current expectations that involve a number of uncertainties and risks. Such uncertainties and 

risks include, but are not limited to, risks associated with management of growth and 

international operations (including the effects of currency fluctuations), variability of operating 

results, the commercial development of the DNA sequencing, genomics and synthetic nucleic 

acid-related markets, as well as the nucleic acid-based molecular diagnostics, applied testing 

markets and genetic vaccination and gene therapy markets, competition, rapid or unexpected 

changes in technologies, fluctuations in demand for QIAGEN's products (including fluctuations 

for certain events including funding, budgets, and others), difficulties in successfully adapting 

QIAGEN’s products to integrated solutions and producing such products, the ability of QIAGEN 

to identify and develop new products and to differentiate its products from competitors, and the 

integration of acquisitions of technologies and businesses. For further information, refer to the 

discussion in reports that QIAGEN has filed with or furnished to the U.S. Securities and 

Exchange Commission (SEC). 


Sample & Assay Technologies 

Agenda 

HPV: Background and Assay Principle 

NextGen Screening Assay and Platform 

NextGen Genotyping Assays 

FASThpv (dcHPV = developing countries) 

QIAGEN’s Global HPV Strategy 


-2- 

-3- 


1

The Cause 

Human Papillomavirus 

• HPV associated with 99.7% of Cervical Cancer 

• ~ 70% of adult women are infected during lifetime 

• Progression from infection to Cervical Cancer takes up 

to 20 years 

.Cervical cancer 

• Is the #2 cancer in women worldwide 

• WW ~500K new cases/year causing ~ 275K deaths 

• 80% of new cervical cancer cases occur in developing 

countries 

• By 2050 cervical cancer may grow to 1 million 

cases/yr* 

*Prof. Peter Boyle, Director. International Agency for Research on Cancer. Lyon 



Hybrid Capture 2 (HC2) Assay – Milestones/Strengths 

• HC2 FDA approval, 1999 – ASCUS Triage 

• HC2 FDA approval, 2003 – Screening women age 30 and older 


-4- 

-5- 


2

HC2: Perfectly Suited 

Analytical Sensitivity vs Clinical Sensitivity 

Delivering Exceptional Clinical Performance 

Hc2 vs PCR / TMA 

Analytical Sensitivity vs Clinical Sensitivity 

The Analytical Sensitivity of 

HC2 is 5,000 copies of HPV 

DNA 

Target 

Amplification 

The Analytical Sensitivity of 

target amplification methods 

can be 1500 CIN 2/3/cancers 

100 

90 

80 

70 

60 

50 

40 

Bigras 05 

Schiffman 05 

Kulmala 04 

Massad 04 

Sotlar 04 

Belinson 03 

Cuzick 03 

Chan 03 

Depuydt 03 

Xi 03 

Studies sorted by year 

Garcia 03 

Ferreccio 03 

Petry 03 

Salmeron 03 

Kulasingam 02 

Hughes 02 

Kjaer 02 

Castellsague 01 

Clavel 01 

Belinson 01 

Schneider 00 

Adam 00 

Wright 00 

Schiffman 00 

Ratnam 00 

Cuzick 99 

HC2 median – 94% 

PCR median – 82% 


-6- 

-7- 


3

Hybrid Capture 2 

The Gold Standard in HPV DNA Testing 

Author 

Year 

No. of Women 

Author 

Year 

No. of Women 

Lorincz 

92 

2,627 

Petry 

03 

7,592 

Cuzick 

99 

1,703 

Cuzick 

03 

10,358 

Bozzetti 

00 

977 

Kulmala 

04 

1,511 

Ratnam 

00 

2,098 

Castle 

05 

5,060 (ALTS 20k+) 

Schiffman 

00 

8,554 

Schiffman 

05 

10,000 

Wright 

00 

1,365 

Schiffman 

05 

3,363 

Zielinski 

01 

278 

Soderlund 

05 

239 

Solomon 

01 

3,488 

Fetterman 

05 

123,909 

Belinson 

01 

1,997 

Sarian 

05 

4,195 

Clavel 

Pretorius 

Kulasingam 

Salmeron 

Sherman 

01 

02 

02 

03 

03 

5,671 

845 

4,075 

7,732 

20,810 

Bigras 

Sankar. 

Ronco 

Kjaer / Iftner 

Franco 

05 

05 

06 

06 

06 

13,842 

36,938 

16,706 

10,234 

9,667 

315,000+ women 

Hundreds of thousands of samples 



Agenda 







-8- 

-9- 


4

QIAGEN’s NextGen HR HPV Screening Assay 

Built upon two extremely powerful differentiating features 

NextGen Objectives: 

NextGen Performance 

Drivers: 

.Leveraging the strengths 

of the Hybrid Capture 2 

Assay Platform 

.Unprecedented levels 

of throughput 

.Set the stage for 

continued market 

leadership/growth 

.Lay foundation for 

broad based, menu 

driven women’s 

health testing 



Ensemble JE2000 Analytical Instrument 

Unprecedented Throughput! 

Powered by 

Hybrid Capture 

Core Technology 

~3500 units sold 


-10- 

-11- 


5

Ensemble Product Vision 

NextGen HPV Genotyping Assay 

Luminex 

Bar-coded 

Sample 

Pre-analytical 

Luminex 

Plate Map 

Manual 

plate transfer 

Analytical 

Sample 

SCM 

LBC 

Plate Map 

Plate Map 

CCU 

Results 

Results 

CCU = Central Control Unit 


LIS 

Bi-directional interface 

Host query 


Ensemble Product Strategy 

Solution by Segment 

Classical 

Ensemble 

Volume 

Low 

Pre-Analytical 

QIAsymphony 

Analytical 

CE400 

Contemporary 

Ensemble 

Medium 

QIAsymphony 

CE400 

LBC 

DCM 

Barcoded 

Samples 

Jazz 

Ensemble 

High 

Ultra 

CE1000 

CE1000 

CE1000 

CE400 

JE2000 

JE2000 

JE2000 

Genotyping 

Bi-directional interface 

Host query 

CCU 

CCU = Central Control Unit 

LIS 


-12- 

-13- 


6

Screening: Scaleable Throughput, Cost Effective 

Ensemble JE2000 

Ensemble CE400 

Europe 

576 

North America 

Low cost/throughput ratio 

2000 

System TIGRIS A 

470 

System VIPER B 408 

System Roche C 384 

HC2 HC2 manual RCS 384 

HC2 144RCS 

HC2 manual 

120 Third Wave Invader 

High cost/throughput ratio 

Test range 

0 500 1000 1500 2000 

Tests / 8 Hour Shift 



Ensemble Status/Timeline 

Ensemble System 

Component 

Current Status 

2008 

2009 

HR HPV Screening 

Assay 

JE2000 

CE1000 

System Software 

Iso-thermal Target 

Amplification 

Technology 

Assessment 

Performance testing; 

Formulation lock 

Prototypes assay 

integration testing; 

Early prototype assay 

integration; 

Lock down software 

specifications 

Assessing QIAGEN’s 

technology portfolio 

Verification and 

Validation testing, 

Including Beta Trial; 

Manufacturing Transfer 

Design freeze and pilot 

manufacturing 

Performance testing, 

final design prototypes 

verification and 

validation testing 

Coding GUI; software 

V&V testing; integration 

on pilot units 

Develop prototype 

CT/GC assay 

Initiate Clinical Trials 




Product development and 

mfg transfer; CE mark 

studies 


-14- 

-15- 


7

Agenda 








Overview: QIAGEN’s HPV Genotyping Program 

HPV Genotyping Program Objectives: 

• Create a true gold standard in HPV genotyping 

• Reflexing HC2 screening positives to HPV genotyping test 

• Drive development of new clinical algorithms for genotyping 

• Win through unparalleled clinical validation 


-16- 

-17- 


8

HPV Genotyping’s Clinical Utility 

Framed by 3 Facts About HPV Infections 

Normal Cervix 

Infection 

Progression 

Invasion 

Clearance 

65 – 70% 

HPV Infected Cervix 

Regression 

Pre-Cancer 

Cancer 

HPV Genotyping: Develop a triage assay for risk of progression in women 

who present as Cytology Normal, HPV DNA+ 

CIN = Cervical Intraepithelial Neoplasia 



QIAGEN HPV Genotyping Test Strategy 

Positive HC2 

Genotyping 

Reflex 

QIAplex 

18 High Risk Types 

2 Low Risk Types 

QIAplex HPV Genotyping Assay 

• 1° Customers: Reference Labs 

• Genotype 18 High Risk and 2 low 

risk types 

• Initial Clinical utility: 16, 18 triage 

• Persistence for other HR types 

• Vaccine monitoring 

• GP 5+/6+ consensus primers 

• Luminex-based 

Ensemble 

High Risk: 16, 18 

(More possible) 

Probe Set Genotyping Assay 

• Run on Ensemble instrument 

• Genotype 16, 18+ x” Hybrid Capture 

format 

• Hybrid Capture format 

• Cytology labs: no PCR capability 

• Reagents: reflex on instrument 


-18- 

-19- 


9

Status of QIAGEN’S Genotyping Assays 

1. QIAplex HPV Genotyping Assay: 

• Initiate manufacturing transfer H1 2008 

• CE Mark H1 2009 

• Initiate US Trials H1 2009 

2. Ensemble Probe Set Genotyping Assay: 

• Finalize assay formulation and initiate 

performance testing in balance of 2008 

• Initiate manufacturing transfer H1 2009 



Agenda 

HPV: Background and Assay Principles 

Next Generation Hybrid Capture 

Screening Assay and Platform 

NexGen Genotyping Assays 

Fast HPV (“dcHPV – developing countries”) 



-20- 

-21- 


10

Cervical Cancer: An Issue of Social and Gender Justice 

■ 

Current situation: 

• ~500,000 women WW 

currently have cervical cancer 

• More than half will die 

. The Paradox: 

• Cervical cancer is a preventable disease 

the Technology needed to eradicate this 

cancer is currently available! 

■ 



The Burden: Low-Resource Countries 

The Basic Challenge 

is a lack of…. 

• Infrastructure 

• Trained personnel 

• Medical Clinics 

More Than 80% of Newly Diagnosed Cervical Cancer Cases in Low-Resource Countries 


-22- 

-23- 


11

Addressing HPV in Developing Countries 

FastHPV 

Developed by QIAGEN 

in close partnership with: 

• FastHPV designed for use in low resource countries 

• Simple to run 

• Rapid, accurate results 

• Requires minimal infrastructure 

• Affordable for public-health programs in those 

countries 

And funding from: 



FastHPV Test - Schematic 

Collect 

specimen 

Transfer 

aliquot to 

single well 

Denature 

Hybridize and Capture 

Add probe and capture beads 

Conjugate 

Thermoshaker 

Thermoshaker 

Thermoshaker 

30 min 40 min 30 min 

Detect 

Add Substrate 

Wash beads 

Luminometer 

results displayed 

on LCD panel 

Luminometer 

Total Time < 2.5 hr 


Thermoshaker 

-24- 

-25- 

15 min 

Magnet 

15 min 


12

First Clinical-Endpoint Trial: China, Jun 2007 

• Wu Xiang County (n = 2380) 

FastHPV performance in predicting cervical disease 

• FastHPV testing performed same day on-site 

• Testing performed by locally trained personnel 

• Reference hc2 testing performed two weeks later in 

advanced clinical lab in Beijing 

•All women testing positive followed up with appropriate 

clinical management…the same day 

Test 

hc2 

FastHPV 

VIA 

Clinical Sensitivity 

95% 

86% 

55% 

Clinical Specificity 

84% 

86% 

94% 

FastHPV could reduce incidence of cervical cancer by as much as 56% 



The Status of FASThpv 

• Clinical studies demonstrate: 

FASThpv test produces rapid, accurate results 

FASThpv is simple to run and requires minimal infrastructure 

• The test will be cost-effective to governments and NGO’s for 

public-health programs in qualifying countries. 

• Moving quickly to leverage QIAGEN’s China-based industry 

leading molecular diagnostic organization to successfully 

manufacture, clinically validate and launch the FastHPV test in 

China. 

• The product is scheduled to be registered for approval in China 

in H1 2009. 

• Planning to follow our launch in China with similar efforts in India 


-26- 

-27- 


13

Agenda 

HPV: Background and Assay Principles 

Next Generation Hybrid Capture 

Screening Assay and Platform 

NexGen Genotyping Assays 

Fast HPV (“dcHPV – developing countries”) 




QIAGEN’s HPV Global Strategy 

DC = Developing Countries 

Tests/shift: 

USA 

EU 

AP 

LA 

0 – 3,000 0 – 200 0 – 50 0 

DC 

Segment Diversity 

Low 

Medium 

High 

Ultra-High 

Low 

Medium 

High 

Low 

Low 

High 

Burden of Disease 

Ensemble HC2 

Ensemble HC2 

Ensemble HC2 

Fast HPV 

Fast HPV 

Hybrid Capture 

Build on the Gold Standard 

Consistent Technology 

Solutions for all segments 

Leadership in all segments 


-28- 

-29- 


14

Questions & Answers 


-30- 


15

QIAGEN- Development Programs in HPV Testing A Special Focus

Create successful ePaper yourself

Delete template?

Save as template?