QIAGEN Research & Development Pipeline 2009/ · PDF fileQIAGEN Research & Development. Pipeline 2009/2010. QIAGEN Analyst and Investor Day 2010. Dr. Joachim Schorr Senior Vice President

Sample & Assay Technologies

QIAGEN Research & Development

Pipeline 2009/2010

QIAGEN Analyst and Investor Day 2010

Dr. Joachim Schorr Senior Vice President Global Research & Development

New York, February 11th, 2010

Sample & Assay Technologies- 2 -QIAGEN Analyst and Investor Day, February 11, 2010

Agenda

R&D @ QIAGEN

- R&D Centers of Excellence

- Development Cycles

- R&D Budget Allocation

New Product Launches & Regulatory Pipelines

Prevention

Profiling

Personalized Healthcare

Point of Need

Regulatory Pipelines


Global R&D Organization

690 Scientists in Research & Development Enabling Technologies for Sample and Assay Technologies

Switzerland

USA

Asia

MDx Prevention

siRNA

Application Lab

Pathway Analysis

Automated System Development

Basic R&D

ApplicationDevelopment

MDx AssayDevelopment

SystemsIntegration

MDx AssayDevelopment

SystemsValidation

SampleTechnologies

GermanyUK


CDx Program Management


PRC PRC

Phase 2 Phase 3 Phase 4 Launch

PRC

Phase 0 Phase 1

PRC PRC/GRMPT

QIAGEN’s Global R&D:

Running Projects: 150+

Status: 60 in phase 3 or later

Development time: Approx. 12 months(LifeSciences ~ 9 months, MDx incl. approval 9 - 24 months)

Employees: 690+ researchers allocated according priorities within portfolios

Investment: Approx. 12% of revenues per year

Return on investment: Approx. 5% of revenue growth from products younger 12 months

IP: Expansion of IP position>2,100 patents (757 issued, 799 pending, 550+ licensed)

QIAGEN Product Development Focus & Execution


R&D Budget Allocation Expenses per Technology Center

Note:MDx Assay & Samples including clinical trials (US$ 18.1 M)Life Science including QIAGEN Manchester

Sample & Assay Technology Instruments & SWFor all customer classes

Life Sciences, Pharma, Applied TestingSample & Assay Technology Consumables

MDxSample & Assay Technology Consumables

~61%

~20%

~11%

~8%

~61%

~20%

~19%


Agenda

R&D @ QIAGEN





Prevention

Profiling


Point of Need



Technology Roadmap 2010: Sample and Assay Technologies Structure Based on Identical Workflows in All Segments

Detection

Collection

Stabilization & Storage

Enrichment

Purification

Content

Disruption

Amplification / Modification

Bio-Informatics

Sample Technologies

Ass

ay T

echn

olog

ies

Aut

omat

ed S

yste

ms

Integrated Microsystem

s

Point of Need


Prevention

RSV

CMVEBV

HBV

GBS

HCV

QIA

symphony

Influenza

Profiling


From Components to Content Strategy for R&D

Rotor-Gene Q

Biology/Chemistry excellence

Automation excellence

Integrated solutions

QIAsymphony QIAensemble PON Devices

EZ1BioRobot MDxBioRobot 8000 QIAcube QIAxcel PyroMarkQIAgility Rotor Gene Q

• Broad portfolio assays, incl. regulated

• Content engine

• Several novel markers in pipeline

1996 2000 Today

Content engine

2008


The QIAGEN Content Engine MDx Roadmap

ExamplesNear-term

ExamplesMid-term

ExamplesLong-term

Prevention QIAensemble Evolutioncare HPV (3rd world)

HPV, CT/GC, Trich, GBS, Vaginosis, etc.Screening and Progression markers

Screening for: cancers incl. colon, ovarian, thyroid etc.

Profiling ResPlex II artus assays for QIAsymphony RGQ

GastroPlex, HHV-6, Adenovirus, JC, HSV,Candida, Aspergillus

Autoimmune diseases, CNS, cardiovascular diseases, women’s health, etc.


KRAS, BRAF A/C-Raf, MEK-1/2, p53, EGFR, BCR-ABL, NRAS, I3-Kinase, N/H-RasAKT, BCR, PTEN et. al. CDx for cancer therapeutics

Autoimmune diseases, CNS, cardiovascular diseases, others

Point of Need MRSA, cDiff, VREPseudomonas, Acinetobacter, other bacteria

Meningitis

Other Blood screening (China)

Blood screening emerging countries


The 4 Ps in MDx

Point of NeedPHC

Profiling

RSV

CMVEBV

HBV

GBSInfluenza

HCV

QIA

symphony

Prevention


Platform Technology Assays Samples

Ultra High/High (up to 2000/shift)

Throughput Instrument Floor model

Configuration

screening: digene HPV eHC Testgenotyping: digene HPV

eHC 16 18/45 Test

Low/Medium (up to 600/shift)

Throughput Instrument Benchtop

Configuration

screening: digene HPV eHC Testgenotyping: digene HPV

eHC 16 18/45 Test

QIAensembleUltra High to Mid Throughput Screening Platform

LBC Vials

Co-collected“DCM”

LBC Vials



Platform Technology Assays Samples

Ultra High/High (up to 5000 CT/GC/shift)Throughput Instrument

Floor model Configuration

Ultra High/High (up to 3000 CT/GC/shift)Throughput Instrument

Floor model Configuration

QIAensemble plusAdds Module for Amplified Assays

HPV, HPV GT

CT/GC AssayGBS

TrichomonasVaginosis

and many more

Amplified:

Non-amplified:

LBC Vials

Urine Vials



CT/GC Assay Workflow (Closed Tube Format)HC tHDA Fluorescent Endpoint Detection

Clinical sample

Lysis & denaturation

~ 20 short RNA probes

Probe hybridization &

capture

DNA-RNA hybrid

Magnetic separation of beads

&wash

Magnet

Beads with

Hybrid Capture antibody

CT and/or NG

DNA

Lysis & denaturation

~ 20 short RNA probes

Probe hybridization &

capture

DNA-RNA hybrid

Magnetic separation of beads

&wash

Magnet

Beads with

hybrid capture

antibody

CT and/or NG

DNA

Hybrid Capture Sample Preparation Amplification & Fluorescent Endpoint Detection

Amplification in the presence ofhybrid capture sample prep beads

QIAensemble SP+ QIAensemble 3000+


Chlamydia trachomatis/Neisseria gonorrhoeae (CT/GC) Assay

Reaction: Isothermal Helicase-Dependent Amplification (tHDA)Detection: End-Point Fluorescent

. Assay performance specificationsAnalytical sensitivity ~1 IFU of CT/GC per assay

10 copies of target per amplificationAnalytical specificity: No cross-reactivity with non-pathogensInput material: Urine, LBC and swabs (more to come)Assay time should allow various throughputs (design goal: 1500/shift, actual 3000/shift)

. Assay automationSame platform as for HPV screeningComplete automation for all throughput labsDe-capping capability of all sample vials

QIAGEN CT/GC Assay Project Goals


CT/GC Assay Performance Sensitivity of 10 Copies in a Multiplex Assay Format

CT1/CT2/NG/IC tHDA multiplex assay performance

0

1

2

3

4

5

6

7

8

NTC 10 copiesCT/NG

100 copiesCT/NG

1000 copiesCT/NG

S/N

IC, 250 copiesNGCT

End-Point Fluorescent Detection Real-Time Detection

*Research Gaithersburg

Detection of Mixture of CT and NG Targets and IC in One Well

IC, 250 copiesNGCT

CT/GC assay


Prevention

The 4 Ps in MDx

Point of NeedPHC

Profiling

RSV

CMVEBV

HBV

GBSInfluenza

HCV

QIA

symphony


Launches and Developments 2009/ 2010 QIAsymphony System Family

QIAsymphony RG-Q family

QIAsymphony SP

QIAsymphony RG-Q

QIAsymphony plus

Launch in Q1/2010artus HIVartus HBVartus HCVartus CMVartus EBV

Launch in Q3/2010artus VZVartus BKVartus HSV

Currently in assay development artus HSVartus CT/GCKras; EGFR; PIK3; MEK; BRAF; JAK2; EGFRvIIIartus Influenza

Planned near term (RUO, CE, 510K)artus HHV-6artus JC (human polyomavirus) artus Adenovirusartus Aspergillusartus GBS


Prevention

The 4 Ps in MDx

Point of Need

Profiling

RSV

CMVEBV

HBV

GBSInfluenza

HCV

QIA

symphony

PHC


KRAS Status Major Impact on Anti-EGFR Drug Efficacy

Cell growth via EGF-Ras-Raf signal transductionControlled normal cell growthUncontrolled oncogenic cell growth = uncontrolled signal amplification

EGFR-Inhibitors against EGF receptor block cell growthAntibodies Erbitux (Imclone), Vectibix (Amgen)About 140 EGF inhibitors in clinical trialsStrategies against colon, lung, head & neck etc.

Oncogenic Ras Mutations in 4 critical positionsFound in up to 30% of all human tumors Send permanent cell growth signal „Down-stream of EGF-Receptor“Lead to drug resistance of EGFR-Inhibitors

Patient stratification increase efficacy of Anti-EGF drugsErbitux and Vectibix only for KRAS Wildtype30-40% of patients with Oncogenic KRASEfficacy significantly increased with KRAS tests

(1) Epidermal Growth Factor Receptor

EGFR

P KRAS KRAS

raf

MEK

ERK

Cell growth

active

Ras-signal transductions pathway

EGF Epidermal growth factor


Personalized Medicine Becomes Reality

Source: Personalized Medicine Coalition, 2008

Molecular Biomarker test Therapy Indication

BCR-ABL Gleevec® Chronic myeloid leukemia

c-KIT Gleevec® Gastrointestinal stromal tumor (GIST)

HER-2/neu receptor Herceptin® Breast cancer

BRCA 1, Breast/ ovarian cancer Pharmaceutical and surgical prevention options

AlloMap® gene profile Immunosuppressiva Monitors immune response to heart transplant

Familion® 5-gene profile Pharmaceutical prevention Inherited cardiac channelopathies:Prevention & drug selection

p16/CDKN2A Melanoma: Preventive treatment Pharmaceutical and surgical prevention options

TruGene®-HIV 1 Genotyping Kit Anti-retroviral drugs Therapy selection based on resistant HIV mutations

Oncotype DX™ 21-gene assay Cancer treatment regimens Quantifies the likelihood of breast cancer

UGT1A1 Camptosar® Drug side effects in colon cancer treatment

Amplichip® CYP2D6/CYP2C19 Drugs metabolized by P450 Treatment dose for drugs that are metabolized by P450

Estrogen receptor Tamoxifen Relevance of tamoxifen citrate in breast cancer therapy

TPMT Purinethol® Dose adjustment in acute lymphoblastic leukemia treatment

KRAS (BRAF) Vectibix Exclusion of KRAS mutants increase efficacy


Discovery Pre- clinical Clinical Trials FDA Launch

5 Years 1.5 Years 6 Years 2 Years 2 Years 10 Years +

ApprovalMarker

Marker

Marker

MarkerMarker

MarkerMarker

Marker

MarkerMarker

Marker Marker Diagnostic

Biomarkers -Possible Companion Dx? Routine UseExplore pathways

and molecules ValidateFile for

IVDClearance

Use IVD for

More data

Approval

Marker

Covering the Entire Pharma Development Process From Discovery through Development to Companion Diagnostics

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Technology Toolbox and Assays Roadmap Personalized Healthcare

PCR

Biomarker

First Indication(Cancer) Partnered CE FDA

KRAS Colon Lung Yes 2008 2011

BRAF Colon Melanoma No 2010/2011 2012

EGFR Lung Yes H1 2009 2012

EGFR vIII Glioblastoma Yes H2 2009 2012

PI3K Breast At proposal 2011 2014

NRAS Melanoma In discussion 2012 2014

ABL

Chronic myelogenous leukemia (CML)

In discussion 2010 2013


Prevention

The 4 Ps in MDx

PHC

Profiling

RSV

CMVEBV

HBV

GBSInfluenza

HCV

QIA

symphony

Point of Need


Sigma 42 Project Core Technologies: Helicase Dependent Amplification (HDA)

tHDA mimics nature’s method of replicating DNA by using helicase (± ssBP) to denature the DNA at a constant temperature of 65°C

Like in PCR two sequence specific primers are flanking the DNA fragment enabling the amplification by using an enzymatic mixture

QIAGEN is adding proprietary hot start function to HDA reaction to improve enzyme function


Sigma 42 Project Portable Device for CT/GC Detection

. BMBF funded Project

. 09/08 applied

. 02/09 approved

. 06/09 launched

CT/GC

Process

50µl

Load chip intothe processingdevice


Fluorescence Detection Technology by ESE Today’s Standard in Point of Need

Target: Amplification specific for Chlamydia trachomatis detecting a portion of the major outer membrane protein (omp)

Method: Genomic DNA from Chlamydia trachomatis was used as template in a tHDA reaction and fluorescence was measured in real-time mode on the ESE Tube Scanner from samples containing the equivalent of 100 copies of the omp gene and negative control samples (NTC).

tHDA Reaction on a ESE Tube Scanner


Agenda

R&D @ QIAGEN





Prevention

Profiling


Point of Need



Q4Q3Q2Q1Q4Q3Q2Q1Q4Q3Q2Q1Q4Q3Q2Q1

2013201220112010YEARPROJECT QUARTER

Regulatory Approval Projects USA

artus EBV RG 6000

NextGen HPV Screening

TheraScreen KRAS

AXpH QIAsymphony for HC 2.0

Resplex II

artus CMV RG 6000

artus Influenza

cador BVDV (USDA)

TheraScreen EGFR

Estimated Approval/Launch (typically 15 months after submission for PMA, 6 months for 510K) PMA Submission510K SubmissionStart clinical trialRunning / planned project




Selected Regulatory Approval Projects Europe

artus HHV-6


TheraScreen KRAS RGQ

TheraScreen EGFR RGQ

AXpH QIAsymphony for HC 2

artus HSV 1,2

Estimated CE Mark

Resplex II Plus

PyroMark Cancer Panel (12 markers)

Running / planned project

artus VZV and artus BKV




Regulatory Approval Projects China / Asia

care HPV


TheraScreen KRAS RGQ

HBV v2

Blood Screening

Digene HC2 HPV

SubmissionStart clinical trialRunning / planned project

UU Test

CT and NG

Flag indicates Estimated Approval/Launch

TheraScreen EGFR RGQ


Regulatory Project Pipeline ( CE, FDA, SFDA) In Preparation

Prevention Profiling Personalized Healthcare Point of Need

CT/GC artus HHV-6 EGFR vIII Tuberculosis

Tricomonas artus JC (human polyomavirus)

PI3K Influenza

Vaginosis artus adenovirus NRAS MRSA

GBS artus aspergillus ABL

Clostridium difficile (CD MEK

BRAF

BCR-ABL


. Thank you !

Documents

QIAGEN Research & Development Pipeline 2009/ · PDF fileQIAGEN Research & Development. Pipeline 2009/2010. QIAGEN Analyst and Investor Day 2010. Dr. Joachim Schorr Senior Vice President