The GeneReader:A Complete NGS System for Your Lab, Live in 30 Days

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Sample to Insight

The GeneReader:

A Complete NGS System for Your Lab, Live in 30 Days

Sylvain Cogne / Massimo Cerfeda Market Development Manager NGS, EMEA May 2017

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2016 Analyst & Investor Day

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Sample to Insight

2016 Analyst & Investor Day 2

Customers want meaningful molecular insights

Moving from tools and components to solutions that provide valuable insights

BIOLOGICAL SAMPLE

VALUABLE MOLECULAR

INSIGHTS

Sample Technologies Assay Technologies

Bioinformatics Automation systems

SAMPLE TO INSIGHT SOLUTIONS

Faster Better More efficiently

Situation

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Sample to Insight

Sample Sample Insight

QC

Library QC

Variant Confirmation

The GeneReader NGS Sample to Insight solution

The GeneReader™ NGS System is the first complete Sample to Insight^® NGS solution designed for any lab to deliver actionable insights

Confidential

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Sample to Insight

Confidential

Workflow overview – Template Sequencing

 Sequencing by synthesis technology

 Automated on GeneReader

 1-3 Flowcells in parallel

 16 samples per flowcell

 16 million reads per flowcell

 100-150 bp maximum read length

 85% of bases > Q25

 Continuous loading mode

 Generate FASTQ files

 Auto transfer to QCI-A

Sequencing

DNA Extraction

Target Enrichment

Clonal Amplification Library

Preparation

Analysis / Interpretation

GR 1.1 specifications

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Sample to Insight

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• LIMS connectivity, iPad-based manual

• True ‘actionability’

The GeneReader NGS System is intended for Research Use Only. Not for use in diagnostic procedures

• Robust and consistent performance

• Bioinformatics & Reporting

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Sample to Insight

The ultimate objective of NGS in molecular pathology

6 GeneReader NGS System PROM-10229-001

A full Sample Report in your hands

• Simple

• Actionable

• Yet comprehensive

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Sample to Insight

Not a Sequencer---but a System

GeneReader NGS System PROM-9303-002 7

Nucleic Acid Extraction

Target Enrichment

Library Preparation

Next- Generation Sequencing

Data

Analysis Interpretation

QIAxcel QIAxcel

RGQ QC

GeneRead Assistant (iPad and App included) Support

Data Management

GeneRead Link and LIMS

QIAcube RGQ QIAcube GeneRead

QIAcube

GeneReader QCI-Analyze QCI-Interpret Automation

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Sample to Insight

QIAGEN | qiagenbioinformatics.com | bioinformaticssupport@qiagen.com | qiagen.com | 2016 8

Designed, built and validated in collaboration with clinical labs

Customizable Reporting

ability to capture /persist internal annotations, integration into LIMS and EMR systems

Comprehensive Curation of Clinical Evidence

reported cases, drug labels, professional guidelines

Decision Support Software

classify variants, identify treatment options, and geographical clinical-trial matching

Treatment and Trial Identification

based upon levels of evidence, expected drug response, prognosis and lab defined rules

QCII – Intuitive and transparent variant interpretation

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Sample to Insight

The QIAGEN Knowledge Base

Title, Location, Date 9

18+ years experience in content acquisition and ontology

Knowledge Base Findings

>13,000,000

>30,000

Publications

>340,000

Samples Analyzed

>20,000

Disease Classes

>30

Integrated Databases

>200

MDs, PhDs Automated &

Manual Curation

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Sample to Insight

GeneRead Link

Workflow management solution for the GeneReader NGS System

Automated transfer of data from LIMS and of results back to LIMS

Electronic lab notebook for complete traceability

Full sample and workflow tracking

Result and QC score mgmt. with recommendation for actions

Minimal manual interaction for data handling

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Sample to Insight

GeneRead Link

The entire workflow on one screen

Integrated Actionable Flexible Affordable Reliable

A B L H C

Workflow phases overview always visible

Work to do Samples waiting in this phase

Work in Progress Guided execution for sample batch

Results to Approve Based on

execution results and QC

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Sample to Insight

QIAact panel portfolio: maximum actionability within 30 days

Actionable Insights Tumor Panel

Lung DNA &

compr. Fusions Panel

Myeloid Leukemia Panel BRCA 1/2 Panel

Custom Panel

Based on QIAGEN knowledge base, enabling maximum actionability Verified from sample to insight, enabling any lab to go live within 30 days

A B L H C

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Sample to Insight

Every GR assay undergoes rigid sample to insight verification

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Systematic Sample-to-Insight verification by multiple experiments, Instruments, users and sites and reviewed on Subsystem and undergo System approval, before going to release

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Sample to Insight

QIAact BRCA precision study

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Very good reproducibility between batches, operators and systems

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Sample to Insight

Robust data of the workflow (HotSpot Panel)

PROM-10667-001 USCAP March 2017 For Research Use Only; Now available in the US with NEW chemistry 15

Achieved consistently high performance regardless of variables* in:

• Sample batch

• Operator and experience level

• Instrument and site

• Plexing (1-10 samples per flow cell)

* 3 batches of Horizon material, 3 sites/instruments, 3 operators

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Sample to Insight

Chr Gene Variant

Expected Allelic Frequency (ddPCR Range)*

GeneReader (Actioanable Insights Tumor Panel) Observed

frequency*

(Standard Deviation)

Average Coverage

3^rdParty Verification

(ddPCR)**

7p12 EGFR L858R 1.00%

(0.6-1.4%)

1.29%

(0.29%) 6,195 0.98

7p12 EGFR ΔE746 - A750 1.00%

(0.6-1.4%)

1.28%

(0.12%) 10,340 1.09

7p12 EGFR T790M 1.00%

(0.6-1.4%)

0.97%

(0.04%) 1,226 1.00

7p12 EGFR V769 -

D770insASV

1.00%

(0.6-1.4%)

0.86%

(0.01%) 4,351 0.89

12p12.1 KRAS G12D 1.30%

(0.78-1.82%)

1.32%

(0.39%) 10,527 1.22

1p13.2 NRAS Q61K 1.30%

(0.78-1.82%)

1.64%

(0.12%) 11,757 1,25

1p13.2 NRAS A59T 1.30%

(0.78-1.82%)

1.34%

(0.08%) 10,552 1.20

3q26.3 PIK3CA E545K 1.30%

(0.78-1.82%)

1.58%

(0.05%) 36,384 1.41

Liquid Biopsy Data with Equally Rigorous Testing

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cfDNA samples at ~1%

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*: 6-plex

Accurately, consistently and robustly detecting cfDNA at 1% sensitivity per design specification

PROM-10622-001 Precision Medicine Webinar For Research Use Only; Now available in the US with NEW chemistry

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Sample to Insight

Our data quality exceeds latest Palmetto standards

PROM-10622-001 Precision Medicine Webinar For Research Use Only; Now available in the US with NEW 17

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Sample to Insight

QIAact panel portfolio: maximum actionability within 30 days

Actionable Insights Tumor Panel

Lung DNA &

compr. Fusions Panel

Myeloid Leukemia Panel BRCA 1/2 Panel

Custom Panel

Based on QIAGEN knowledge base, enabling maximum actionability Verified from sample to insight, enabling any lab to go live within 30 days

A B L H C

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Sample to Insight

Most actionable panel for first-line testing

• KRAS

• NRAS

• KIT

• BRAF

• PDGFRA

• ALK

• EGFR

• ERBB2

• PIK3CA

• ERBB3

• ESR1

• RAF1

Targeting solid tumors with:

• Highest prevalence

• Greatest need for testing

• Variants associated with actionable insights 12 genes

QIAGEN

Knowledge Base

Lung Breast

Ovarian Colorectal

Melanoma

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Sample to Insight

QIAact Lung Panel on GeneReader NGS System

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Number of Variants

Genes QIAact Lung DNA Panel VOIs QIAact AIT V2 VOIs

NRAS 20 41

NTRK1 3 0

DDR2 2 0

ALK 30 39

RAF1 0 2

PIK3CA 14 167

PDGFRA 1 47

KIT 17 257

RICTOR (CNV) 0

ROS1 3 0

ESR1 6 11

EGFR 325 (+CNV) 466

MET 20 (+CNV) 0

BRAF 22 157

FGFR1 (CNV) 0

PTEN 1 0

KRAS 66 152

ERBB3 0 10

AKT1 1 0

MAP2K1 14 0

ERBB2 4 (+CNV) 62

Total Variants 549 1411

QIAact Lung panel covers more Lung relevant variants

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Sample to Insight

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Thank you Questions?

GeneReader NGS System PROM-9303-002

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Sample to Insight

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Additionals

GeneReader NGS System PROM-9303-002

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Sample to Insight

DNA Extraction

Confidential

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Workflow overview – target enrichment

Gene Panels – focus on the genomic region of interest

Target Enrichment

Clonal

Amplification Sequencing Library

Preparation

Analysis / Interpretation

GR 1.0 specifications as shared in May 2016

QIAact V2.0 Assay technology

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Sample to Insight

Actionable Insights Tumor Panel RAS sample study

Outstanding coverage achieved even with challenging FFPE samples

Parameter Detail

Instrument 3 GeneReader NGS Systems

Reagents GeneReader Reagents

Bioinformatics solution QCI-Analyze, QCI-Interpret

Sample number and type 43 FFPE Colorectal Cancer (CRC) samples

Sample age 3 to 20 years

Sample quality Highly fragmented DNA

Variant insight coverage 98.6% of bases covered at >500x 99.8% of bases covered at >200x

A B L H C

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Sample to Insight

Parameter Detail

Instrument 5 GeneReader NGS Systems

Reagents GeneReader Reagents

Bioinformatics solution QCI-Analyze, QCI-Interpret

Sample number and type 39 FFPE Colorectal Cancer (CRC) samples

Sample age 3 to 20 years

Sample quality Highly fragmented DNA

Amplicon coverage 94.45% of bases covered at >500x 97.27% of bases covered at >200x Variant insight coverage 99.36% of bases covered at >500x 99.89% of bases covered at >200x

QIAact V2.0 - RAS Sample Study

Note: Positive samples included into the study have all been confirmed with Sanger sequencing and passed Quantimize <0.04. ) For the repeat study performed with updated sequencing chemistry, four wildtype samples were not available anymore reducing the sample number to 39 compared to results shown earlier.

Outstanding coverage achieved even with challenging FFPE samples

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Sample to Insight

QIAact V2.0 - RAS concordance study with therascreen

Confidential

RAS agreement study

>5% Ras variant Allele Frequency Cutoff

therascreen PCR and Pyro Assays (1)

+ (MT) –(WT) Total

GeneReader NGS System (2)

+ (MT) 14 0 14

– (WT) 0 25 25

Total 14 25 39

Note: (1) If KRAS status regarded as mutant (MT) as identified by either therascreen KRAS PCR Assay or by therascreen RAS Extension Pyro Assay.

(2) Variants from codons 12, 13, 59, 61, 117, 146 contained in established QIAGEN therascreen assays are called.

100 % Agreement between GeneReader NGS System and QIAGEN therascreen PCR

& Pyro Assays

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Sample to Insight

QIAact BRCA 1/2 Panel: not just for Inherited Breast Cancer

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Cancer Types Mutation Types

NCCN/SGO Guidelines on Testing

Clinical Actionability

• Breast

• Ovarian

• Germline

• Somatic

• All patients with Ovarian

• Patients with high-risk Breast Cancer

• PARP inhibitor

• Active trials for somatic

mutations

Need to detect mutations in blood & FFPE and in multiple cancer types

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Sample to Insight

QIAact BRCA Performance on GeneReader NGS System

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QIAact BRCA 1/2

On GeneReader NGS System

VAF cut off >=5% (in FFPE)

ROI full exons + 20bp flanking

True Positives 274

False Positives 0

False Negatives 0

PPV 100 %

Sensitivity 100 %

Accuracy 100%

Coverage of ROI 98.84% @ 5% LAF

99.84% @ 10% LAF

showing 100% PPV and PPA @ VAF of 5%

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Sample to Insight

QCI Provides Clear Insights Into Variant Pathogenicity

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 Variant list screen shows overview of validated variants

 Colour coded classification of variants

 Complete transparency of classification evidence

 Actionable variants highlighted

QIAGEN-AZ confidential

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Sample to Insight

QCI Provides Clear Insights Into Variant Pathogenicity

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 See approved drugs from EMA, FDA, ESMO, ASCO and NCCN (configurable)

 See clinical trials specific to geographical location

QIAGEN-AZ confidential

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Sample to Insight

QIAact Lung All-in-One Assay – need for test consolidation

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Complex genetic changes.

Examples:

Point mutation: EGFR T790M Large deletion: MET: exon 14 CNV: ALK

Fusion: RET, ROS1

Tests typically deployed:

• PCR

• IHC

• FISH

• Array

Need for one single assay that includes all the results

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Sample to Insight

QIAact Lung DNA Panel Specifications

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KPI Specification

Actionable mutations 100% (~ 550)

SNV Detection Yes

Small Indel Detection (<6 bp) Yes Large Indel Detection (<18 bp) Yes

CNV Yes

VAF Threshold 5% (FFPE), <1% (LB)

Specificity >90%

Variant Coverage >1000x 99%; >100x 99% UMIs

Fusion Yes (via RNA Seq)

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Sample to Insight

QIAact Lung RNA Panel for the GeneReader NGS System

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Fusions of Interests

QIAact Lung RNA Panel

Total number of genes 72

Total number of 5‘ partners 60

Total number of 3‘ partners 14

Total number of fusions 77

Frequency cut off 20% tumor cells in wild type background

QIAact Lung DNA Panel + QIAact Lung RNA Panel

= QIAact Lung All-in-One Assay