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Jeremiah McDole, PhD

Product Manager, Oncology

Illumina

Enabling Advancements in Cancer Research

2

New cases Deaths Living with

http://www.cancer.org/cancer/cancerbasics/lifetime-probability-of-developing-or-dying-from-cancer (current 02/09/2016)Globocan 2012: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx

14M 8M 32M

Global Cancer

1 in 3 1 in 2

The War on Cancer

3

Understanding The Puzzle of Cancer Biology Through Genomic Solutions Enabled by Illumina

Identification

of Driver

Mutations

Pathway

Analysis

Tumor Micro-

environment

Understanding

Drug

Resistance

The Role of

Germline

Variants

Gene

Regulation &

Epigenetics

Understanding

Response To

Therapy

The Role of the

Microbiome

Tumor Sub-

type

Classification

Building a Catalog of Driver MutationsIdentification

of Driver

Mutations

The Cancer Genome Atlas Pan-Cancer analysis project, Nature Genetics 45, 1113–1120 (2013)

Building a Catalog of Driver MutationsOver 3,000 tumor samples, 12 tumor types

TCGA Pan-Cancer Analysis Kandoth et al., Nature, Oct 2013See: http://www.nature.com/tcga/

Identification

of Driver

Mutations

Lawrence, et al. Nature 2014

Building a Catalog of Driver MutationsHow much more is there to discover?

“We now know what it would take to get a complete catalog. And we now know we’re not close to done. We have a lot left to learn.”

ERIC LANDERNYT Interview,

Feb 6, 2014

“Creating a comprehensive catalogue of genes in which somatic point mutations propel cancer at both high (>20%) and intermediate (2–20%) frequency will require analysing an average of approximately 2,000 tumours for each of at least 50 tumour types, corresponding to approximately 100,000 tumours.”

Lawrence et al., Nature 2014

Identification

of Driver

Mutations

Towards a Molecular Classification of Tumors

8

Tumor Sub-

type

Classification

Mechanisms of Response

9

Understanding

Response To

Therapy

Understanding The Puzzle of Cancer Biology Through Genomic Solutions Enabled by Illumina

Identification

of Driver

Mutations

Pathway

Analysis

Tumor Micro-

environment

Understanding

Drug

Resistance

The Role of

Germline

Variants

Gene

Regulation &

Epigenetics

Understanding

Response To

Therapy

The Role of the

Microbiome

Tumor Sub-

type

Classification

11 For Research Use Only. Not for use in diagnostic procedures.

Portfolio of Sequencing PlatformsTo serve every application

High ThroughputWGS | WES | T-OME

Personal ScaleFew samples | Run

Low ThroughputTGRS | WGS (Microbes)

Production ScaleMany samples | Run

MiniSeq MiSeq

NextSeq 500HiSeq Series

NextSeq 500

Serious

Production Scale

HiSeq X Series

HiSeq Series

Translate

Apply

Discover

Transforming the Practice of Oncology with Genomics Scientists, Clinicians, Pharma, Regulatory Bodies and New Technologies

Mapping the biology of cancer

Defining clinical utility

Responsible implementation

The Sample Challenge

Small tissue samples:

Lung biopsies Fine Needle Aspirates

An increasing number of variants of known significance

More variants to query More tests to be performed

The ChallengeHow to find more with less?

Image from Chen et al., J Thorac Dis. 2013 Jun;5(3):E93-7. doi: 10.3978/j.issn.2072-1439.2013.04.17. Figure 2

ChallengeIterative testing

§Roth AD1, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on thePETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010 Jan;28(3): 466-474.*Irahara N, Baba Y, Nosho K, et al. NRAS mutations are rare in colorectal cancer. Diagn Mol Pathol. 2010 Sep;19(3): 157-163.**Duration of testing time begins after the sample material becomes available. Turn-around time and cost will vary from lab to lab.

Today:Iterative testing increases demands for tissue, time, and costs

Colon Cancer investigation

Cumulative testing time** 7 days 14 days 21 days…

Cumulative cost** $400 $800 $1200

Cumulative sample needed 10 ng 135 ng 145 ng

Positive30%-50% of results§Negative

KRAS test

Positive5%-10% of results§Negative

BRAF test

Positive1%-3% of results*

Negative

NRAS test …

Colon sample

Multi-Gene AssaysAccelerate investigation

*Duration of testing time begins after the sample material becomes available. Turn-around time and cost will vary from lab to lab.**Cost of library prep and sequencing consumables per sample on MiSeq®.

Colon Cancer investigation Savings

Testing Time *3 days 21 days

Reagent Cost **$167 $400-1000+

Sample needed 20 ng No additional biopsy

Comprehensive solutions designed with your cancer research in mind

Minimize tissue burden Potential to reduce time to action

NGS cancer assay(15 genes)

Positive

Investigationaldata analyzed

PositiveColon sample

For Research Use Only. Not for use in diagnostic procedures.

Multi-Gene NGS Test Maximizes Resources

Faster time to results Cost savings Maximized results withminimal tissue

Improved stratification

Multi-Gene NGS Cancer AssaysNow available

TruSightCancer

TruSightMyeloid

TruSight RNAPan-Cancer

TruSeqAmplicon

Cancer Panel

TruSightTumor 15

TruSeqCustom

Amplicon Low Input

PanelType

Germline Hematology Pan-cancer Solid Tumor Custom

Genomic content

94 genes 54 genes 1385 genes 48 genes 15 genesUp to 1536 amplicons

Variant detection

(frequency)Germline As low as 5%

Detects gene expression, fusions and

SNVs

As low as 5% As low as 5% As low as 5%

Blood, FFPEBlood Blood, FFPEBlood, Bone

Marrow, FFPE

For Research Use Only. Not for use in diagnostic procedures.

Multi-Gene Cancer PanelTruSight® Tumor 15

Single assay:Detect pathogenic variants for 7 types of cancer

BRAFEGFRERBB2KRASMETPIK3CARETTP53

Lung

BRAFGNA11GNAQKITPDGFRATP53

Melanoma

AKT1ERBB2PIK3CA

Breast

KITKRASMETPDGFRA

Gastric

BRAFKRASMETTP53

Colon

PIK3CA

Prostate

FOXL2TP53

Ovary

For Research Use Only. Not for use in diagnostic procedures.

Precision Oncology Treatment From companion diagnostics to companion therapeutics

Patient Multi-target test

Target 1

Target 2

Target 3

The Drug

CRx

Partners