Blood test for colon cancer

www.epigenomics.com

2nd Generation Septin9 Test Epi proColon® 2.0

Dr. Gunter Weiss Vice President Product Development Dr. Jürgen Beck Senior Vice President Medical Affairs

Stockholm, 2011

2 | 25.10.2011

CRC accounts for ~ 10 % of total cancer burden

Lifetime risk of CRC is ~ 6 %

People diagnosed with colon cancer:

Facts about Colorectal Cancer

•…413,000 citizens in Europe are newly diagnosed every year

•List of people diagnosed with colorectal cancer

•From Wikipedia, the free encyclopedia

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•P <0.001

screen detected

not-screen detected

Survival rate for colorectal cancer with and without screening Source: Gupta et al.: Changing trends in the incidence, stage, survival, and screen-detection of colorectal cancer: A population-based study. Clinical Gastroenterology and Hepatology 2005; 3:150-158. Winawer et al.: Colorectal Cancer Screening: Clinical Guidelines and Rationale. Gastroenterology 1997;112:594–642.

5-year survival

Local disease

With screening

73% 68%

Without screening

46% 40%

CRC Screening Saves Lives

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Blood-based Septin9 Test: Screening the Unscreened

Why patients will want it:

non-invasive

no dietary/medication restrictions

quick and easy, done anytime

affordable/reimbursable

Why doctors will use it:

performance

body of evidence

easy to explain/perform

helps with screening resistant patients

encourages colonoscopy

screened

Current CRC Screening Compliance in the EU

Septin9

~90% EU citizens are unscreened!

References:

Zavoral et al.: Colorectal cancer screening in Europe. World J Gastroenterol 2009 Dec 21; 15(47): 5907-5915.

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Epi proColon 2.0 : A 2nd Generation Septin9 Test

BETTER Higher sensitivity Improved accuracy Improved clinical performance

EASIER Fewer components Fewer handling steps

FASTER 8 hours time to result Less hands-on time Easier to automate

Available Soon in Europe

6 | 25.10.2011

EASIER: Components

smaller volumes

less components

GMP quality

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1.0 Assay 2 days

FASTER: Work Flow

•STEP 1

•3.5 ml Blood Plasma

•STEP 2

•DNA Isolation

•STEP 3

•Bisulfite Conversion

•STEP 4

•Duplex real-time PCR •DATA ANALYSIS

< 8h 2.0 Assay

shorter reaction

fewer handling

steps

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BETTER: Analytical Performance

fewer handling

steps

PCR Replicates Limit of Detection (LOD)

one 23 pg/ml

two 10 pg/ml

three <6 pg/ml

higher sensitivity

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•Principle of the Test

Real-time PCR based test

Detection of cell-free tumor DNA in blood

Biomarker: methylated SEPT9 gene

13 published retrospective clinical studies for Septin9 performed, >4,300 subjects tested

Prospective clinical screening study in ~8,000 subjects

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Clinical Application of the Septin9 Test

•Asymptomatic

•patient

•10 ml

• blood •Septin9 test

•Colonoscopy

•Clinical

•workup

•Positives •Positives

•Negatives •Negatives

•Repeat blood test conducted at intervals

•consistent with practise guidelines and other

•non-invasive CRC screening tests, e. g. annually.

•Next CRC screening colonoscopy

•to be performed according to

•guidelines, e. g. 10 years later.

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# patients # positive positive fraction

NED 149 1 1%

CRC 98 79 81%

Stage I 27 18 67%

Stage II 29 25 86%

Stage III 31 27 87%

Stage IV 11 9 82%

Stage Specific Performance

specificity 99%

sensitivity 81%

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Method Specificity Sensitivity Negative

Predictive Value

Positive Predictive Value5

2nd Generation Septin9 Epi proColon® 2.0 1 99.3% 80.6% 99.9% 45.7%

Guiac Fecal-Occult Blood Test2

97.7% 37.1% 99.6% 10.1%

OC-Sensa Micro qFIT1x3

93.7% 69.2% 99.8% 7.5%

OC-Sensa Micro qFIT3x4

89.8% 84.6% 99.9% 5.6%

1 Tetzner et al. UEGW 2011, 2 Allison et al. 1996 NEJM, 3 + 4 Park et al. 2010. Am. J. Gastro. 5 Orange figure: CRC with positive test result, grey figure: healthy with positive test result assuming a prevalence for CRC of 0.7%.

Comparison of Clinical Performance of CRC Screening Methods

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Method Sensitivity@Specificity

Current Compliance4

Detected CRC in 1 Million

Patients5

Tomorrow’s Compliance

Detected CRC in 1 Million

Patients5

Blood-Based Epi proColon® 2.0 1 81%@99% NA 0 29%6 1,644

Guiac Fecal-Occult Blood Test2

37%@98% 16% 414 16% 414

Colonoscopy3 97%@98% 30% 2,037 30% 2,037

2,451 4,095 1 Tetzner et al. UEGW 2011.

2 Allison et al. 1996 NEJM.

3 Davies RJ et al. (2005). Nat Rev Cancer 5:199-209.

4 Altenhofen l et al. Jahresbericht Zi 2008.

5 Assuming a prevalence for CRC of 0.7%.

6 Telephone survey Colorectal Cancer Alliance. CCA Denver 2011.

CRC Detection Rate with CRC Screening

+67%

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The New Epi proColon® 2.0 Early Detection Assay

Unmatched performance in non-invasive colorectal cancer detection

(PPV 45%, sensitivity of > 80% @ 99% specificity)

Unmatched convenience for the patient (blood-based)

Conclusions

Available Soon in Europe

15 | 25.10.2011

Thank You for Your Attention

•Berlin, Germany •Seattle, WA, U.S.A.

16 | 25.10.2011

Backup

2 of 3 Algorithm

Specificity 99%

Sensitivity 81%

1 of 3 Algorithm

Specificity 85%

Sensitivity 95%