Epi proColon: a plasma test for methylated SEPT9 DNA for

colorectal cancer screening.

Dr. Jeffrey Cossman

Possible conflicts of interest

• Chairman, Medical Advisory Board, Epigenomics

Dr. Jeffrey Cossman

Plasma testing – Epi proColon

Dr. Jeffrey Cossman

EPI proColon

Dr. Jeffrey Cossman

• FDA approved as a screening test for colorectal cancer

• Specifically approved by FDA for the 35% of eligible Americans who go unscreened

• Approved, and in use, in Europe, China and other countries

• The clinical value has been firmly established in large scale control and prospective clinical trials

Development Studies – Case Control

Dr. Jeffrey Cossman

Study # Samples Sensitivity Specificity Assay

Study 1 312 52 95 Experimental Workflow

Study 2 600 57 96

Study 3 725 48 93

Study 4 370 48 96

Study 5 550 72 90

Study 6 269 74 92 mSEPT9 Detection Assay

Study 7 245 69 89

Study 8 158 71 99 Abbott mS9 Assay

Study 9 257 67 88 Epi proColon Assay (Duplicate)

Study 10 128 86 93 Epi proColon Assay (Triplicate)

Study 11 168 90 89 ARUP mSEPT9 Assay

Study 12 256 91 87 Epi proColon 2nd Generation Prototype

Total 4,038

Prospective Analysis - PRESEPT

Dr. Jeffrey Cossman

2010 PRESEPT Study PRESEPT Study post-hoc

Subjects collected

7,940 7,940

Subjects tested

Stratified Random Sampling

1516 1478

Sensitivity 48.2% 63.9%

Specificity 91.5% 88.4%

Assay / Kit

Epi proColon® CE

(duplicate)

Epi proColon® CE

(triplicate)

Church et.al., Gut. 63:317-325. Doi10.1136/gutjnl-2012-304149

Prospective Analysis – Epi proColon

Dr. Jeffrey Cossman

2012 Prospective Performance Evaluation

Subjects tested 1544

Sensitivity 68.2% (CI 53.4-80.0%)

Specificity 80.0% (CI 77.9-82.1%)

Assay / Kit

Epi proColon FDA

Potter et.al., Clinical Chemistry. 60(9):1183-1191.

Comparison to FIT – SEPT9

Dr. Jeffrey Cossman

2014 SEPT9 FIT

Subjects tested 301 290

Sensitivity 73.3% (CI 63.9-80.9%) 74/101

68.0% (CI 58.2-76.5%) 66/97

Specificity 81.5% (CI 75.5 – 86.3) 37/200

97.4% (CI 94.1-98.9%) 5/193

Assay / Kit Epi proColon FDA OC-Auto (100ng)

Johnson et.al. PLOS ONE. 9(6):1-8. e98238

Comparison to FIT – Stage Detection

Dr. Jeffrey Cossman

2014 Epi proColon FIT

Stage 0 100% (2/2) 0.0% (0/2)

Stage I 61.5% (16/26) 65.4% (17/26)

Stage II 80.0% (16/20) 80.0% (16/20)

Stage III 65.2% (15/23) 82.6% (19/23)

Stage IV 92.3% (12/13) 58.3% (7/12)

Unclassified 76.5% (13/17) 50.0% (7/14)

Total 73.3% (74/101) 68.0% (66/97)

Johnson et.al. PLOS ONE. 9(6):1-8. e98238

SEPT9 Studies- Chinese Population

Name of presenter

Jin et.al. J Gastroenterol Hepatol. 2014 Dec 4. doi: 10.1111/jgh.12855.

Opportunistic Screening - China

Dr. Jeffrey Cossman

Wu et.al. J Mol Diagn 2016; http://dx.doi.org/10.1016/ j.jmoldx.2016.02.005

Future Studies

• Longitudinal Performance – as part of US FDA Post Approval

• Comparison to FIT in matched patients- Germany

• Opportunistic Screening & General Population screening – China

• Extension of indication – familial syndromes US

• Extension of indication – response monitoring – South America

Dr. Jeffrey Cossman

Summary

• Methylated SEPT9 testing is available in approved form in the US, Europe, China and other countries

• Performance levels are comparable in different geographies – depend on the algorithm

• Early stage detection >60% in multiple studies

• When combined with FIT, sensitivity ~90%

• In positives who went on to scope >50% had lesions

• In a behavioral study, 99.5% went on to take the test

• A blood test option will complement other methods and improve screening rates

Dr. Jeffrey Cossman