Update on Exact Sciences Molecular CRC Screening Test. November 16 th, 2011

Transcription

1 Update on Exact Sciences Molecular CRC Screening Test November 16 th,

2 Safe Harbor Statement Certain matters contained in this presentation, other than historical information, consist of forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 relating to, among other things, our expectations concerning the timing of potential commercial and clinical milestones, the efficacy of our technology, our commercial and FDA regulatory strategy, our available cash and cash equivalents, and our business and financial outlook. These forward-looking statements are not guarantees of future performance and are subject to a variety of risks and uncertainties that could cause actual results to differ materially from the results contemplated thereby. Any forward-looking statements we make should be considered in light of the risks and uncertainties contained in our filings with the Securities and Exchange Commission, including but not limited to those contained in our most recent Form 10-K and subsequent Forms 10-Q. We incorporate herein the discussion of those factors. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today. We undertake no obligation to update or revise the information provided herein, whether as the result of new information, future events or circumstances or otherwise. 1

3 Agenda 2

4 Exact Sciences at a Glance Molecular test detects cancer and pre-cancerous polyps DeeP-C pivotal clinical study underway Exclusive IP Proven management team 3

5 Colon Cancer The most preventable, yet least prevented cancer. 141,210 new cases in U.S. U.S. Annual Cancer Mortality 49, ,940 49,380 deaths in U.S. 33,720 37,660 39, ,000 deaths worldwide 4,290 15,460 J Natl Cancer Inst Aug 21. [Epub ahead of print] ACS: Cancer Facts and Figures 2011 Cervix Ovary Prostate Pancreas Breast Colorectal Lung 4

6 Pre-Cancer Progression to Cancer Pre-Cancerous Polyps 10 years to develop Early-Stage Cancer 1-3 years to develop Late-Stage Cancer 60% of new cases are detected late stage Stage I Stage II Stage III Stage IV 1 cm 2 cm 3cm 100% 94% 82% 62% 8% Five Year Survival Rates* * J Natl Cancer Inst 2009;101:

7 The Exact Sciences Solution: 3 Distinct Pathways 2 DNA methylation markers + 7 DNA mutation markers + Single Test Result If positive, refer to diagnostic colonoscopy Fecal Hemoglobin ELISA 6

8 Exact Sciences Molecular CRC Screening Test Offers Simple, Non-Invasive Solution Detects pre-cancers and cancer Non-invasive No bowel preparation No diet or medication restrictions Ease of access, can be mailed Affordable Fast results 7

9 Test Overview DNA Capture Bisulfite Conversion KRAS Cleanup QuARTS Assay Test Result ELISA-based Hemoglobin Assay 8

10 DNA Preparation Stool Supernatant + Hybridization & Capture Probe-coupled magnetic particles Eluted DNA Target-specific DNA Capture Bisulfite Conversion 8

11 Multiplex Methylation QuARTS Assay DNA Amplification and Target Probe Forward Primer / Invasive oligo Forward Primer / Invasive oligo Forward Primer / Invasive oligo Marker Specific Probe Reverse Primer Marker Specific Probe Reverse Primer Marker Specific Probe Reverse Primer FRET and Fluorescent Signal Generation Quencher Quencher Quencher Quasar670 Dye FRET Cassette FAM Dye FRET Cassette HEX Dye FRET Cassette ACTB (beta-actin) NDRG4 BMP3 10

12 Multiplex KRAS QuARTS Assay DNA Amplification and Target Probe Forward Primer / Invasive oligo Forward Primer / Invasive oligo Forward Primer / Invasive oligo Marker Specific Probe Reverse Primer Mutation Specific Probe Reverse Primer Mutation Specific Probe Reverse Primer FRET and Fluorescent Signal Generation Quencher Quencher Quencher Quasar670 Dye FRET Cassette FAM Dye FRET Cassette HEX Dye FRET Cassette ACTB (beta-actin) KRAS 34T, 35T, 38A KRAS 34A, 34C, 35A, 35C 11

13 KRAS Assay Specificity Forward Primer / Invasive oligo Forward Primer / Invasive oligo Mutation Specific Probe Mutation Specific Probe Reverse Primer Reverse Primer KRAS WT contains 2 mismatches KRAS Mutant contains 1 mismatch 12

14 Methylation Marker Selection DNA methylation markers Epigenetic event, DNA is methylated at promoter regions and gene expression is modulated Sequencing Study 32 methyl. Markers Narrowed markers to 9 Tissue Study 9 markers With 4-marker subset, 100% of cancers and pre-cancers detected at 100% specificity AACC poster Pilot Study 4 methyl. markers 118 total samples AACR abstract submission Aberrant methylation in neoplasia leads to reduced gene expression Validation Study 4 methyl. markers 1178 total samples 2 Methylation markers NDRG4 and BMP3 13

15 Optimized DNA Mutation Marker Detection DNA Mutation markers KRAS mutations at Codons 12 and 13 highly associated with Colorectal neoplasia (~35%) First single reaction multiplex assay for any of 7 KRAS mutations Known positives and negatives by sequencing, colonoscopy and histology (191 tissue samples) QuARTS assay is 100 times more sensitive than sequencing 14

16 Fecal Hemoglobin ELISA Fecal Hemoglobin ELISA Immuno-detection of human hemoglobin in stool Independent of carcinogenesis pathway High analytical sensitivity and specificity No dietary or medicinal restrictions 15

17 Automation Solution is On Track DNA extraction Bisulfite conversion QuARTS assay setup 16

18 Indications for Use The Exact CRC screening test is intended for use as an adjunctive screening test for the detection of colorectal cancer markers and for the presence of occult hemoglobin in human stool. A positive result may indicate the presence of colorectal cancer or advanced adenoma. The Exact CRC screening test is not intended as a replacement for colonoscopy. A positive result on the Exact CRC screening test should be followed by colonoscopy. The Exact CRC screening test should be used on subjects who are typical candidates for colorectal cancer screening, adults of either sex, 50 years or older, who are at average risk for colorectal cancer. 17

19 Assay Evaluation Study assessed assay performance on clinical samples using the first development lot of reagents. 355 stool samples were processed and analyzed. 277 Normal samples were collected from subjects, age cancer and 32 advanced adenoma samples were collected from affected subjects. 18

20 Study Comparison 2010 and Specimen Collection Multiple sites over 7 years Various sample processing methods No hemoglobin collection Assay Prototype assay R&D reagents utilized Markers 4 methylation markers with ACTB KRAS Hemoquant Whole stool collection processed in the last year Consistent sample processing Hemoglobin collection for all samples Optimized assay Development lots of reagents Final Cologuard assay configuration 2 methylation markers (NDRG4, BMP3) with ACTB High sensitivity FIT 19

21 of 2010 Validation Study Results Combined Training and Test Sets 85% sensitivity cancer Specificity 88% 64% sensitivity pre-cancer (advanced adenoma >1 cm) 54% sensitivity for pre-cancer (advanced adenoma 1 cm) 20

22 2011 Study Considerations Purpose To assess Cologuard performance on stools from normal, cancer, or pre-cancer subjects. Small sample size Cancer and pre-cancer samples were collected primarily from referred subjects. Post-colonoscopy collection could elevate sensitivities. Not representative of screening population. 21

23 Assay Performance Overall Study Results 98% sensitivity cancer n=355 59% sensitivity pre-cancer (advanced adenoma 1 cm) 91% specificity 22

24 Sensitivity (%) Sensitivity by Cancer Stage Study 2011 Study Stage I II III I, II, III IV Number of Samples * *20 un-staged; waiting for post-surgery pathology 23

25 Improved Assay Performance Number of samples Cancer detection 85% 98% Adenoma detection 1 cm 54% 59% Observed Specificity 88% 91% Right-sided Cancer 87% 94% Left-sided Cancer 84% 100% Right-sided Adenoma 58% 60% Left-sided Adenoma 70% 70% 24

26 DeeP-C Pivotal Clinical Trial Design Number of Patients >10,000 Projected Enrollment Sites ~60 Expected Cancer Patients Expected Pre-cancer Patients Target Status Timing > 85% cancer sensitivity > 90% specificity Q initiation: 12- to 15-month enrollment 25

27 and Conclusions In this study, we demonstrated 98 % cancer sensitivity at 91 % specificity Sensitivity for detecting pre-cancer increases with size and associated risk for progression Dataset established initial cutoff specifications Verification and validation studies to be completed Automation will be ready for DeeP-C study 26