AGA Partners in Quality Meeting

Improving Colorectal Cancer Detection:

A Diagnostic Company Perspective

Barry M. Berger, MD FCAP, Chief Medical Officer

January 16, 2014

Exact Sciences Company Overview

• Founded in 1995, Exact Sciences is a molecular diagnostics company focused on colorectal cancer with downstream exploratory initiatives in other aero-digestive neoplasias.

• The company has developed a non-invasive, a multi-target stool DNA based molecular screening technology for colorectal neoplasia associated DNA alterations currently undergoing FDA PMA/CMS NCD parallel review

− CLIA high complexity laboratory − Patient navigation system − Broad academic collaborations

(EDRN, SPORE, PROSPER) − ~100 full-time employees − Madison, Wisconsin based

Commitments

• Systems approach to improving non-invasive CRC screening

• Professional engagement and collaboration with all stakeholders involved in the process

• Comprehensive, thoroughly documented test development approach with FDA PMA review

• Clinical utility demonstrated in well powered screening study

• Comparative data to other non-invasive screening tests and colonoscopy/histopathology as the reference method

• Transparency through publications

1/13/2014 CC - 3 CONFIDENTIAL

Improving colorectal cancer (CRC) detection: a diagnostics company perspective

Current Condition

• CRC is a major public health problem

• Early detection of CRC and advanced precursors through effective screening decreases colorectal neoplasia associated mortality and morbidity

• Patients exhibit strong preferences for key screening features: accuracy, convenience, comfort, interval and access

• Current screening rates significantly lag those of cervical and breast cancer

4,030

14,030

29,720

38,460 40,030

50,830

159,480

Cervix Ovary Prostate Pancreas Breast Colorectal Lung

Colorectal cancer is the second most deadly cancer in the US with over 50,000 deaths and 140,000 new cases annually

Source: ACS: Cancer Facts and Figures 2013

U.S. Cancer Mortality By Type

Screening and removing advanced adenomas is proven to significantly reduce the likelihood of cancer

Winawer SJ, Zauber AG. (2002) The Advanced Adenoma as the Primary Target of Screening. Gastrointest Endosc Clin N Am. 12(1):1-9.

Cumulative CRC Incidence Over Time

-90%

Early removal of lesions decreases CRC

incidence by up to 90%

A diagnostics view of improving CRC detection: Consider what makes a test effective at CRC detection

Compliance (Patient preferences)

Access (Test distribution)

Sensitivity (Goal of screening)

Screening Test Effectiveness =

X X

Compliance: Increasing compliance increases CRC detection

• Develop a test process that accommodates patient preferences, attract previously unscreened patients:

– Accuracy

– Risk

– Screening interval

– Least impact on daily activities

– Perform on your own schedule

– Privacy

– Acceptability of process

– Ease of performance

– Patient navigation

Access: Increasing access to testing increases CRC detection

• Develop a test that is easily and broadly distributable

– Accommodates shipping systems requirements; outbound collection devices and inbound specimen returns

– Accommodates patient factors related to physical aspects of specimen collection

– Accommodates language diversity and education level

– Analyte stability maintained throughout a variety of environmental conditions experience in transportation

– Automatable, scalable format for use in general MoDx laboratory environment

– Build environment of knowledgeable physicians, willing patients, guidelines incorporation, FDA approval, coverage

Sensitivity: Increase technical sensitivity for detection of colorectal neoplasia increases CRC detection

• Identify the most efficient panel of discriminant markers

• Identify the richest source of biomarkers

• Maintain biomarker integrity throughout the entire process

• Build a robust assay focused on detection of advanced neoplasia

– Low limit of detection of biomarkers

– High signal to noise ratio

– High reproducibility at the cut-off threshold

• Optimize the data analytic approach to maximize sensitivity

• Provide clear, actionable test result

Collaboration: Increasing the performance of other screening strategies increases CRC detection

• Enhance the performance of other strategies to broadly increase the value of screening programs

– Raise the index of suspicion for patients with potentially challenging lesions (Right side, SSP) referred for colonoscopy

– In colonoscopy capacity constrained environments, help focus resource on those most likely to benefit

– Provide an alternative for patients with “colonoscopy fatigue” from intensive surveillance who are no longer compliant and at high risk (HNPCC, IBD)

Where can AGA play a role in a diagnostics company context

• Evidence review and promulgation of effective tests

AGA is a critical, grounded voice in setting healthcare practice and policy in colorectal cancer screening

– Upon full review of the evidence by appropriate practice committees on the value of test/test system:

• Regulatory - Support efforts to clear regulatory hurdles through positive public comment on test

• Coverage - Support coverage of the test as improving the current standard of practice in non-invasive CRC screening

• Guidelines - Convene and perform timely reviews and updates of CRC screening guidelines

Where can AGA play a role in a diagnostics company context

• Education - build an environment of knowledgeable physicians, willing patients

– Benefits of replacing current non-invasive testing with superior techniques/systems

– Systems synergy of colonoscopy and multi-target sDNA as the holistic approach that accommodates all patient preferences and produces high sensitivity CRC detection

– Role of multi-target sDNA testing in appropriately triaging patients and raising index of suspicion for significant lesions, especially , right sided (SSP)

– Knowledge building: Educate GI members to support questions and issues arising in the GI-Primary care interface

– Educate patients - AGA website links, articles and blogs

Where can AGA play a role in a diagnostics company context

• Research

– Identify areas of unmet need that can enhance endoscopic diagnostic techniques

• Increased detection of CRC and advanced neoplasia in IBD

• Provide alternatives for patients with “colonoscopy fatigue” from intensive surveillance now non compliant and at high risk (HNPCC, IBD)

– Convene forums that bring stakeholders together to brainstorm ideas of significant clinical importance and to develop problem solving collaborations

Where can AGA play a role in a diagnostics company context

Collaborate:

• Explore endoscopy procedure/access enhancing processes related to non-invasive diagnostics:

– Raise the index of suspicion for patients with potentially challenging lesions

– Inter-colonoscopic screening interval assessment of interval/missed lesions

– Design strategies to focus colonoscopy resource in resource constrained areas

1/13/2014 CONFIDENTIAL CC - 16