Creating a Leader in Blood-Based Multi-Cancer Screening October 27, 2020

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Safe Harbor Statement

Forward-Looking Statements

Some of the information presented here today may contain projections or other forward-looking statements regarding future events or the future financial performance of the Company. These statements are based on management’s current expectations and the actual events or results may differ materially and adversely from these expectations. We refer you to the documents the Company files from time to time with the Securities and Exchange Commission, including the Company’s annual reports on Form 10-K, its quarterly reports on Form 10-Q, and its current reports on Form 8-K. These documents identify important risk factors that could cause the actual results to differ materially from those contained in the Company’s projections of forward-looking statements.

Non-GAAP Disclosure

In this presentation, the Company’s financial information is provided in accordance with accounting principles generally accepted in the Unites States (GAAP) and using certain non-GAAP financial measures, including non-GAAP gross margin. The company believes that these non-GAAP measures are useful in evaluating the company’s operating performance. The company uses this non-GAAP financial information to evaluate ongoing operations and for internal planning and forecasting purposes. For additional information and a reconciliation of these non-GAAP measures to GAAP, see the Company’s press release issued in connection with its third quarter financial results.

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Presentation Participants

Jeff Elliott Exact Sciences

Chief Financial Officer

Kevin Conroy Exact Sciences

Chairman of the Board & Chief Executive

Officer

David Daly Thrive

Chief Executive Officer

Transforming the future of cancer diagnostics with a premier R&D team

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Establishing Exact Sciences as a Leader in Blood-Based Multi-Cancer Screening

By combining the expertise of Exact Sciences and Thrive, we believe we can bring this powerful technology to patients faster

Accelerating the approval, availability, and adoption of blood-based multi-cancer screening

Demonstrating Exact Sciences is a research and commercial partner-of-choice

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Screen Fewer People to Detect 1 Cancer with Multi-Cancer Approach

166 People need to be screened

to detect 1 colorectal cancer

~30 People need to be screened to detect 1 type of multiple cancers

Sources: Centers for Disease Control and Prevention; U.S. Census Bureau; Imperiale TF et al., N Engl J Med (2014); Karwinski 1990, Burton 1998, Sens 2009, Ahlquist 2017;

Assumes ~85% sensitivity for a multi-cancer test

#1 Cancer is leading cause of

death in people under 85 in U.S.

90% ~9/10 people can survive if it’s caught at an early stage

114M People between ages 50

and 85 in the U.S. who could be screened

Problem Solution Market

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Thrive: Integrating Earlier Detection of Multiple Cancer Types into Routine Medical Care

CancerSEEK is a DNA- and protein-based liquid biopsy test designed to detect multiple cancers from one blood draw

Multiple Cancers Based on innovation and established cancer biology curated by Dr. Bert Vogelstein and colleagues at Johns Hopkins University

Trusted Results Multi-cancer “rule-in” approach emphasizing high specificity to give physicians confidence in next steps

Seamless Experience Proprietary Integrated Service model couples low-cost blood test with clinically proven PET-CT to localize cancer

Headquartered in Cambridge Rooted in work from The Vogelstein Lab at Johns Hopkins University Focused on advancing CancerSEEK

8 Proteins

Multi-analyte approach

Irrefutable links to multiple types

of cancer

Safe-SeqS

Machine learning classifier

Proprietary chemistry

Cohen et al., Science 23 Feb 2018: Vol. 359, Issue 6378, pp. 926-930

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Transforming Cancer Diagnostics with a Premier R&D Team

Methylation + PCR

Mutations + sequencing

Research across top 15 cancers

3,000 marker patents filed

215K+ blood sample repository

Real-world clinical evidence

Superior bioinformatics

Liquid biopsy expertise

Exact Sciences’ talented team and robust clinical and evidence generation capabilities will be complemented and enhanced by the addition of Thrive’s best-in-class R&D team specializing in next-generation sequencing and bioinformatics in liquid biopsy

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Accelerating Approval, Availability, and Adoption of Multi-Cancer Screening

Exact Sciences’ powerful and proven platform Exact Sciences is uniquely positioned to maximize CancerSEEK’s success

Proven clinical and regulatory teams

Established payer relationships

230K+ square feet of clinical lab space

Scaled IT capabilities

500-person primary care sales team

Consumer marketing & customer support

expertise

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Advances Exact Sciences’ Mission to Serve Patients Across Cancer Continuum

Uniquely positioned to develop and provide innovative products across the cancer continuum

Home to two of the strongest and fastest-growing brands in cancer diagnostics

A research and commercialization partner-of-choice

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A Leader in Large Markets Across the Cancer Continuum

Total Addressable Markets

Cologuard Oncotype Multi-Cancer

$18B $3.5B

$25B+ Steps to bring this potentially life-saving advancement to patients

Optimize test and finalize development

Launch large scale trial and secure FDA approval

Enable widespread availability through primary care team

Source: Exact Sciences estimates

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Transaction Overview

TERMS

• Acquisition of 100% of the equity interests of Thrive, a privately held company, via a two-step merger transaction

• Cash and stock transaction valued at up to $2.15 billion

• $1.7 billion payable at closing, subject to Thrive maintaining an agreed upon net cash balance, comprising 65% in EXAS common stock and 35% in cash

• Additional $450 million payable in cash in accordance with achievement of certain performance-based milestones

TIMING AND CLOSING

• Anticipated to close in first quarter 2021

• Subject to customary closing conditions and regulatory approvals

PRIVATE PLACEMENT

• Sold $869M in common stock in a private placement at a price of $101.00 per share

• Placed shares with 10 institutional investors, including some of Exact Sciences’ largest shareholders, as well as healthcare specialist firms Casdin Capital and Rock Springs Capital

PROFORMA CASH

• Assuming acquisitions of Thrive and Base Genomics both closed (but milestone payments not yet earned), and the net proceeds from the registered direct offering, cash balance at the end of Q3 would have been nearly $1.4B

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Exact Sciences third quarter 2020 financials

Q3 2020 Q3 2019

Revenue $408.4 million $218.8 million

Screening $214.6 million $218.8 million

Precision Oncology $91.6 million —

COVID testing $102.2 million —

Gross margin 72% 76%

Non-GAAP gross margin 77% 76%

Operating expense $283.5 million $201.4 million

Ending cash balance $1.3 billion $1.2 billion

Non-GAAP gross margin excludes amortization of acquisition-related intangibles Operating expense includes R&D, S&M, and G&A, and excludes COGS and amortization of acquired intangibles

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Acquiring Thrive is a Giant Leap Toward Achieving Our Mission

A turning point in making blood-based multi-cancer testing a reality

Transforms the future of cancer diagnostics with a premier R&D team

Accelerates the approval, availability, and widespread adoption of multi-cancer screening

Positions Exact Sciences as a leader in a large market and as a research and commercial partner-of-choice

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Advancing Mission to Detect Cancer Earlier with Acquisition of Base Genomics

DNA quantity & quality preserved

Genetic & epigenetic data simultaneously generated

Detection cost significantly reduced

Highly complementary to Exact Sciences’ methylation expertise and multi-marker approach

Innovative, low-cost technology enabling highly accurate multi-marker detection

in a single sample

Exact Sciences 15