Corporate Presentation

November 2015

Safe Harbor statement Certain statements made in this presentation contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities and Exchange Act of 1934, as amended that are intended to be covered by the "safe harbor" created by those sections. Forward-looking statements can generally be identified by the use of forward-looking terms such as "believe," "expect," "may," "will," "should," "could," "seek," "intend," "plan," "estimate," "anticipate" or other comparable terms. All statements other than statements of historical facts included in this presentation regarding our strategies, prospects, financial condition, operations, costs, plans and objectives are forward-looking statements. Examples of forward-looking statements include, among others, statements we make regarding expected future operating results, anticipated results of our sales and marketing efforts, expectations concerning payer reimbursement and the anticipated results of our product development efforts. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: our ability to successfully and profitably market our products; the acceptance of our products by patients and health care providers; the amount and nature of competition from other cancer screening products and procedures; our ability to maintain regulatory approvals and comply with applicable regulations; our success establishing and maintaining collaborative and licensing arrangements; our ability to successfully develop new products; and the other risks and uncertainties described in the Risk Factors and in the Management's Discussion and Analysis of Financial Condition and Results of Operations sections of our most recently filed Annual Report on Form 10-K and our subsequently filed Quarterly Report(s) on Form 10-Q. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. We have filed a registration statement, including a prospectus, with the U.S. Securities and Exchange Commission (the “SEC”) for the offering to which this communication relates. Before you invest, you should read the prospectus in that registration statement and other documents the issuer has filed with the SEC for more complete information about the issuer and this offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, the issuer, any underwriter, or any dealer participating in the offering will arrange to send you the prospectus if you request it by calling 877-547-6340 or 800-792-2413. 2

To work with patients, payers and providers to help play a role in the

eradication of colorectal cancer

OUR FIRST MISSION

3

Source: ACS Cancer Facts & Figures 2015; all figures annual

Colon cancer: America’s second deadliest cancer

new diagnoses in 2015

15,590 27,540

40,560 40,730 [VALUE]

158,040

Esophageal Prostate Pancreas Breast Colorectal Lung

Annual US cancer deaths

132,700

deaths in 2015 49,700

4

132,700 new diagnoses in US

5 Sources: J Natl Cancer Inst. 2009; 101:1225-1227 (Itzkowitz) N Engl J Med 2012;366:687-96 (Zauber); Gastro 1997;112:594-692 (Winawer)

Why is colon cancer the “Most preventable, yet least prevented form of cancer”?

Pre-cancerous polyp Four stages of colon cancer

10+

years

6 Source: SEER 18 2004-2010

Detecting colorectal cancer early is important…

9 out of 10 Survive 5 years if

Diagnosed in Stages I or II

1 out of 10 Survive 5 years if

Diagnosed in Stage IV

Source: CDC MMWR 2013; 64(17);464-468 (Sabatino)

… But many Americans aren’t getting screened

42%

of Americans not current on colon cancer screening

7

Source: J Natl Cancer Inst. 2011; 103:1-12 (Mariotto)

Rising cost of colorectal cancer treatment

2010 2015 2020

Projected annual treatment costs

in 2020

$20B

$14B

8

Cologuard®: Foundation to our success

§  FDA-approved & Medicare-covered

§  Developed in collaboration with Mayo Clinic

§  New England Journal of Medicine results:

•  92% cancer sensitivity (all stages)

•  69% high grade dysplasia sensitivity

•  87% specificity

•  94% sensitivity for stages I to II cancer

§  Included in American Cancer Society & U.S. Preventive Service Task Force guidelines

Source: American Cancer Society Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015. 9

10 Source: Zauber A, et. al. “Evaluating the Benefits and Harms of Colorectal Cancer Screening Strategies: A Collaborative Modeling Approach.” AHRQ (2015). See Appendix Tables 3(a) – 10(c).

CISNET modeling suggests Cologuard® screening strategy is effective

Incidence reduced by

72% over lifetime versus

no screening

Mortality reduced by

81% over lifetime versus

no screening

Median USPSTF model output for screening patients 50-85 with Cologuard every 3 years

11 Source: Mayo Clinic Proceedings, Oct 2015

Alaska study confirms Cologuard’s® performance

Cologuard Alaska Native

people

Cologuard Deep-C

Cancer detection

100% (10/10)

92% (60/65)

Precancer detection

41% (31/76) p=0.006

42% (321/757)

Specificity (clean colon)

93% p=0.0005 90%

12 Source: Family Medicine and Community Health 2015;3(3):2–8 2 www.fmch-journal.org DOI 10.15212/FMCH.2015.0125

Independent study shows patients prefer sDNA test

Case Western Reserve University study

Patient preference 75% of patients deemed sDNA “more

suitable” than a colonoscopy

Likely to repeat test 84% of patients would take another

sDNA test, if recommended

10 30

High-quality sales force driving Cologuard® demand

200

Sales Team on June 1

Creating a results-driven sales force

§  Average 10-years sales experience

§  Focused on high-value physicians §  Real-time data guides strategy

13

Primary Care Field Force

Inside Sales Representatives

Health System Representatives

§  IRONWOOD: Strategically aligned co-promote partner with 160 sales professionals

14 Source: ZS surveys conducted for Exact Sciences Before FDA approval, awareness of stool DNA testing was measured in lieu of Cologuard awareness

Growing unaided physician awareness of Cologuard®

8%

28%

49%

0%

10%

20%

30%

40%

50%

60%

Jan 2014 Dec 2014 Oct 2015

Physicians surveyed who are familiar with Cologuard without prompting

15

World-class lab delivering results

Capable of processing more than 1 million Cologuard® tests per year

Completed Cologuard® tests continues growing

4K 11K

21K

34K >42K

Q4 Q1 Q2 Q3 Q4

16

Completed Cologuard Tests

Guidance

Aug 2014 Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep

Physicians ordering Cologuard® continues expanding

•  ~21,000 ordering physicians

•  Adding ~500 new physicians per week

Q4 2014 Q1 2015 Q2 2015 Q3 2015

4,100

8,300

14,700

21,000

17

18

Insurance covers Cologuard ® for majority of people ages 50-84

55% of screening population covered for Cologuard

•  Medicare covers 46%

•  Commercial insurance covers 9%

•  Total people covered: 44 million

•  In-network contracts: 35% or 28 million people

Sources: US Census, “Health Insurance Coverage Status and Type of Coverage by Selected Characteristics: 2013” US Census, “State Characteristics: Vintage 2013” AIS Directory of Health Plans: 2015 Exact Sciences internal analysis *market share for individuals ages 50-64

Growth strategy to expand coverage and contracting

Quality of Care

Cost Savings

Member Satisfaction

Compelling payer value proposition

19

NEJM publication – 92% sensitive, Medicare NCD

Easy, non-invasive test; >70% patient compliance

Cologuard® delivering positive budget impact

20 *Patient compliance rate: number of valid test results reported divided by the number of collection kits shipped to patients 60 or more days prior to September 30, 2015.

Comprehensive screening program driving compliance

73% Patient Compliance*

Physician orders

Customer outreach

Cologuard completed

Physician provided result

Increasing America’s screening population (ages 50-74)

49% screened with colonoscopy

Screening history of Cologuard® users

42% never screened before

Source: Colorectal Cancer Screening with Multi-target stool DNA-based Testing Previous Screening History of the Initial Patient Cohort, poster presented at American College of Gastroenterology's Annual Scientific Meeting (ACG 2015), Oct. 16-21, 2015

9% screened only with FIT/FOBT

21

22

Keys to Cologuard’s® future success

Ease of ordering Expanding integration with EMR systems

Insurance Focus on large commercial insurance plans

Sales execution Focusing on 21K physicians already ordering

23

Financial performance remains strong

Third Quarter 2015

Revenues $12.6 million

Operating expense $48.4 million

Cash utilization $41.5 million

Quarter-end cash balance $343.5 million