#1EXACT SCIENCES Making earlier cancer detection a routine part of medical care Third quarter 2022 earnings call November 3, 2022 EXACT SCIENCES 1#2Safe harbor This presentation contains forward-looking statements concerning our expectations, anticipations, intentions, beliefs or strategies regarding the future. These forward-looking statements are based on assumptions that we have made as of the date hereof and are subject to known and unknown risks and uncertainties that could cause actual results, conditions and events to differ materially from those anticipated. Therefore, you should not place undue reliance on forward-looking statements. Examples of forward-looking statements include, among others, statements we make regarding expected future operating results; expectations for development of new or improved products and services; our strategies, positioning, resources, capabilities and expectations for future events or performance; and the anticipated benefits of our acquisitions, including estimated synergies and other financial impacts. Please refer to our third quarter 2022 earnings release for discussion of non-GAAP financial measures and reconciliations to GAAP financial measures. EXACT SCIENCES 2#3We're making earlier cancer detection a routine part of medical care to help eradicate the disease OUR TEAM 450 R&D team members 1,300 person commercial team 90 country presence EXACT SCIENCES OUR FLAGSHIP TESTS 960K people tested in 3Q22 cologuard® oncotype DXⓇ oncomap™ ExTra STRONG Q3 RESULTS Record revenue of $523M, 20% growth excluding COVID-19 testing Raising 2022 revenue guidance by $33M, decreasing OpEx guidance by $113M Accelerating adjusted EBITDA profitability to 3Q23 from 2024 3#4Total revenue excluding COVID testing grew 20% in 3Q22 Total revenue (excluding COVID testing) $426M +20% $512M Screening revenue ■ Cologuard® ■ Prevention Genetics +29% $280M / $361M $351M 3Q21 3Q22 3Q21 Cologuard revenue includes immaterial revenue from Biomatrica products and Oncoguard® Liver; Precision Oncology includes laboratory service revenue from global Oncotype® products and therapy selection products, including Oncomap™ and OncomapTM ExTra, formerly known as Oncotype MapTM and GEM ExTra®, respectively; Precision Oncology revenue grew 9% excluding a $2.9M FX headwind and the divestiture of the Oncotype DX Prostate test Note: revenue charts are not to scale EXACT SCIENCES 3Q22 Precision Oncology revenue Domestic International $145M 3Q21 +4% $151M 3Q22 4#5Updated 2022 guidance Total revenue Screening Precision Oncology COVID testing S&M G&A R&D Amortization CapEx Prior guidance $1,980 - 2,022M $1,350 -1,372M EXACT SCIENCES $580-590M $50 - 60M $870-890M $770 - 790M $425 445M ~$99M ~$200M November 3 update $2,025 - 2,042M $1,375 -1,382M Exact Sciences guidance provided November 3, 2022; Screening guidance includes $1,335-1,340M from Cologuard and $40-42M from Prevention Genetics; Cologuard revenue includes immaterial revenue from Biomatrica products and Oncoguard Liver $595-600M $55 - 60M $825 - 845M $740 - 760M $390 - 405M ~$97M ~$200M A at midpoint +$33M +$18M +$13M +$3M -$45M -$30M -$38M -$2M LO 5#6Completed DeeP-C enrollment Nov 2012 2013 FDA approval Aug EXACT SCIENCES Medicare NCD Oct 2014 Announced DeeP-C results Apr 2015 USPSTF guidelines Jun HEDIS measures Oct 2016 2017 Medicare Stars Apr 1M people screened Feb 2018 ~90% insurance coverage Jul 2020 2019 2M people screened Feb 2021 10M people screened Nov 2022 2023 [₁] 2024 10 million people screened November 2022 2025 Expected USPSTF update 2026 2028 2027 Expect 30M+ people screened 6#7The longer providers order Cologuard, the more engrained it becomes in their practice [] [₁]* Ordering rate of 1Q15 providers Total annual new providers EXACT SCIENCES 23K 33K 2015 42K 45K 50K 31K 36K 39K 2016 2017 2018 2019 2020 2021 Source: Exact Sciences data; 2022 new providers and order rate estimated based on YTD data and historical trends 2022E 7#8Cologuard is having a meaningful impact and powering leadership in colorectal cancer screening 10M people screened 315K precancerous cases detected 300K providers ordered 46K early-stage cancers detected 56.0 20.9 1999 Source: based on extrapolation of findings in DeeP-C pivotal trial population to the nearly 10M people screened with Cologuard since launch; Imperiale TF et al., N Engl J Med (2014); Centers for Disease Control and Prevention EXACT SCIENCES Rate of new cases Rate of deaths Colorectal cancer rates per 100,000 people 2004 2009 2014 36.3 12.8 2019 € 8#9Providing a more complete picture to inform better treatment decisions riskguard™ Hereditary Cancer Test limited oncology pilot now available EXACT SCIENCES Exact Sciences precision oncology offerings expected in 2023 X HEREDITARY CANCER PROGNOSIS/ THERAPY GUIDANCE MINIMAL RESIDUAL DISEASE RECURRENCE MONITORING THERAPY SELECTION 2021 X xxxxx X X X X 2022 xxxxx xxxxx X X 9#10Working to bring the best multi-cancer test to patients Presented data at ESMO 4 biomarker classes 61% 98.2% sensitivity specificity 11 of 15 organ types detected have no screening option methylation EXACT SCIENCES protein mutation aneuploidy Source: Douville et al., ESMO congress poster (2022); we expect our multi-cancer test to detect dozens of cancers when measured by all subtypes included Upcoming milestones Feasibility data X X X X Early-access program to generate evidence Clinical validation data Finalize test design Begin prospective study 10#11Uniquely positioned to support the two biggest patient needs in residual and recurrent disease Annual MRD testing opportunities by cancer type gastric skin kidney bladder lung EXACT SCIENCES Note: includes annual U.S. addressable populations Source: Exact Sciences estimates colon prostate 328K breast 1.3M Upcoming milestones Initiate additional studies Tumor-naive colon data at ASCO '22 X Tumor-naive breast data at SABCS '22 X Tumor-informed/naive colon data at ASCO GI '23 XFinalize tumor-informed design X Make available as an LDT 11#12Detecting cancer earlier and providing smarter answers at every step TUMOR BURDEN sc HEREDITARY CANCER EXACT SCIENCES X SCREENING/ SURVEILLANCE DIAGNOSIS X PROGNOSIS/ THERAPY GUIDANCE X X MINIMAL RESIDUAL DISEASE RECURRENCE X X RELAPSE X RECURRENCE MONITORING X THERAPY SELECTION X 12#13EXACT SCIENCES EXACT SCIENCES 13#14EXACT SCIENCES Revenue Operating expenses Cost of sales (exclusive of amortization of acquired intangible assets) Research and development Sales and marketing General and administrative Amortization of acquired intangible assets Impairment of long-lived assets Total operating expenses Other operating loss Loss from operations Other income (expense) Investment income (loss), net Interest expense Total other income (expense) Net loss before tax Income tax benefit Net loss EXACT SCIENCES CORPORATION Selected Unaudited Financial Information Condensed Consolidated Statements of Operations (Amounts in thousands, except per share data) Net loss per share-basic and diluted Weighted average common shares outstanding basic and diluted Three Months Ended September 30, $ $ 2022 147,937 90,813 187,697 191,968 23,526 5,946 647,887 523,073 $ 456,379 $ (13,244) (138,058) (8,584) (5,235) (13,819) (151,877) 3,116 (148,761) $ (0.84) 2021 176,997 115,738 75,356 196,617 186,541 23,940 20,210 618,402 (4,093) (4,680) (8,773) (170,796) (13,244) (162,023) (474,629) 3,858 Nine Months Ended September 30, (166,938) (0.97) $ 171,978 2022 2021 1,531,284 $ 1,293,275 427,242 299,144 635,800 543,410 74,536 12,537 1,992,669 (13,790) (14,224) (28,014) (502,643) 6,882 (495,761) $ (2.82) $ 175,935 339,699 297,158 577,585 621,897 70,954 20,210 1,927,503 (634,228) 30,524 (13,948) 16,576 (617,652) 242,638 (375,014) (2.19) 170,978 14#15EXACT SCIENCES EXACT SCIENCES CORPORATION Selected Unaudited Financial Information Condensed Consolidated Balance Sheets (Amounts in thousands) Assets Cash and cash equivalents Marketable securitie Accounts receivable, net Inventory Prepaid expenses and other current assets Property, plant and equipment, net Operating lease right-of-use assets Goodwill Intangible assets, net Other long-term assets, net Total assets Liabilities and stockholders' equity Current liabilities Convertible notes, net Long-term debt Other long-term liabilities Operating lease liabilities, less current portion Total stockholders' equity Total liabilities and stockholders' equity September 30, 2022 $ 235,306 433,808 189,206 114,699 75,487 670,506 175,945 2,345,180 1,977,690 88,739 6,306,566 423,676 2,184,625 50,000 354,998 184,633 3,108,634 6,306,566 December 31, 2021 $ $ 315,471 715,005 216,645 104,994 74,122 580,248 174,225 2,335,172 2,094,411 74,591 6,684,884 517,068 2,180,232 417,782 182,166 3,387,636 6,684,884 15#16EXACT SCIENCES (In thousands) Net loss Interest expense Depreciation and amortization Income tax benefit EBITDA (¹) Stock-based compensation (2) Investment loss (income) Acquisition and integration costs (3) Reduction-in-force severance (4) EXACT SCIENCES CORPORATION Selected Unaudited Financial Information EBITDA and Adjusted EBITDA Reconciliations (Amounts in thousands) Loss on sale of asset and divestiture related costs (5) Impairment of long-lived assets (6) Legal settlement (7) Adjusted EBITDA Three Months Ended September Nine Months Ended September 30, 30, $ 2022 (148,761) $ 5,235 48,569 (166,938) 4,680 46,200 (3,116) (3,858) $ (98,073) $ (119,916) 58,328 66,855 8,584 4,093 (4,992) 10,150 $ 17,165 5,946 2021 (13,042) 20,210 10,064 (8,544) For associated footnotes, please refer to the table in the third quarter 2022 results press release labeled EBITDA and Adjusted EBITDA Reconciliations 2022 (495,761) $ 14,224 148,077 (6,882) (340,342) 188,303 13,790 (54,695) 14,613 17,256 12,537 2021 (375,014) 13,948 135,221 (242,638) (468,483) 198,869 (30,524) 141,401 20,210 10,064 (148,538) $ (128,463) 16#17EXACT SCIENCES EXACT SCIENCES CORPORATION Selected Unaudited Financial Information Non-GAAP Gross Profit and Non-GAAP Gross Margin Reconciliations (Amounts in thousands) Revenue Cost of sales (exclusive of amortization of acquired intangible assets) Amortization of acquired intangible assets (1) Gross profit Gross margin Amortization of acquired intangible assets (¹) Non-GAAP gross profit Non-GAAP gross margin Three Months Ended September Nine Months Ended September 30, 30, $ $ $ 2022 523,073 147,937 21,296 353,840 68 % 21,296 375,136 72% For associated footnote, please refer to the table in the third quarter 2022 results press release labeled Non-GAAP Gross Profit and Non-GAAP Gross Margin Reconciliations 2021 $ 456,379 115,738 21,214 319,427 70% $ $ 2022 $ 1,531,284 $ 427,242 66,250 $ 1,037,792 68% 21,214 340,641 $ 75% 66,250 1,104,042 72% $ 2021 1,293,275 339,699 62,957 890,619 69 % 62,957 $ 953,576 74% 17