Published Data Shows Oncoguard™ Liver Delivers Enhanced Performance for Early-stage Detection of HCC

MADISON, Wis. – Aug. 13, 2021 – Exact Sciences Corp. (Nasdaq: EXAS) announced today that the performance of its Oncoguard^™ Liver liquid biopsy test is now published online in the peer-reviewed journal Clinical Gastroenterology and Hepatology (CGH). The test delivers 82% early-stage sensitivity, and an overall 88% sensitivity and 87% specificity^[1] for the detection of hepatocellular carcinoma (HCC), the leading form of liver cancer.

An estimated 3 million^[2] Americans are eligible for HCC testing. Currently, only one in three^[3] at-risk patients receive recommended testing.

“The Oncoguard^™ Liver test advances our work to defeat cancer through earlier detection and bring effective, accessible liquid biopsy tests to health care providers and patients,” said Kevin Conroy, chairman and CEO of Exact Sciences. “The clinical validation study published in CGH is the third peer-reviewed publication for our liver test, reflecting Exact Sciences’ commitment to scientific rigor and innovation.”

The newly published clinical validation study details the performance of the Oncoguard^™ Liver test in a group representative of the U.S. population recommended for HCC surveillance. The sensitivity demonstrated by the Oncoguard^™ Liver test highlights the potential for significant advances in early-stage HCC detection. Early-stage detection can increase five-year survival rates for HCC from less than 12%^{[4], [5]} to upwards of 70%.^[6]

“We have been working for years to build a simple, high performing blood test for HCC surveillance, and these results indicate that the Oncoguard^™ Liver test is poised to be the major advancement our patients deserve and need,” said Dr. Naga Chalasani, interim chair of the Department of Medicine at Indiana University and lead author of the Clinical Gastroenterology and Hepatology-published paper. “The robust validation results were due to a rigorously conducted study, which could not have been possible without diligence and commitment of the entire study team and Exact Sciences’ commitment to developing early cancer detection biomarkers.”

The current standard of care^[7] for HCC surveillance is visual monitoring via ultrasound, with or without an alpha-fetoprotein (AFP) blood test. These methods have variable sensitivity for detecting early-stage disease.^{[5], [8]}

 
The Oncoguard^™ Liver test aims to bridge gaps in ongoing HCC testing. It offers a single, blood-based test analyzing a unique panel of DNA methylation and protein biomarkers. The test is intended as an aid in the detection of HCC for adults with liver cirrhosis and/or chronic hepatitis B who are at risk for HCC.

“The Oncoguard^™ Liver test was created with the hope of enhancing early detection of liver cancer, thus putting improved outcomes within reach and empowering patients to stay current with recommended testing ordered by their health care provider,” said Mayo Clinic’s Dr. Lewis Roberts, who helped develop the test. “It’s rewarding and exciting to be a part of the team that is bringing this new test to patient care.”

The Oncoguard^™ Liver test is currently available via an early access program designed to familiarize provider offices with the test and its Patient Engagement Program. The test identifies biomarkers associated with HCC. A positive Oncoguard^™ Liver test should be followed with a conventional diagnostic work up.

To learn more about the Oncoguard^™ Liver test visit www.OncoguardLiver.com.

The CGH article is available at: https://www.cghjournal.org/article/S1542-3565(21)00866-1/fulltext#%20.

Rising number of liver cancers

Each year, more than 40,000 Americans learn they have liver cancer, and more than 30,000 die from the disease.^[9] By 2035, liver cancer is projected to surpass prostate and breast cancer to become a third leading cause of cancer death in the United States.^[10] Up to 85%^[11] of liver cancers diagnosed are hepatocellular carcinoma, commonly referred to as HCC.

Outcomes for HCC are improved with early-stage detection.^[12] However, most cases of HCC are detected in late stages when curative treatments may no longer be an option.^[13] Routine surveillance to find early-stage HCC in at-risk patients is the key to giving these patients the chance they each deserve at successful, even curative treatment.

In the United States, HCC has been linked to a condition known as cirrhosis. In cirrhosis, liver tissue that has become damaged over time is slowly replaced by scar tissue.^[14] This growing scar tissue makes it harder for the liver to do its job and raises the risk of cancer developing. Cirrhosis may be caused by a variety of things, including chronic viral infections, heavy alcohol use, fatty liver, and some rare genetic conditions.^[15] Medical organizations recommend HCC surveillance for all people with cirrhosis and for select patients with chronic Hepatitis B.^[7]

Simplifying testing, supporting patients 

Exact Sciences undertook a scientifically rigorous development path to address the unmet need for reliable early-stage detection of HCC. Early tissue and plasma discovery efforts^[20] conducted by leading experts at Mayo Clinic and marker selection studies^[21] by Exact Sciences resulted in Breakthrough Device designation from the U.S. Food and Drug Administration in 2019. 

Development and validation of the Oncoguard^™ Liver test was supported by one of the largest HCC case-control studies ever conducted. Designed with input from leading hepatologists, the study followed robust enrollment criteria informed by HCC guidelines, yielding 700 cases and 1,400 controls. Unique cohorts from this study were then used throughout the Oncoguard Liver test’s marker selection, algorithm development, and clinical validation stages. The cohort used in the clinical validation study reported in the CGH included 156 HCC cases (50% early-stage) and 245 disease etiology-matched controls.

The Oncoguard^™ Liver test demonstrated consistently high performance regardless of sex, body mass index (BMI), or viral status making it a robust solution in this complex disease space.

A variety of hurdles may interfere with ongoing testing, such as scheduling challenges if patients have to make multiple office visits to complete their recommended tests for each round of surveillance. As a result, of the estimated 3 million^[16] patients qualifying for HCC surveillance in the United States, fewer than one-in-three are compliant with their testing.^[17]

The Oncoguard^™ Liver test includes a Patient Engagement Program designed to encourage patients to adhere to recommended testing. It is informed by the customer care program for Cologuard^®, Exact Sciences’ noninvasive colorectal cancer screening test that has been used more than 6 million times since 2014. 

The Patient Engagement Program features education and personalized reminders to reinforce the importance of ongoing HCC surveillance testing and regular office visits. Data indicates these can be critical interventions that drive routine surveillance needed to detect cancer early. Patient engagement and outreach programs have been shown to increase patient adherence to HCC surveillance test orders.^{[10],[18],[19]} Interventions, such as electronic medical record reminders and mailed outreach, increased relative HCC testing utilization by 60%-80%.^[17]

The clinical validation study in CGH is the third journal publication documenting the Oncoguard^™ Liver test’s development. The first, detailing the identification and verification of the use of methylated DNA for HCC detection, appeared March 2019 in Hepatology.^[20] The second, published September 2020 in CGH, documents marker selection for the test.^[21]

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Investor Contact

Megan Jones, Exact Sciences, 608-535-8815, meganjones@exactsciences.com 

Media Contacts

Scott Larrivee, Exact Sciences, 608-287-9261, slarrivee@exactsciences.com

 Joe Dangor, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu

About Exact Sciences Corp.

A leading provider of cancer screening and diagnostic tests, Exact Sciences relentlessly pursues smarter answers to give people the clarity to take life-changing action, earlier. Building on the success of Cologuard and Oncotype tests, Exact Sciences is investing in its product pipeline to support patients throughout their cancer diagnosis and treatment. Exact Sciences unites visionary collaborators to help advance the fight against cancer. For more information, please visit the company's website at www.exactsciences.com, follow Exact Sciences on Twitter @ExactSciences, or find Exact Sciences on Facebook.

Forward-Looking Statements
This news release 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. You should not place undue reliance on forward-looking statements. Risks and uncertainties that may affect our forward-looking statements are described in the Risk Factors sections of our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q, and in our other reports filed with the Securities and Exchange Commission. 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.

[1] Chalasani NP, Porter K, Bhattacharya A, Book AJ, Neis BM, Xiong KM, Ramasubramanian TS, Edwards V DK, Chen I, Johnson S, Roberts LR, Kisiel JB, Reddy KR, Singal AG, Olson MC, Bruinsma JJ, Validation of a novel multi-target blood test shows high sensitivity to detect early-stage hepatocellular carcinoma, Clinical Gastroenterology and Hepatology (2021), doi: https:// doi.org/10.1016/j.cgh.2021.08.010.

[2] 3M U.S. patients calculated using Census Bureau estimates of population and prevalence of cirrhosis as reported in Beste et al., Gastroenterology (2015).

[3] Singal AG et al., J Hepatology (2020).

[4] National Cancer Institute. Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. 2021. https://seer.cancer.gov/statfacts/html/livibd.html

[5] Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019;380(15):1450-1462.

[6] Tzartzeva K, Obi J, Rich NE, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology.2018;154(6):1706-1718.e1. doi:10.1053/j.gastro.2018.01.064

[7] Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723-750

[8] Samoylova ML, Mehta N, Roberts JP, Yao FY. Predictors of Ultrasound Failure to Detect Hepatocellular Carcinoma. Liver Transpl. 2018;24(9):1171-1177.

[9] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590

[10] Rahib L, Wehner MR, Matrisian LM, Nead KT. Estimated projection of US cancer incidence and death to 2040. JAMA Network Open. 2021;4(4):e214708. doi: 10.1001/jamanetworkopen.2021.4708

[11] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249.

[12] Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11(4):e1001624.

[13] American Cancer Society. Cancer Facts and Figures, 2021. Atlanta, GA: American Cancer Society; 2021.

[14] Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358-380. doi:10.1002/hep.29086

[15] National Cancer Institute website. Liver (hepatocellular) cancer prevention (PDQ®)–patient version. Updated April 21, 2020. Accessed July 26, 2020. https://www.cancer.gov/types/liver/patient/liver-prevention-pdq.

[16] Beste LA, Ioannou GN, Yang Y, Chang MF, Ross D, Dominitz JA. Improved surveillance for hepatocellular carcinoma with a primary care-oriented clinical reminder. Clin Gastroenterol Hepatol. 2015;13(1):172-179. doi: 10.1016/j.cgh.2014.04.033

[17] Wolf E, Rich NE, Marrero JA, Parikh N, Singal AG. Utilization of hepatocellular carcinoma surveillance in patients with cirrhosis: a systematic review and meta-analysis. [published online ahead of print, 2020 May 8].Hepatology. 2020;10.1002/hep.31309. doi:10.1002/hep.31309

[18] Younossi Z, Stepanova M, Ong JP, et al. Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates. Clin Gastroenterol Hepatol. 2019;17(4):748-755 e743. doi: 10.1016/j.cgh.2018.05.057

[19] Desai A, Sandhu S, Lai JP, Sandhu DS. Hepatocellular carcinoma in non-cirrhotic liver: a comprehensive review. World J Hepatol. 2019;11(1):1-18. doi: 10.4254/wjh.v11.i1.1

[20] Kisiel, J. B., B. A. Dukek, V. S. R. Kanipakam R, H. M. Ghoz, T. C. Yab, C. K. Berger, W. R. Taylor, P. H. Foote, N. H. Giama, K. Onyirioha, M. A. Abdallah, K. N. Burger, S. W. Slettedahl, D. W. Mahoney, T. C. Smyrk, J. T. Lewis, M. Giakoumopoulos, H. T. Allawi, G. P. Lidgard, L. R. Roberts, and D. A. Ahlquist. 2019. 'Hepatocellular Carcinoma Detection by Plasma Methylated DNA: Discovery, Phase I Pilot, and Phase II Clinical Validation', Hepatology, 69: 1180-92.

[21] Chalasani, N. P., T. S. Ramasubramanian, A. Bhattacharya, M. C. Olson, V. Dk Edwards, L. R. Roberts, J. B. Kisiel, K. R. Reddy, G. P. Lidgard, S. C. Johnson, and J. J. Bruinsma. 2020. 'A Novel Blood-based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma', Clin Gastroenterol Hepatol.