Exact Sciences Diagnostic Portfolio

Complete Product Analysis: 20+ Cancer Diagnostics Across the Care Continuum

Exact Sciences operates a comprehensive cancer diagnostics portfolio spanning 20+ products across screening, risk assessment, treatment selection, and monitoring. The company has exactly two FDA-approved tests while operating most products as Laboratory Developed Tests (LDTs) under CLIA certification.

Their portfolio uniquely combines stool-based DNA tests, liquid biopsies analyzing circulating tumor DNA, tissue-based gene expression assays, and hereditary cancer panels.

Strategic acquisitions—Genomic Health ($2.8B, 2019), Thrive Earlier Detection ($2.15B, 2021), PreventionGenetics ($190M, 2022)—and technology licenses from TwinStrand (2024) and Freenome (2025)—have created an integrated cancer continuum from hereditary risk through early detection, treatment selection, and recurrence monitoring.

FDA Approved

2

Cologuard & Cologuard Plus

LDT Products

15+

CLIA/CAP Certified

Total Portfolio

20+

Comprehensive Coverage

Colorectal Cancer Screening Portfolio

From stool-based to liquid biopsy innovations

Cologuard (Original)

FDA APPROVED

FDA Status: Pre-Market Approval (PMA) P130017, approved August 11, 2014; expanded to ages 45+ in May 2019

Biomarkers Measured (11 total):

  • DNA methylation (2 markers): NDRG4 promoter hypermethylation, BMP3 promoter hypermethylation
  • DNA mutations (7 markers): Seven KRAS gene point mutations including codons 35T and 38A
  • Reference gene (1 marker): Beta-actin (ACTB) for quantitative DNA estimation
  • Protein (1 marker): Hemoglobin via immunochemical ELISA

Clinical Performance: Detects CRC with 92.3% sensitivity and advanced adenomas with 42.4% sensitivity at 86.6% specificity. Used for over 20 million screenings (as of May 2025).

Technology: QuARTS (Quantitative Allele-specific Real-time Target and Signal Amplification) for DNA; ELISA for hemoglobin

Cologuard Plus

FDA APPROVED

FDA Status: Pre-Market Approval (PMA) P230043, approved October 4, 2024; launched March 2025

Biomarkers Measured (5 total):

  • DNA methylation (3 markers): LASS4, LRRC4, PPP2R5C
  • Reference gene (1 marker): ZDHHC1
  • Protein (1 marker): Hemoglobin via enhanced bead-based immunoassay

Clinical Performance: BLUE-C study (n=20,176) demonstrated 95% CRC sensitivity, 43.4% advanced precancerous lesion sensitivity, and 94% specificity. Achieves 40% reduction in false positives versus original Cologuard.

Technology: Next-generation LQAS (Long-probe Quantitative Amplified Signal) with bisulfite conversion

Blood-based Colorectal Cancer Screening Test

IN DEVELOPMENT

FDA Status: PMA submission expected H1 2025. Exact Sciences also holds exclusive US license to Freenome's blood-based CRC test (PMA submitted, pending approval)

Biomarkers:

  • cfDNA/Methylation: DNA methylation signatures at single-base resolution from circulating cell-free DNA
  • Multiomics platform: Epigenomic and potentially proteomic biomarkers
  • Machine learning: AI-based models to detect cancer-specific signals

Target Market: 60 million unscreened Americans as alternative to colonoscopy or stool-based tests

Performance: Internal algorithm: 88.3% CRC sensitivity, 31.2% APL sensitivity at 90.1% specificity. Freenome PREEMPT: 81.1% CRC sensitivity, 13.7% APL sensitivity at 90.4% specificity

Oncodetect - Molecular Residual Disease Test

LDT - MEDICARE COVERED

FDA Status: Laboratory Developed Test (LDT), NOT FDA-approved. Launched April 2025 with Medicare coverage through MolDX program for stage II-IV CRC

Technology:

  • Circulating tumor DNA (ctDNA): Tumor-informed personalized test tracking up to 200 patient-specific tumor variants
  • Ultra-sensitive detection: Low limit of detection of 15 parts per million (0.0015% tumor fraction); observed detection down to 2 parts per million in clinical validation studies
  • Platform: Licensed TARDIS technology from TGen/Broad Institute with TwinStrand Duplex Sequencing

Clinical Impact: Alpha-CORRECT study showed 78% post-surgical sensitivity, 91% surveillance sensitivity. Detects recurrence up to 2 years earlier than imaging. Patients with positive ctDNA detection are 50× more likely to experience recurrence.

Oncotype DX Portfolio: Tissue-Based Gene Expression

All Oncotype DX tests are Laboratory Developed Tests without FDA clearance—operating under CLIA/CAP certification using quantitative RT-PCR to measure mRNA expression from FFPE tumor tissue.

Oncotype DX Breast Recurrence Score

LDT

21-Gene Panel (16 cancer-related + 5 reference genes):

  • Proliferation genes (5): Ki-67, STK15, Survivin, Cyclin B1, MYBL2
  • Estrogen receptor genes (5): ER, PGR, BCL2, SCUBE2, GSTM1
  • HER2 genes (2): GRB7, HER2
  • Invasion genes (2): MMP11, CTSL2
  • Other genes (2): CD68, BAG1
  • Reference genes (5): ACTB, GAPDH, GUS, RPLPO, TFRC

Clinical Use: HR+/HER2- early-stage breast cancer. Predicts 10-year distant recurrence risk and chemotherapy benefit. Recurrence Score 0-100: Low (0-17), Intermediate (18-30), High (>30)

Validation: Over 1.5 million patients tested. Validated in TAILORx and RxPONDER prospective trials. Included in ASCO, NCCN, ESMO guidelines

Oncotype DX Breast DCIS Score

LDT

12-Gene Panel (7 cancer-related + 5 reference genes):

  • Cancer genes (7): Ki-67, STK15, Survivin, Cyclin B1, MYBL2, PR, GSTM1
  • Reference genes (5): ACTB, GAPDH, RPLPO, GUS, TFRC

Clinical Use: Ductal carcinoma in situ (stage 0 breast cancer). Predicts 10-year local recurrence risk to guide radiation therapy decisions. DCIS Score: Low (<39), Intermediate (39-54), High (≥55)

Oncotype DX Colon Recurrence Score

LDT

PLA code: 81525

12-Gene Panel (7 cancer-related + 5 reference genes):

  • Stromal/activated stroma genes (3): BGN, INHBA, FAP
  • Cell cycle/proliferation genes (3): Ki-67, MYBL2, MYC
  • Stress response gene (1): GADD45B

Clinical Use: Stage II (T3/T4) MMR-proficient or stage IIIA/B colon cancer. Guides adjuvant chemotherapy decisions. Recurrence Score: Low (<30), Intermediate (30-40), High (≥41)

Multi-Cancer Early Detection & Monitoring

Cancerguard - Multi-Cancer Early Detection (MCED)

LDT

Launched: September 10, 2025

Multi-Analyte Approach:

  • DNA methylation: ctDNA methylation patterns from plasma cell-free DNA
  • Protein biomarkers (9): CA15-3, CA-125, CEA, CA19-9, HGF, AFP, Osteopontin, TIMP-1, Prolactin
  • Machine learning: Proprietary algorithms for signal detection

Target Cancers: Detects 50+ cancer types and subtypes with 68% sensitivity for the six deadliest cancers (pancreatic, ovarian, liver, esophageal, lung, stomach), 64% overall sensitivity, and 97.4% specificity. Covers cancers responsible for 80%+ of annual U.S. diagnoses.

Future Enhancement: Cancerguard EX with DNA mutation reflex planned for H2 2025

Oncoguard Liver

LDT - EARLY ACCESS

Biomarkers:

  • Methylated DNA: cfDNA methylation panel specific for hepatocellular carcinoma
  • AFP (Alpha-fetoprotein): Traditional liver cancer protein marker
  • Machine learning: Integrated algorithm combining methylation and AFP

Clinical Use: Early detection and surveillance of hepatocellular carcinoma (HCC) in high-risk patients with chronic liver disease or cirrhosis

Comprehensive Genomic Profiling

OncoExTra

LDT - MEDICARE COVERED

Medicare Coverage: MolDX approval for advanced solid tumors; CPT code 81479

Comprehensive Analysis:

  • Whole exome sequencing (WES): ~20,000 protein-coding genes
  • Whole transcriptome sequencing (RNA-seq): Gene expression, fusions, splice variants
  • Mutations: SNVs, indels across all genes
  • Copy number variations (CNVs): Amplifications and deletions
  • Tumor mutational burden (TMB): High TMB predicts immunotherapy response
  • Microsatellite instability (MSI): MSI-High status

Technology Platform: Uses FDA-cleared Illumina NextSeq 550Dx with research use only (RUO) reagents

Clinical Application: Advanced solid tumors for treatment selection, therapy matching, and clinical trial eligibility

Oncotype MAP Pan-Cancer Tissue Test

LDT

Targeted Panel:

  • Gene coverage: Hundreds of genes
  • Alterations detected: Mutations, copy number variations, gene fusions
  • Source material: FFPE tumor tissue

Clinical Use: Tumor agnostic tissue profiling for advanced cancers and rare tumor types

Hereditary Cancer Risk Assessment

Riskguard Hereditary Cancer Test

LDT - MEDICARE COVERED

Launched: February 2024 with Medicare coverage

59-Gene Hereditary Cancer Panel:

  • Germline DNA sequencing: Comprehensive analysis of hereditary cancer genes
  • Cancer types covered: Breast, ovarian, colorectal, pancreatic, prostate, uterine, gastric, melanoma, and others
  • Technology: Next-generation sequencing (NGS) of blood or saliva samples

Clinical Application: Identifies inherited cancer predisposition for risk assessment, screening recommendations, and preventive strategies

Patient Support: Includes genetic counseling and actionable recommendations

PreventionGenetics Portfolio

LDT - 5,000+ TESTS

Acquired: January 2022 for $190M

Comprehensive Genetic Testing:

  • Test catalog: Over 5,000 distinct genetic tests; 1,933 tests registered in NIH Genetic Testing Registry
  • Whole exome sequencing (PGxome): Comprehensive exome analysis
  • Whole genome sequencing (PGnome): Comprehensive genome analysis
  • Custom gene panels: Patient-specific panels
  • Germline DNA/RNA: Nearly all clinically relevant genes, CNV analysis

Clinical Applications: Hereditary cancer risk, rare genetic diseases (neuromuscular, neurologic, cardiovascular, metabolic, pediatric/adult), proactive health/wellness, pharmacogenomics

Global Reach: Orders from 84 countries; CLIA/CAP/ISO 15189:2012 accredited

Location: Marshfield, Wisconsin with 25+ PhD geneticists

Regulatory Status Summary

FDA-Approved Products

2
  • Cologuard (PMA P130017, Aug 2014)
  • Cologuard Plus (PMA P230043, Oct 2024)

Laboratory Developed Tests

15+

CLIA/CAP Certified - Most with Medicare Coverage

Pipeline Products (FDA Submission Pending):

  • Blood-based CRC screening: PMA submission expected H1 2025
  • Freenome licensed CRC blood test: PMA submitted, pending approval
  • Cancerguard EX: LDT launch planned H2 2025

Biomarker Type Comparison Table

Product Name Circulating DNA
(cfDNA/ctDNA)		 Tissue DNA Stool DNA RNA/mRNA Protein Peptide Small Molecules
Cologuard (Original) — — ✓
(Methylation + KRAS)		 — ✓
(Hemoglobin)		 — —
Cologuard Plus — — ✓
(Methylation)		 — ✓
(Hemoglobin)		 — —
Blood-based CRC Test ✓
(cfDNA Methylation)		 — — — Potentially — —
Oncodetect MRD ✓
(ctDNA Mutations)		 — — — — — —
Oncotype DX Breast — — — ✓
(21-gene mRNA)		 — — —
Oncotype DX DCIS — — — ✓
(12-gene mRNA)		 — — —
Oncotype DX Colon — — — ✓
(12-gene mRNA)		 — — —
Oncotype DX AR-V7 — — — — ✓
(AR-V7 in CTCs)		 — —
Cancerguard MCED ✓
(ctDNA Methylation)		 — — — ✓
(9 proteins)		 — —
Oncoguard Liver ✓
(cfDNA Methylation)		 — — — ✓
(AFP)		 — —
OncoExTra — ✓
(WES)		 — ✓
(RNA-seq)		 — — —
Oncotype MAP Pan-Cancer — ✓
(Targeted NGS)		 — — — — —
Riskguard — ✓
(Germline DNA)		 — — — — —
PreventionGenetics Portfolio — ✓
(Germline DNA)		 — ✓
(Select tests)		 — — —

📊 Key Observations from Biomarker Table:

  • Protein biomarkers are used selectively: hemoglobin protein via immunochemical ELISA (Cologuard products), 9-protein panel combined with methylation (Cancerguard MCED: CA15-3, CA-125, CEA, CA19-9, HGF, AFP, Osteopontin, TIMP-1, Prolactin), AFP protein (Oncoguard Liver), and AR-V7 protein in CTCs (Oncotype AR-V7). Small molecule metabolite biomarkers are not currently used in the portfolio.
  • DNA methylation (from cfDNA, stool, or tissue) is the most common biomarker type across the portfolio
  • RNA/mRNA expression is limited to the Oncotype DX tissue-based tests and OncoExTra
  • Circulating DNA (cfDNA/ctDNA) represents the fastest-growing segment with Oncodetect, Cancerguard, Oncoguard Liver, and blood-based CRC test
  • Stool DNA remains unique to the Cologuard franchise with no competitors in this space

Comparative Biomarker Analysis

ctDNA/cfDNA-Based Products

Liquid Biopsy Blood-based
  • Oncodetect MRD: Tumor-informed ctDNA tracking up to 200 variants; detects 1 molecule in 20,000 cfDNA molecules
  • Blood-based CRC screening: DNA methylation from cfDNA with multiomics approach
  • Cancerguard MCED: ctDNA methylation patterns combined with protein biomarkers
  • Oncoguard Liver: Methylated DNA from cfDNA combined with AFP protein

DNA Methylation-Focused Products

Epigenetic Core Technology
  • Cologuard: NDRG4, BMP3 methylation from stool DNA
  • Cologuard Plus: LASS4, LRRC4, PPP2R5C methylation from stool DNA
  • Cancerguard: cfDNA methylation patterns
  • Oncoguard Liver: Methylated DNA panel
  • Blood CRC test: cfDNA methylation signatures

Protein Biomarker Products

Immunoassay
  • Cologuard/Cologuard Plus: Hemoglobin immunochemical detection
  • Oncotype DX AR-V7: AR-V7 splice variant protein in CTC nuclei
  • Cancerguard: 9 proteins (CA15-3, CA-125, CEA, CA19-9, HGF, AFP, Osteopontin, TIMP-1, Prolactin)
  • Oncoguard Liver: Alpha-fetoprotein (AFP)

RNA/mRNA Expression Products

Gene Expression RT-PCR
  • All Oncotype DX tests: Quantitative RT-PCR measuring mRNA expression from tumor tissue
  • Oncotype Breast: 21-gene panel
  • Oncotype DCIS: 12-gene panel
  • Oncotype Colon: 12-gene panel
  • OncoExTra: Whole transcriptome sequencing (RNA-seq) for fusions and transcript variants

DNA Mutation/Genomic Sequencing Products

NGS Whole Exome
  • Cologuard: 7 KRAS point mutations from stool DNA
  • Oncodetect: Patient-specific somatic mutations via whole exome sequencing
  • OncoExTra: Whole exome sequencing (~20,000 genes), somatic mutations, CNVs, TMB
  • Oncotype MAP: Hundreds of genes for mutations, CNVs, fusions
  • Cancerguard (enhanced): DNA mutation reflex approach in development

Germline Sequencing Products

Hereditary Risk Assessment
  • Riskguard: 59 hereditary cancer genes
  • PreventionGenetics: 5,000+ tests including whole exome/genome sequencing

Key Findings & Strategic Insights

🔬 LDT Dominance Over FDA Approval

Despite having two FDA-approved products, Exact Sciences operates most of its 20+ product portfolio as LDTs under CLIA certification rather than pursuing FDA clearance. This regulatory strategy enables faster market entry while maintaining Medicare reimbursement for clinically validated tests like Oncodetect, OncoExTra, and Riskguard. The company has secured Medicare coverage through MolDX for multiple LDT products despite lack of FDA approval.

🧬 DNA Methylation as Core Technology Platform

Methylated DNA biomarkers appear across the majority of Exact Sciences products—from stool-based Cologuard to liquid biopsies (Cancerguard, Oncoguard Liver, blood CRC test). This represents a consistent technological focus differentiating Exact Sciences from competitors using primarily mutation-based or protein-based approaches. Methylation markers enable early cancer detection before extensive mutational accumulation occurs.

💼 Strategic Acquisition Integration

The $2.8B Genomic Health acquisition brought not only Oncotype DX tests but also laboratory infrastructure enabling OncoExTra and Oncodetect development. The $190M PreventionGenetics acquisition delivered hereditary testing capabilities and 25+ PhD geneticists, enabling Riskguard launch and expansion into germline cancer risk assessment. Technology licenses from TwinStrand (duplex sequencing), TGen (TARDIS platform), and Thrive/Freenome (blood CRC test) demonstrate strategic "build and buy" approach.

🔄 Cancer Continuum Coverage

The portfolio spans the complete cancer care journey: hereditary risk assessment (Riskguard, PreventionGenetics) → screening and early detection (Cologuard, Cancerguard, Oncoguard Liver) → treatment selection (Oncotype DX, OncoExTra) → monitoring and surveillance (Oncodetect MRD). This comprehensive approach positions Exact Sciences to capture value across multiple clinical touchpoints rather than single-indication focus.

🎯 Biomarker Class Diversity

Unlike companies focused exclusively on ctDNA or protein markers, Exact Sciences employs multiple complementary biomarker classes often within single products. Cancerguard combines methylation + proteins with planned mutation reflex. Oncoguard Liver pairs methylation with AFP protein. This multi-analyte strategy improves sensitivity across cancer stages and types compared to single-biomarker approaches.

🚫 No Peptides or Small Molecules

Notably absent from the portfolio are peptide-based or small molecule metabolite biomarkers, despite these being explored by some competitors. The portfolio focuses on nucleic acids (DNA, RNA, ctDNA) and select protein markers, suggesting strategic technology focus on genomic/epigenomic approaches over metabolomic or peptidomic platforms.

💰 Medicare Coverage as Validation

Multiple LDT products have secured Medicare coverage (Oncodetect, OncoExTra, Riskguard) through MolDX and other programs, demonstrating that clinical validation and health economics evidence can enable reimbursement without FDA approval. This pathway has become central to Exact Sciences' commercial strategy for new product launches.