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Corus™ CAD Overview Corus CAD Intended Use Statement referenced at the end of this presentation © 2010 CardioDx. Content is Confidential and Proprietary.

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Presentation on theme: "Corus™ CAD Overview Corus CAD Intended Use Statement referenced at the end of this presentation © 2010 CardioDx. Content is Confidential and Proprietary."— Presentation transcript:

1 Corus™ CAD Overview Corus CAD Intended Use Statement referenced at the end of this presentation © 2010 CardioDx. Content is Confidential and Proprietary

2 38% obstructive coronary
Better Diagnostic Methods are Needed to Stratify Patients for Elective Invasive Angiography8 Patient population: 397,954 stable patients with clinical risk factors and/or symptoms of CAD (but no prior history of CAD) undergoing cardiac catheterization for evaluation Study found: 62% of patients who underwent elective cardiac catheterization did not have significant CAD 40% of patients had minimal to no CADi Majority of patients (83.9%) received noninvasive diagnostic testsii prior to referral to catheterization 120 100 80 % of total patients 38% obstructive coronary artery disease 60 40 20 Pre-Coronary Angiography Post-Coronary Angiography i Minimal to no CAD is defined as < 20% stenosis ii Resting ECG, exercise or pharmacological stress, echocardiography, radionucleotide, CT scans, or other heart scans N=397,954 N=149,739 © 2010 CardioDx. Content is Confidential and Proprietary

3 The Challenge of Assessing CAD1-5
Despite advances in imaging technology, non-invasive assessment of obstructive CAD continues to be subjective and challenging The complexity of CAD diagnosis lies not only in the variation of presenting symptoms, but also in the patient’s unique characteristics Implementation of standard of care involving non-invasive imaging assessment of CAD is highly variable regarding the type, number, and sequence of tests © 2010 CardioDx. Content is Confidential and Proprietary

4 Cardiac Imaging Procedures Deliver Significant Amounts of Ionizing Radiation6
Estimates of Effective Doses for Selected Cardiac Imaging Procedures (in mSv) Study reported: MPI procedures contributed to 74.2% of cumulative effective radiation dose from overall cardiac imaging procedures © 2010 CardioDx. Content is Confidential and Proprietary

5 MPI is the Largest Contributor of Radiation Overall6
Contribution to Cumulative Effective Radiation Dose by Type of Cardiac Imaging Procedures (in mSv) Study design: This is a subset of the NEJM Fazel 2009 study, focused only on cardiac imaging procedures Study reported: MPI procedures contributed to 74.2% of cumulative effective radiation dose from overall cardiac imaging procedures Radiation dose and risk accumulates over a person’s lifetime © 2010 CardioDx. Content is Confidential and Proprietary

6 Women Receive Higher Radiation Dosing From Medical Imaging7
In 2009, the NEJM reported: Cumulative effective doses of radiation from imaging procedures were higher in women than in men Computed tomography and nuclear imaging accounted for 75.4% of the cumulative effective dose © 2010 CardioDx. Content is Confidential and Proprietary

7 Genomics: A New Era in Medicine
The Human Genome Project has ushered in the era of genomic medicine and the promise of more individualized patient care Genomic testing has the power to inform about disease processes at the molecular and cellular level CardioDx delivers the first and only clinically validated gene expression test to turn the promise of genomic medicine into practice for assessing obstructive* coronary artery disease (CAD) *Obstructive CAD is defined as at least one atherosclerotic plaque causing ≥50% luminal diameter stenosis in a major coronary artery (≥1.5mm lumen diameter) as determined by invasive quantitative coronary angiography (QCA). © 2010 CardioDx. Content is Confidential and Proprietary

8 Genetic Testing VS Gene Expression Tests
© 2010 CardioDx. Content is Confidential and Proprietary

9 About Corus™ CAD The first clinically validated gene expression test for assessing obstructive coronary artery disease (CAD) in non-diabetics Enables more informed decision-making and risk stratification Test has high sensitivity and negative predictive value Test score reflects the presence and extent of obstructive CAD Test improves classification of patient disease status A safe and convenient genomic test Blood sample collection takes minutes, and test results are delivered promptly to the clinician’s office © 2010 CardioDx. Content is Confidential and Proprietary LEN Rev.01 © 2010 CardioDx. Content is Confidential and Proprietary

10 Clinically Validated Gene Expression Test for the Assessment of Obstructive CAD10,11
Delivers a biological view into a patient’s disease state Algorithm comprised of expression levels of 23 genes demonstrated to indicate obstructive CAD Molecular basis includes genes and pathways with known involvement in atherosclerosis and its progression Based on the detection of a reliable molecular signature for obstructive CAD © 2010 CardioDx. Content is Confidential and Proprietary

11 Rigorous Multi-Center Product Development and Validation
© 2010 CardioDx. Content is Confidential and Proprietary LEN Rev.01 © 2010 CardioDx. Content is Confidential and Proprietary

12 Corus™ CAD Gene Term Examples3-8
© 2010 CardioDx. Content is Confidential and Proprietary LEN Rev.01 © 2010 CardioDx. Content is Confidential and Proprietary

13 Corus™ CAD Algorithm Terms and Genes4
Males Females 1) Neutrophil Activation - Apoptosis Innate Immunity (IL18RAP, TNFAIP6 CASP5) – (IL8RB TNFRSF10C, TLR4, KCNE3) 2) Neutrophil Activation/Lymphocytes Innate Immunity/Cell Necrosis (S100A8, S100A12, CLEC4E) - RPL28 3) NK Activation/T cells SLAMF7, KLRC4 - TMC8, CD3D 4) B/T Ratio - Adaptive Immune Response SPIB, CD79B - TMC8, CD3D 5) AF2- TFCP2, HNRPF 6) TSPAN - TFCP2,HNRPF 1) Neutrophil Activation - Apoptosis Innate Immunity (IL18RAP, TNFAIP6 CASP5) – (IL8RB TNFRSF10C, TLR4, KCNE3) 2) Normalized Neutrophil Activation Innate Immunity/Cell Necrosis (S100A8, S100A12, CLEC4E) - (NCF4, AQP9) 3) NK Activation/T cells SLAMF7, KLRC4 - TMC8, CD3D 4) B/T Ratio - Adaptive Immune Response SPIB, CD79B - TMC8, CD3D 5) AF2 - TFCP2,HNRPF © 2010 CardioDx. Content is Confidential and Proprietary LEN Rev.01 © 2010 CardioDx. Content is Confidential and Proprietary

14 Corus™ CAD is Multifactorial
Gene Expression Derived Cell Type Ratios MOLECULAR & CELLULAR FACTORS Gene Expression Changes Within a Certain Cell Type CELL TYPE-SPECIFIC GENE EXPRESSION Gender-Specific, Age Dependent Coronary Disease Risk Functions GENDER & AGE RISK FUNCTIONS U.S. Prevalence of Coronary Heart Disease by Age & Sex, NHANES © 2010 CardioDx. Content is Confidential and Proprietary

15 Clinical Validation Trials PREDICT TRIAL

16 Corus™ CAD Validation Data Published in Annals of Internal Medicine – October 201010
“Rosenberg and colleagues’ study lies at the vanguard of clinical genetics in cardiovascular care. ” -Excerpt from AIM editorial, Donna Arnett Ph.D., M.S.P.H.

17 PREDICT Summary9,10 Prospective, multi-center, blinded* study
1,343 nondiabetic patients enrolled to develop and validate Corus™ CAD 39 U.S. sites participated Study PI: Eric Topol, MD, Scripps Research Institute QCA Core Lab: Alexandra Lansky, MD, Columbia University/CRF Enrolling sites and investigators included: Vanderbilt Heart and Vascular Institute (TN) John McPherson, MD Washington Hospital Center (DC) Ron Waksman, MD Cleveland Clinic Foundation (OH) Steven Ellis, MD Minneapolis Heart Institute (MN) Robert Schwartz, MD Duke University Medical Center (NC) Bill Kraus, MD & Kristin Newby MD Intermountain Medical Center (UT) Brent Muhlestein, MD Piedmont Hospital Research Institute (GA) Szilard Voros, MD Oklahoma Cardiovascular Research Group (OK) Naeem Tahirkheli, MD Allegheny General Hospital (PA) Tony Farah, MD *Data was analyzed in a blinded fashion © 2010 CardioDx. Content is Confidential and Proprietary

18 Personalized Risk Evaluation and Diagnosis In the Coronary Tree
PREDICT Trial Design9,10 Personalized Risk Evaluation and Diagnosis In the Coronary Tree © 2010 CardioDx. Content is Confidential and Proprietary

19 Probability of CAD in Females and Males as Observed in PREDICT1,2
© 2010 CardioDx. Content is Confidential and Proprietary LEN Rev.01 © 2010 CardioDx. Content is Confidential and Proprietary

20 Corus™ CAD Score is Proportional to Disease Severity4
© 2010 CardioDx. Content is Confidential and Proprietary LEN Rev.01 © 2010 CardioDx. Content is Confidential and Proprietary

21 Clinical Validation Trials COMPASS TRIAL

22 COMPASS Study Overview
Second validation study for Corus™ CAD in the intended use population Will also evaluate MPI performance in the real-world clinical setting Prospective, multi-center, blinded* study 450 patients to be enrolled at 21 U.S. sites QCA Core Lab: Cardiovascular Research Foundation Study completion: Q4 2010 Steering committee: John McPherson, MD, Alexandra Lansky, MD, Greg Thomas, MD, Szilard Voros, MD Enrollees include patients referred for a clinically indicated MPI who meet the following criteria**: Symptomatic (chest pain or anginal equivalent) who have been referred for MPI for the workup of suspected obstructive CAD Non-diabetic No known obstructive CAD, prior myocardial infarction, or prior revascularization procedure *Data to be analyzed in a blinded fashion **Complete inclusion and exclusion criteria may be found in protocol NCT at ClinicalTrials.gov. © 2010 CardioDx. Content is Confidential and Proprietary 22

23 COMPASS Trial Design All non-diabetic patients referred for clinically indicated MPI for chest pain or anginal equivalent symptoms without known obstructive CAD, MI or revascularization were enrolled. MPI positive patients received invasive angiography if clinically indicated. MPI negative patients received CT angiography. If clinically indicated, patients went onto catheterization for further evaluation. © 2011 CardioDx. Content is Confidential and Proprietary

24 Rigorous Data Analysis and Approach Undertaken in the COMPASS Trial
Core lab interpretation with QCA QCA Core Lab: Cardiovascular Research Foundation Invasive Angiography CTA Core Lab Readers: Szilard Voros, MD James R Adams, MD Core lab interpretation CT Angiography On site interpretation MPI Core lab interpretation MPI Core Lab Reader: Timothy M Bateman, MD © 2011 CardioDx. Content is Confidential and Proprietary

25 Corus® CAD vs. MPI Performance
Site-read MPI P-value Sensitivity 89% 27% p<0.001 NPV 96% 88% In the COMPASS trial, Corus CAD outperformed MPI in sensitivity and (89% vs. 27%, p<0.001) and negative predictive value (96% vs. 88%, p< 0.001) for ruling out obstructive coronary artery disease There were 199 (46%) of patients with GES <=15. Corus CAD shows very good sensitivity and NPV for obstructive CAD. This suggests the Corus CAD is significantly better at ruling-out disease without missing patients. *Summary statistics at a pre-specified threshold of 15 Core-read MPI Sensitivity: 36% Core-read MPI NPV: 88% © 2011 CardioDx. Content is Confidential and Proprietary

26 Corus™ CAD Decreases the Rate of False Positive Classifications From MPI4
Case/Total (case %) MPI Positive* Corus CAD Overall 76/223 (34%) Corus CAD Low 6/57 (11%) Corus CAD Intermediate 21/78 (27%) Corus CAD High 49/88 (56%) Legend MPI Positive 76 cases/223 patients (34% case rate) When Corus CAD and MPI disagreed, Corus CAD was correct* 89% of the time and MPI was correct 11% of the time *MPIs were defined as positive if at least one reversible or fixed defect consistent with obstructive CAD was reported. Indeterminate or intermediate defects were considered negative. 60% of PREDICT validation cohort patients had MPI. Data from the PREDICT validation cohort, as determined by quantitative coronary angiography (QCA). © 2010 CardioDx. Content is Confidential and Proprietary LEN Rev.01 © 2010 CardioDx. Content is Confidential and Proprietary

27 Potential New Paradigm of Care based on COMPASS Results
Thomas et al, Circ Cardiovasc Genetics 2 /15/2013; DOI: /CIRCGENETICS © 2011 CardioDx. Content is Confidential and Proprietary

28 COMPASS Trial Follow-up: Patients with Low Corus® CAD Scores Showed Very Low Event Rates at 6 Months
6-month Follow-up n=420/431 (97%) Early Revascularization (within 1 month) Late Revascularization and MACE (between 1 and 6 months) Corus CAD ≤15 (n=192) 1 (0.5%) 0 (0%) Corus CAD >15 (n=228) 24 (11%) 3 (1.3%) Corus CAD had a sensitivity of 96% and NPV >99% for events and revascularizations at 6-month follow-up Significant correlation between increasing Corus CAD scores and increased event likelihood* *p-value = © 2011 CardioDx. Content is Confidential and Proprietary

29 Relationship Between Corus® CAD Score and Percent Coronary Artery Stenosis
In patients with low Corus CAD scores ( ≤ 15), 96% of patients did not have obstructive CAD The higher the Corus CAD score, the higher the likelihood of obstructive (≥ 50% stenosis), minimal (1-24%) and moderate (25-49%) CAD, and the lower the likelihood of no disease © 2011 CardioDx. Content is Confidential and Proprietary

30 CORUS CAD PERFORMANCE at threshold score of 15
Corus® CAD Demonstrates Consistent, Strong Performance in Three Independent Cohorts CORUS CAD PERFORMANCE at threshold score of 15 COMPASS (total N=431) PREDICT-CTA* (total N=216) PREDICT (total N=526) Sensitivity 89% 83% 85% Specificity 52% 45% 43% NPV 96% 93% Prevalence 15% 16% 37% Corus CAD outperformed MPI in diagnostic accuracy in the assessment of obstructive CAD in symptomatic patients Corus CAD AUC** = 0.79*** and MPI AUC = 0.59**** Statistically significant with p < 0.001 *Core-lab CTA **AUC: Area under the curve, a method of measuring diagnostic accuracy ***95% CI **** 95% CI © 2011 CardioDx. Content is Confidential and Proprietary

31 Corus™ CAD Intended Patients
Corus CAD is intended for use in the following non-diabetic patients that a clinician suspects may have coronary artery disease (CAD): Asymptomatic High-Risk Patients Patients with a recent positive or inconclusive test result (ECG, ETT, Echo, MPI, CTA, Calcium Score) and/or Patients with 3 or more major risk factors for CAD (e.g., high cholesterol, hypertension, family history, smoker, morbid obesity, known non-cardiac vascular disease, male > 50, female > 60) Corus CAD is NOT intended for patients: With known prior myocardial infarction, or who have had a revascularization procedure Younger than 21 or older than 99 years of age Who are asymptomatic and not considered at high risk for CAD © 2010 CardioDx. Content is Confidential and Proprietary

32 Corus™ CAD Patient Sample Kit
All-in-one solution in a convenient patient sample kit All-in-one solution: sample collection kit, sample shipper, self-contained cooling system PAXgene®-based sample collection means no processing, no spin-down at the clinic On-demand cooling system* means no dry-ice, no ice packs for sample shipment back to CardioDx *Evaporative, adsorption cooling system. Validated to maintain 4°C for 48 hours. For more information visit © 2010 CardioDx. Content is Confidential and Proprietary

33 Corus™ CAD Test Requisition Form
Account Information Patient Information Ordering Clinician's Signature Billing Information Blood Draw Information Comments © 2010 CardioDx. Content is Confidential and Proprietary

34 Corus™ CAD Patient Report
Patient Score: Ranges between 1 and 40, with higher values associated with higher likelihood of obstructive CAD. Graph: Depicts the relationship between test score and the likelihood of obstructive CAD in the clinical validation study. Likelihood of Obstructive CAD: Derives from the patient score and is reported with a 95% confidence interval (CI). A 95% CI indicates there is a 95% chance that the actual likelihood is within this range. © 2010 CardioDx. Content is Confidential and Proprietary

35 Corus™ CAD Intended Use (page 1 of 2)
The Corus CAD test is a quantitative in vitro diagnostic test performed in a single laboratory, using the gene expression profile of cells found in peripheral blood specimens to be used as an aid to identify patients who are likely to have coronary artery stenosis of at least 50%. The test should be performed on patients with a history of chest pain, with suspected anginal equivalent to chest pain, or with a high risk of coronary artery disease, but with no known prior myocardial infarction or revascularization procedures. The test is not intended for patients with acute myocardial infarction, high risk unstable angina, systemic infectious or systemic inflammatory conditions, diabetes, and/or who are currently taking steroids, immunosuppressive agents, or chemotherapeutic agents. © 2010 CardioDx. Content is Confidential and Proprietary

36 Corus™ CAD Intended Use (page 2 of 2)
The test is performed on a blood specimen obtained from the patient. The test incorporates the expression levels of multiple genes using an algorithm with weighted functions to generate a quantitative score. The results of the test should be used by clinicians in conjunction with other tests and clinical information in their assessment of a patient’s coronary artery disease. The Corus CAD test is for prescription use only. The test is not intended to be used to screen for stenosis among patients who are asymptomatic and not considered at high risk for coronary artery disease, to predict or detect response to therapy, or to help select the optimal therapy for patients. © 2010 CardioDx. Content is Confidential and Proprietary


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