Early Detection of Lung Cancer by a FISH-based Sputum Test

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1 Early Detection of Lung by a FISH-based Sputum Test

2 US Lung Statistic at Glance Estimated New Cases by Sites, Estimated Deaths by Sites, , , ,000 Prostat e 158, , ,000 0 Breast Colorecta l Other s 221,200 Lung & Bronchus Lung Cncer Other s Lung 2 Localized (Confined to primary site) Distant (cancer has metastasized) Regional (spread to lymph nodes) UnStaged tumors not shown 1. American Society. Facts and Figures, U.S. National Institutes of Health. National Institute. SEER Statistics Early Detection Decreasing Lung Mortality

3 LOW DOSE CT SCAN (LDCT) Screening Test for High Risk 96% False Positive 3 NEGATIVE INDETERMINATE POSITIVE Invasive Procedures Healthcare Costs Benign Nodules Radiological Surveillance PET CT Patient Anxiety Radiation Exposure Malignant Nodules Invasive Intervention Early Detection Reduced Mortality 3 Aberle DR, et el, NLST Study, 2011

4 The Unmet Need Aid In Early Detection Reduce Invasive Tests Improving LDCT Specificity Reduce CT Scans Increase Accuracy

5 BioView LCD Test Non-Invasive Test for Lung Detection BioView Duet Imaging System Enables to examine the same cell twice, once with morphology stain and once in FISH Scan Cytogenetics Biomarkers 3p22.1 and 10q22.3 express numerical chromosomal alteration in malignant bronchial epithelial cells of lung tumor via Fluorescence In Situ Hybridization (FISH) Induced Sputum Non invasive specimen contains exfoliated bronchial cells from the lower respiratory tract and can be used for detecting cancerous cells as an aid for lung cancer diagnosis

6 Study Objectives Evaluate LCD Test performance for the detection of lung cancer from induced sputum Multi Center Clinical Study Design Participate 6 Medical Centers in US and Israel 3 Labs, 2 CLIA labs in US 1 in Israel CRO Group: ICON plc, USA Study Population Subjects with 0.8-3cm pulmonary nodules suspected for lung cancer undergoing lung biopsy Induced sputum Lung biopsy (Non-Surgical and Surgical) BioView LCD TEST Combined analysis of sputum cytology and Target-FISH on the same cell Positive % of ous cells > cutoff Negative % of ous cells < cutoff Positive Surgical and non surgical biopsy confirm malignancy Lung Determinate Negative 1. Surgical biopsy rule out malignancy 2. Detect Benign disease Non Indeterminate Negative non-surgical biopsy does not role out malignancy Follow up for 2 years 1. Establish final diagnosis 2. Confirm nodule stability LCD Test Result Compare Final clinical Diagnosis Indeterminate Not Included

7 LCD Test Target-FISH Flow Chart

8 Excluded Subjects Demographics Included Subjects GROUPS n % Total Enrolled Subjects 173 Excluded Subjects % UnMet IE % Biopsy not done % Sputum Failure % Other % Included Subjects % Under Follow up % Determinate Results % Total Male % Female % Age, Years Race GROUPS n % Mean (Range) 64.7 (35-86) White % Black % Hispanic % Smoking Status Non-Smoker % Current Smoker % Former Smoker %

9 LCD Test Performance LCD Test vs. Clinical Diagnosis CLINICAL DIAGNOSIS Biopsy Pathology Result and Nodule Stability LCD Test Performance (95% C.I) LCD Test Positive Initial Biopsy Lung No 62 2 Follow Up Lung No 9 5 Final Diagnosis Lung No 71 7 Initial Biopsy Sensitivity: 86.7% ( ) Sensitivity: 85.5% ( ) Specificity: 74 % ( ) Negative PPV: 91% ( ) NPV: 62.5% ( ) In 9/11 subjects, LCD Test revealed cancerous cells within 17 to 402 days before the final diagnostic biopsy Accuracy: 82.7% ( ) Prevalence: 75.5 % ( )

10 Sensitivity: LCD Test vs. Lung Biopsy According to Radiologic Imaging Characteristics Nodule Location & Size All Patients Patients Initial Biopsy LCD Test All (75%)* [72] 86.7% ( ) [71] 85.5% ( ) Nodule Location Central Peripheral (73%) 64 (76%) [16] 84.2% ( ) [56] 87.5% ( ) [18] 94.7% ( ) [53] 82.8% ( ) Nodule Size < 1.5 cm cm (20%) 33 (75%) [14] 82.4% ( ) [27] 81.8% ( ) [14] 82.4% ( ) [30] 90.9% ( cm (75%) [31] 93.9% ( ) [27] 81.8% ( )) * Percent of cancer patients /all patients

11 Sensitivity: LCD Test vs. Lung Biopsy According to Lung Histology Histology Patients Initial Biopsy LCD Test N S C L C Adenocarcinoma Squamous Cell Carcinoma NOS % ( ) 100.0% ( ) 66.7% ( ) 83.3% ( ) 95.2% ( ) 66.7% ( ) Small Cell Lung % ( ) 100.0% ( ) Other % ( ) 50.0% ( )

12 Sensitivity: LCD Test vs. Lung Biopsy According to Lung Stage Stage Patients Initial Biopsy LCD Test Early Stages I II % ( ) 100.0% ( ) 87.2% ( ) 75.0% ( ) Advanced Stages III IV Unknown % ( ) 82.4% ( ) 50.0% ( ) 82.4% ( ) 94.1% ( ) 50.0% ( )

13 Conclusion THE LCD TEST MAY BE USEFUL AS A DECISION SUPPORT TOOL AT CRITICAL POINTS OF CLINICAL DILEMMA FOR SUBJECTS WITH HIGH RISK OF CANCER Small nodules 8-22 mm with moderate probability LCD Test detect 44/50, Initial biopsy detect 41/50 INCREASE NODULES MANAGEMENT ACCURACY LCD Test detects 17/22 benign nodules 22 mm and 6/7 central benign lesions LCD Test detects cancer in 9/11 subjects after initial negative non-surgical biopsy