HPV OncoTect E6, E7 mrna Kit A highly specific molecular test for early detection of cervical cancer

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1 Revolutionizing healthcare one cell at a time HPV OncoTect E6, E7 mrna Kit A highly specific molecular test for early detection of cervical cancer

2 Numerous studies confirm that the presence of HR HPV DNA is a necessary cause of cervical cancer. 1 However, only a small percentage of HR HPV DNA infections result in pre-cancerous lesions ( CIN2). 2 Additional data now demonstrates that E6 and E7 mrna is a more specific indication of cellular transformation and the presence of CIN2. 3,5,6,7,8,9,10

3 HPV OncoTect E6, E7 mrna Kit A highly specific molecular test for early detection of cervical cancer NOW AVAILABLE: The HPV OncoTect E6, E7 mrna Kit is a unique detection method that measures both the number of transforming cells and the quantity of E6, E7 mrna in each cell. 5 These two measurements precisely assess the overexpression of E6, E7 mrna in routine patient samples collected in ThinPrep and Surepath vials to further refine accuracy and specificity of HPV testing. Flow cytometry simplified: No requirement for extraction of nucleic acid, eliminating cross contamination Results available in 3 hours for fast turnaround time Variable batch sizes (24 or 96 specimens) for flexible throughput Result output is clearly stated to indicate positive or negative Adaptable to most flow cytometers Clinical Performance of HPV OncoTect E6, E7 mrna Kit: Equivalent clinical sensitivity to HR HPV DNA Tests (95% detection of CIN2) Significant increase in specificity Unique specimen adequacy feature: > Quantifies number of ectocervical and endocervical cells > Quantifies the presence of obscuring inflammatory cells

4 REVOLUTIONIZING HEALTHCARE ONE CELL AT A TIME Overexpression of E6, E7 within the cell makes the difference Many women with positive test results from a HR HPV DNA Test will have normal biopsy. The HPV OncoTect E6, E7 mrna Test is only positive if there is overexpression of E6, E7. In the life cycle of the human papillomavirus, the overexpression of E6, E7 mrna in a cell is the molecular switch leading to cervical cancer. 3,4 Mature Squamous Layer HR HPV DNA Positive HPV OncoTect E6, E7 mrna Test Positive Normal Biopsy CIN 3 E6, E7 inside nucleus Squamous Layer Para-Basal (non-dividing) Keratinocytes Transit Layer Cell Cell Nucleus APC Epithelial Basement Membrane APC=Antigen Presenting Cell Developed from: N. Muñoz et al. / Vaccine 24S3 (2006) The HPV virus invades the mucosa of the basal membrane of the cervix. From there the infected cell divides and spreads out in a lateral fashion. Some of the virus migrates to the suprabasal layers where viral genes are activated. Performance of HPV OncoTect E6, E7 mrna Test Percentage Sens = Clinical Sensitivity in CIN2+ Spec = Clinical Specificity in CIN2+ PPV = Positive Predictative Value Sens Spec PPV Hybrid Capture 2 High-Risk APTIMA HPV Assay 6 HPV OncoTect E6, E7 HPV DNA Test 6 mrna Test 11,12,13,14

5 REVOLUTIONIZING HEALTHCARE ONE CELL AT A TIME Simple Workflow Sample Collection Aspirate Add Vortex Centrifuge Analyze 24 & 96 Test Procedure Aspirate Add Vortex Centrifuge Waterbath 1 1 ml PBS Start To Finish: Approx. 3 Hours ul R1 1 ml R2 (1 hr. wait) 3 1 ml R3 Make the master mix by combining 100 ul R4 and 3 ul R5 per sample, vortex ul R4/R5 mix 30 min 1 ml R6 5 1 ml R7 15 min ul PBS Action No Action Required The sample is ready for analysis on the flow cytometer.

6 Product Design Features Analytical Sensitivity Clinical Decision Point Specimens Specimen Adequacy Control External Controls Result Interpretation Input Volume 5-10 E6, E7 mrna copies per cell 2% of cells expressing ThinPrep, SurePath Quantification of minimum level of endocervical cells and cells per microliter (FSC versus SSC) 15,16,17 Preserved cell lines well characterized as positive or negative Positive or Negative, based on clinical decision cut-off 500 ul HPV Products Available C12100 Controls Kit includes all reagents and FL-labeled HPV probes (100-Test Kit) Positive and Negative Control Cells in LBC preservative Other incelldx Products HIV HIV TROPISM HCV Coming Soon! EBV CMV In Development Breast Cancer Ovarian Cancer 1700 El Camino Real Menlo Park, CA Phone: OncoTect is a trademark of incelldx ThinPrep is a registered trademark of Hologic, Inc. SurePath is a trademark of BD APTIMA is a registered trademark of GenProbe, Inc. Hybrid Capture 2 is a registered trademark of QIAGEN 2009 incelldx, Inc. 1 Wallboomers JM, et al. Human papilloma virus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999: 189:12. 2 Schiffman M, Kjaer SK, Chapter 2: Natural history of anogenital human papillomavirus infection and neoplasia J Natl Cancer Inst Monograph ; zur Hausen, H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002, 2: Schwartz E, et al. Structure and Transcription of the human papillomavirus sequences in cervical carcinoma cells. Nature 1985;314: Grundhoefer, D and B.K. Patterson 2001 Determination of liquid-based cervical cytology specimen adequacy using cellular light scater and flow cytometry. Cytometry 46: Szarewski, et al, Comparison of Predictors for High Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears, CEBP 2008:17 (ii). Nov Ratnam, et al, Clinical Correlation of APTIMA HPV Assay in Comparison with hc2 Test in Cervical Cancer Screening ISSTDR Poster July Dockter, et al, Clinical Performance of APTIMA HPV Assay for Detection of E6/E7 mrna from HR HPV Types in Liquid Based Cytology Specimens ISSTDR Poster July S Dockter, J, et al. Clinical performance of the APTIMA HPV Assay for the detection of high-risk HPV and high grade cervical lesions J. Clin Virol 2009 Jul; 45 Suppl 1: Miralles, R., Editorial in ginecologia y obstetrician clinica, Volumen 9 Numero 3/2008, July/September 11 Kottaridi C, et al J. Inf Dis 2009 in press 12 Patterson B K, et al; Eurogin Pierry, D et al Eurogin 2010 abstract accepted 14 Irwin D, et al Clinical Virology Symposium Kottaridi C, et al. Use of flow cytometry as a quality control device for liquid-based cervical cytology specimens. Cytometry Sep 10. [Epub ahead of print] 16 Narimatsu, R and B K Patterson, High throughput cervical cancer screening using intracellular human pailloma virus E6 and E7 mrna quantification by flow cytometry. Am J Clin Pathol Polina R, Sturgis C, Patterson J, Patterson BK. Rapid, high throughput determination of cervical cytology specimen adequacy using a capillary-based cytometer. Cytometry Mar;74(2): Item Number: