Diagnostics: The Effect on Evidence Based Clinical Pathways. DNA vs Disease. Bruce K. Pa+erson MD CEO and President, IncellDx, Inc.

Transcription

1 Diagnostics: The Effect on Evidence Based Clinical Pathways DNA vs Disease Bruce K. Pa+erson MD CEO and President, IncellDx, Inc.

2 Who Who are we? We Are Cancer First platform to combine proteomic and genomic biomarkers in a single assay on intact cells. Infectious Disease Organ Transplant

3 Our Company! Privately-held molecular diagnostics company" Patented technology focuses on cancer and infectious disease screening, specifically targeting cervical cancer! IncellDx technology is the only assay family to combine proteomic and genomic biomarkers in a single assay on morphologically intact cells in suspension"! Highly-disruptive, high-specificity, high-throughput HPV OncoTect cervical cancer screening assay now selling in market, with next-generation extensions ready to go" HPV OncoTect! E6, E7 mrna overexpression quantified" HPV OncoTect 3Dx! adds morphometrics, cell cycle analysis (FDA )! HPV OncoTect 3Dx Imaging! adds individual cell images" HPV OncoTect 3Dx Imaging will replace the Pap test!

4 Our Technology! IncellDx assays identify and quantitate proteomic and genomic biomarkers while retaining the ability to provide! morphometric measurements of cells and their nuclei,! critical keys for identifying cancer.!!

5 DNA vs Disease Ø Bacterial commensalism model Ø Viral commensalism (e.g. cervical cancer, CMV/transplant) Ø DNA commensalism - is a gene present and a marker of disease or is it involved in the pathway of disease (e.g. CD14 in the OncoType panel by Genomic Health)

6 Personalized Medicine vs Personalized Tissues Ø Should Personalized Medicine fall under the Companion DiagnosQcs rubric Ø Genomics and Proteomics- is plasma or blood indicaqve of the Qssue of interest? Ø NGS and new technologies- only as good as the diagnosqc sample? Ø DiagnosQcally is the body the sum of its parts?

7 OncoTect TM Roadmap 2 OncoTect q E6, E7 mrna Quantification q Ectocervical/endocervical cell differentiation q Simple morphometric measurements (cell size/ shape) q High throughput + OncoTect 3Dx q E6, E7 mrna Quantification with DNA Quantification q Ploidy/Proliferation q Cell cycle analysis q Complex morphometric measurements q 3D morphology

8 Technology Driven Paradigm Shifts Classic 2D X-Ray Modern 3D MRI 2D Pap Smear Slide OncoTect 3Dx Morphology E6, E7 mrna (green) DNA content (purple) N/C Ratio

9 Cervical Cytology Criteria (Slides) - Findings in Order of Importance LSIL" HSIL" 3Dx" (Mild) N/C Ratio (Moderate-Marked) N/C Ratio X Caviation Coarse Chromatin X Hyperchromasia Hyperchromasia " Irregular Nuclear Contour X " Single Abnormal Cells X " Syncytial Aggregates " Pleomorphism X

10 FDA Audit Comment Staging Cervical Dysplasia with E6 E7 and Ploidy E6/E LSIL Note E6,E7 overexpression in the normal DNA peak DNA Content (x 10000) E6/E HSIL Note E6,E7 overexpression in the increased DNA peaks DRAQ 5

11 Combined E6, E7 mrna (green) and DNA (purple) Clearly Stages FDA Audit Comment Cervical Disease (HPV OncoTect 3Dx ) LSIL Note E6,E7 overexpression in the normal DNA peak LSIL E6/E DNA Content (x 10000) icyt DNA Content FlowSight

12 Measurement of Nuclear C2IS to Cytoplasmic Ratios LSIL Cells HSIL Cells The overall accuracy of participants in estimating nuclear area ratios was low, especially for ratios in the range of ASCUS versus LSIL Cancer(CancerCytopathol)2008;114:

13 And Morphology C2IS with Image Cytometry Gallery CIN 3 (N/C > 0.25) Normal (N/C < 0.25)

14 3Dx Analysis Enables a Slideless Pap ( Wells) WNL LSIL E6, E7 mrna HSIL E6, E7 mrna E6, E7 mrna

15 ..and MORPHOLOGY WNL LSIL E6, E7 mrna HSIL E6, E7 mrna E6, E7 mrna

16 Bringing Pathway Science to Reality!

17 Making Infectious Disease Testing Personal

18 Providing Value Added Information-Test Bundles Ø HIV Complete pvl HIV Reservoirs- ViroTect VR IncellCept

19 Providing Value Added Information-Test Bundles Ø HCV Complete pvl HCV Genotyping HCV Reservoirs (HCV ViroTect VR ) CD16 CD16 HCV RNA Count Count NS5A HCV RNA NS5A Figure 3. Confirmation of HCV replication (NS5A+) in cells containing HCV RNA

20 OncoBreast 3Dx: IncellDX Entry into the Breast Cancer Prognostic Market

21 SK-BR-3 cells FS INT LIN FS INT LIN MCF-7 cells 800 Simultaneous e-cadherin, ER/PR, her-2neu and DNA cell cycle on Breast FNA SS INT LIN SS INT LIN Her-2-neu mrna DNA Content

22 Diagnotics Need to Make Economic Sense: Cervical Cancer Screening in the US - The Problem!! Too many false positives = Too many unnecessary biopsies! There is currently no assay available in market that effectively deals with abnormal pap results! " Cervical cancer screening in US done by Pap smear (c. 1949) and HPV DNA tests." Only 4% of women with a positive HPV test using the current FDA approved tests will ever go on to cervical cancer if left untreated." " Boston Healthcare estimates 1.1 million women are sent to invasive procedures who donʼt need it at a annual cost of $300-$600 Pie million chart to the US healthcare system." " 3.3 million Pap tests Atypical Squamous Cells of Undetermined Significance (ASCUS)." SOLUTION: IncellDxʼs HPV OncoTect! $1,200,000,000 $1,000,000,000 $800,000,000 $600,000,000 $400,000,000 $200,000,000 $0 Annual Costs Based on Model Inputs $357,162,430 $34,969,789 $310,096,054 OncoTect $795,385,028 $34,969,789 $206,183,796 HPV DNA Colposcopies (including those with diagnostic biopsies) Office visits associated with tests Molecular tests

23 Q & A Sexually Transmi/ed Disease Panel Atopobium vaginae Chlamydia trachomacs Gardnerella vaginalis Haemophilus ducreyi Mycoplasma hominis Mycoplasma genitalium Neisseria gonorrhoeae Treponema pallidum Trichomonas vaginalis Ureaplasma urealyccum