#1Theranos Science & Technology: The Miniaturization of Laboratory Testing Elizabeth Holmes theranos August 1, 2016#2Scientific Exchange Some of the medical device technologies discussed today are regulated by the FDA and are not yet cleared or approved. ● This presentation is not intended to promote Theranos devices or testing. • Theranos technologies are not intended or offered for sale or commercial use at this time. The purpose of our presentation is to provide an exchange of scientific information about Theranos' inventions and technologies. This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 7#3Our mission is to make actionable health information accessible at the time it matters This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 8#4Theranos Technologies Reagents and Assays for Small-Volume Samples theranos This technology has not been cleared or approved by the FDA and is not for sale in the United States. theran s theranos 9#5Theranos Technologies Collection Technologies Sample Collection Device (SCD) therane Nanotainer™ Tubes Reagents and Assays for Small-Volume Samples theranes This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos theranos 9#6Theranos Technologies Collection Technologies Sample Collection Device (SCD) theranes Nanotainer™ Tubes Reagents and Assays for Small-Volume Samples High Throughput Platforms theranes This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos theranos 9#7Theranos Technologies Collection Technologies Sample Collection Device (SCD) theranes Nanotainer™ Tubes Reagents and Assays for Small-Volume Samples High Throughput Platforms theranes This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos Theranos Sample Processing Unit (miniLab) theranos 9#8Theranos Technologies Collection Technologies Sample Collection Device (SCD) theranes Nanotainer™ Tubes Reagents and Assays for Small-Volume Samples High Throughput Platforms theranes This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos Theranos Sample Processing Unit (miniLab) Theranos Virtual Analyzer (TVA) theranos 9#9Theranos Technologies Collection Technologies Sample Collection Device (SCD) theranes Nanotainer™ Tubes Reagents and Assays for Small-Volume Samples High Throughput Platforms N theranos This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranes Theranos Sample Processing Unit (miniLab) Theranos Virtual Analyzer (TVA) theranos 9#10Presentation Overview 1. Miniaturization of laboratory testing II. miniLab results across detection methodologies III. Small sample volumes: collection of capillary blood and analysis This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 10#11Miniaturization and Integration of Detection Systems Spectrophotometer Clinical Chemistry Images not to scale Luminometer & Fluorometer Immunochemistry This technology has not been cleared or approved by the FDA and is not for sale in the United States. Cytometer Hematology & Immunology Fluorescence-based Isothermal Detector Molecular Biology theranos 11#12Miniaturization and Integration of Processing Modules Images not to scale Camera Sonicator This technology has not been cleared or approved by the FDA and is not for sale in the United States. Material Handling Robot Thermocycler Cartridge Centrifuge theranos 12#13Theranos Sample Processing Unit (miniLab) Material Handling Robot Thermal System Luminometer & Fluorometer Spectrophotometer Sonicator Cartridge Camera Images not to scale * Optional component This technology has not been cleared or approved by the FDA and is not for sale in the United States. Fluorescence-based Isothermal detector Cytometer* Thermocycler* Centrifuge theranos 13#14Theranos Sample Processing Unit (miniLab) Luminometer & Fluorometer Spectrophotometer Images not to scale * Optional component This technology has not been cleared or approved by the FDA and is not for sale in the United States. Fluorescence-based Isothermal detector Cytometer* theran s 13#15Theranos Sample Processing Unit (miniLab) theranos Images not to scale * Optional component This technology has not been cleared or approved by the FDA and is not for sale in the United States. 13½" 22" 17¾" theranos 13#16Multi-faceted Material Handling Robot Allows Versatility Multiple volumes simultaneously • Transports consumables • Transfers fluids ● • Precision: 2.75% at 2 μL • Accuracy: 2 μL ± 2.0% ● This technology has not been cleared or approved by the FDA and is not for sale in the United States. 4.2" 3.5" herane 6.9" theranos 14#17Cartridge Carries Sample and Reagents • Single use On-board controls ● All reagents and waste onboard No tubing Barcode control This technology has not been cleared or approved by the FDA and is not for sale in the United States. T 1.5" 1 Cartridge Lid 3.5" theranes Barcode B Speeg 2004 7285 A NanotainerTM DOM M RE 4.6" theran s 15#18Cartridges: Customized to the Assays 3.5" 4.6" This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos COME theranos 16#19Cartridges: Customized to the Assays Touchoff pads Reagents Bulk reagents Imaging slidě Mini tips Reaction cuvettes Nanotainer 3.5" 4.6" Tips and vessels This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos POTASSAN 2005 C theran s 16#20Piercing Tool Centrifuge Vessel (20-80 uL) High Capacity Tips (5 - 60 UL) This technology is not cleared or approved by the FDA and is not for sale in the United States. Reaction Cuvette (30 - 60 UL) Microtips (2-20 uL) Cytometry Slide Reagent and Processing Vessels (15-65 uL)#21Piercing Tool Centrifuge Vessel (20-80 uL) High Capacity Tips (5 - 60 UL) nanotainer™M tubes This technology is not cleared or approved by the FDA and is not for sale in the United States. Reaction Cuvette (30 - 60 UL) Microtips (2-20 uL) Cytometry Slide Reagent and Processing Vessels (15-65 uL)#22Theranos Virtual Analyzer (TVA) Enables Remote Processing and Analysis Recognizes barcode on cartridge • Facilitates two-way communication ● • Dictates protocol for device Remote interpretation of digital images and results, reviewed and released through clinical lab ● • Protocols remotely downloaded for novel analytes on existing systems This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 18#23therancs This technology has not been cleared or approved by the FDA and is not for sale in the United States#24theranes This technology has not been cleared or approved by the FDA and is not for sale in the United States#25HIME PRE S 1₁ This technology has not been cleared or approved by the FDA and is not for sale in the United States#26Hematology#27Frise F L-OV 1230 Hematology Video Speed: 3x This technology has not been cleared or approved by the FDA and is not for sale in the United States#28Clinical Chemistry#29SUBJOut TEMP LI-OVS mittts 444 Clinical Chemistry Video Speed: 1x This technology has not been cleared or approved by the FDA and is not for sale in the United States#30S D 7 () J ENG 6:25 PM 8 & Visual Studio Code File Explorer (1) Chrome Remote Desktop Excel Microsoft Edge μTorrent 3D Viewer 7-Zip 78 Zip Access Adobe Acrobat Calendar Microsoft Edge Cloudy 10° Moscow Google Chrome S 13⁰ 4° Mail NFL Draft results 2023: Seahawks pass on d-line, but... ******* OneNote... N chemistry#31Presentation Overview 1. Miniaturization of laboratory testing II. miniLab results across detection methodologies III. Small sample volumes: collection of capillary blood and analysis This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 20#32Clinical Chemistry: Precision and Method Comparison This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 21#33Clinical Chemistry: Spectrophotometer T 2.0" 5.3" 5.1" • Measures absorbance across UV- ● visible spectrum assays • Colorimetric and turbidimetric ● This technology has not been cleared or approved by the FDA and is not for sale in the United States. Intensity spectrum Intensity Wavelength Reaction cuvette O LWP optical filter Grating-based optical system Xe arc lamp CCD line sensor Laser diode theranos 22#34Clinical Chemistry: Precision Study Overview Sample type and matrix Control levels Study Design Analysis Li-Hep venous plasma Low analyte concentration High analyte concentration 3 miniLabs x 5 Days x 5 Tests per day (CLSI EP05-A3) Analysis of variance to determine repeatability, within-lab variability, and reproducibility This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 23#35Multi-miniLab Precision Study Design 3 devices 5 days 5 tests miniLab 1 Repeatability (within-run/day) one day-one device baseline variance of assay system miniLab 2 Within-laboratory (within-miniLab) intermediate precision, includes day-to-day variability CLSI EP05-A3 This technology has not been cleared or approved by the FDA and is not for sale in the United States. miniLab 3 Reproducibility encompasses imprecision across multiple devices or sites theranos 24#36Clinical Chemistry: Precision Results Meet Performance Criteria Analyte Total Cholesterol Triglycerides LDL Cholesterol HDL Cholesterol Potassium Mean 120 mg/dL 320 mg/dL 78 mg/dL 405 mg/dL 71 mg/dL 203 mg/dL 40 mg/dL 84 mg/dL 2.9 mmol/L 6.0 mmol/L Repeatability CV Within-laboratory CV Reproducibility CV (Within-miniLab) (Across 3 miniLabs) (Within-day) 1.5% 1.6% 1.6% 1.7% 2.0% 1.9% 2.6% 3.9% 4.4% 3.6% 3.7% 2.2% 2.4% 2.4% 2.5% 2.3% 2.8% 2.8% 6.6% 2.6% 2.8% This technology has not been cleared or approved by the FDA and is not for sale in the United States. 1.8% 1.9% 4.4% 3.6% 2.4% 2.4% 2.5% 3.4% 2.7% theranos 25#37Clinical Chemistry: Method Comparison Study Overview Population Sample type and matrix Comparator Number of miniLabs Study design Analysis Apparently healthy subjects and archived samples Li-Hep venous plasma Siemens ADVIA 1800 7 for potassium 9 for lipids n> 100 subjects (per CLSI EP09-A3) Passing-Bablok regression analysis and calculate median bias This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 26#38Potassium on miniLab Correlates to Comparator Method for Venous Plasma 10 8 miniLab (mmol/L) 6- 4 y = 1.02 x -0.15 r² = 0.98 : 104 n= 4 8 Siemens ADVIA 1800 6 1 CLIA (Federal Register 1992;57(40):7002-186) (mmol/L) This technology has not been cleared or approved by the FDA and is not for sale in the United States. 10 Legend: Unity (y = x) Allowable total error¹ = ±0.5 mmol/L Points within ATE = 100% Median bias = -0.08 mmol/L theran s 27#39Lipids on miniLab Correlate to Comparator Method for Venous Plasma miniLab (mg/dL) miniLab (mg/dL) 350 300- 250- 200- 150- 100 250- 200 150 100- 50 y = 0.97 x + 3.74 = 0.99 n = 103 100 150 200 250 300 350 Siemens ADVIA 1800 (mg/dL) Total Cholesterol Median bias = -0.9 % ATE = + 9% Points within ATE = 100% y = 0.98 x + 4.01 2=0.95 n=103 LDL Cholesterol Median bias = 2.4% ATE = ± 12% Points within ATE = 92% 50 100 150 200 250 Siemens ADVIA 1800 (mg/dL) This technology has not been cleared or approved by the FDA and is not for sale in the United States. miniLab (mg/dL) 800- 600- 400- 200 0 0 140- 120- miniLab 100- (mg/dL) 80- 60- 40- 20- y= 1.03 x 1.58 r² = 0.99 n = 103 200 400 600 800 Siemens ADVIA 1800 (mg/dL) y = 1.03 x + 3.09 ²=0.95 n-103 Legend: Unity (y = x) - Allowable total error 20 NCEP (Clin Chem 1988;34:193-201) NCEP (Clin Chem 1997;43:2164-2168) Triglycerides Median bias = 0.6% ATE = ± 15% Points within ATE = 98% HDL Cholesterol Median bias = 9% ATE = ± 13% Points within ATE = 76% 40 60 80 100 140 Siemens ADVIA 1800 (mg/dL) theranos 28#40miniLab HDL Assay Accuracy Confirmed With NIST Standard Instrument NIST True Value miniLab Comparator Method Replicates N/A 9 25 Assigned Mean Difference Mean Difference This technology has not been cleared or approved by the FDA and is not for sale in the United States. Level 1 41.0 mg/dL 39.9 mg/dL -3% 36.7 mg/dL -10% Level 2 64.9 mg/dL 67.1 mg/dL 3% 63.9 mg/dL -2% theranos 29#41Clinical Chemistry Assays on miniLab Meet Allowable Total Error Criteria Analyte Potassium (mmol/L) Total Cholesterol (mg/dL) Triglycerides (mg/dL) LDL Cholesterol (mg/dL) HDL Cholesterol (mg/dL)* Total analytical error = median bias + 2* within-laboratory CV or SD *HDL bias against NIST standard was used in this calculation miniLab Total Analytical Error Allowable Total Error 0.28 mmol/L < 0.5 mmol/L¹ 1 CLIA (Federal Register 1992;57(40):7002-186) 2 NCEP (Clin Chem 1988;34:193-201) 3 NCEP (Clin Chem 1997;43:2164-2168) This technology has not been cleared or approved by the FDA and is not for sale in the United States. 4.0% 4.5% 9.5% 7.8% <9%² <15%3 < 12%3 < 13%3 theran s 30#42Immunochemistry: Precision and Method Comparison This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 31#43Immunochemistry: Luminometer & Fluorometer T 2.2" BLOCOS SO #A38 29918-20 N/A 3.7" Fluorometer Luminometer 2.4" 1 This technology has not been cleared or approved by the FDA and is not for sale in the United States. Photodetector Luminometer Microtip Collection mirror theranos 32#44Immunochemistry: Precision Study Overview Sample type and matrix Control levels Study Design Analysis Venous serum Low titre sample (High Negative) High titre sample (Low Positive) 3 miniLabs x 5 Days x 5 Tests per day (CLSI EP05-A3) Analysis of variance to determine repeatability, within-lab variability, and reproducibility This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 33#45Immunochemistry: HSV-2 IgG Precision Results Show Acceptable %CV Analyte HSV-2 Index Value 0.75 (L) 1.06 (H) Repeatability CV Within-laboratory CV Reproducibility CV (Within-day) (Within-miniLab) (Across 3 miniLabs) 7.6% 7.6% 7.7% 7.3% 7.5% 7.7% (L): low titre sample; (H): high titre sample Other industry standard assays approved by FDA: K120625, K090409, K081687 This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 34#46Immunochemistry: Method Comparison Study Overview Population Samples type and matrix Comparator Number of miniLabs Study design Analysis At risk for Herpes (intended use population) Venous serum Focus HerpeSelect 1 & 2 Immunoblot 7 CLSI EP12-A2 Compute negative and positive percent agreement compared to comparative method This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 35#47Immunochemistry: HSV-2 IgG Measurements are Consistent with Comparator Method Negative percent agreement (specificity) Positive percent agreement (sensitivity) Theranos/ Immunoblot 127 / 127 71/75 Other industry standard assays approved by FDA: K120625, K090409, K081687 This technology has not been cleared or approved by the FDA and is not for sale in the United States. Percent Agreement 100% 94.7% 95% Confidence Interval (97.1%, 100%) (87.1%, 97.9%) theranos 36#48Hematology and Immunology: Precision and Method Comparison This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 37#49Hematology and Immunology: Cytometer Automated imaging cytometer 3 Lasers, 5 Emission Filters Slide containing multiple samples 11.8" 19.4" T 6.1" Fluorescence excitation light sources (laser diodes) This technology has not been cleared or approved by the FDA and is not for sale in the United States. Ringlight for dark field illumination Objective lens Excitation system optics (filters, lenses, mirrors) Imaging system optics (filters, lenses, mirrors) Camera theranos 38#50Hematology and Immunology: Assay Methodology CD3+T cells CD4+ T cells CD8+ T cells CD19+ B cells CD56+/CD16+ NK cells Two reaction tubes stained on-board Erythrocytes lysed and leukocytes fixed This technology has not been cleared or approved by the FDA and is not for sale in the United States. Samples are loaded into an imaging slide Images and cell properties analyzed using classification algorithms theran s 39#51Hematology and Immunology: Image Processing CD8+ Cell CD4+ Cell Pseudocolor image of T-cell image with select staining shown. CD4 in green, CD8 in magenta, CD3 in blue, Nucleus in Red. Image segmentation This technology has not been cleared or approved by the FDA and is not for sale in the United States. CD14 CD3 CD4 MONO CD4 T CELLS CD45 CD4 10⁰ SSC CD8 Scatterplot reviewable by trained personnel LYM CD4+ CD8+ DN DP theranos 40#52T Cell, B Cell, NK Cells (TBNK, Lymphocyte Subset): Precision Study Overview Sample type and matrix Control levels Study Design Analysis Quality control material (R&D Systems Status Flow) CD4 Low (all other analytes normal) CD4 Normal (all other analytes normal) 3 miniLabs x 5 Days x 5 Tests per day (CLSI EP05-A3) Analysis of variance to determine repeatability, within-lab variability, and reproducibility This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 41#53Lymphocyte Subset: Precision Results Meet Performance Criteria Analyte Total T cells CD4+ T cells CD8+ T cells B cells NK cells Mean Repeatability CV Within-laboratory CV Reproducibility CV (cells/μL) (Within-day) (Within-miniLab) (Across 3 miniLabs) 841 2.5% 3.2% 3.3% 153 (L) 838 (N) 571 357 308 4.6% 1533 2.7% 3.5% 4.5% 5.3% Lymphocytes (L): low cell count; (N): normal cell count This technology has not been cleared or approved by the FDA and is not for sale in the United States. 2.7% 5.0% 2.7% 3.9% 4.7% 5.4% 2.8% 5.3% 2.8% 4.1% 4.7% 6.1% 3.1% theranos 42#54Lymphocyte Subset: Method Comparison Study Overview Population Sample type and matrix Comparator Number of miniLabs Study design Analysis Apparently healthy subjects, and <15% adjusted to abnormal levels K2-EDTA venous whole blood BD Multitest 6-color TBNK Reagent with Trucount Tubes on FACSCanto II (BD TBNK) 6 n> 100 subjects (per CLSI EP09-A3) 1 replicate on miniLab, 2 replicates on comparator method Weighted Deming regression analysis and calculate median bias This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 43#55Lymphocyte Subset: Counts Correlate with Comparator Method 20000 10000 5000 - 2000 miniLab 1000 (cells/μL) 500 200 100 50- Total CD3+ T Cells¹ y = 0.99 x 1.62 = 0.98 n=111 50 Median bias = 0.4% ATE= 19.8% Points within ATE = 96.4% 200 Legend: SEGE= 1000 5000 20000 BD TBNK (cells/μL) Adjusted sample 10000 5000 2000 1000 500 200 100- 50 CD4+ T Cells¹ y = 1.00 x 2.62 r² = 0.98 n=111 50 Median bias = 0.7% ATE=19.6% Points within ATE = 95.5% 200 1000 5000 BD TBNK (cells/μL) Native sample 1 Clin Chim Acta, 2015;438:166-170. Ann Clin Biochem 1997;34:8-12. This technology has not been cleared or approved by the FDA and is not for sale in the United States. 366= - Unity (y = x) 5000 2000 1000 500- 200 100- 50 20 10 10 CD8+ T Cells¹ y = 1.00 x - 0.87 r² = 0.99 n=111 -- Median bias = 1.3% ATE = 21.4% Points within ATE = 97.3% 200 1000 5000 50 330338 BD TBNK (cells/μL) Allowable total error theran s 44#56Lymphocyte Subset: Counts Correlate with Comparator Method miniLab (cells/μL) 5000 2000 1000 500 200- 100 50 20 10 5 CD19+ B cells¹ y = 0.98 x + 0.56 r² = 0.98 n=111 5 N Median bias = -0.9% ATE = 26.1% Points within TE = 95.5% 20 50 200 1000 5000 BD TBNK (cells/μL) 5000 2000 1000 500 200 100 50 20 10 5 2 CD56+/CD16+ NK Cells¹ y = 1.02 x + 0.43 r² = 0.98 n=111 2 5 Median bias = 3.5% ATE=35.8% Points within TE = 98.2% 20 100 500 2000 BD TBNK (cells/μL) Legend: Adjusted sample Native sample ¹ Clin Chim Acta, 2015;438:166-170. Ann Clin Biochem 1997;34:8-12 2 Ricos specifications available from www.westgard.com/biodatabase1.htm This technology has not been cleared or approved by the FDA and is not for sale in the United States. - 20000 10000 5000- Unity (y = x) 2000 1000 500 200 100 50 y = 1.00 x 0.64 r² = 0.99 n = 111 50 Lymphocytes² -- BE Median bias = 0.5% ATE= 17.6% Points within TE = 94.6% T 200 1000 5000 20000 BD TBNK (cells/μL) Allowable total error theranos 45#57Lymphocyte Subset: Counts Meet Allowable Total Error Criteria Analyte (cells/µL) Total T cells CD4+ T cells* CD8+ T cells B cells NK cells Lymphocytes Total analytical error = median bias + 2 * within-laboratory CV *CV of Low CD4 cell count was used in this calculation miniLab Total Analytical Error 6.7% 10.8% 9.2% 10.3% 14.3% 6.1% 1 Clin Chim Acta, 2015;438:166-170; Ann Clin Biochem 1997;34:8-12 This technology has not been cleared or approved by the FDA and is not for sale in the United States. Allowable Total Error¹ < 19.8% < 19.6% <21.4% < 26.1% <35.8% < 17.6% theranos 46#58Molecular Biology: Nucleic Acid Amplification (NAA) Zika Assay in Venous Serum on miniLab - Performance Characteristics This technology has not been cleared or approved by the FDA and is not for sale in the United States. theran s 47#59Nucleic Acid Amplification (NAA): Fluorescence- based Isothermal Detector and Thermocycler Fluorescence-based Isothermal Detector 2.5" 5.4" Thermocycler 3.9" 13.1" 8.5" Optical Filters Fluorescence-based Isothermal Detector Sample Vessels in Isothermal Block 8 X 8 5.7" This technology has not been cleared or approved by the FDA and is not for sale in the United States. Excitation LEDs Photodetectors Excitation beam Fluorescence Fluorescence Signal Time theranos 48#60miniLab NAA Assays - Methodology Magnetic bead-based extraction of nucleic acids • Isothermal amplification and detection • RT-PCR based pre-amplification using thermocycler module ● High sensitivity achieved through integrated on-board sample extraction, amplification, and detection • Primers designed using multisequence gene alignment ● This technology has not been cleared or approved by the FDA and is not for sale in the United States. theran s 49#61Molecular Biology: NAA Zika Assay is Sensitive for the Target Gene Zika Concentration (copies/mL) 1920 960 480 (LOD) 160 32 0 N (Positive) / N (Replicates) 6/6 6/6 25/26 4/6 2/6 0/6 LoD for CDC Zika test = 930 copies/mL Emerg Infect Dis 2008;14:1232-1239 This technology has not been cleared or approved by the FDA and is not for sale in the United States. % Positive 100% 100% 96% 67% 33% 0% theranos 50#62Molecular Biology: NAA Zika Assay Does Not Cross- React or Show Interference with Pathogens Virus/Bacteria/Parasite P. falciparum Dengue Virus Types 1-4 West Nile Virus Types 1 & 2 Chikungunya Virus Yellow Fever Virus Parvovirus Mayaro Virus Concentration (copies/mL) 1 x 106 1 x 106 1 x 106 5 x 103 1 x 104 1 x 106 IU/mL 1 x 106 n = 3 replicates per test This technology has not been cleared or approved by the FDA and is not for sale in the United States. Cross-Reactivity (0 copies/mL Zika) % Positive 0% 0% 0% 0% 0% 0% 0% Interference (recovery of 960 copies/mL Zika) % Positive 100% 100% 100% 100% 100% 100% 100% theranos 51#63Molecular Biology: NAA Zika Assay Does Not Cross- React or Show Interference with Pathogens Virus/Bacteria/Parasite P. falciparum Dengue Virus Types 1-4 West Nile Virus Types 1 & 2 Chikungunya Virus Yellow Fever Virus Parvovirus Mayaro Virus Concentration (copies/mL) 1 x 106 1 x 106 1 x 106 5 x 103 1 x 104 1 x 106 IU/mL 1 x 106 n = 3 replicates per test This technology has not been cleared or approved by the FDA and is not for sale in the United States. Cross-Reactivity (0 copies/mL Zika) % Positive 0% 0% 0% 0% 0% 0% 0% Interference (recovery of 960 copies/mL Zika) % Positive 100% 100% 100% 100% 100% 100% 100% theranos 51#64Molecular Biology: NAA Zika Assay Does Not Cross- React or Show Interference with Pathogens Virus/Bacteria/Parasite P. falciparum Dengue Virus Types 1-4 West Nile Virus Types 1 & 2 Chikungunya Virus Yellow Fever Virus Parvovirus Mayaro Virus Concentration (copies/mL) 1 x 106 1 x 106 1 x 106 5 x 103 1 x 104 1 x 106 IU/mL 1 x 106 n = 3 replicates per test This technology has not been cleared or approved by the FDA and is not for sale in the United States. Cross-Reactivity (0 copies/mL Zika) % Positive 0% 0% 0% 0% 0% 0% 0% Interference (recovery of 960 copies/mL Zika) % Positive 100% 100% 100% 100% 100% 100% 100% theranos 51#65Molecular Biology: NAA Zika Assay Inclusive for Other Zika Strains Zika Virus Strain DakArD 41662 MR 766 Zika Concentration (copies/mL) 960 960 Current outbreak strain: PRVABC59 (Asian) This technology has not been cleared or approved by the FDA and is not for sale in the United States. N Positive/N Replicates 3/3 3/3 theranos 53#66Molecular Biology: NAA Zika Assay Shows No Carryover Round 1 2 3 4 5 Zika Concentration (copies/mL) 1.3 x 107 0 1.3 x 107 0 1.3 x 107 0 1.3 x 107 0 1.3 x 107 0 This technology has not been cleared or approved by the FDA and is not for sale in the United States. N Positive/N Replicates 5/5 0/5 5/5 0/5 5/5 0/5 5/5 0/5 5/5 0/5 % positive 100% 0% 100% 0% 100% 0% 100% 0% 100% 0% theranos 54#67NAA Zika Assay - Clinical Study Overview Population Healthy, febrile, or Zika symptomatic pathologicals Sample type and matrix Venous serum Analyzers & Assays Study design Analysis 24 miniLabs CDC RT-PCR assay altona RealStar® (EUA Authorized Method) FDA EUA guidance Compute negative and positive percent agreement compared to the comparative methods This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 55#68Molecular Biology: NAA Zika Assay with Venous Serum is Consistent with Comparators Negative percent agreement Positive percent agreement Theranos/ Comparator 108 / 113 67/67 Percent Agreement 95.6% This technology has not been cleared or approved by the FDA and is not for sale in the United States. 100% Venous Serum (N=180) 78 from US (healthy and febrile subjects) 102 from Dominican Republic and Colombia (Zika symptomatic) 95% Confidence Interval (90.1%, 98.1%) (94.6%, 100.0%) theranos 56#69Theranos Sample Processing Unit (miniLab) Material Handling Robot Thermal System Luminometer & Fluorometer Spectrophotometer Sonicator Cartridge Camera Images not to scale * Optional component This technology has not been cleared or approved by the FDA and is not for sale in the United States. Fluorescence-based Isothermal detector Cytometer* Thermocycler* Centrifuge theranos 57#70Presentation Overview 1. Miniaturization of laboratory testing II. miniLab results across detection methodologies III. Small sample volumes: collection of capillary blood and analysis This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 58#71Capillary Collection Optimization of Collection Variables ● Sample site preparation (detergent-based wipes and alcohol dry time) • Wiping away first drop(s) • Finger-stick techniques (minimize milking) ● Lancet selection (gauge and depth) ● • Arterialization of capillary blood This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 59#72Theranos Sample Collection Device 0.4" I 0.6" Sample Collection Device (SCD) therangs 2.6" This technology has not been cleared or approved by the FDA and is not for sale in the United States. Nanotainer™M Tubes 0.51" T 0.67" 0.40" theranos 60#73Sample Collection Device Design Challenges Hemolysis Clotting Altered cell morphology Theranos Design Considerations Capillary tubes Shape and diameter of capillary tubes and needles Anti-coagulant coating • Anti-coagulant concentration ● ● Rapid mixing of sample with anti-coagulant Fill volume indicators Optimized anti-coagulant concentration This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 61#74Collection and Activation 1 2 Blood drawn from lanced fingertip via capillary action Collection unit pressed into housing. Needles puncture through nanotainer caps, sliding plungers downward, like the action of a syringe. Specimen is drawn into each nanotainer (170 μL blood total) and simultaneously mixed with anti- coagulant (EDTA and/or Li-Hep) This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 62#75Collection and Activation 1 2 3 Blood drawn from lanced fingertip via capillary action Collection unit pressed into housing. Needles puncture through nanotainer caps, sliding plungers downward, like the action of a syringe. Specimen is drawn into each nanotainer (170 μL blood total) and simultaneously mixed with anti- coagulant (EDTA and/or Li-Hep) Nanotainer tubes removed for storage, transport, and processing. 2D barcode used to maintain traceability This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 62#76D This technology has not been cleared or approved by the FDA and is not for sale in the United States#77Sample Container Box for Shipping 4.0" This technology has not been cleared or approved by the FDA and is not for sale in the United States. 5.2" T 2.3" 1 theranos 64#78Matrix Comparison on miniLab This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 65#79Lipid Panel: Matrix Comparison Study Overview Population Sample type and matrix Analyzers Study design Analysis Apparently healthy subjects Li-Hep capillary whole blood and venous plasma 8 miniLabs Siemens ADVIA 1800 2 replicates each matrix on miniLab 2 replicates for venous on comparator method Passing-Bablok regression analysis and calculate median bias This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 66#80Capillary Total Cholesterol Correlates to Venous Capillary on mini Lab (mg/dL) Legend: 300 250 200 150 y = 1.00 x + 0.89 r² = 0.98 n = 60 150 Unity (y = x) -- Allowable total error¹ = +9% Points within ATE = 100% 200 250 Venous on miniLab (mg/dL) 300 1 NCEP (Clin Chem 1988;34:193-201) This technology has not been cleared or approved by the FDA and is not for sale in the United States. 300 250 200 150- y = 0.97 x + 4.32 r² = 0.98 n = 60 150 Points within ATE = 100% 250 200 Venous on ADVIA 1800 (mg/dL) 300 theranos 67#81Lipid Panel: Capillary Bias Summary Capillary miniLab vs Venous miniLab Analyte R² Total Cholesterol (mg/dL) 0.98 HDL Cholesterol (mg/dL) 0.96 LDL Cholesterol (mg/dL) 0.97 Triglycerides (mg/dL) 1.00 Median Bias 0.6% 1.9% 0.6% 3.7% Passing-Bablok regression This technology has not been cleared or approved by the FDA and is not for sale in the United States. Capillary miniLab vs Venous ADVIA R² 0.98 0.96 0.95 1.00 Median Bias -0.5% 11.6% 1.4% 5.5% theranos 68#82Lymphocyte Subset: Matrix Comparison Study Overview Population Sample type and matrix Analyzers Study design Analysis Apparently healthy subjects K₂-EDTA capillary and venous whole blood 6 miniLab TBNK on Becton Dickinson FACSCanto II 1 replicate each matrix on miniLab 2 replicates venous on comparator method Passing-Bablok regression analysis and calculate median bias This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 69#83Capillary CD4+ T cell Count Correlates to Venous Capillary on mini Lab (cells/uL) Legend: 2000 1500 1000 500 y = 1.06 x 9.88 r² = 0.94 n=70 500 1000 Venous on miniLab (cells/µL) Points within ATE = 91% 1500 2000 Unity (y = x) --Allowable total error¹ = ±19.6% 1 Clin Chim Acta, 2015;438:166-170; Ann Clin Biochem 1997;34:8-12 This technology has not been cleared or approved by the FDA and is not for sale in the United States. 2000 1500 1000 500 y = 1.06 x 9.02 -0.93 n = 72 500 Points within ATE = 96% 1000 1500 Venous on BD TBNK (cells/µL) 2000 theran s 70#84Lymphocyte Subset: Capillary Bias Summary Capillary miniLab vs Venous Capillary miniLab vs Venous miniLab BD TBNK Analyte Total T cells CD4+ T cells CD8+ T cells B cells NK cells Lymphocytes Passing-Bablok regression This technology has not been cleared or approved by the FDA and is not for sale in the United States. R² 0.93 0.94 0.92 0.93 0.84 0.88 Median Bias 3.7% 4.2% 5.9% 6.1% 9.6% 4.3% R² 0.92 0.93 0.94 0.92 0.90 0.89 Median Bias 4.9% 4.6% 6.4% 5.6% 8.9% 6.8% theranos 71#85NAA Zika Assay: Clinical Study Overview Population Healthy or Zika symptomatic Sample type and matrix Capillary whole blood, venous serum, and urine Analyzers & assays Study design Analysis 20 miniLabs CDC RT-PCR assay altona RealStar® (EUA Authorized Method) FDA EUA guidance Compute negative and positive percent agreement compared to the comparative methods This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranos 72#86Molecular Biology: NAA Zika Assay with Capillary Whole Blood is consistent with Comparators Negative percent agreement Positive percent agreement NAA/ CDC & altona 56/56 Capillary LoD = 320 copies/mL 50/51 Capillary whole blood, venous serum, and urine (n = 107) 77 from US (apparently healthy) 30 from the Dominican Republic (Zika symptomatic) Percent Agreement 100% This technology has not been cleared or approved by the FDA and is not for sale in the United States. 98% 95% Confidence Interval [93.6, 100.0]% [89.7, 99.7]% theranos 73#87Theranos Technologies Collection Technologies Sample Collection Device (SCD) theranes Nanotainer™ Tubes Reagents and Assays for Small-Volume Samples High Throughput Platforms theranes This technology has not been cleared or approved by the FDA and is not for sale in the United States. theran s Theranos Sample Processing Unit (miniLab) Theranos Virtual Analyzer (TVA) theranos 74#88Acknowledgments FAR AND AWAY THE BEST PRIZE THAT LIFE OFFERS IS THE CHANCE TO WORK HARD AT WORK WORTH DOING. This technology has not been cleared or approved by the FDA and is not for sale in the United States. theranus lab to theranos 75