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Single Molecule Array (Simoa) technology for ultrasensitive, multiplexed detection of proteins and nucleic acids 06/25/2013 1 Corporate Overview • Founded 2007 by David Walt and Nicholas Naclerio • Exclusive licensee of patent portfolio developed by David Walt at Tufts University • ̴ 50 employees, 15 Ph.D’s • Expanded to state-of-the-art 20,000 sq. ft. facility April 2012 in Lexington, MA • Venture-backed by leading life science investors and strategic partners • Cumulative $47M Raised in Series A, B, C Board of Directors • • • • • • • Martin Madaus, Ph.D. (Executive Chairman) John Connolly (Bain Capital Ventures) David Walt, Ph.D. (Tufts University, Illumina) Keith Crandell (ARCH Venture Partners) Doug Cole, M.D. (Flagship Ventures) Simon Davidson (In-Q-Tel Ventures) Dennis Sandstedt (bioMérieux) 06/25/2013 2 Serum Concentration 10−3 1x M to -12 1 x 10 M Total Number of Serum Proteins All Protein Blood Tests are Based on the Currently Measurable 250 Proteins Clinical Chemistry 130 FDA Approved Tests1 2501 ELISA Quanterix Opportunity How many proteins Are below 1 x 10-12 M? Potential is Large: Human Proteome = 25,000 genes Secreted Proteins >2,500 1Anderson 2Klee and Anderson, Molecular & Cellular Proteomics 2002: 1.11 845-867 et al., Nucleic Acids Research 2004: 32, 1414-1421 06/25/2013 3 Single Molecule Arrays (Simoa) Provide a Digital Advantage 0 pM 10 pM • Reaction volume = 100 ×10−6 L • Diffusion = dilution = low sensitivity • Millions of molecules needed to reach detection limit • Reaction volume = 50 ×10−15 L (2 billion times smaller) • Diffusion defeated = single molecule resolution = ultimate sensitivity • One molecule needed to reach detection limit 06/25/2013 4 Counting Single Protein Molecules in Blood using Simoa 06/25/2013 06/25/2013 55 Simoa Enables Single Molecule Diagnostics 06/25/2013 6 Simoa Uses Digital Counting and Intensity to Determine Average Number of Enzymes per Bead (“AEB”) AEB ~ 0.1 AEB ~ 0.6 AEB ~ 3.0 Rissin et al., Anal.Chem. 2011, 83, 2279-2285 06/25/2013 7 10 10 AEB of IL-6 beads AEB of TNF-α α beads Multiplexed Single Molecule Immunoassays 1 0.1 0.01 0 0.1 1 10 1 0.1 0.01 100 0 0.1 [TNF-α α ] (pg/mL) AEB of IL-1β β beads 1 0.1 0.01 0.1 1 [IL-1α α ] (pg/mL) 10 10 100 100 10 100 10 1 0.1 0.01 0 0.1 1 [IL-1β β ] (pg/mL) 20 [cytokine] (pg/mL) AEB of IL-1α α beads 10 0 1 [IL-6] (pg/mL) 15 10 5 0 06/25/2013 8 Digital ELISA Detects Proteins in the fg/mL Range Protein SiMoA LOD (pg/mL) Gold Standard Assay LOD (pg/mL) Vendor Sensitivity Fold Increase IL-1β TNF-α GM-CSF p24 IL-6 PSA Aβ42 tau IL-1α GLP-1 p-tau (181 + 231) IL-5 troponin p-tau-231 p-tau-181 0.001 0.003 0.003 0.005 0.005 0.006 0.02 0.02 0.024 0.033 0.04 0.049 0.05 0.05 0.1 0.057 0.106 0.26 15 0.039 10 50 60 1 11 NA 0.115 3 NA 60 R&D Systems R&D Systems R&D Systems OCD R&D Systems Roche/Siemens Innotest Innotest R&D Systems Luminex NA R&D Systems Abbott Architect (HS) NA Innotest 57 35 87 3000 8 1667 2500 3000 42 333 ND 2 60 ND 600 06/25/2013 9 Simoa Addresses Many Opportunities That Exist for High Sensitivity Clinical and Companion Diagnostics Neurology Enables blood tests for neurological disease Cardiac Inflammation First to quantify effect of antiTNF-α α drugs on target protein Infectious Disease World’s most sensitive troponin test First IA as sensitive to virus as PCR Signal Transduction HomeBrew Oncology Shorten detection of recurrence (years to months) Metabolism 06/25/2013 10 Application Demonstration: Infectious Disease HIV (p24 capsid protein) • Achieved 2,000-fold greater sensitivity than benchmark commercial immunoassays (LoD = 5 fg/mL), which is equivalent to about 50 copies of virus per mL. First immunoassay that has shown equivalent sensitivity as nucleic acid testing (NAT). • Demonstrated full analytical performance (blinded positive and negative sera, blinded seroconversion panels, spiked HIV virus etc.) • Demonstrated SiMoA is as sensitive as PCR for detecting HIV virus in early infection (seroconversion panels) • Clinical value: HIV screening for acute infection (prior to seroconversion) and monitoring therapy. Blood screening for infection. • Commercial leverage: Simplicity, cost and throughput vs. NAT. 06/25/2013 11 Detection of DNA using Simoa [bacteria] in blood (fM) 0 0.067 0.67 6.7 1,000 10,000 100,000 0.4 Streptavidin-βgalactosidase Substrate Target sequence Product 0.3 AEB Biotinylated detection sequences 0.2 0.1 0.0 Capture DNA sequence 0 No. bacteria per 25 µ L blood sample Magnetic Particle [bacteria] in river water (fM) 0.033 0.33 1,000 10,000 3.3 33.3 0.4 • Detected S. aureus spiked into whole blood and Charles River water • Same sensitivity as PCR (~70 aM) • Greatly reduced risk of cross-contamination of samples vs. PCR because direct detection of DNA AEB 0.3 0.2 0.1 0.0 100,000 1,000,000 No. bacteria per 50 µ L river water sample 06/25/2013 12 Simoa HD-1 Analyzer • Unprecedented ultrasensitivity • Full automation • Precision • Wide dynamic range • Easy & cost-effective implementation • Multiplexing capability with small sample volumes • Homebrew capabilities • >500 samples per shift • Available October 2013 for RUO • IVD clinical studies begin 2014 Sensitivity Means Knowing Simoa is a high definition diagnostics system that gives you the power to see more clearly, know with certainty, and reach new heights in lab productivity. 06/25/2013 13 Simoa Disc • Low-cost consumable • 24 arrays/disc (4 discs = 96 well plate) • 216,000 femtoliter wells per array • Manufactured using state-of-the art Blue-ray™ technology by Sony DADC • High volume production easily scaleable 216K wells 06/25/2013 14 Quanterix Instrument Workflow Step 1. Load Consumables • Kits (singleplex or multiplex) • Cuvettes and disposable tips • Simoa discs Step 2. Menu Setup • Select assay • Calibrators and controls Step 3. Load Samples • 96 well plates or tubes Step 4. Run Samples • Simoa HD-1 Analyzer performs all mixing, washing, incubation, and sample readout, with first result in 30 minutes and subsequent samples every 45 seconds thereafter. Ultra-sensitive with fully automated simplicity Multiplexed analysis and small sample volumes Open platform (Homebrew for RUO) High volume, low cost production of 24array discs 06/25/2013 15 Simoa HD-1 Roadmap 2011 Instrument Development 2011-13 Menu Dev. 2013 RUO Launch 2015 Increased plex DNA, RNA 2016 IVD SiMoA Research Use Only Companion Dx In vitro diagnostics Non-regulated clinical studies Biomarker validation Pharma, Biotech, Core Labs, CROs 16 06/25/2013 16 Exclusive Partner Quanterix Value Map in Biomedical Industry Clinical IVD RUO Pharma & BioPharma Clinical CRO Novel Markers Differentiated Value Quanterix Revenue Streams Sensitivity – Efficiency – Precision – Multiplexing - Value • • • • • Simoa HD-1 Analzyer Assay Kits Homebrew Service Boutique Testing & Custom Assay Dev. Blood Screening Quanterix or Co-Exclusive Academic Research LDTs cDx POC Food Safety, Biothreat, etc. 06/25/2013 17 Thank You 06/25/2013 18