Quantum-si Incorporated · NASDAQ:QSI
Quantum-si — Investor Day (November 2024)
78 slides from Quantum-si's investor day presentation, Nov 21, 2024
Slide 1: Investor & Analyst Day November 20, 2024
Investor & Analyst Day November 20, 2024
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation includes “forward-looking statements” within the meaning of the “safe harbor” provisions of the United States Private Securities Litigation Reform Act of 1995. The actual results of the Company may differ from its expectations, estimates, and projections
Slide 3: Investor Day Agenda
Investor Day Agenda Jeff Hawkins, CEO Proteomics Market: Current & Future Perspective 10:00–10:20 AM Todd Rearick, CTO Technology Architecture for the Future 10:20–10:40 AM Brian Reed, PhD Innovating Discovery Applications in Proteomics 10:40–11:00 AM John Vieceli, CPO Platform Roadmap 11:00–11:20 A
Slide 4: Proteomics Market: Current & Future Perspective
Proteomics Market: Current & Future Perspective
Slide 5: Proteins are the vital engines of biological systems
Proteins are the vital engines of biological systems, playing crucial roles in both health and disease Proteins are the Core of Biological Discoveries Therapeutic Development Biotech Innovation Disease Biomarkers
Slide 6: Proteome Complexity
Proteome Complexity GENOME TRANSCRIPTOME AlternativePromoters Alternative splicingmRNA editing Post-translationalModifications PROTEOME COMPLEXITY ~20–25,000 GENES ~100,000 TRANSCRIPTS PROTEOME >1,000,000 PROTEOFORMS
Slide 7: Transcriptomics Does Not Accurately Predict Protein Profiles
Transcriptomics Does Not Accurately Predict Protein Profiles Human Proteoform Project: https://www.science.org/doi/10.1126/sciadv.abk0734
Slide 8: Disease Progression Goes Beyond the Protein Level
Disease Progression Goes Beyond the Protein Level Human Proteoform Project: https://www.science.org/doi/10.1126/sciadv.abk0734
Slide 9: Proteomics is a Large and Growing Market
$75B+ Proteomics Market1 $8B+ Initial Target Market2 Proteomics is a Large and Growing Market Opportunity Identification $3B+ Expression + Quantification $3B+ Proteoforms + PTMs $1.5B+ SVB Leerink Research, “Proteomics: The Next Frontier in Life Science Tools and Diagnostics.” September 28, 2021 Dec
Slide 10: Platinum Use Cases Today
Post-translational modifications Amino acid variants RNA isoforms Platinum Use Cases Today Identify ProteinsCritical to Biology Screen and Characterize Proteins with Barcodes Uncover + Understand Proteoforms In-gel digest of bio samples Characterize antibodies Identify co-IP proteins Protein/antibod
Slide 11: How QSI Customers Are Leveraging Platinum
How QSI Customers Are Leveraging Platinum MRNA screening with protein barcodes for gene therapy Studying citrullination PTMs Characterizing far-flungextremophiles Studying mRNAtranslation and PTMs Studying disease isoforms Mapping protein conformationsusing protein barcodes
Slide 12: The Proteomics Market is Poised for Significant Growth
The Proteomics Market is Poised for Significant Growth The proteome is dynamic — longitudinal data will be needed (i.e., repeat testing) Routine use of multiomics requires creating new data analysis tools — these tools will require large amounts of training data Large-scale screening studies designe
Slide 13: Technical Challenges in Proteomics Today
Technical Challenges in Proteomics Today Top-down vs Bottom-up Sensitivity vs Dynamic Range Unbiased vs Biased Standardization + Reproducibility Throughput + Costs Breadth(# of Proteins) vs Depth(Amino Acid, PTM)
Slide 14: Multiple Specialized Platforms Required to Fully Interrogate the Proteome
Multiple Specialized Platforms Required to Fully Interrogate the Proteome HT Affinity Assays Mass Spec EdmanDegradation Western Blots + ELISA Samples: 100s–1,000s per study Proteins: 100-1,000s per sample Resolution: Protein Samples: 10s–100s per study Proteins: <50 per sample Resolution: Amino acid
Slide 15: QSI is Best Positioned to Usher in a New Paradigm in Proteomics
QSI is Best Positioned to Usher in a New Paradigm in Proteomics Proteus™ Platinum® Pro Core technology is the only commercially available tech that can enable single-molecule, top-down, and bottom-up proteomics methods New architecture (Proteus™), combined with other ongoing technology development i
Slide 16: Distribution Agreement in Place to Scale Adoption Across the US + Canada
Distribution Agreement in Place to Scale Adoption Across the US + Canada
Slide 17: Technology Development Pipeline
Technology Development Pipeline
Slide 18: Quantum-Si Core Technologies
Quantum-Si Core Technologies Peptide Mapping Barcode Applications Variant Calling PTM Characterization Protein Identification Platinum® System 2M Chip Chemistry Biomolecules Algorithms Applications
Slide 19: End-to-End Protein Analysis
End-to-End Protein Analysis Protein Peptides Data Analyzed Excitation ‘R’ Sequenced Wells Prepared IL4(78-84)-QLI — IL4(85-102)-RLD — IL4(43-61)-ETF — IL4(22-37)-TLC — IL4(3-12)-CDI — IL4(13-21)-TLN — IL4(103-117)-EAN — 15,548.0, FDR:0.00 ALIGNMENTS IL4 (22,160 Reads) FDR <0.05 0.05 ≤ FDR <0.1 FDR ≥
Slide 20: Prepare Proteins for Sequencing
Prepare Proteins for Sequencing Proteins are digested into short fragments (peptides) Peptides are immobilized at the bottom of reaction chambers on our chip
Slide 21: Kinetic Signatures Uniquely Identify Proteins + Proteoforms
Kinetic Signatures Uniquely Identify Proteins + Proteoforms Recognizers bind amino acids in sequence Recognition events produce kinetic signatures R L I F DQQ 600 500 400 300 200 100 0 0.24s 3.23s 0.23s 0.97s TIME (min) Kinetic signature plot Excitation ’R’ Sequenced ‘L’ Sequenced ‘I’ Sequenced ‘F’
Slide 22: Rationale for New Technology Architecture
Rationale for New Technology Architecture Semiconductors require large R&D investment Re-partitioning of system allows for less expensive consumable Leverage optical magnification to pack wells closer together and scale to billions of reads Leverage high-performance, commercially-available imaging c
Slide 23: QSI Core Technologies
QSI Core Technologies Trying to show all components of core tech. Do not need “chip” box and SW image could be something else Chip Surface Chemistry Instrument Library Prep + Sequencing Reagents Software
Slide 24: Chip + Surface Chemistry
Chip + Surface Chemistry Simple passive device with approximately 20M wells (per flow cell) at initial launch Heavily de-risked — leverages existing design, materials, and fabrication methods Compatible with existing surface chemistry Surface passivation Functionalized well bottom
Slide 25: Proteus Consumable Development
Proteus™ Consumable Development Wafer process flow developed in production foundry Prototype wafers fabricated and tested Simple process has low-risk path to high-volume production
Slide 26: Wafer Fabrication Process Development
Wafer Fabrication Process Development Foundry process modules work and produce the desired well structure Foundry partner for development and production is in place Fused Silica Wafer
Slide 27: Proteus Instrument Development
Proteus™ Instrument Development Move imaging components to the system Increase workflow automation Leverage commercially available technologies for imaging and liquid handling Takes advantage of significant investment in optics driven by NGS industry
Slide 28: Library Prep + Sequencing Chemistry
Library Prep + Sequencing Chemistry Existing library prep and sequencing chemistry are completely portable New system discriminates dyes with color rather than lifetime Some new dye development is necessary, but is underway and low risk
Slide 29: Color Ratio is a Viable Alternative to Current Lifetime Detection
Color Ratio is a Viable Alternative to Current Lifetime Detection Key elements have already been de-risked Move to color means we can leverage off-the-shelf camera technology
Slide 30: Registration Deconvolution Analysis Software
Registration Deconvolution Analysis Software Pulse detection, ROI calling, alignment, protein inference, and other applications Backend processing is completely portable to new system Development required for frontend image processing Well within state-of-the-art capability Camera Image Reconstitute
Slide 31: Instrument Roadmap
Instrument Roadmap New architecture scales upto 10B reads per consumable Enables shotgun proteomics of complex samples Puts us on path tode novo sequencing Platinum (2M) ProteusTM 1.0 (50M+) ProteusTM 2.0 (10B)
Slide 32: Innovation Toward the Most Advanced Set of Discovery Applications in Proteomics
Brian Reed Innovation Toward the Most Advanced Set of Discovery Applications in Proteomics
Slide 33: Agenda
Agenda Innovation at the Forefront of Proteomics The path to complete proteome coverage 1 Deep, unbiased interrogation of high-complexity samples 3 Beyond sequencing: the first platform for top-down single-molecule proteomics 4 Ultrasensitive PTM detection for proteoforms 2
Slide 34: Acceleration on the Path to Complete Proteome Coverage
Acceleration on the Path to Complete Proteome Coverage
Slide 35: Sequence Proteins on Platinum
Sequence Proteins on Platinum Each recognizer binds 1-3 cognate N-terminal amino acids (NAAs) Rapid on-off binding generates a pulsing pattern detected by the chip Extremely information-rich data output: 10s-100s of pulsing events per amino acid
Slide 36: A Rapid Path to Complete Amino Acid Coverage
A Rapid Path to Complete Amino Acid Coverage Our team has mastered the engineering and evolution of amino acid recognizers As a result of our rich kinetic output, we have more data on our recognizers than possibly any other set of proteins in biotechnology Recognizers in the V3 kit recognize 13 of t
Slide 37: Kinetic Signatures are Sensitive to Downstream Sequence
Kinetic Signatures are Sensitive to Downstream Sequence Recognizers physically contact residues downstream of bound NAA Influence is encoded in the peptide’s kinetic signature and is highly predictable Kinetic signatures are a unique and powerful feature of Quantum-Si's core technology The acquisiti
Slide 38: Ultrasensitive PTM Detection for Proteins and Proteoforms
Ultrasensitive PTM Detection for Proteins and Proteoforms
Slide 39: Phosphorylation is the Most Abundant PTM in the Human Proteome
Phosphorylation is the Most Abundant PTM in the Human Proteome Post-translational modifications (PTMs) are central to protein function and implicated in human diseases There are more than 400 different types of PTMs; phosphorylation is the dominant type (~72% of all PTM sites) Phosphorylation has th
Slide 40: Affinity Reagents as Ultrasensitive PTM Recognizers
Affinity Reagents as Ultrasensitive PTM Recognizers Anti-PTM antibodies and other affinity reagents work on chip for ultrasensitive PTM detection Deliver the same real-time kinetic information as NAA recognizers Recognize PTMs anywhere in the peptide (not just at the N-terminus) PTM Recognition AQRY
Slide 41: Phosphotyrosine Affinity Reagents as Ultrasensitive PTM Recognizers
Phosphotyrosine Affinity Reagents as Ultrasensitive PTM Recognizers 30 min Step1: PTM detection for 30 minutes with PTM recognizer Step 2: Normal protein sequencing with NAA recognizers PTM recogizers can be multiplexed and combined with kinetic signatures to pinpoint PTMs in multisite configuration
Slide 42: Ultrasensitive Phosphotyrosine Detection with CDNF
Ultrasensitive Phosphotyrosine Detection with CDNF Extreme sensitivity to PTM stoichiometry due to the clear pulsing pattern from PTM recognition Example: a CDNF peptide is detected at a ratio of less than 1 phosphorylated peptide in 1,000 Method can be extended to other types of PTMs, e.g., ubiquit
Slide 43: Recognition of Human TAU Proteoforms
Recognition of Human TAU Proteoforms Affinity reagents can be used in a bottom-up or top-down configuration Example: bottom-up recognition of pT* on human TAU peptides, top-down detection of immobilized full-length TAU proteoforms Real-time approach enables proteoform detecting reagents to be run si
Slide 44: Unbiased Interrogation of High-Complexity Samples with Quantum-Si's Core Technology
Unbiased Interrogation of High-Complexity Samples with Quantum-Si's Core Technology
Slide 45: Sequencing Complex Biological Samples Unlocks Broad Access to Proteomics
Sequencing Complex Biological Samples Unlocks Broad Access to Proteomics PROTEIN CONTENT COMPLEXITY Protein complexes Viral particles Sub- cellular protein fractions Plasma extra- cellular vesicles Serum/ plasma Cell lysates Tumor tissue samples Cerebro- spinal fluid 1,000s 100s 10s Biological sampl
Slide 46: Unbiased Interrogation of High-Complexity Samples
Unbiased Interrogation of High-Complexity Samples New chip architectures and advances in sequencing chemistry will enable sequencing biological samples at ever-increasing depth Future versions of the platform will see shotgun sequencing with thousands of proteins identified Barcoding approaches and
Slide 47: Fast Sequencing for Deep Coverage and Rapid Sample-to-Answer
Fast Sequencing for Deep Coverage and Rapid Sample-to-Answer Standard chemistry FAST chemistry v1 Example peptide We have developed new sequencing chemistry with a much faster rate of sequencing With FAST chemistry, we achieve equal performance to 10-hour runs in just 90 minutes (version 1) Path to
Slide 48: Beyond Sequencing: Top-Down Single-Molecule Proteomics
Beyond Sequencing: the First Commercially Available Platform for Top-Down Single-Molecule Proteomics
Slide 49: Detecting Antibody Binding Events with the Power of Real-Time Kinetics
Dye-cycling enables ultrasensitive real-time detection of biomarkers Detecting Antibody Binding Events with the Power of Real-Time Kinetics IL6 Capture antibody Detection antibody Detection of fixed protein panels with high sensitivity is an increasingly important application in proteomics We develo
Slide 50: Ultrasensitive Detection of Proteins in Serum
Ultrasensitive Detection of Proteins in Serum Interleukin 6 Lysozyme GFP Spike-in titration experiments in serum demonstrate 0.1–1 pg/mL detection (path down to 10 fg/mL with further development) Direct detection of proteins in serum with high sensitivity
Slide 51: Multiplexed Ultrasensitive Protein Biomarker Detection
Multiplexed Ultrasensitive Protein Biomarker Detection Affinity reagents against multiple biomarkers can be loaded on the chip Dye-cycling approach enables discrimination of biomarkers by fluorescence and kinetic properties in multiplexed assays, along with PTMs IL6 TNF-α Multiplexed detection of hu
Slide 52: A Platform for Ultrasensitive Detection of Protein Panels
A Platform for Ultrasensitive Detection of Protein Panels Sensitivity on Platinum is suitable for commercialization of panels with up to 10 proteins Panel size scales with the platform, as well as capacity to multiplex samples Proteins detected directly in serum on chip, eliminating complex sample p
Slide 53: Platform Roadmap
Platform Roadmap Nov 20, 2024 John Vieceli
Slide 54: Innovation Pipeline is Robust and Accelerating
2025 2H24 2023 2026 2022 1H24 Innovation Pipeline is Robust and Accelerating Sequencing V1 Instruments + Software UI/UX ProteinInference AI KineticDatabase V2 AI KineticDatabase V3 Library Prep V1 Platinum Pro ProteoVue ScientificCollaborations V2 Low Input LI V2 V3 V4 ProteusTM
Slide 55: Sequencing Analysis Software
Sequencing Analysis Software Sequence Measure fluorescence from single molecule binding of N-terminal amino acid recognizers Pulse Caller Assign pulses to a recognizer based on fluorescence intensity and lifetime Analyze Determine amino acid sequence using kinetic signature Excitation ’R’ Sequenced
Slide 56: Software Workflows for Next-Gen Protein Sequencing
Software Workflows for Next-Gen Protein Sequencing™ Protein Inference Kinetic signature enables inference of sample protein from whole human proteome panel ProteoVue™ Variant Calling Kinetic signature enables differentiation of protein variations at the single amino acid level Rank Inferred Protein
Slide 57: Artificial Intelligence
Artificial Intelligence
Slide 58: N-terminal Amino Acid Recognizer Development
N-terminal Amino Acid Recognizer Development Science Publication Oct 2022 FYW LIV R Version 1 Kit Mar 2023 AS NQ Version 2/3 Kit Jan/July 2024 DE
Slide 59: Recognizer Protein Design AI
Recognizer Protein Design AI Orthogonal verification of amino acid recognizer protein design Amino acid recognizer backbone design Amino acid recognizer sequence design Protein design AI leverages NVIDIA GPUs on-premises and in Amazon Cloud
Slide 60: Pulse Width Prediction Using Artificial Intelligence
Pulse Width Prediction Using Artificial Intelligence Platinum Sequencing QSI is continually increasing the size of the training data with more proteins and/or new binders Pulse Width Prediction AI Currently predicts ~4.6 million pulse widths used in analysis Better Performance Pulse width prediction
Slide 61: Platinum Pro
Platinum® Pro
Slide 62: Platinum Instrument
Platinum® Instrument Customers identified opportunities to improve workflow and UI/UX Functionality limited to protein & peptide sequencing Local analysis enabledby additional server
Slide 63: Introducing Platinum Pro
Introducing Platinum® Pro Streamlined workflowand reduced hands-on time Pro Mode enables new applications Onboard analysis or via the cloud Enhanced user interface
Slide 64: Streamlined Workflow Improves Usability
Streamlined Workflow Improves Usability
Slide 65: Pro Mode
Pro Mode Available only on Platinum Pro Dye-labeling Kit Binding Kinetics Protein Binding Protein of Interest Kit and platform enable detection of single-molecule protein binding and kinetics
Slide 66: Peptide Barcodes can be Used to Monitor Protein Expression
Peptide Barcodes can be Used to Monitor Protein Expression Both In Vivo or In Vitro IN VIVO IN VITRO Equimolar 5 barcode mix encoded as mRNA and packaged into LNPs Enrich for target protein, functionalize, cleave, and sequence barcodes Inject into mouse model; harvest target tissues 5433.0, FDR:0.00
Slide 67: V2 Library Preparation Kit Improvements
V2 Library Preparation Kit Improvements Simplified workflow reduces need for buffer exchange Improved performance with ~80% of proteins successfully inferred Reduced protein input five-fold
Slide 68: Proteus
ProteusTM
Slide 69: Proteus Increases Throughput + Automation
ProteusTM Increases Throughput + Automation Switch from semiconductor to optical architecture with patterned array for throughput scalability Liquid handling automation simplifies workflow and reduces hands-on time Up to an order of magnitude throughput increase per sample relative to Platinum at in
Slide 70: Proteus Increases Number of Samples
ProteusTM Increases Number of Samples Reagent cartridges with sequencing workflow automation Run up to 8 samples inone sequencing run Run one or two samples simultaneously
Slide 71: The Proteomics Lab of the Future
The Proteomics Lab of the Future
Slide 72: QSI's Pipeline is Heavily De-risked Compared to Other Proteomics Companies
QSI’s Pipeline is Heavily De-risked Compared to Other Proteomics Companies Builds upon QSI’s existing commercially available technologies Industry-leading protein and enzyme engineering program operating at scale and with high success rates Manufacturing infrastructure in place and routinely produci
Slide 73: Strategic Partnerships to Accelerate Commercial Adoption
Strategic Partnerships to Accelerate Commercial Adoption and Deliver on Innovation Roadmap
Slide 74: QSI is Best Positioned to Usher in a New Paradigm in Proteomics
QSI is Best Positioned to Usher in a New Paradigmin Proteomics QSI core technology is the only commercially available tech that can enable single-molecule, top-down, and bottom-up proteomic analysis New platform architecture designed so QSI will not be feature limited (can scale to billions of reads
Slide 75: QSI Near-term Pipeline Will Unlock Opportunities Across All Market Segments
QSI Near-term Pipeline Will Unlock Opportunities Across All Market Segments
Slide 76: Proteomics Lab Today
Proteomics Lab Today Many specialized platforms needed to fully interrogate the proteome Technical tradeoffs when selecting between the breadth of protein coverage and depth of insights High capital costs and manual workflows limit the number of laboratories capable of performing proteomics
Slide 77: QSI Will Power the Proteomics Lab of the Future
QSI Will Power the Proteomics Lab of the Future One platform and core technology capable of addressing the broadest range of proteomics analysis methods Eliminate technical tradeoffs – single-molecule, amino acids and PTMs, top-down or bottom-up, ultrasensitive, scalable throughput Affordable and au
Slide 78: Q&A
QUANTUM SI Q&A