Nautilus Biotechnology(NAUT) - 2021 Q4 - Annual Report

Part I Item 1. Business Nautilus is a development-stage life sciences company creating a platform for high-sensitivity, high-scale proteome quantification, aiming for broad commercialization by late 2023 or early 2024 Background of Business Combination The company completed a business combination on June 9, 2021, involving domestication to Delaware and merger with Legacy Nautilus - Nautilus Biotechnology, Inc. (f/k/a ARYA Sciences Acquisition Corp III) completed a business combination on June 9, 2021, involving domestication to Delaware and merger with Legacy Nautilus[21][22] - Common Stock began trading on Nasdaq Global Select Market under symbol 'NAUT' on June 10, 2021[25] PIPE Financing Details | Item | Value | | :--- | :--- | | Shares issued | 20,000,000 | | Price per share | $10.00 | | Aggregate gross proceeds | $200,000,000 | Overview Nautilus is a development-stage life sciences company focused on creating a platform technology to quantify the proteome with extreme sensitivity and scale - Nautilus is a development stage life sciences company creating a platform technology for quantifying and unlocking the complexity of the proteome, aiming to transform proteomics by democratizing access and enabling advancements in human health and medicine[26] - The Nautilus platform, leveraging novel design and machine learning, has the potential to rapidly and reproducibly identify approximately 95% of proteins in a sample and detect/map modifications, addressing limitations of existing affinity-based and mass spectrometry methods[29][30] - The existing proteomics research market is estimated at $25 billion annually (2021) and is projected to reach $50 billion by 2027, growing at a 12% CAGR[30][57] Our Strengths Nautilus's proteome analysis platform offers disruptive single-protein molecule analysis with extreme sensitivity, scale, and ease-of-use - Nautilus' proteome analysis platform is a disruptive, single protein molecule analysis technology designed for extreme sensitivity, scale, and ease-of-use, leveraging novel system architecture and advanced machine learning[35] - The platform is open and customizable, compatible with a wide variety of affinity binding reagents, and has initiated a strategic partnership with Abcam for antibody development and supply[35] - The Nautilus platform is expected to generate up to approximately 20 terabytes of digital protein data per run, decoded by proprietary machine learning algorithms that continuously improve over time[35] Our Strategy Nautilus aims to lead the global proteomics market through a three-phase commercial strategy and continuous innovation - Nautilus aims to be a leader in the global proteomics market (estimated $25 billion in 2021, projected $50 billion by 2027 at 12% CAGR) with potential expansion into clinical diagnostics, precision medicine, and drug discovery[38] - The company employs a three-phase commercial strategy: initial partnerships (Genentech, Amgen, MD Anderson), an early access program, and a broad commercial launch of its proteome analysis system, consumables, and software[38][31] - Nautilus plans continuous innovation through R&D and collaborations, and is building manufacturing capacity using off-the-shelf components, external contract manufacturers, and internal resources[38][39] A Primer on Proteomics Proteomics involves identifying, characterizing, and quantifying proteins in biological samples, which is crucial for understanding disease and developing precision medicine - Proteomics is the identification, characterization, and quantification of proteins in biological samples, crucial for understanding disease mechanisms, drug targets, and precision medicine[40][41][42] - Unlike the largely unchanging genome, the proteome is dynamic, continuously responding to various signals and treatments, making its detailed characterization vital for novel insights[42] - Advancements in proteomics can unlock new insights, identify novel drug targets, enable patient stratification, predict disease/treatment outcomes, and guide wellness choices[44] Our Market Opportunity The global proteomics market is rapidly growing, with significant unmet needs in comprehensive protein and proteoform quantification for drug development and biomarker discovery - The global proteomics market was valued at approximately $25 billion as of 2021 and is projected to reach approximately $50 billion in 2027, representing a CAGR of 12% for the six-year period[57] - Approximately 95% of FDA-approved drug targets are proteins, yet existing methods only quantify a fraction of the proteome, hindering biomarker discovery and drug development[48][49] - The human proteome is estimated to contain up to 6,000,000 different proteoforms, offering over 100 times more information complexity than the genome, which current technologies cannot routinely access[54][55][56] Existing Proteomics Technologies and Shortfalls Current proteomics technologies, including mass spectrometry and affinity-based methods, face limitations in sensitivity, scale, and proteoform characterization - Mass spectrometry-based approaches are complex, time-consuming, lack sensitivity for low-frequency proteins, and cannot identify proteoforms due to protein fragmentation[61] - Affinity-based approaches offer greater sensitivity but are limited by the availability, specificity, and scale of affinity reagents, preventing comprehensive proteome and proteoform characterization[62][63] - Both existing platforms force researchers into trade-offs between sample numbers and analysis depth/breadth, hindering progress in proteome characterization[30] The Nautilus Approach The Nautilus platform is an end-to-end single protein molecule analysis solution integrating instrumentation, reagents, and software for extreme sensitivity and scale - The Nautilus platform is an end-to-end single protein molecule analysis solution designed for extreme sensitivity, scale, and ease-of-use, integrating instrumentation, reagent consumables, and software[65] - Key innovations include a single protein molecule flow cell (10 billion landing pads), an integrated multi-cycle optical and fluidics instrument, a novel class of multi-affinity reagents (PrISM) for efficient whole proteome analysis, and machine learning protein decoding analytics[73][74][76][81][86][88] - The platform can detect proteoform patterns by measuring individual proteins at specific post-translational modification sites over multiple cycles, distinguishing different proteoforms quantitatively[105][106][108] A Single Protein Molecule Flow Cell The Nautilus platform utilizes a hyper-dense single molecule protein nanoarray with 10 billion landing pads for extreme sensitivity and wide dynamic range detection - The Nautilus platform is designed to measure billions of individual protein molecules at a time using a hyper-dense single molecule protein nanoarray with 10 billion landing pads[76] - The flow cell captures one individual scaffold-protein complex per landing pad, enabling self-assembling, high-density single protein molecule arrays[77][78] - This single protein molecule nature enables extreme sensitivity and a wide dynamic range of detection[75][78] Our Proteome Analysis System: An Integrated Multi-cycle Optical and Fluidics Instrument The Nautilus instrument integrates reagent fluidics with high-resolution optical imaging to cyclically measure single protein molecules and generate vast datasets - The Nautilus instrument integrates reagent fluidics with a sensitive high-resolution optical imaging system to cyclically measure single protein molecules[81] - Repeated probing of each protein molecule at its unique coordinate address on the flow cell enables deeper characterization and proteoform analysis[80] - A typical full-scale proteome run generates approximately 20 terabytes of data, compressed into a digital binding matrix for cloud-based SaaS analytics[82] A Novel Class of Affinity Reagents for Efficient Whole Proteome Analysis The Nautilus platform employs both high-specificity and low-specificity multi-affinity reagents for broad proteome identification and proteoform detection - The Nautilus platform exploits both high-specificity affinity reagents for single-molecule detection and low-specificity multi-affinity reagents for broad proteome identification[84][85](index=