Financial Data and Key Metrics Changes - For fiscal year 2022, operating expenses increased to $63.6 million from $50.5 million in 2021, representing a 26% increase driven by personnel costs and expenses related to operating as a public company [1] - The net loss for the full year was $57.9 million, up from $50.3 million in fiscal year 2021, marking a 15% year-over-year increase [2] - Total operating expenses for Q4 2022 were $16.3 million, which was $500,000 less than the same quarter last year, indicating a focus on controlling spending while investing in growth [33] Business Line Data and Key Metrics Changes - Research and development expenses in Q4 2022 were $9.6 million compared to $9.9 million in the prior year, while general and administrative expenses were $6.7 million, down from $6.9 million [34] - The company anticipates overall operating expenses to grow by approximately 40% from 2022 levels in 2023, while managing spending tightly to preserve investment capabilities [3] Market Data and Key Metrics Changes - The company ended the year with approximately $314 million in cash, cash equivalents, and investments, representing a trailing 12-month cash burn of approximately $48.5 million, with expectations for the cash runway to extend well into 2025 [5] Company Strategy and Development Direction - The company aims to revolutionize proteomics and positively impact health and lives globally, with a focus on commercial expansion leading up to a platform launch in mid-2024 [8][4] - The Nautilus First Access Challenge was announced to inspire researchers and unlock creativity in exploring biological insights, indicating a commitment to engaging the scientific community [11][12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to manage resources effectively amid challenging financial conditions, with a focus on maximizing runway and balancing investments for scientific progress [32] - The management team believes that the product being developed has a strong value proposition and a wide competitive moat, with no significant competitive advancements observed in the proteomics space [96][97] Other Important Information - The company nearly doubled its patent portfolio to over 40 pending patent families filed in the U.S. and abroad, with a total of 11 granted U.S. patents [30] - The company is focused on building a commercial team closer to the launch date, reflecting a cautious approach to scaling operations in the current economic environment [76] Q&A Session Summary Question: Has the company's appetite for M&A changed recently? - Management indicated that while the M&A environment has picked up, there are no near-term plans for M&A, focusing instead on leveraging the balance sheet for platform development [42][55] Question: What advancements should be expected in the near term? - Management highlighted the importance of scientific conferences and continued data sharing with the scientific community as key indicators of progress towards the commercial launch [43][44] Question: What feedback has been received from the scientific community? - Positive feedback was noted regarding the platform's sensitivity, scale, and potential to complement existing mass spectrometry methods, with researchers expressing excitement about the capabilities [45][46] Question: What are the key features the clinical market will look for? - The management believes that the transition from single biomarker assays to broader protein panels will occur naturally, driven by the need for comprehensive analysis in clinical settings [98][99]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 __________________________________________________________________________ FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ___________ Commission file number 001-39434 NAUTILUS BIOTECHNOLOGY, INC. (Exact nam ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2022 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _________ to _________ Commission File Number 001-39434 NAUTILUS BIOTECHNOLOGY, INC. (Exact name of registrant as specified in its charter) Delaware 98-15 ...

Nautilus Biotechnology, Inc. (NASDAQ:NAUT) Q3 2022 Earnings Conference Call November 1, 2022 8:30 AM ET Company Participants Sujal Patel - Co-Founder and CEO Parag Mallick - Co-Founder and Chief Scientist Anna Mowry - CFO Conference Call Participants Max Masucci - Cowen David Delahunt - Goldman Sachs Brandon Couillard - Jefferies Operator Ladies and gentlemen, thank you for standing by, and welcome to the Nautilus Q3 2022 Earnings Call. [Operator Instructions] I would now like to turn the call over to your ...

PART I. FINANCIAL INFORMATION This section presents Nautilus Biotechnology, Inc.'s unaudited condensed consolidated financial statements and management's analysis [Item 1. Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) This section presents the unaudited condensed consolidated financial statements, including balance sheets, statements of operations, and cash flows, with detailed explanatory notes [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The balance sheets show a decrease in total assets and stockholders' equity from December 31, 2021, to June 30, 2022, primarily due to a reduction in short-term investments and an increase in accumulated deficit Condensed Consolidated Balance Sheets (in thousands) | Metric | June 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | Change ($) | | :--------------------------- | :--------------------------- | :-------------------------- | :--------- | | Total Assets | $371,707 | $398,450 | $(26,743) | | Total Liabilities | $34,149 | $34,874 | $(725) | | Total Stockholders' Equity | $337,558 | $363,576 | $(26,018) | | Accumulated Deficit | $(111,092) | $(80,640) | $(30,452) | [Condensed Consolidated Statements of Operations](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The statements of operations reveal increased operating expenses and a larger net loss for both the three and six months ended June 30, 2022, compared to the same periods in 2021 Net Loss (Three and Six Months Ended June 30) (in thousands) | Metric | Three Months Ended June 30, 2022 (in thousands) | Three Months Ended June 30, 2021 (in thousands) | Six Months Ended June 30, 2022 (in thousands) | Six Months Ended June 30, 2021 (in thousands) | | :------------------------------------------------- | :---------------------------------------------- | :---------------------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Net Loss | $(14,689) | $(10,713) | $(30,452) | $(19,122) | - Research and development expenses increased by **$7.3 million (65%)** for the six months ended June 30, 2022, primarily due to higher salaries, benefits, stock-based compensation, development services, and facilities costs[23](index=23&type=chunk)[137](index=137&type=chunk) - General and administrative expenses increased by **$5.1 million (64%)** for the six months ended June 30, 2022, mainly due to increased salaries, benefits, stock-based compensation, insurance, and facilities costs[23](index=23&type=chunk)[138](index=138&type=chunk) [Condensed Consolidated Statements of Comprehensive Loss](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Comprehensive%20Loss) The comprehensive loss increased for both the three and six months ended June 30, 2022, compared to 2021, reflecting the higher net loss and a notable increase in unrealized losses on available-for-sale securities Comprehensive Loss (Three and Six Months Ended June 30) (in thousands) | Metric | Three Months Ended June 30, 2022 (in thousands) | Three Months Ended June 30, 2021 (in thousands) | Six Months Ended June 30, 2022 (in thousands) | Six Months Ended June 30, 2021 (in thousands) | | :----------------- | :---------------------------------------------- | :---------------------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Comprehensive Loss | $(14,903) | $(10,725) | $(31,036) | $(19,135) | - Unrealized loss on securities available-for-sale increased from **$(13) thousand** in 2021 to **$(584) thousand** in 2022 for the six-month period[25](index=25&type=chunk) [Condensed Consolidated Statements of Redeemable Convertible Preferred Stock and Stockholders' Equity](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Redeemable%20Convertible%20Preferred%20Stock%20and%20Stockholders%27%20Equity) This statement shows that all redeemable convertible preferred stock was converted to common stock in June 2021, resulting in no preferred stock outstanding as of June 30, 2022 Stockholders' Equity and Accumulated Deficit (in thousands) | Metric | June 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | | :------------------------- | :--------------------------- | :-------------------------- | | Total Stockholders' Equity | $337,558 | $363,576 | | Accumulated Deficit | $(111,092) | $(80,640) | - Stock-based compensation expense for the six months ended June 30, 2022, was **$4,677 thousand**, an increase from **$3,156 thousand** in the prior year[28](index=28&type=chunk)[91](index=91&type=chunk) - As of June 30, 2022, **124,562,745 shares** of common stock were issued and outstanding[27](index=27&type=chunk)[28](index=28&type=chunk)[78](index=78&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) For the six months ended June 30, 2022, net cash provided by investing activities significantly increased, while net cash provided by financing activities sharply decreased compared to 2021 Cash Flow Summary (Six Months Ended June 30) (in thousands) | Cash Flow Activity | 2022 (in thousands) | 2021 (in thousands) | Change ($) | | :---------------------------------------- | :------------------ | :------------------ | :--------- | | Net cash used in operating activities | $(25,864) | $(14,545) | $(11,319) | | Net cash provided by (used in) investing activities | $50,258 | $(61,048) | $111,306 | | Net cash provided by financing activities | $341 | $327,373 | $(327,032) | | Net increase in cash, cash equivalents and restricted cash | $24,735 | $251,780 | $(227,045) | - Cash, cash equivalents and restricted cash at the end of the period was **$211,196 thousand** as of June 30, 2022[30](index=30&type=chunk) [Notes to Condensed Consolidated Financial Statements](index=12&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) These notes provide comprehensive details on business, accounting policies, recapitalization, fair value, equity, income tax, stock compensation, and commitments [1. Description of Business and Basis of Presentation](index=12&type=section&id=1.%20Description%20of%20Business%20and%20Basis%20of%20Presentation) Nautilus is a development-stage biotechnology company focused on its proteomics platform, with significant capital raised but an accumulated deficit and ongoing COVID-19 impacts - Nautilus Biotechnology, Inc. is a development-stage company incorporated in 2016, focused on research and development of its proteomics platform[31](index=31&type=chunk)[110](index=110&type=chunk) - The company consummated a Business Combination (reverse recapitalization) and PIPE Financing on June 9, 2021, raising approximately **$345.5 million** in gross proceeds[32](index=32&type=chunk)[33](index=33&type=chunk)[115](index=115&type=chunk) - As of June 30, 2022, the company had an accumulated deficit of **$111.1 million** and cash, cash equivalents, and short-term investments of **$299.3 million**, which are expected to fund operations for the next 12 months[36](index=36&type=chunk)[37](index=37&type=chunk)[115](index=115&type=chunk) - The COVID-19 pandemic has led to supply disruptions (e.g., extended chip lead times, diverted lab materials, lower reagent availability) and economic volatility, with its full impact on the business remaining unpredictable[39](index=39&type=chunk)[119](index=119&type=chunk) [2. Significant Accounting Policies](index=13&type=section&id=2.%20Significant%20Accounting%20Policies) This section details significant accounting policies, including estimates, credit risk, segment reporting, investments, leases, and comprehensive loss, noting no material impact from recent pronouncements - The preparation of financial statements requires management to make significant estimates and assumptions, which are evaluated on an ongoing basis[41](index=41&type=chunk)[42](index=42&type=chunk) - The company relies on single-source suppliers for certain components, reagents, and antibodies used in its Nautilus platform, posing concentration of credit risk[44](index=44&type=chunk) - Nautilus operates in one operating and one reportable segment, with all long-lived assets located in the United States[46](index=46&type=chunk) - Investments are classified as available-for-sale and reported at fair value, with unrealized gains and losses recorded in accumulated other comprehensive income (loss)[49](index=49&type=chunk) - The company adopted ASU 2020-04 (Reference Rate Reform) effective January 1, 2022, with no material impact on its financial statements, and does not anticipate a material impact from ASU 2016-13 (Credit Losses) and ASU 2019-12 (Income Taxes) upon future adoption[59](index=

Nautilus Biotechnology, Inc. (NASDAQ:NAUT) Q2 2022 Earnings Conference Call August 2, 2022 8:30 AM ET Company Participants Sujal Patel - Founder and Chief Executive Officer Anna Mowry - Chief Financial Officer Parag Mallick - Founder and Chief Scientist Conference Call Participants Stephanie Yan - Cowen and Company, LLC Tejas Savant - Morgan Stanley David Delahunt - Goldman Sachs Operator Thank you for standing by, and welcome to the Nautilus Biotechnology Second Quarter 2022 Earnings Conference Call. At th ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 OR Delaware 98-1541723 (State or other jurisdiction of incorporation or organization) 2701 Eastlake Avenue East Seattle, Washington 98102 (Address of principal executive offices) (Zip Code) (206) 333-2001 o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ...

Financial Data and Key Metrics Changes - Total operating expenses for Q1 2022 were $16.0 million, a 90% increase from $8.4 million in Q1 2021, primarily due to increased headcount and costs associated with being a public company [16][17] - Research and development expenses for Q1 2022 were $9.7 million, compared to $4.8 million in Q1 2021 [17] - General and administrative expenses for Q1 2022 were $6.4 million, compared to $3.6 million in Q1 2021 [17] - Overall net loss for Q1 2022 was $15.8 million, compared to $8.4 million in Q1 2021 [17] - The company ended the quarter with approximately $349 million in cash, cash equivalents, and investments, providing a strong cash runway through commercialization [18] Business Line Data and Key Metrics Changes - The company reported solid progress against scientific goals and maturation of development processes for consumables and instruments [10] - Significant attention was received for the collaboration results with Genentech, indicating strong interest in the company's technology [10][11] Market Data and Key Metrics Changes - The company noted increased engagement with the scientific community and potential customers, indicating growing interest in new proteomics approaches [30] - The investment community has become more informed about the proteomics market, with increased interest in the company's offerings [29] Company Strategy and Development Direction - Nautilus aims to revolutionize biomedical research by unlocking the potential of the proteome, focusing on target identification and therapeutic development [6][9] - The company is committed to scaling up a world-class team and maintaining a high-performance culture to support its long-term mission [8] - The upcoming Analyst Day in September will include a preview of the planned pricing model and public unveiling of instruments [20][21] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to navigate supply chain challenges and maintain progress towards commercialization [26] - The company remains focused on scientific advancements and plans to provide updates through publications and presentations at conferences [49] Other Important Information - The appointment of Gwen Weld as Chief People Officer is expected to enhance the company's culture and collaborative environment [8] - The company is actively working on partnerships with Amgen and MD Anderson, although specific details on progress remain limited [48] Q&A Session Summary Question: Supply chain diversification benefits - Management confirmed ongoing efforts to diversify suppliers and manage single-source component supply effectively, with no significant impact on progress [25][26] Question: Evolving conversations in the proteomics market - Management noted increased awareness and interest from investors and the scientific community regarding proteomics, leading to more informed discussions [29][30] Question: Operating expenses and headcount expectations - Management expects operating expenses to grow, driven by headcount increases, with a positive outlook on the ability to grow the team [33] Question: Key learnings from the Genentech collaboration - The collaboration highlighted the importance of proteoforms and the need for efficient onboarding of commercially available content [37] Question: Update on partnerships with Amgen and MD Anderson - Management stated it is still early to share detailed information about these partnerships, but progress is being made [48] Question: Tracking progress towards launch - Management advised investors to look for data updates through publications and presentations as the company moves towards commercialization [49]

Financial Data and Key Metrics Changes - Total operating expenses for Q4 2021 were $16.8 million, up from $5.3 million in Q4 2020, primarily due to scaling the team to a headcount of 113, roughly doubling year-over-year [31] - Research and development expenses for Q4 2021 were $9.9 million compared to $3.9 million in Q4 2020, driven by increased personnel costs and development pipeline scaling [31] - Net loss for Q4 2021 was $16.7 million, compared to $5.4 million in Q4 2020 [32] - The company ended the year with approximately $362 million in cash, cash equivalents, and investments [33] Business Line Data and Key Metrics Changes - The company is focused on developing its proteomics platform, which aims to democratize access to proteomics and improve drug discovery and diagnostics [10][12] - Significant progress has been made in R&D, with a focus on consumables and instruments, including a reduction in reagent creation time by a factor of 10 and an increase in yield by a factor of 2 [15] Market Data and Key Metrics Changes - The proteomics market is estimated to be approximately $25 billion, growing at a 12% CAGR [9] - The company anticipates reaching comprehensive coverage of the human proteome by mid-2023 and a commercial launch by the end of 2023 [22] Company Strategy and Development Direction - The company aims to revolutionize biological science by providing accessible proteomics technologies that can accelerate target identification and drug development [10][12] - Nautilus is building strategic partnerships to diversify its supply chain and enhance its probe development capabilities [17][27] - The company is focused on expanding its intellectual property portfolio, having recently been awarded its fourth U.S. patent [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving commercial launch timelines despite some delays in probe development and characterization processes [49][50] - The company is optimistic about the market's excitement for single molecule protein analysis methods and believes it can outperform existing methods [20][29] - Management highlighted the competitive landscape, noting that Nautilus offers significant advantages in sensitivity and dynamic range compared to mass spectrometry and peptide sequencing methods [61][64] Other Important Information - The company plans to host its inaugural Analyst Day in late September to discuss its pricing model and market analysis [35] - The management team emphasized the importance of early customer engagement and the need for ongoing investments in R&D and commercial activities [33][36] Q&A Session Summary Question: What is the current headcount compared to Q3 and any key roles still looking to add? - The company ended the year at 113, doubling year-over-year, and plans to continue investing in R&D and commercial teams [38][39] Question: Clarification on the Genentech collaboration update? - The company will present work from the Genentech collaboration at the US HUPO meeting [41] Question: Updates on MD Anderson-Amgen partnerships? - The agreements were recently signed, and the company is in the early stages of understanding the biological questions to address [42] Question: Details on agreements with three new partners? - The new partners are focused on increasing probe development strategies and complementing existing agreements [44] Question: Drivers of the compressed probe schedule? - The company is behind schedule but remains confident in achieving its milestones due to scaled-up internal and external efforts [48][49] Question: Value addition in the clinical diagnostics market? - The company sees the need for research use partners to lay the foundation for downstream clinical applications, particularly in orphan diseases [58] Question: Positioning versus competitors in protein sequencing? - Nautilus provides significant advantages in coverage, sensitivity, and dynamic range compared to mass spectrometry and peptide sequencing methods [60][61] Question: Impact of wage and cost input inflation? - The company is experiencing competitive labor costs and supply chain challenges but is prioritizing spending to meet objectives [65]

Part I [Item 1. Business](index=7&type=section&id=Item%201.%20Business) 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](index=7&type=section&id=BACKGROUND%20OF%20BUSINESS%20COMBINATION) 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](index=21&type=chunk)[22](index=22&type=chunk) - Common Stock began trading on Nasdaq Global Select Market under symbol 'NAUT' on June 10, 2021[25](index=25&type=chunk) PIPE Financing Details | Item | Value | | :--- | :--- | | Shares issued | 20,000,000 | | Price per share | $10.00 | | Aggregate gross proceeds | $200,000,000 | [Overview](index=7&type=section&id=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](index=26&type=chunk) - 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](index=29&type=chunk)[30](index=30&type=chunk) - 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](index=30&type=chunk)[57](index=57&type=chunk) [Our Strengths](index=9&type=section&id=OUR%20STRENGTHS) 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](index=35&type=chunk) - 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](index=35&type=chunk) - 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](index=35&type=chunk) [Our Strategy](index=10&type=section&id=OUR%20STRATEGY) 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](index=38&type=chunk) - 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](index=38&type=chunk)[31](index=31&type=chunk) - 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](index=38&type=chunk)[39](index=39&type=chunk) [A Primer on Proteomics](index=11&type=section&id=A%20PRIMER%20ON%20PROTEOMICS) 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](index=40&type=chunk)[41](index=41&type=chunk)[42](index=42&type=chunk) - 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](index=42&type=chunk) - Advancements in proteomics can unlock new insights, identify novel drug targets, enable patient stratification, predict disease/treatment outcomes, and guide wellness choices[44](index=44&type=chunk) [Our Market Opportunity](index=12&type=section&id=OUR%20MARKET%20OPPORTUNITY) 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](index=57&type=chunk) - 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](index=48&type=chunk)[49](index=49&type=chunk) - 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](index=54&type=chunk)[55](index=55&type=chunk)[56](index=56&type=chunk) [Existing Proteomics Technologies and Shortfalls](index=15&type=section&id=Existing%20Proteomics%20Technologies%20and%20Shortfalls) 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](index=61&type=chunk) - 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](index=62&type=chunk)[63](index=63&type=chunk) - Both existing platforms force researchers into trade-offs between sample numbers and analysis depth/breadth, hindering progress in proteome characterization[30](index=30&type=chunk) [The Nautilus Approach](index=16&type=section&id=THE%20NAUTILUS%20APPROACH) 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](index=65&type=chunk) - 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](index=73&type=chunk)[74](index=74&type=chunk)[76](index=76&type=chunk)[81](index=81&type=chunk)[86](index=86&type=chunk)[88](index=88&type=chunk) - The platform can detect proteoform patterns by measuring individual proteins at specific post-translational modification sites over multiple cycles, distinguishing different proteoforms quantitatively[105](index=105&type=chunk)[106](index=106&type=chunk)[108](index=108&type=chunk) [A Single Protein Molecule Flow Cell](index=17&type=section&id=A%20Single%20Protein%20Molecule%20Flow%20Cell) 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](index=76&type=chunk) - The flow cell captures one individual scaffold-protein complex per landing pad, enabling self-assembling, high-density single protein molecule arrays[77](index=77&type=chunk)[78](index=78&type=chunk) - This single protein molecule nature enables extreme sensitivity and a wide dynamic range of detection[75](index=75&type=chunk)[78](index=78&type=chunk) [Our Proteome Analysis System: An Integrated Multi-cycle Optical and Fluidics Instrument](index=19&type=section&id=Our%20Proteome%20Analysis%20System%3A%20An%20Integrated%20Multi-cycle%20Optical%20and%20Fluidics%20Instrument) 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](index=81&type=chunk) - Repeated probing of each protein molecule at its unique coordinate address on the flow cell enables deeper characterization and proteoform analysis[80](index=80&type=chunk) - A typical full-scale proteome run generates approximately **20 terabytes of data**, compressed into a digital binding matrix for cloud-based SaaS analytics[82](index=82&type=chunk) [A Novel Class of Affinity Reagents for Efficient Whole Proteome Analysis](index=20&type=section&id=A%20Novel%20Class%20of%20Affinity%20Reagents%20for%20Efficient%20Whole%20Proteome%20Analysis) 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](index=84&type=chunk)[85](index=