NASDAQ: NAUT

As of the open of trading on June 10, 2021, the Common Stock began trading on the Nasdaq Global Select Market under the symbol “NAUT.” On October 29, 2025, the Company transferred the listing of its Common Stock to the Nasdaq Capital Market (“Nasdaq”).

Unless expressly indicated or the context requires otherwise, the terms “Nautilus,” “New Nautilus,” the “Company,” the “Registrant,” “we,” “us” and “our” in this Form 10-K refer to Nautilus Biotechnology, Inc., the parent entity formerly named ARYA Sciences Acquisition Corp III, and where appropriate, our wholly-owned subsidiaries (including Legacy Nautilus).

OVERVIEW

We believe the proteome represents one of the largest and least characterized areas of opportunity in modern biology and medicine. Proteins are the primary drivers of cellular function and disease biology and account for approximately 95% of historically approved FDA drug targets. Despite decades of investment in life sciences research, researchers continue to lack the ability to routinely and comprehensively measure the full complement of proteins present in cells, tissues, and biological systems with sufficient breadth, depth, and reproducibility. We believe these limitations have constrained progress in areas such as drug discovery, biomarker development, and precision medicine.

The global proteomics research market is projected to grow to approximately $57 billion by 2030, representing a compound annual growth rate (or CAGR) of approximately 13% according to BCC Research report “Proteomics: Technologies and Global Markets”, issued in May 2025. This market is currently served primarily by mass spectrometry-based and affinity-based technologies. While these approaches have enabled important scientific advances, they remain limited in their ability to deliver comprehensive, reproducible, and scalable characterization of the proteome.

To more fully unlock the value of the proteome, we anticipate that researchers will require measurement capabilities that deliver breadth, depth, and reproducibility. Together, these three attributes form the foundation for understanding biological systems, interpreting disease mechanisms, and translating proteomic data into meaningful scientific and clinical insight.

“Breadth” refers to the ability to identify and quantify a large proportion of the proteins expressed in a biological sample, across diverse sample types and large cohorts. At Nautilus, we refer to this capability as broadscale proteome analysis, or “broadscale”, in which common representative proteins, referred to as “canonical proteins”, are identified and quantified without prior selection or targeting. In the context of the human proteome, which comprises approximately 20,000 canonical proteins encoded by the genome, broadscale analysis aims to enable efficient and confident measurement of unknown proteins present in a given sample. We believe this breadth is essential for discovery-driven research, as it may allow researchers to observe global changes in protein expression, uncover previously unrecognized biological signals, and avoid bias introduced by predefined target panels.

“Depth” refers to the ability to resolve protein measurements down to functional protein variants, known as proteoforms. Proteoforms arise from the combination of genomic variation, alternative processing events, and post-translational modifications. The resulting change often determines the functional state of a protein in a biological system. While the human genome encodes approximately 20,000 canonical proteins, it is estimated that these give rise to millions of distinct proteoforms, reflecting the true functional complexity of the proteome. At Nautilus, we refer to the identification and quantification of these functional variants as

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“targeted proteoform analysis”. In contrast to broadscale proteome analysis, targeted proteoform analysis focuses on a defined subset of proteins and resolves the specific proteoforms present within a sample, which may enable deeper investigation of biological mechanisms, disease states, and therapeutic response.

“Reproducibility” refers to the ability to generate consistent and comparable measurements across runs, instruments, time, and laboratories. We believe high reproducibility is essential for both broadscale and targeted proteoform analyses, particularly in large-scale studies, longitudinal experiments, and translational research settings. Without reproducible measurements, researchers may be required to perform additional experiments to confirm results, increasing cost and complexity while reducing confidence in biological conclusions. Furthermore, reproducible datasets enable reliable comparison across samples and cohorts, support integration with other data modalities such as genomics and transcriptomics, and provide the consistency required to train and apply artificial intelligence (“AI”) models to biological data. We believe that large, high-quality, and reproducible proteomic datasets are critical for building accurate biological models and generating clinically meaningful insights.

By combining comprehensive proteome breadth with proteoform-level depth, and by delivering both with high reproducibility, researchers can begin to fully understand how proteins function within complex biological systems. We believe that measurement approaches capable of uniting these attributes may provide a necessary foundation for advancing basic research, translational science, and the application of proteomics to drug discovery, precision medicine, and diagnostics. Additionally, combining breadth and depth may unlock discovery of novel biology not previously accessible.

Existing commercially available proteomics technologies require researchers to make trade-offs between breadth, depth, throughput, and reproducibility. Mass spectrometry approaches offer flexibility across applications but typically require a trade-off between breadth, depth, and throughput, limiting their ability to comprehensively analyze large numbers of samples. Current affinity-based approaches, while capable of higher throughput, are inherently constrained by the availability and performance of affinity reagents, which can affect reproducibility and scalability, and cannot currently achieve the level of depth required to measure proteins at their functional level due to the bulk nature of these approaches. As a result, researchers are often unable to generate proteomic data that delivers breadth and depth and reproducibility across experiments.

Nautilus is a development stage life sciences company focused on creating a platform technology to quantify and unlock the complexity of the proteome. We were founded to address longstanding challenges in proteomics through the development of a new measurement method, “Iterative Mapping”, for the analysis of single, intact protein molecules at scale. Our mission is to transform the field of proteomics by broadening access to high-quality proteomic data and to help support fundamental advancements across human health and medicine. We believe that incremental improvements to existing technologies are insufficient to overcome the limitations of current approaches, and that a fundamentally new measurement paradigm is required. Iterative Mapping is designed to enable broad and deep characterization of the proteome while delivering high reproducibility through direct single molecule counting. By repeatedly interrogating individual protein molecules and aggregating results across billions of measurements, Iterative Mapping generates digital protein counts that are intended to support consistent comparison across samples, experiments, and time.

The Nautilus VoyagerTM platform is designed to implement the Iterative Mapping method. The Nautilus Voyager platform integrates nanofabricated protein arrays, affinity reagent probing, advanced optics and fluidics, and machine learning–based analysis into an end-to-end workflow inclusive of instrumentation, consumables, and software. We believe this integrated design enables accurate, reproducible, and scalable measurement of protein abundance and proteoform diversity on the same platform, thereby supporting both broadscale proteome and targeted proteoform analyses, and addressing key limitations of existing proteomics technologies. Furthermore, the Nautilus Voyager platform is designed to generate nuanced, single‑molecule counts of protein and proteoform abundance that directly reflect biology. We believe the data generated by the Nautilus Voyager platform will have the breadth, depth, and reproducibility needed to cleanly integrate with other biological methods (including genomics, transcriptomics, and metabolomics), effectively train AI models, and help prevent those models from generating misleading conclusions about health and disease.

To bring the Nautilus Voyager platform to market, we are executing a phased commercialization strategy intended to balance scientific validation with disciplined expansion of commercial access. Following an initial phase focused on building a foundation of collaborators and validating core platform capabilities, we launched our “Iterative Mapping Early Access Program” in January 2026. This program provides select customers with standardized applications delivered through our “Nautilus Proteomics Analysis Services”, allowing us to broaden engagement, generate reference datasets, refine workflows, and build commercial momentum while maintaining a high level of scientific and operational control. We believe this approach positions us to transition over time toward broader platform commercialization.

Our ability to execute this strategy is supported by a highly interdisciplinary organization that combines scientific expertise with experience scaling complex technology platforms. Our team includes personnel with background in chemistry, molecular biology, nanofabrication, engineering, machine learning, software, and life sciences commercialization, and over one-third of our employees hold Ph.D. degrees. Our leadership team has experience building and commercializing platform technologies in both life sciences and data-driven industries, and our Scientific Advisory Board includes experts who provide scientific and strategic guidance. We believe

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this combination of technical depth, commercial experience, and customer-facing scientific capability is important to the successful scaling of Nautilus. By combining measurement capabilities designed to deliver breadth, depth, and reproducibility with a phased commercialization strategy and an experienced team, we believe Nautilus is positioned to support long-term value creation across research, drug discovery, and healthcare.

OUR STRENGTHS

•Differentiated proteomics technology platform. The Nautilus VoyagerTM platform is an integrated, single-molecule proteomic analysis platform designed to implement our Iterative Mapping methodology. The Nautilus Voyager platform is designed to support both broadscale proteome analysis and targeted proteoform analysis, and integrates instrumentation, consumables (including flow cells and affinity reagents), and software into a single, end-to-end platform. The Nautilus Voyager platform is also designed to be open and customizable, with the ability to support a range of affinity reagents, including proprietary and commercially available reagents, subject to platform compatibility and performance requirements. We believe this integrated design helps enable researchers to generate proteomic data with a high degree of breadth, proteoform-level depth, and reproducibility in a laboratory setting.

Leveraging Iterative Mapping and advanced machine-learning–based analysis, we believe the Nautilus Voyager platform has the potential to identify and quantify a substantial majority of proteins present in a sample across a wide range of organisms. In addition, by directly measuring single, intact protein molecules, we believe the Nautilus Voyager platform is designed to enable detection and quantification of functional protein variants, or proteoforms, including those defined by specific patterns of post-translational modification. These proteoform-level features are widely believed to be critical drivers of biological function and disease and have historically been difficult to resolve using existing proteomics technologies.

•Novel end-to-end proteomics detection platform of extreme sensitivity. We aim to be the first commercially available proteomics detection platform technology and integrated solution to decode and quantify approximately 95% of the entire proteome including the variations and modifications of proteins that combine to create proteoforms. The Nautilus Voyager platform consists of instruments, consumables, and software that we believe has the potential to deliver to the market, broad proteome profiling adaptable to many applications with industry-leading reproducibility across instruments, users, and labs. We believe the Nautilus Voyager platform has the potential to unlock the vast, dynamic, and valuable biological information contained in the proteome. With each Nautilus Voyager instrument sale, we anticipate the potential for accompanying recurring revenue comprised of consumable sales, instrumentation service, support, and software that creates the basis for a comprehensive proteomics solution.

•Immense data production capacity coupled with machine learning may deliver results that are more easily integrated into multi-omics for rapid insight generation. We have designed the Nautilus Voyager platform to create and process a vast amount of proteomic data that we plan to decode using our proprietary machine learning algorithms and cloud-based data processing infrastructure. As we expand and enrich our database with increasing amounts of digital proteomic data over time, we plan to deploy our machine learning algorithms to continuously improve and benefit from each new experiment conducted on the Nautilus Voyager platform. We believe that this feedback loop has the potential to deliver future value to our customers through continuous improvements in our analytics, thereby encouraging the analysis, and re-analysis, of more samples through the Nautilus Voyager platform. Coming in the form of single-molecule digital counts, our proteomic data is designed to be a direct and accurate representation of biology that is more comparable to data generated by other methodologies such as genomics and transcriptomics than data generated by traditional proteomics platforms and potentially easier to integrate into our customer’s multi-omic workflows.

•Single-molecule data that is well-suited for AI integration and training. We anticipate that the Nautilus Voyager platform will generate the large volumes of high‑quality data needed to train AI models of biology—much as large language models depend on massive internet datasets. The Nautilus Voyager platform is designed to produce single-molecule counts that are nuanced and direct representations of biology. We believe that proteomic data with the breadth, depth, and reproducibility these counts are designed to provide will optimally train AI models and help prevent them from generating misleading conclusions about health and disease.

•Commercial model with clear market entry point, designed to support a wide variety of customers and applications. Many successful life sciences research tools companies with disruptive technology have employed a business model similar to our planned commercial model. However, we believe a key advantage for us is the potential near-term commercial opportunity of capitalizing on the existing mass spectrometry-based proteomics marketplace estimated at over 16,000 installed instruments. We expect our price point to be comparable to high-end mass spectrometry instrument budgets allocated for broadscale proteomics applications, and thus with a premium instrumentation average selling price, we plan to operate with a very efficient sales model. Further, since the early days of our product development, we have consulted with biopharma companies, academic institutions, and research organizations to inform our product development plan and help specifically address our target customer needs.

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•Nautilus VoyagerTM Platform and Iterative Mapping could position us as a leader in a large initial life sciences research market and provide a path to clinical diagnostics. The global proteomics market is expected to grow at an estimated 13% CAGR from 2025 to 2030 according to BCC Research report “Proteomics: Technologies and Global Markets”, issued in May 2025. Furthermore, we believe the Nautilus VoyagerTM platform has the potential to facilitate a broader transformation across life sciences and healthcare, and therefore augment our total addressable market over time. We believe there are multiple high-value research applications in precision and personalized medicine, drug discovery, and clinical diagnostics that can be unlocked by accurate, reproduceable, and cost-effective proteomic profiling. As the proteomics market continues to mature, and if our technology is validated across translational research applications, we believe Iterative Mapping could transfer well into the clinical setting that many prior technologies have thus far been unable reach.

•Our experienced, multidisciplinary team brings together a group of individuals with diverse backgrounds to disrupt the field of proteomics. Nautilus’ leadership team represents a unique and valuable hybrid of technology and biotech experience. Members of the executive team and board of directors have held leadership roles at Illumina, Agilent Technologies, Yahoo! Inc., and Isilon, among others, and helped to guide strategy and manage execution both before and throughout the rapid growth and success for those businesses. We view the core design thesis behind Iterative Mapping technology development as a non-traditional approach to new product development within life sciences that requires thinking at the intersection of three distinct disciplines —life sciences, computer and data sciences, and physical sciences and engineering. As such, we have assembled a team of individuals with experience across many different disciplines, including protein biochemists, nano-fabrication engineers, software and machine learning engineers, single-molecule biophysicists, optical engineers and others, all working together toward our common goal.

OUR STRATEGY

•Establish Iterative Mapping as a differentiated measurement approach for proteomics. Our strategy is centered on establishing Iterative Mapping as a differentiated measurement approach in proteomics. Iterative Mapping is the foundational method delivered by the Nautilus Voyager platform and is designed to address the breadth, proteoform-level depth, and reproducibility that we believe is required for comprehensive proteomic analysis. We believe that existing proteomics technologies require researchers to make fundamental tradeoffs among coverage, detail, throughput, and reproducibility. Iterative Mapping is designed to reduce these tradeoffs by enabling massively parallel, single-protein measurements that can be applied across a wide range of biological questions using a single, integrated platform. We believe this approach has the potential to expand access to comprehensive proteomic measurement and support applications across the life sciences ecosystem, including basic research, translational research, and, over time, clinical and diagnostic applications.

•Enable multiple applications on a single platform. Iterative Mapping is designed to support multiple application categories on a single platform, including:

◦Broadscale proteomics, intended to enable large-scale interrogation of canonical proteins across biological states; and

◦Targeted proteoform analysis, intended to resolve specific protein forms, modifications, and variants that are not accessible using existing proteomics methods.

These application categories are built on the same underlying Iterative Mapping capability. The Nautilus Voyager platform is designed to be flexible, including compatibility with a wide range of affinity reagents giving customers potential access to diverse applications for their specific research needs on the same measurement platform, rather than relying on multiple, fragmented technologies.

•Execute a land-and-expand commercialization strategy. Our commercialization strategy follows a land-and-expand model, with multiple potential entry points beginning with targeted applications such as our “Tau Proteoforms” assay. Following commercial launch, we anticipate customers will be able to adopt either broadscale or targeted proteoform as their first application, depending on their research priorities. We believe access to both application types on a single platform allows customers to expand usage over time without adopting additional instrumentation or proteomics technologies.

Our land-and-expand approach also applies to how our capabilities are delivered. We plan to initially offer access through a fee-for-service model provided by Nautilus, followed by the opportunity for customers to purchase our platform, including instruments, reagent kits, software, and related services.

Our objective is to support customers in addressing a growing share of their proteomics needs across discovery, validation, and deeper biological characterization using a single, extensible platform. We believe this approach may support deeper customer engagement, broader adoption within organizations, and long-term platform value.

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•Drive adoption through strategic collaborations and phased commercialization. We intend to drive adoption of the Nautilus VoyagerTM platform through a phased commercialization strategy that began with research collaborations with leading biopharma companies, academic institutions, and research organizations. These collaborations are intended to validate platform capabilities, support application development, and generate scientific data demonstrating real-world utility.

As of the date of this filing, we have established research collaborations with Genentech, the Michael J. Fox Foundation and Weill Cornell Medicine–Qatar (WCM-Q), and The Buck Institute for Research on Aging, and an agreement with the Allen Institute, among others. Through these collaborations, partners gain early experience with the Nautilus Voyager platform and contribute to application development across diverse biological contexts. Our plan is to follow this collaboration phase with pre-sales activities and Early Access Programs designed to broaden awareness, validate standardized applications, and build demand in advance of broader commercial launch. In January, 2026, we announced the launch of our first Early Access Program for targeted proteoform analysis with our Tau Proteoforms Assay.

•Continuously expand platform capabilities. We plan to expand the capabilities of the Nautilus Voyager platform through internal research and development and collaboration with customers and partners. This includes the development of additional applications, workflows, consumables, and analysis tools intended to simplify and accelerate proteomic research. We believe our long-term opportunity lies in translating our core measurement technology into additional high-value applications, while maintaining platform flexibility, including the ability for customers to select reagents and workflows suited to their specific needs. If our customers succeed in advancing their science, we believe we succeed alongside them.

•Build scalable manufacturing and supply chain capabilities. Our technology is designed with scalability in mind and incorporates commercially available components intended to support efficient sourcing and manufacturing. We have established manufacturing processes that combine external contract manufacturing with internal capabilities at our San Carlos, California facility. We believe we have multiple pathways to scale production to meet commercial demand, including to expand outsourced manufacturing and supplier diversification to support quality, reliability, and capacity as adoption grows.

•Develop a long-term platform ecosystem. We plan to build long-term value by leveraging the open and extensible design of the Nautilus Voyager platform to support an ecosystem of products and services built around Iterative Mapping. The platform’s compatibility with a broad range of affinity reagents and customizable workflows are designed to support both standardized applications and customer-driven innovation. We believe this approach positions the Nautilus Voyager platform to support a broad and evolving set of proteomics use cases over time.

•Expand into adjacent and future markets. While our initial focus is on life sciences proteomics research, we believe the measurement capabilities of Nautilus Voyager platform may support expansion into adjacent pharmaceutical areas such as, but not limited to, drug discovery, translational research, clinical research, trial design and diagnostics. We intend to pursue these opportunities by development and validation of additional workflows and product configurations, either independently or in collaboration with partners in those markets.

A PRIMER ON PROTEOMICS

Over the past decade, the study of genomics, or DNA, and transcriptomics, or RNA, have been central to drug development and healthcare. We believe proteomics is the next step in the study of biological information systems and it is believed by many to be one of the most important disciplines for exposing disease-causing protein pathways, uncovering new drug targets, highlighting novel therapeutic indications and identifying clinically relevant biomarkers for use in precision medicine.

Molecular profiling techniques, such as next generation sequencing (“NGS”), have led to widespread genomic characterization and unprecedented access to genomic information. While this information has certainly enhanced our knowledge of complex biological systems, there is still a tremendous amount of detail at the protein level that remains largely unknown. The field of proteomics seeks to address this gap, and is an area of scientific research that involves the identification, characterization, and quantification of proteins in whole cells, tissues, or biofluids. To date, there has been relatively little technological advancement in how to physically measure a protein, and this has been a major impediment towards creating the same level of access to proteomic detail as we have with genomic detail today.

The proteome ultimately drives the function of a cell and tissue, and therefore it dictates the physically observable characteristics known as the phenotype. The proteome undergoes dynamic changes as it continuously responds to chemical signals, blood-borne mediators, temperature, drug treatment, and developing disease over time. This complex interplay of factors contributes to the complexity of proteomics research. However, we believe the detailed and complex information provided from proteomics has the

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potential to help in identifying novel and causal drug targets and to help enable more efficient and effective drug development. A few examples of the way we believe proteomics may lead to novel insights in research are highlighted below.

•Better understanding of biology. Protein research contributes to a better understanding of how molecular information controls and influences an individual’s physiology.

•Identification of novel drug targets. Cellular function and dysfunction is driven by our proteins; increasing our ability to directly measure even the rarest proteins involved in disease may increase the likelihood of identifying new drug targets.

•Patient stratification. The separation of patients into groups with similar molecular features that may be more likely to respond to specific therapeutic treatments.

•Prediction of disease and treatment outcome. The identification of biomarkers that can assist in the early diagnosis of diseases, inform prognosis or monitor the efficacy and safety of ongoing treatments.

•Wellness: from health to disease. Biomarkers can monitor and guide individuals to tailor lifestyle choices to maximize health and avoid the onset of diseases before they develop.

Not only would advancements in the field of proteomics have the potential to unlock new insights on their own, but they may also have the potential to increase the value of data and insights generated in related fields such as genetics, gene expression, and metabolism.

OUR MARKET OPPORTUNITY

We believe that the Nautilus VoyagerTM platform has the potential to be uniquely positioned in the proteomics market. In our mission to democratize proteomics, we aim to support initial research applications in precision and personalized medicine, with a natural growth path into clinical diagnostics, as well as in AI powered drug discovery. However, we believe that the opportunity could extend far beyond this.

Market Environment

At Nautilus, we recognize the need for a radical breakthrough in proteomics. Since 2002, global R&D expenditure has increased close to three-fold and is expected to reach approximately $343.0 billion by 2030 according to EvaluatePharma's 2025 report. Despite such investments, the number of new drugs approved each year has failed to increase proportionally. It can take more than 10 years to bring a drug to market, and the cost has grown significantly in the past decade from approximately $1.5 billion in 2015 to approximately $2.2 billion in 2024 according to a 2025 report by the Deloitte Center for Health Solutions. Approximately 95% of FDA-approved drug targets are proteins, and most other drugs interact with, or are influenced by, signal transduction cascades mediated by proteins. As such, an understanding of the proteome is paramount to understanding pharmacology.

As existing approaches only allow us to routinely quantify a fraction of the proteome, biopharmaceutical companies have become increasingly adept at identifying possible targets within what is currently observable, and as such, many viable targets have been exhausted. Despite the many hundreds of thousands of biomarker research studies estimated to have been published to date, there are only approximately 180 unique pharmacogenomic biomarkers with approval for use with therapies according the current FDA Table of Pharmacogenomic Biomarkers. We believe this number of approved biomarkers is alarmingly low, and further highlights the shortfall of attempting to predict a protein biomarker’s expression level and function primarily from genetic data. Unfortunately, researchers have been forced to use this method, given the availability of powerful tools in genomics without the corresponding power and breadth of tools available in proteomics. With an advancement such as Iterative Mapping, we believe researchers may have the power to deeply and comprehensively measure the physical proteins at the root of disease, and significantly increase the potential to identify more clinically meaningful biomarkers with greater precision in the practice of medicine. We believe a breakthrough increase in throughput would enable researchers to more deeply measure large cohorts, thereby powering studies at the scale required to quickly and cost-effectively discover new critically important biomarkers.

We believe the inability to easily and reliably quantify the proteins that drive every aspect of human physiology has been a fundamental hindrance to a greater understanding of cellular and molecular biology. With this in mind, we aim to democratize proteomics to make it possible for the broader scientific community to undertake a wider range of high-value scientific inquiries, thereby accelerating research and ultimately, we believe, enhancing our fundamental understanding of biology and the mechanisms of disease.

The Missing Piece: The Proteome

Improvements in NGS technology have greatly enhanced the understanding of the genome, but when contemplating the number of proteins that can arise from a single gene and their role in the regulation of biological processes, both physiological and pathological, we believe that a better understanding of DNA is simply insufficient. Beyond the genome lies a vast multi-level network

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of biological interactions with important ramifications across the organism that remains coded and hidden within unique protein patterns. Many scientific and industry leaders believe these patterns may hold the key to a deeper understanding of biological processes at both a molecular and a systems level.

From the day we are born to the day we die, proteins are responsible for regulating all aspects of our physiology. The genome, which represents the complete set of genes within each organism, remains largely unchanged throughout the course of life. Over the years, it has been estimated that humans possess approximately 20,000 canonical proteins, many of which have been studied extensively. However, to coordinate the myriad of processes that occur within organisms at all times, organisms have evolved multiple ways to generate further biological complexity. DNA genes are expressed in the form of RNA transcripts, which control the expression and regulation of these different genes in the cell. These RNA transcripts are then translated into individual proteins, and protein isoforms, which are subtle variations of the individual proteins themselves. Scientists have estimated that there may be as many as 70,000 or more human protein isoforms. The resulting proteome is not only highly dynamic and in a constant state of flux by regulating the quantity and type of each protein isoform, but it also exhibits great diversity across cells and tissues. This complexity, which we believe governs all biological processes, both healthy and sick, cannot be captured or characterized routinely by current methods.

However, the molecular complexity of our proteome doesn’t stop here, it actually grows dramatically even beyond the abundance of protein isoforms that are dynamically rising and falling. After a protein isoform has been translated, it can be modified further by biological processes that more precisely control that protein isoform’s location, specific activity, or interaction partners, and these downstream changes are together called post-translational modifications. There are a wide variety of post-translational modifications known today, which result in a tremendous increase in molecular complexity by creating different “forms” of the same protein, known as “proteoforms”. In total, our original 20,000 canonical proteins are estimated to produce as many as 6,000,000 different proteoforms, as illustrated in the figure below. We believe the existence of these proteoforms indicates that there may actually be well over two orders of magnitude (or 100 times) more complexity present across our proteome than there is across our genome. We strongly suspect that it is within this proteoform space of molecular information that fundamental biological processes are present that govern our cells, and our molecular health, which are waiting to be discovered.

Post-Translational Modifications Create Multiple Forms of Proteins That Are Estimated to Contain Over 100 Times More Information Complexity Than the Coding Genes in the Genome

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While the past several decades have seen advances in proteomics technologies, typical solutions only capture a fraction of the proteome in samples derived from blood or cells, as illustrated in the figure below.

Commercially Available Technologies are Unable to Routinely Access the Full Proteome or Detect Proteoforms

On the left, using mass spectrometry-based methods, approximately 8% of proteins are routinely detectable from blood and approximately 30% are routinely detectable from cells. On the right, there is currently no commercially available method to easily detect and map the landscape of proteoforms, which would allow for the exploration of the estimated 6,000,000 different forms and patterns of modified proteins serving some biological function. Furthermore, we believe that shortfalls in the ability of bioinformatics to predict the existence as well as the function of genes further illustrates the need for enhanced protein analysis techniques. Moreover, there is a large amount of discordance in the data generated by proteomics technologies today. These technologies often fail to measure the same proteins and when they do, they often produce contrasting protein abundance measurements. This may leave researchers unsure of which technologies to trust and which proteins they should focus on in follow-up studies - a more comprehensive and consistent solution is needed.

Today, we believe the field of proteomics is at the very beginning of a significant growth phase. We are of the firm belief that every scientist should have access to the proteome, including proteoforms, in the same way that access to the genome has been made broadly available over recent years.

Market Opportunity

Due to the extensive applications and broad potential, we believe that the proteomics market represents one of the largest untapped opportunities in the biological sciences today. According to BCC Research report “Proteomics: Technologies and Global Markets”, issued in May 2025, the overall proteomics market is projected to reach approximately $57 billion in 2030, representing a projected CAGR of 13% in global market growth from 2025 through 2030.

We believe that as the proteomics market evolves, substantial adjacent opportunities will also arise due to the potential applications in precision and personalized medicine, clinical diagnostics, and AI powered drug discovery, as well as other disciplines such as food and environmental science. Within the biomedical sciences, we anticipate that the application of proteomic technologies to clinical specimens has the potential to revolutionize multiple aspects of the diagnosis and treatment of many diseases, propelled by biomarker discovery and validation of personalized therapies which we believe will greatly increase the power of prediction, diagnosis and prognosis.

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Existing Proteomics Technologies and Shortfalls

Over the past decade, the importance of proteomics in diagnostics and drug research and development has increased due to the central role proteins play in biological function and disease. However, comprehensive analysis of the proteome remains significantly more complex for scientists today than analysis of the genome or transcriptome. Unlike DNA and RNA, proteins cannot be amplified, requiring measurement technologies to directly detect very low-abundance targets directly from biological samples. This challenge is compounded by the wide dynamic range of protein abundance, which can span more than seven orders of magnitude within a single cell or biofluid such as blood. For example, transcription factors and signaling proteins that play critical roles in disease biology may be present at many fold lower abundance than structural proteins that may be present in millions of copies per cell. Accurately quantifying both low-abundance and high-abundance proteins within the same sample is therefore substantially more difficult than genome or transcriptome analysis, which typically involves a dynamic range of approximately three orders of magnitude. In addition, proteins exhibit substantially greater biochemical and structural diversity than nucleic acids. Proteins are composed of 20 distinct amino acids and undergo extensive post-translational modifications that generate multiple functional variants, known as proteoforms. These complexities have limited the development of tools capable of sensitively, comprehensively, and reproducibly measuring the proteome. Currently commercially available technologies are generally unable to routinely identify and quantify proteoform composition and frequency within complex samples. Existing proteomics technologies generally fall into two categories: mass spectrometry-based approaches and affinity-based approaches.

Mass Spectrometry-based Approaches

Mass spectrometry has been a foundational technology in proteomics and has significantly advanced the field. However, despite analytical capabilities, mass spectrometry workflows are often complex, time-consuming, and labor-intensive. Sample preparation and instrument operation typically require highly trained personnel, and workflows are not fully automated, limiting scalability and accessibility. Mass spectrometry approaches also face sensitivity limitations when detecting proteins present at very low abundance, where many biologically important signals are believed to reside. In addition, commonly used methods, including shotgun mass spectrometry, require proteins to be enzymatically digested into peptides prior to analysis. Because measurements are performed on peptide fragments rather than intact proteins, these approaches have limited ability to resolve protein isoforms and proteoforms or to characterize specific patterns of post-translational modifications across samples. As a result, researchers using mass spectrometry often must accept trade-offs in breadth - in terms of proteome coverage and throughput, depth - in terms precision and sensitivity, and reproducibility. Despite these limitations, demand for protein data remains strong, and the global proteomics research market includes an installed base of more than 16,000 mass spectrometry instruments.

Affinity-based Approaches

Affinity-based proteomics methods have traditionally been used for targeted protein measurements and have increasingly been applied to larger-scale studies with broader, though still incomplete, coverage of the canonical proteome. These approaches rely on affinity reagents designed to bind specific, predefined protein targets. The performance of affinity reagents can be affected by protein structure, orientation, and modification state, and multiplexed assays require a distinct reagent for each target. Despite decades of

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development, the number of high-quality, specific affinity reagents remains insufficient to comprehensively measure the proteome, including its many protein isoforms and proteoforms. As a result, affinity-based approaches are generally best suited for applications involving relatively small, predefined target panels. Because these methods typically detect only limited regions of target proteins and are performed as bulk sample measurements, they have limited depth and are not able to resolve proteoform diversity or patterns at the single-molecule level.

Limitations Across Existing Technologies

Neither mass spectrometry–based nor affinity-based approaches provide direct measurement of individual, intact protein molecules, and achieving high-confidence, reproducible quantification across experiments remains challenging. Abundance measurements generated by these approaches are often not directly comparable, making it difficult for researchers to prioritize targets or reconcile results across studies. These limitations also complicate integration of proteomic data with genomic and transcriptomic datasets, which we believe is increasingly important for understanding biological systems across multiple layers of regulation. Furthermore, limitations in quantification accuracy, reproducibility, and throughput at proteome scale limit the ability of existing technologies to generate large, consistent datasets suitable for training data-driven and AI-based models of biology. Inconsistent, incomplete proteomic measurements may reduce the reliability of insights derived from such approaches.

THE NAUTILUS APPROACH

Our Guiding Principles

Nautilus is driven by the objective of enabling the research community to access and quantify the proteome in a comprehensive, reproducible, and scalable manner, including the ability to characterize proteoforms. We believe that broader access to high-quality proteomic data can support improved understanding of disease biology and inform the development of new therapeutics and diagnostics. While genomics and transcriptomics have benefited from technologies that enable routine, large-scale measurement, progress in proteomics has historically lagged due to the absence of tools capable of measuring proteins with comparable breadth, depth, and reproducibility.

We believe that incremental improvements to existing proteomics technologies are insufficient to address these limitations and that unlocking the value of the proteome requires a fundamentally different measurement approach. In pursuit of this objective, we are developing the Nautilus VoyagerTM platform, designed to deliver the Iterative Mapping approach through an end-to-end system that includes instrumentation, consumables, and software. The Nautilus Voyager platform is designed to process biological samples and generate proteomic data intended to support downstream biological analysis and interpretation.

Our guiding principles emphasize the importance of combining broad proteome coverage with proteoform-level depth and high reproducibility, without sacrificing scalability or usability. The Nautilus Voyager platform is designed to support sensitive, single-molecule protein analysis at scale, with the goal of enabling comprehensive characterization of protein abundance and functional variation across diverse sample types. Leveraging its system architecture and data analysis capabilities, we believe the Nautilus Voyager platform is designed to quantify a substantial majority of the proteins present in a sample across a wide range of organisms and sample types, and to generate reproducible measurements suitable for large-scale and longitudinal studies with both breadth and depth. Developing the Nautilus Voyager platform has required and we believe will continue to require approaches that differ from those historically applied in proteomics. Achieving our objectives has necessitated interrogation across life sciences, computer and data sciences, and physical sciences and engineering. The Nautilus Voyager platform is designed to combine experimental measurement, computational analysis, and multiple measurement modalities within a single platform.

We believe that recent advances in enabling technologies, including cloud computing and machine learning, have reached a level of maturity that have the potential to support this integrated approach at scale. We believe the convergence of these technologies has created a timely opportunity to pursue the scientific and engineering work required to develop a new class of proteomic measurement capability. By integrating these elements into the Nautilus Voyager platform, we aim to support biomarker discovery and precision medicine research and to broaden access to reproducible proteomics data.

Nautilus VoyagerTM Platform Design Criteria

The limitations of existing proteomics technologies underscore the need for a different approach to protein measurement. We believe that incremental improvements to mass spectrometry or affinity-based approaches are not sufficient to address the combined challenges of breadth, depth, and reproducibility required for comprehensive proteome analysis. In response, we designed the Nautilus Voyager platform from the ground up to address these challenges through a distinct measurement approach, Iterative Mapping.

The Nautilus Voyager platform is designed to enable Iterative Mapping, a measurement approach based on repeated interrogation of intact, single protein molecules at scale. Rather than relying on a limited number of stochastic observations, Iterative Mapping is designed to generate confidence through multiple, sequential measurements of individual protein molecules. Information is

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accumulated across independent measurement events and aggregated across billions of molecules, producing what we expect will be highly reproducible, digital counts intended to support consistent comparison across samples, experiments, and time.

In contrast to traditional “shotgun” proteomics approaches, which stochastically sample subsets of the proteome and generate limited information per protein, and affinity-based approaches that often rely on one or two binding events per target, Iterative Mapping is designed to systematically characterize proteins and their functional variants across samples with improved confidence and reproducibility.

In defining the design criteria for the Nautilus VoyagerTM platform, we identified a set of core performance requirements intended to support breath, depth, and reproducibility in proteomics:

•High sensitivity. Because proteins cannot be amplified, comprehensive proteome measurement requires the ability to directly detect and quantify low-abundance proteins. The Nautilus Voyager platform is designed to support single-molecule detection to address this requirement.

•Scalability across dynamic range. The platform is designed to quantify proteins across a wide dynamic range while remaining suitable for large-scale studies involving many samples.

•Reproducibility and robustness. Consistent measurement across runs, instruments, and time is important for longitudinal studies, large cohorts, and data integration. The Nautilus Voyager platform is designed to support reproducibility through standardized workflows and digital single-molecule counting.

•Throughput. To support large-scale research workflows, the platform is designed to enable analysis of tens of thousands of samples within practical timeframes.

•Usability. We anticipate that broad adoption of proteomics technologies requires systems that can be operated by a wide range of laboratories, including those without specialized expertise in analytical chemistry or proteomics. The platform is designed with an integrated workflow as well as hands-off fluidics and produces easy-to-understand data that should be usable across labs.

•Adaptability. The platform is designed to support multiple run configurations and assay formats to address diverse research needs, including both broadscale proteome profiling and targeted proteoform analysis.

Based on these design criteria, we developed an integrated Nautilus Voyager platform encompassing sample preparation, consumables, instrumentation, and downstream data analysis. Together with the Iterative Mapping approach, the Nautilus Voyager platform incorporates multiple technical innovations intended to operate in concert to support comprehensive, reproducible, and scalable proteome characterization. We believe that four key technical innovations, each addressing a distinct limitation of existing proteomics approaches and collectively enabling the performance characteristics of the platform, are central to achieving the design objectives of the Nautilus Voyager platform and differentiating it from existing technologies:

1.Hyper-dense Single-molecule nanoarrays

2.Integrated Proteomics Platform

3.Probes for multi-cycle analysis

4.Machine-learning powered quantification

Key Innovations

1.Hyper-dense Single-molecule nanoarrays

The vast majority of protein analysis tools, such as affinity-based approaches like ELISA (Enzyme-Linked Immunosorbent Assay), typically measure proteins in bulk. This approach works well for measuring small numbers of proteins, however, it quickly becomes very challenging when measuring hundreds to thousands of proteins. Furthermore, various practicalities surrounding bulk analysis limit sensitivity and dynamic range. Nautilus recognized early on that in order to achieve its goals for creating extreme protein detection sensitivity it would require measuring proteins whose frequency in a sample might vary from only a few, to hundreds of millions of molecules in a sample. In our view, it was clear that any bulk measurement technology would struggle to cover this immense dynamic range, and that a single protein molecule detection approach would be required to overcome a problem that has long been a barrier to major advancement in the field. Additionally, transitioning from bulk protein measurements to single protein molecule measurements fundamentally changes the nature of the protein quantification problem where the challenges of protein identification and quantification converge. If one is able to identify each protein molecule, quantification arises simply from counting

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those identifications, and furthermore, single protein molecule counters are by definition the most sensitive detection modalities available.

To break through these barriers, we designed the platform to measure billions of individual protein molecules at a time, in a massively parallel and efficient workflow. Our internal testing has demonstrated that our hyper-dense single-molecule protein nanoarrays contain over 3 billion landing pads per chip. Our team has developed a process for manufacturing our nanoarray as the foundational component of our flow cell consumable. The flow cell itself is comprised of a nanometer-scale fabricated chip that holds the individual protein molecules in place on the surface in a landing pad, encapsulated by a fluidics channel that allows for reagents to flow across the surface. Our design includes the isolation of individual proteins in a protein library preparation process by binding them to a much larger nanoparticle scaffold which has been created to hold exactly one protein molecule.

Source: Internal data

These nanoparticle scaffolds can be reliably made to precise sizes, and the flow cell nanoarray surface can then be generated by well understood manufacturing processes to create surface features, which we call landing pads, that match the dimension of the scaffold. As each landing pad can only hold one scaffold, and each scaffold can only hold one protein molecule, the introduction of scaffold-protein complex onto the nanoarray surface generates a self-assembling, high-density single protein molecule array (as seen in the above and below illustrations). The attachment between the scaffold and the nanoarray surface is extremely robust, enabling scaffolds to persist through extensive reagent washing across many cycles.

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Nautilus Single Protein Molecule Flow Cell Designed to Capture One Individual Scaffold-Protein Complex per Landing Pad

Source: Internal Data

As discussed above, our flow cell is designed with the capability to capture up to tens of billions of individual, intact protein molecules. The single protein molecule nature of the Nautilus VoyagerTM platform is designed to enable extreme sensitivity, and the sheer scale of molecules captured enables the measurement of proteins across an exceptionally wide dynamic range. Flow cells with loaded protein libraries can then be introduced into our Nautilus Voyager instrument for the analysis and quantitation of the captured protein library.

2.Integrated Proteomics Platform

Typically, protein measurement approaches, like the ELISA described earlier, are designed to perform a single measurement of the proteins in a sample, after which the sample is either damaged, destroyed or discarded. However, if proteins captured in a sample can be repeatedly probed, it becomes possible to gain far more insight on the individual molecules. This ability describes the fundamental approach and benefit of our Iterative Mapping method. With our platform designed to deliver the Iterative Mapping method, each protein molecule has a unique coordinate address on the flow cell, and repeated probing enables deeper characterization of each individual molecule with each cycle, unlocking the ability to characterize proteoforms, potentially decode approximately 95% of the proteome, and achieve a wide variety of applications powered by detailed understanding of new protein biology.

To achieve extreme sensitivity and scale, we have designed the Nautilus Voyager instrument to integrate reagent fluidics with a sensitive, high-resolution optical imaging system to cyclically measure all single protein molecules captured on the flow cell. Our affinity reagents are labeled with proprietary fluorescent labels that help improve both the signal-to-noise and speed of our assay chemistry. The high-resolution imaging components allow resolution sufficient to characterize each individual protein molecule, generating data as shown in the illustration below.

The protein counts in the image above are for illustration purposes only. Source: Internal data

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3.Probes for multi-cycle analysis

The Nautilus VoyagerTM platform is designed with fundamentally different principles of how to use and exploit the properties of affinity reagents compared to prior approaches. Affinity reagents enable two key applications of the Nautilus Voyager Platform:

•Targeted proteoform analysis is designed to use of-the-shelf reagents to resolve specific protein forms, modifications, and variants that are not accessible using existing proteomics methods.

•Broadscale proteomics is designed to enable large-scale, system-level interrogation of canonical proteins across biological states using proprietary multi-affinity reagents.

By using more traditional high specificity reagents in our multi-cycle system, we can detect specific protein targets, such as tau, at the single-molecule level, enabling digital quantitation. We believe it is possible to expand this concept, and use Iterative Mapping with a wide variety of “off-the-shelf” affinity reagents that are highly specific to multiple individual protein targets. Of particular importance, we can also use off-the-shelf affinity reagents that target specific sites on the protein itself, such as post-translational modifications. Using affinity reagents that target these specific locations and features of proteins will allow the Nautilus Voyager platform to detect and quantify the different patterns and varieties of post-translational modifications that define proteoforms. We refer to this as targeted proteoform analysis.

In a highly innovative and counterintuitive way, the Nautilus Voyager platform can also exploit low specificity affinity reagents. Identifying the tens-of-thousands of different proteins in a proteome would require a prohibitively large number of traditional highly specific affinity reagents. We therefore explored the possibility of using affinity reagents that bind short, linear epitopes (e.g., target protein sequences of 3-4 amino acids each) with moderate specificity, such that each affinity binding reagent probes and binds to many different proteins that contain the short linear epitope target. We describe these probes as “multi-affinity reagents”. While the binding of a single multi-affinity reagent is not sufficient to identify a given protein, conducting Iterative Mapping using a series of multi-affinity reagent can create enough information that there is sufficient statistical power to accurately identify an exceptionally broad number of proteins present in a sample. In this approach, each new multi-affinity reagent that is introduced in a cycle of binding and imaging provides additional evidence and gradually narrows the list of possible protein identities. Hereafter, we refer to this approach as broadscale proteomics. The Nautilus Voyager platform is designed to achieve the detection of the vast majority of proteins in the proteome using a combination of approximately 300 unique multi-affinity reagents.

4.Machine Learning-Powered Quantification

Among the most unique aspects of the Nautilus Voyager platform we believe is the integration of a proprietary machine learning-based protein quantification analysis software engineered to work with the type of data our system generates. As discussed, more typical measurements for high specificity affinity reagents can be used in our system to identify, and thereby quantify, each protein from a single binding and imaging step. Protein identification and quantification can be extended to proteoform-resolution by incorporating high specificity affinity reagents against protein targets of interest. These high specificity affinity reagents can provide a lot of information about a small number of proteins, and as such it would take an exceedingly large number of highly specific affinity reagent and therefore an exceedingly large number of cycles to measure every protein in the proteome. To enable broadscale proteomics on our system, we instead use our multi-affinity reagents that can bind to hundreds or even thousands of individual proteins in a given cycle.

Our proprietary algorithm is thereby trained using experimental data from our probe development process that provides a baseline estimate of how likely each probe is to bind to each protein in a reference proteome database. As data is collected, a binding matrix is generated for each protein coordinate. For example, a given coordinate [2,1] may have bound probes during cycles [4, 11, 25, 26, 27, 65, and 201]. This data is then fed into our machine learning protein identification analysis to determine which protein is most compatible with the observed pattern of binding. The illustration below provides a view of our machine learning protein identification analysis at work by observing the confidence the algorithm has with respect to each protein as additional cycles of data are collected. On average, it takes roughly 15 cycles of multi-affinity reagent binding events to uniquely identify a protein. Prior to 15 cycles, there is a lot of variability in which protein is likely to be at a given spot, but then after 15 cycles, the algorithm locks in on a precise protein and becomes increasingly more confident in its identification. Further, with each additional cycle the other potential proteins become increasingly less likely.

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The Nautilus VoyagerTM Platform Can Identify a Protein by Analyzing Data from Multiple Cycles of Affinity Reagent Binding Event with High Probability.

Source: Internal Data

The machine learning protein identification analysis is run for each of the 10 billion protein molecules captured across three flow cells in parallel to identify each protein molecule present. Following this, identifications are coalesced to infer an estimate of the quantity of each protein. As the algorithm learns more and more about each affinity reagent probe’s binding characteristics, both within and across Nautilus Voyager platform data sets, it is able to adapt and update its confidence in each protein identification, essentially getting “smarter” over time. As a result, the machine learning protein identification analysis is able to re-analyze data collected in the past and continuously improve upon its ability to identify proteins within that data.

This machine-learning powered analysis is designed to provide nuanced, single-molecule data about billions of protein molecules in every experiment conducted in any lab. We thus believe that the Nautilus Voyager platform will be able to provide the high volume of high-quality data needed to train AI models of biology. Just as large language models were trained on massive amounts of internet data, we anticipate effective AI models of biology will need massive amounts of biological data like that produced by the Nautilus Voyager platform. We further believe that only proteomic data with the level of breadth, depth, and reproducibility we aim to provide will be easy-to-integrate with data from other methodologies (such as genomics, transcriptomics, and metabolomics) and able to help prevent these models from coming to erroneous conclusions about health and disease.

Nautilus VoyagerTM Platform Development Plan Key Areas of Focus

In order to commercialize our platform, we plan to advance the development of our technology across all components including chemistries, reagents, consumables, instrumentation and analysis software. The prototype of the Nautilus Voyager platform has generated all of our internal data to date, and we are continuing the development process to optimize, improve upon, and validate the final designs, formulations, protocols, manufacturing processes, and software code.

Our development plan is designed to build upon the foundational achievements our prototype has made in several key areas, with the goal of ultimately allowing us to fully realize the potential of our technology. We plan to focus on the continued improvement of our flow cell designs. Having initially demonstrated that prototype versions of our flow cells can functionally achieve approximately 10 billion discrete single protein molecule landing pads per instrument run, we plan to further optimize the landing pad spacing, density, manufacturing process and chemistries of the first commercially available flow cells. We also intend to focus on the completion of the final engineering design of the Nautilus Voyager instrument, where we plan to complete the development of manufacturing processes to integrate and test all completed sub-systems including the high-speed optical subsystem, fluorophore excitation laser, and micro-fluidics system in combination with our flow cell. We also plan to continue expanding the number of affinity reagent probes and chemistries that can be used within the Nautilus Voyager platform for both broadscale proteomics quantification and target quantification of proteoforms at the single-molecule level. Our aim is to create a broad portfolio of affinity reagent probes through in-house reagent development efforts and through strategic partnerships where we qualify already developed

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reagents for compatibility with our technology. Lastly, we intend to continue the development of our analysis software, where we expect improvements to our algorithms and analysis that will help with the speed, accuracy, and reliability of our commercial platform performance.

APPLICATIONS OF OUR TECHNOLOGY

The Nautilus VoyagerTM platform is designed to employ Iterative Mapping as an adaptable solution that leverages a wide variety of reagents to read and quantify the proteome, proteoforms, and other critical aspects of biology

We believe that the Nautilus VoyagerTM platform represents one of the first truly novel platforms for the detection and quantitation of proteins and proteoforms by leveraging Iterative Mapping, our single protein molecule flow cell, and a broad range of affinity reagents. By design, the Nautilus Voyager platform is open to the use of virtually any affinity reagent, where each reagent can be efficiently chemically labeled and used in our multi-cycle process to identify and quantify a protein library. We further believe one of the inherent strengths of the open design of the Nautilus Voyager platform is the ability to use reagents across a range of different binding profiles to create unique applications that unlock different types of important biological information.

On one end of the spectrum (above left), our technology is designed to harness the power of low specificity multi-affinity reagents that will potentially allow us to detect substantially all the proteome. On the other end of the spectrum (above right), we believe we can apply high specificity affinity reagents that detect and quantify individual target proteins of interest, and the post-translational modifications on these target proteins to detect and quantify the various proteoforms that may exist. We believe it is this inherent adaptability to different reagents that will enable a broad suite of uses for the Nautilus Voyager platform across research, discovery, translational and clinical applications. Because of this inherent flexibility, we also believe the Nautilus Voyager platform will spark the creation of new and unforeseen applications of Iterative Mapping, in a similar market expansion and innovation trend that was experienced in the years following the launch of open and flexible NGS platform technologies.

The open nature of the Nautilus Voyager platform creates the opportunity to partner with third-parties on the development and supply of affinity reagents for use on our instrument.

Basic Research and Discovery Use Cases

The Discovery Potential of the Nautilus VoyagerTM Platform

One of the long-standing challenges to accelerating the discovery and understanding of protein biological function has been the overwhelming dynamic range of proteins present in a cell or a biospecimen. We believe that a sensitivity of detecting 1 protein molecule in as little as 1,000 cells will be required to identify the exceptionally rare but biologically significant proteins in a sample. The Nautilus Voyager platform is designed with this extreme sensitivity in mind, which we believe makes it ideally suited for capturing and cataloging the variation of the proteome in a comprehensive way, both in human and non-human species.

Further, we believe speed, scale, and single protein molecule data quality will be required to enable research projects with aims to create new species-specific, tissue-specific, or disease-specific reference datasets that have the potential to accelerate discovery across academic and industry research communities. We believe our customers could embrace the Nautilus Voyager platform for these applications broadly. Comparatively, during the initial market adoption of NGS, as the instrumentation and methods improved in speed and data production scale, projects increased dramatically in size. Sample cohorts grew from dozens of samples to hundreds, and then to thousands in an effort to use the speed and data production capacity to improve the statistical power required to make new discoveries. We believe the Nautilus Voyager platform could experience a similar trajectory of utilization in research and discovery, making very large sample size studies that were not feasible using prior proteomic detection methods now practical for our customers to implement.

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A deeper level of detail and molecular complexity also clearly exists beyond the estimated 20,000 proteins in the human proteome, and we expect our customers to utilize proteoform specific reagents for the profiling, mapping, and characterization of post-translational modification patterns on proteins of interest. It is estimated there are as many as 6,000,000 different proteoforms produced through protein modification pathways that hold critical biological and contextual information on the function and purpose of the proteins in our cells. We believe our customers could show strong interest in this important field of research given the lack of existing technologies and tools capable of mapping multiple features on a single protein in one analysis workflow. We believe discovery-focused proteoform specific reagents could be used in combination with our multi-affinity reagent Iterative Mapping of proteins method to enhance the output of our analyses.

Multi-Omic Systems Biology

We believe the creation of matched DNA, RNA, protein and metabolomic data sets for integrated multi-omic (DNA, RNA, protein, and metabolite) analyses will enable a more complete understanding of the path of information transfer from gene, to transcript, to protein, to metabolites, and back. It is estimated that only 40% of protein expression can be predicted by gene expression data. Integrated multi-omic data sets with deeper and more complete proteomic data are expected to have far greater potential for revealing the mechanisms underlying this discordance, its biological origin, and ultimately its impact on cell function. By understanding this discordance, drug developers may later discover new and more effective ways to alter biology and treat disease. We expect the creation of workflows with matched NGS and proteomic data will become standard practice in the community, further driving the utility and value of the Nautilus VoyagerTM platform.

Within multiomics, proteogenomics is an emerging area of research, with the goal of identifying brand new proteins or proteoforms not currently captured in the protein reference sequence. In proteogenomics, individual protein sequence databases are generated using matched transcriptomic and genomic data to aid in the identification of novel peptides and proteins detected but not yet mapped within the reference databases of known proteins. In this area of research, the integration of genomics and gene expression data enhances the predictive capability to determine what new proteins are present in a sample, and further brings functional context to genomic information and gene expression patterns. The Nautilus Voyager platform represents an entirely new single protein molecule data source for proteogenomics, which we believe could contribute significantly to the field by increasing the scale of proteomic data accessible for these analyses, and ultimately increasing the discovery potential of the integrated dataset. Given the current level of access to genomic and transcriptomic information enabled by NGS, we believe the research community could rapidly integrate data from the Nautilus Voyager platform into these studies to leverage matched genomic and proteomic data.

Translational Research and Discovery Use Cases

Biomarker Discovery

It has been published that approximately 95% of FDA-approved drug targets are proteins. The Human Protein Atlas collaborative research project identified that FDA-approved drugs are targeting up to 854 separate human proteins and that there are 4,906 genes in the UniProt database that have experimental evidence for being involved in disease. We believe that the drug development and diagnostic industries have suffered from an inability to access the low frequency and rare proteins present in biological samples due to the tremendous dynamic range present across proteins in a specimen. As already described, we believe that the Nautilus Voyager platform is designed with the scale to adequately overcome the dynamic range problem in proteomics, and provide researchers with access to the rare, but biologically important protein detection where biomarkers are believed to exist. We believe the Nautilus Voyager platform’s sensitivity targeting the detection of events as rare as 1 protein molecule in 1,000 cells will be critically important and may unlock the potential for many new biomarkers to accelerate the development of precision medicine diagnostics and therapeutics.

Proteoform Patterns as Biomarkers and Mechanism of Action Studies

We believe the study of proteoform patterns, proteoform frequency, and proteoform diversity of critically important drug targets will be a widely used application of the Nautilus Voyager platform. Which drugs work on specific protein drug targets may be determined by how combinations of specific post-translational modification operate together in proteoforms. Our technology is designed to enable the research community to see these proteoform patterns and to measure their relationship to one another. Every disease is the result of a dysregulation of molecular functions that create biological consequences compared to normal healthy function. Given the inability to detect proteoform patterns today, we believe that the study of how proteoforms contribute to disease at the molecular level will become an essential use-case for our technology. We further believe that proteoform analysis on the Nautilus Voyager platform has the potential to advance precision medicine by making an entire layer of molecular complexity and information available to researchers for the first time.

Longitudinal Monitoring of Proteome Dynamics

The study of proteome composition, protein and proteoform frequency, patterns, and variations over time represents an opportunity to survey and understand the biological changes resulting from environmental factors that influence our health and

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wellness. Individual or small panel protein surveillance tools have existed in the healthcare market for decades using traditional assay methods across a range of biospecimens, all of which have the same inherent limitations as those in the research space. Also, cell-free nucleic acid methods have emerged recently as amongst the first oncological molecular surveillance tools for the emergence of disease progression post treatment or surgery, and may also prove to enable the detection of disease at earlier stages in some cancers where cell-free nucleic acids are present at higher levels. However, the same fundamental challenges exist in this setting. Nucleic acids are still only a proxy for measuring the biological consequences of the functional proteins, and further, the sensitivity needed to find early-onset molecular features of disease before it presents clinically is incredibly high. We believe the routine surveillance of proteins at sufficient breadth and depth to capture even the exceptionally low-frequency protein changes will be a key area of interest in the future. This application has implications across not only oncology, but across virtually any human disease where the molecular underpinnings driving that disease may one day be revealed and then tracked to identify that disease earlier, measure the response to treatments, and create a comprehensive and dynamic view of our overall molecular health.

Diagnostics, Clinical Research and Drug Development Use Cases

Transitioning from Discovery into Clinical Application

We believe one of the largest and most impactful uses for our technology in the future will be the development of diagnostics that leverage the sensitivity, speed, stability, and ease of use we are designing our system to achieve. Significant technical and practical barriers have existed with prior high-throughput proteomic technologies preventing them from accessing the clinic. Despite advances in sample preparation methods, we believe the detection of enriched and modified protein samples by mass spectrometry will continue to experience challenges in the effort to transition to the clinic. We believe our novel protein detection method embodies the performance characteristics and design criteria that will be desirable for clinical applications. We further believe there will be opportunities to identify and develop content for proteomic clinical diagnostic tools as a result of the more direct nature of measuring the individual proteins at the source of biological function, as opposed to inferring biological function from genomic or gene expression measurements.

We also believe there will be an opportunity to leverage the proteoform pattern detection methods established in a translational research setting into the development of clinical tests in the future. We expect that once our technology is validated in a translational research setting for the identification of proteoform patterns which are themselves biomarkers of disease, we could potentially be in the position of being the only technology capable of physically detecting such patterns. We believe this presents an opportunity to use the Nautilus VoyagerTM platform to continue to advance these applications and methods of proteoform pattern biomarker detection from discovery all the way through to future diagnostics using our technology. As we work to build evidence with our customers and partners on the utility of new proteoform patterns as translational and clinical biomarkers, we believe such applications of the Nautilus Voyager platform could have a profound impact on precision medicine.

Precision Medicine Development & Clinical Trial Support

We believe there is tremendous demand for broadscale proteomic data across the continuum of preclinical and clinical drug development. Starting at the earliest stages of therapeutic asset development, the ability to strategically inform and prioritize experimental compounds with deep proteomic data will provide a much more comprehensive view of cellular responses and resistance mechanisms. This data may also create a new perspective on how to modify experimental therapies to interact with molecular pathways in much more specific and intentional ways. We believe these types of applications present a very compelling use-case for the Nautilus Voyager platform.

We first expect adoption of the Nautilus Voyager platform could occur in the preclinical and clinical retrospective settings, where we believe single-molecule proteomic and proteoform composition and frequency data will become essential tools in building a more complete picture of how experimental medicines are interacting in complex molecular pathways. Each individual tissue type offers its own unique profile of expressed proteins and functions, where advances in proteomic data breadth and depth may elucidate how and where a compound is interacting within these different cell types. We also believe this type of comprehensive proteomic analysis could become an important tool for improving our understanding of drug toxicities, metabolism and distribution. For this application, our technology has the potential to substantially improve visibility to the entire landscape of drug-target interactions, and consequently may help to improve the probability of creating strong therapeutic responses while minimizing detrimental or off-target effects. As these new insights become available, we further believe our customers may engage in very large-scale studies to catalog the frequency of target proteins and proteomic patterns across large and diverse biobanks that represent the intent to treat populations of interest, which will help inform and prioritize the development strategy and the potential impact of their experimental therapy pipelines.

We believe that as these advances in the application of large-scale proteomic data are realized in preclinical and retrospective settings, a natural transition will occur where our customers and partners will seek to apply their learnings in prospective settings. In the prospective clinical development environment, we believe the same design features which make the Nautilus Voyager platform desirable in a research setting can be fully realized. Prior proteomic profiling technologies have struggled to make an impact in prospective clinical settings due to a lack of run-to-run data reproducibility, slow turn-around-time, and overall complexity of practical implementation. We believe the Nautilus Voyager platform design is ideally suited for the quality, stability, and speed required to fully

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realize the value of accessing deep proteomic profiling data to identify biomarkers that stratify patients for clinical trials and improve drug development.

OUR PRODUCTS

Overview

Our primary business model is anticipated to be focused on the commercialization of the Nautilus VoyagerTM platform through the sale of instrumentation, reagents and consumables, software and services. As shown in the diagram below, our platform includes the Nautilus Voyager instrument at the center of our product suite, supported by consumables for the preparation and analysis of proteins, and followed by sophisticated machine learning software architecture for the analysis and reporting of our data in the cloud. Our fundamental positioning is that the Nautilus Voyager platform, based on the new measurement method of Iterative Mapping, enables an expanding capability of Iterative Mapping based applications. The value of our platform grows with the number of applications, starting with Tau proteoforms with planned releases of Broadscale, expansion into additional targeted proteoforms and other new Iterative Mapping applications.

Enabling Iterative Mapping Applications using the Nautilus VoyagerTM Platform

Nautilus VoyagerTM Instrument

The Nautilus Voyager instrument is a high-resolution optical imaging system coupled with integrated fluidics and liquid handling sub-systems. The instrument is designed to deposit protein libraries onto a flow cell and to process labeled multi-affinity reagent binding and imaging cycles rapidly in order to decode and quantify the vast majority of proteins present in biological samples. After the reagent kits, samples (protein libraries), and flow cells are loaded onto the instrument, the remainder of the workflow is automated.

Consumables

Our consumables are comprised of four main components: single-molecule library preparation kits, flow cell(s), affinity reagents, and instrument run buffers used to perform multi-cycle analysis runs.

Our proprietary library preparation kits will be designed for the isolation and preparation of a library of proteins from a variety of input materials including cell cultures, tissues and biospecimen. The library preparation includes an automatable workflow consisting of chemically labeling target proteins and attaching them to a scaffold used to deposit proteins on our flow cell. We also expect our customers and partners may wish to design their own custom process to target specific proteins prior to creating a library with them, and we intend to ensure our kits will be compatible with pre-treated or enriched protein samples. Our protein library preparation process is designed to be simple, efficient, and robust, all features which are expected to allow for easy automated processing for high throughput applications.

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In an effort to provide maximum flexibility, our initial flow cell design includes four physically separated and independent fluid channels, or “lanes,” such that a customer can introduce a unique biological sample into each lane for multi-cycle analysis. The Nautilus VoyagerTM instrument is designed to hold and concurrently analyze up to three flow cells in a single run, for a total of 12 lanes. Additional sample throughput may also be achieved by the use of a molecular barcode in our consumables kits that will enable the multiplexing of more than one barcoded sample library together within a single lane for analysis in the future.

Affinity reagents will also be included as a reagent kit. Kits will be offered in configurations that cover a catalog of proteomic content. We intend to supply a standardized set of multi-affinity reagents for the broadscale detection of proteins, or “proteome kits,” as well as protein-specific or proteoform-specific kits, or “targeted proteoform kits,” focused on high interest protein targets in key disease areas. Other elements of the platform remain the same for both applications, where it is simply a matter of running different types of affinity reagents for each application. Broadscale proteomics is intended to enable large-scale interrogation of canonical proteins across biological states using proprietary multi-affinity reagents and targeted proteoform analysis is intended to resolve specific protein forms, modifications, and variants that are not accessible using existing proteomics methods using reagents based on commercially available antibodies.

Additionally, custom affinity reagent labeling kits are expected to be supplied in the future to enable customers to label their own in-house developed or purchased affinity reagents to be compatible with Nautilus workflows for use on the system.

Software & Analysis

Our machine learning analysis software suite also is expected to be utilized as the analysis engine to decode the proteome system raw data into protein identifications and counts. Our software is expected to be a SaaS based service, utilizing Nautilus’ machine learning computational algorithms required to identify and quantify the proteins or proteoforms present in a sample run on the system. Our software is a learning and evolving system, which we are designing to improve in accuracy over time as the multi-affinity reagent binding profiles are refined and trained across a growing database. We expect our software enhancements in performance will also be accessible to customers who wish to re-analyze prior run data with later versions to deliver new insight and discovery value.

SALES & MARKETING

Commercial Strategy

Our commercial strategy is designed to support a phased transition from early customer access to full platform commercialization, while establishing Iterative Mapping as a new measurement class in proteomics. We are currently executing the initial stages of this strategy through our Early Access Program, which reflects our growing confidence in the performance, robustness, and scientific value of Nautilus Voyager platform based on successful collaborations over the past year. Our long-term business model is centered on the direct commercialization of an integrated, end-to-end Nautilus Voyager platform, consisting of our proteome analysis system, consumable reagent kits and flow cells, cloud-based software and analytics, and associated services. We expect this model to generate revenue through a combination of fee-for-service offerings, instrument sales, recurring consumables, software subscriptions, and service and support arrangements. We believe this integrated approach enables us to deliver a compelling value proposition by substantially improving the scale, sensitivity, reproducibility, and interpretability of proteomic data.

At our current stage, we are prioritizing controlled market entry through service-based access and limited system exposure rather than broad instrument deployment. This approach allows us to standardize early applications, refine workflows, and ensure a high-quality customer experience while continuing to build scientific evidence and reference datasets. Over time, we expect this strategy to support a smooth transition to broader instrument placements and recurring consumables and software revenue as the platform matures. We are initially focused on customers with established expertise in proteomics and strong research budgets, including laboratories within large pharmaceutical and biotechnology companies, academic research institutions, and multi-omics research centers. Many of these customers already utilize mass spectrometry, next-generation sequencing, or affinity-based technologies, and are seeking new tools that overcome the limitations of existing approaches. As adoption grows within these segments, we believe the Nautilus Voyager platform is well positioned to expand into translational and, over time, clinical research settings, including pharmaceutical clinical development groups, contract research organizations, and eventually diagnostic laboratories.

Our pricing strategy is designed to be consistent with existing capital equipment budgets for high-end mass spectrometry platforms. We expect consumables to be priced to reflect the value of comprehensive proteome and proteoform analysis, with ongoing improvements in multiplexing and throughput expected to reduce cost per sample over time. We believe these economics will support large-scale proteomics and multi-omics studies and enable centralized core laboratory use cases. Given the novel nature of Iterative Mapping and single-molecule proteomics, peer-reviewed publications and externally validated biological insights are a critical component of our commercial strategy. Publications, presentations, and customer references generated through collaborations and the Early Access Program are key indicators of platform adoption and credibility. We expect to continue investing in internal and external research efforts to accelerate the pace of high-quality scientific output before and after full commercial launch.

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Go-To-Market Strategy

Our go-to-market strategy is designed to support the introduction and adoption of Iterative Mapping as a new measurement class in proteomics through a phased, evidence-driven approach. We are currently operating in the Early Access Program stage of this strategy, while continuing to build on and expand our collaborations and partnerships with leading academic and biopharmaceutical organizations. Recognizing that Iterative Mapping represents a significant departure from existing proteomics technologies, we have prioritized early market engagement that emphasizes scientific validation, application development, and operational readiness. Rather than pursuing immediate broad instrument deployment, our strategy focuses on controlled access, standardized early applications, and close collaboration with customers to ensure a high-quality user experience and robust scientific outcomes.

Go-to-market plan

Collaborations and Partnerships

Collaborations and partnerships remain a foundational element of our go-to-market approach. We continue to work closely with select academic institutions, biopharmaceutical companies, and research organizations to generate high-quality biological data, validate platform performance, and demonstrate the unique capabilities of Iterative Mapping across a range of biological contexts. These collaborations serve multiple strategic objectives: they support peer-reviewed publications and presentations, inform application prioritization, provide real-world feedback on workflows and system performance, and help establish credibility within the scientific community. We believe ongoing collaboration alongside the Early Access Program is critical to sustaining scientific momentum and expanding awareness of the Nautilus VoyagerTM platform as it moves toward broader commercialization.

Early Access Program

Building on the scientific and technical foundation established through our collaborations, we launched the Nautilus Iterative Mapping Early Access Program in January 2026. The Early Access Program provides select customers with access to Iterative Mapping through fee-for-service offerings delivered by Nautilus Proteomics Analysis Services. The initial application offered through this program is the Nautilus Tau Proteoforms assay, which is designed to enable quantitative analysis of tau proteoforms that are not readily accessible using existing proteomics methods. The Early Access Program is designed to broaden access to Iterative Mapping beyond our initial collaborators while maintaining a controlled and standardized deployment of the platform. Through this program, customers are able to conduct proof-of-concept and pilot studies, generate quality datasets, and evaluate the potential applicability of Iterative Mapping to their research objectives. In parallel, we expect Early Access engagements to support the development of reference datasets and use cases that may inform broader adoption of the Nautilus Voyager platform over time.

In addition to the initial Tau Proteoforms assay, we expect the Early Access Program to serve as a framework for the introduction and evaluation of additional Iterative Mapping–based applications. These may include new targeted assays as well as other workflows intended to explore the broader platform capabilities. The timing, scope, and availability of additional applications will depend on

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ongoing technical development, customer feedback, and operational readiness. Engagements under the Early Access Program are also intended to allow us to continue refining system performance, workflows, software, and customer support processes in real-world research environments. We believe participants in the Early Access Program, together with our collaborators, may serve as reference sites and contributors to application development, supporting broader awareness and adoption of the Nautilus VoyagerTM platform in advance of broader commercial availability.

Transition to Platform Launch and Commercial Scale

As we progress through the Early Access Program, we are preparing for broader commercial availability of the Nautilus Voyager platform and the introduction of Iterative Mapping into routine customer use. Insights gained through collaborations and Early Access engagements are expected to inform final system configuration, application prioritization, workflow design, and customer support infrastructure as we move toward commercialization. Initial customer access to the platform during this phase is expected to continue through Nautilus Proteomics Analysis Services, in which sample analysis is performed at our facility and results are delivered to customers through a cloud-based platform. We do not anticipate that Early Access activities will result in material revenue.

Our initial commercial model is expected to continue incorporating Nautilus Proteomics Analysis Services alongside instrument placements. Service offerings are intended to support customer evaluation, enable early use cases, and facilitate onboarding and expansion within customer organizations, while also allowing us to maintain quality control and accumulate additional application data during the early phases of market adoption.

We plan to initiate our commercial launch in late 2026 by opening the Nautilus Voyager platform for pre-orders, with instrument installations at customer sites expected to begin in early 2027. At launch, we expect general availability to include the Voyager instrument, the Tau proteoforms assay, and a second targeted proteoform assay. We anticipate general availability of Broadscale proteomics capabilities in the first half of 2027 as we continue expanding the platform’s assay portfolio. Our first generally available broadscale consumable kits are designed to deliver strong baseline performance, with subsequent releases expected to further expand capabilities over time.

Consistent with our overall go-to-market strategy, commercialization is expected to follow a land-and-expand model. Customers may initially adopt the platform through a targeted application aligned with a specific biological question and subsequently expand usage across additional applications, including both targeted proteoform analysis and broadscale proteomics workflows, depending on their research priorities. We believe providing multiple application entry points on a single extensible platform may support deeper adoption within customer organizations over time.

We initially expect to commercialize in North America, with international expansion anticipated as adoption grows and commercial readiness increases. Our commercialization approach is expected to include direct sales in the United States and a combination of direct and distributor relationships in selected international markets. Given our stage of development, we currently have limited commercial infrastructure and intend to build the necessary sales, marketing, distribution, service, and support capabilities in phases across the United States, Europe, the United Kingdom, and potentially Asia-Pacific as we execute our commercialization strategy.

Partnerships

We have established and continue to expand a set of strategic research collaborations with leading biopharmaceutical companies and academic research institutions to validate the performance of our platform, generate high-quality biological data, and demonstrate the ability of Iterative Mapping to uncover novel proteoform-level insights. These collaborations have played, and continue to play, a central role in advancing our technology, shaping early applications, and building scientific and commercial momentum as we progress through the Early Access Program phase of commercialization.

In December 2020, we entered into a research collaboration agreement with Genentech to conduct a pilot study investigating proteoforms of the Tau protein, a key biomarker associated with neurodegenerative disease. This collaboration represented one of the first external validations of our platform’s potential to characterize proteoform complexity at single-molecule resolution. In February 2025, we entered into a research collaboration with The Buck Institute for Research on Aging, under which the Nautilus Voyager platform is being used across multiple projects focused on proteoform analysis of the Tau protein. In July 2025, we entered into an agreement with the Allen Institute focused on investigating the connection between the tau protein and neurodegenerative conditions such as Alzheimer’s disease. More recently, in January 2026, we initiated a research collaboration with The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and Weill Cornell Medicine–Qatar, a partnership between Cornell University and the Qatar Foundation (WCM-Q), supported by a research grant from MJFF, to develop a single-molecule assay to measure proteoforms of alpha-synuclein, a protein strongly implicated in Parkinson’s disease. This collaboration leverages expertise in neurodegenerative disease biology, chemical biology, and affinity reagent development and extends our Iterative Mapping approach to an additional neurodegenerative disease target beyond Tau.

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Collectively, these collaborations are consistent with and continue to advance the objectives of our go-to-market strategy by generating peer-reviewed publications, reference datasets, and application-specific validation of our platform. We believe the scientific credibility, biological insights, and customer relationships established through these engagements directly support the expansion of our Early Access Program and lay the groundwork for broader commercial adoption of the Nautilus VoyagerTM platform.

Commercial Organization

We intend to build out a world-class commercial organization, focused on delivering value and support through every stage of the sales cycle. Our company is driven by the advancement of science and the improvement of human health, and we anticipate our commercial organization to be scientifically oriented to align with the goals and objectives of our customers. We believe strongly in building an exceptional support infrastructure, which we believe will be particularly important for our customers given the scale and novelty of data we anticipate our systems will provide. We aim to build long-term loyalty with our customers by enhancing their individual research programs, enabling their successes, and driving growth within their organizations through their successful use of our technologies.

MANUFACTURING AND SUPPLY

Reagent and Flow Cell Consumables

We have designed and sourced our consumables primarily from third-party suppliers. While some of these components are sourced from a single supplier, we have identified or qualified second sources for several of our critical reagents. We currently source base nanoarray chips and flow cell components, sample preparation and assay reagents. We believe that our suppliers have sufficient capacity to meet our near-term development needs through to commercialization. We believe it may be advantageous to have multiple sources for our consumable components and reagents in the future, to help reduce the risk of production delays or quality issues that may cause a disruption to our development timelines or pre-commercial activities. For further discussion of the risks relating to our third-party suppliers, see the section titled “Risk Factors— Risks Related to our Business.”

Instrumentation

The Nautilus Voyager instrument automates the Nautilus assay chemistry concurrent with rapid optical imaging of the flow cell. The current system is an early-stage design, used for optimization of the function and design of each component. We currently source components for our systems from external manufacturers and assemble them in-house at our San Carlos, CA facility or at our manufacturing partner facilities. Once development is completed, we will determine the most appropriate path for high volume production. This may consist of a process developed by contract manufacturing of major system components with final assembly and testing in-house, or fully outsourced production, or some combination of both.

COMPETITION

The life sciences market is highly competitive. There are other companies, both established and early-stage, that have indicated that they are designing, manufacturing and marketing products for, among other things, multiplexed or high-throughput proteomic analysis. Nautilus currently competes with technology and diagnostic companies that supply components, products, and services to customers engaged in proteomics analysis. Major competitors include Thermo Fisher Scientific (including Olink); Bruker Corporation; Agilent Technologies; Danaher (SCIEX); Becton, Dickinson and Company; Quanterix; Illumina, Inc. (through its acquisition of the former Somalogic business from Standard Biotools, Inc.). Nautilus also competes with a number of emerging companies that are developing proteomic products and solutions. Some of these companies may be further along in their commercial and operating plans than we are, including actively commercializing products and growing established marketing and sales forces. Other competitors are earlier than us and in the process of developing their technologies for the life sciences market which may lead to products that rival or replace our products.

However, we believe we are substantially differentiated from our competitors for many reasons, including our novel approach to high throughput and massively parallel proteomic technology, the unique and proprietary nature of our technologies, the novel detail of protein modification mapping our platform can achieve, our rigorous product development processes and quality of science, our multidisciplinary teams, and our access to an immediate growing market with opportunities to expand into adjacent translational and clinical markets. We believe our customers will favor our products and company because of these differentiators.

GOVERNMENT REGULATION

The development, testing, manufacturing, marketing, post-market surveillance, distribution, advertising and labeling of certain medical devices are subject to regulation in the United States by the Center for Devices and Radiological Health of the U.S. Food and Drug Administration (“FDA”) under the Federal Food, Drug, and Cosmetic Act (“FDC Act”) and comparable state and international agencies. FDA defines a medical device as an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent or other similar or related article, including any component part or accessory, which is (i) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (ii) intended to affect the

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structure or any function of the body of man or other animals and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes. Medical devices to be commercially distributed in the United States must receive from the FDA either clearance of a premarket notification, known as 510(k), or premarket approval pursuant to the FDC Act prior to marketing, unless subject to an exemption.

We intend to label and sell our products for research purposes only (“RUO”) and expect to sell them to academic institutions, life sciences and research laboratories that conduct research, and biopharmaceutical and biotechnology companies for non-diagnostic and non-clinical purposes. Our products are not intended or promoted for use in clinical practice in the diagnosis of disease or other conditions, and they are labeled for research use only, not for use in diagnostic procedures. Accordingly, we believe our products, as we intend to market them, are not subject to regulation by FDA. Rather, while FDA regulations require that research use only products be labeled with – “For Research Use Only. Not for use in diagnostic procedures.” – the regulations do not subject such products to the FDA’s jurisdiction or the broader pre- and post-market controls for medical devices.

In November 2013, the FDA issued a final guidance on products labeled RUO, which, among other things, reaffirmed that a company may not make any clinical or diagnostic claims about an RUO product, stating that merely including a labeling statement that the product is for research purposes only will not necessarily render the device exempt from the FDA’s clearance, approval, or other regulatory requirements if the totality of circumstances surrounding the distribution of the product indicates that the manufacturer knows its product is being used by customers for diagnostic uses or the manufacturer intends such a use. These circumstances may include, among other things, written or verbal marketing claims regarding a product’s performance in clinical diagnostic applications and a manufacturer’s provision of technical support for such activities. If FDA were to determine, based on the totality of circumstances, that our products labeled and marketed for RUO are intended for diagnostic purposes, they would be considered medical devices that will require clearance or approval prior to commercialization. Further, sales of devices for diagnostic purposes may subject us to additional healthcare regulation. We continue to monitor the changing legal and regulatory landscape to ensure our compliance with any applicable rules, laws and regulations.

In the future, certain of our products or related applications could become subject to regulation as medical devices by the FDA. If we wish to label and expand product lines to address the diagnosis of disease, regulation by governmental authorities in the United States and other countries will become an increasingly significant factor in development, testing, production, and marketing. Products that we may develop in the molecular diagnostic markets, depending on their intended use, may be regulated as medical devices or in vitro diagnostic products (“IVDs”) by the FDA and comparable agencies in other countries. In the U.S., if we market our products for use in performing clinical diagnostics, such products would be subject to regulation by the FDA under pre-market and post-market control as medical devices, unless an exemption applies, we would be required to obtain either prior 510(k) clearance or prior premarket approval from the FDA before commercializing the product.

The FDA classifies medical devices into one of three classes. Devices deemed to pose lower risk to the patient are placed in either class I or II, which, unless an exemption applies, requires the manufacturer to submit a pre-market notification requesting FDA clearance for commercial distribution pursuant to Section 510(k) of the FDC Act. This process, known as 510(k) clearance, requires that the manufacturer demonstrate that the device is substantially equivalent to a previously cleared and legally marketed 510(k) device or a “pre-amendment” class III device for which pre-market approval applications (“PMAs”) have not been required by the FDA. This FDA review process typically takes from four to twelve months, although it can take longer. Most class I devices are exempted from this 510(k) premarket submission requirement. If no legally marketed predicate can be identified for a new device to enable the use of the 510(k) pathway, the device is automatically classified under the FDC Act as class III, which generally requires PMA approval. However, FDA can reclassify or use “de novo classification” for a device that meets the FDC Act standards for a class II device, permitting the device to be marketed without PMA approval. To grant such a reclassification, FDA must determine that the FDC Act’s general controls alone, or general controls and special controls together, are sufficient to provide a reasonable assurance of the device’s safety and effectiveness. The de novo classification route is generally less burdensome than the PMA approval process.

Devices deemed by the FDA to pose the greatest risk, such as life-sustaining, life-supporting, or implantable devices, or those deemed not substantially equivalent to a legally marketed predicate device, are placed in class III. Class III devices typically require PMA approval. To obtain PMA approval, an applicant must demonstrate the reasonable safety and effectiveness of the device based, in part, on data obtained in clinical studies. All clinical studies of investigational medical devices to determine safety and effectiveness must be conducted in accordance with FDA’s investigational device exemption (“IDE”) regulations, including the requirement for the study sponsor to submit an IDE application to FDA, unless exempt, which must become effective prior to commencing human clinical studies. PMA reviews generally last between one and two years, although they can take longer. Both the 510(k) and the PMA processes can be expensive and lengthy and may not result in clearance or approval. If we are required to submit our products for pre-market review by the FDA, we may be required to delay marketing and commercialization while we obtain premarket clearance or approval from the FDA. There would be no assurance that we could ever obtain such clearance or approval.

All medical devices, including IVDs, that are regulated by the FDA are also subject to the quality system regulation. Obtaining the requisite regulatory approvals, including the FDA quality system inspections that are required for PMA approval, can be expensive

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and may involve considerable delay. The regulatory approval process for such products may be significantly delayed, may be significantly more expensive than anticipated, and may conclude without such products being approved by the FDA. Without timely regulatory approval, we will not be able to launch or successfully commercialize such diagnostic products. Changes to the current regulatory framework, including the imposition of additional or new regulations, could arise at any time during the development or marketing of our products. This may negatively affect our ability to obtain or maintain FDA or comparable regulatory clearance or approval of our products in the future. In addition, regulatory agencies may introduce new requirements that may change the regulatory requirements for us or our customers, or both.

As noted above, although our products are currently labeled and sold for research purposes only, the regulatory requirements related to marketing, selling, and supporting such products could be uncertain and depend on the totality of circumstances. This uncertainty exists even if such use by our customers occurs without our consent. If the FDA or other regulatory authorities assert that any of our RUO products are subject to regulatory clearance or approval, our business, financial condition, or results of operations could be adversely affected.

For example, in some cases, our customers may use our RUO products in their own laboratory-developed tests (“LDTs”) or in other FDA-regulated products for clinical diagnostic use. The FDA has historically exercised enforcement discretion in not enforcing the medical device regulations against LDTs and LDT manufacturers, and has issued warning letters to genomics labs for illegally marketing genetic tests that claim to predict patients’ responses to specific medications, noting that the FDA has not created a legal “carve-out” for LDTs and retains discretion to take action when appropriate, such as when certain genomic tests raise significant public health concerns. Legislative and administrative proposals to amend the FDA's oversight of LDTs have been introduced, including the Verifying Accurate Leading-edge IVCT Development Act of 2021 (“VALID Act”), which aims to create a new category of medical products separate from medical devices called “in vitro clinical tests,” or IVCTs, and bring all such products within the scope of the FDA’s oversight. To date, Congress has not passed the VALID Act. In May 2024, the FDA issued a final rule that phased out its enforcement discretion for most LDTs and amended the FDA’s regulations to make explicit that in vitro diagnostics are medical devices under the Federal Food, Drug, and Cosmetic Act, including when the manufacturer of the diagnostic product is a laboratory. However, on March 31, 2025 the U.S. District Court for the Eastern District of Texas vacated and set aside the FDA LDT Final Rule in its entirety, asserting that the FDA does not have jurisdiction to regulated professional services performed by clinical laboratories and qualified professionals.

In June 2024, the U.S. Supreme Court overruled the Chevron doctrine, which gives deference to regulatory agencies’ statutory interpretations in litigation against federal government agencies, such as the FDA, where the law is ambiguous. This landmark Supreme Court decision may invite various stakeholders to bring lawsuits against the FDA and other federal agencies to challenge longstanding decisions and policies of the FDA. Further, the new administration, including changes in the leadership at the FDA and other federal agencies, may issue new policies and regulations that can impact the compliance status of our products or that of our customers. It is unclear how future litigation and legislation by federal and state governments and FDA regulation will impact the industry, including our business and that of our customers.

Any future legislative or administrative rule making or oversight of LDTs and LDT manufacturers, if and when finalized, may impact the sales of our products and how customers use our products, and may require us to change our business model in order to maintain compliance with these laws. We would become subject to additional FDA requirements if our products are determined to be medical devices or if we elect to seek 510(k) clearance or premarket approval. If our products become subject to FDA regulation as medical devices, we would need to invest significant time and resources to ensure ongoing compliance with FDA quality system regulations and other post-market regulatory requirements, including U.S. healthcare fraud and abuse laws, such as the federal Anti-Kickback Statute and the False Claims Act, as well as reporting and transparency laws, such as the Sunshine Act.

International sales of medical devices are subject to foreign government regulations, which vary substantially from country to country. In the future, if we decide to distribute or market our diagnostic products as IVDs in Europe, such products will be subject to regulation under the IVD Medical Device Regulation (“IVDR”) European Union (“EU”) 2017/746. The EU IVDR was entered into application on May 26, 2022, which replaced the IVD Directive and aims to improve the quality, safety and reliability of in vitro diagnostic medical devices with a new risk-based device classification system, provide for more detailed and stringent rules on the evaluation of device performance, and to enhance vigilance and post-market surveillance, among other changes. Outside of the EU, regulatory authorization needs to be sought on a country-by-country basis in order to market medical devices. Although there is a trend towards harmonization of quality system, standards and regulations in each country may vary substantially which can affect timelines of introduction.

In the future, to the extent we develop any clinical diagnostic assays, we may pursue payment for such products through a diverse and broad range of channels and seek coverage and reimbursement by government health insurance programs and commercial third-party payors for such products. In the United States, there is no uniform coverage for clinical laboratory tests. The extent of coverage and rate of payment for covered services or items vary from payor to payor. Obtaining coverage and reimbursement for such products can be uncertain, time-consuming, and expensive, and, even if favorable coverage and reimbursement status were attained for our tests, to the extent applicable, less favorable coverage policies and reimbursement rates may be implemented in the future. Changes in

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healthcare regulatory policies could also increase our costs and subject us to additional regulatory requirements that may interrupt commercialization of our products, decrease our revenue and adversely impact sales of, and pricing of and reimbursement for, our products.

For further discussion of the risks we face relating to regulation, see the section titled “Risk factors— Risks Related to our Business— Risks Related to Regulatory and Legal Compliance Matters.”

The federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their implementing regulations, which impose obligations, including mandatory contractual terms, with respect to safeguarding the transmission, security and privacy of protected health information by covered entities subject to HIPAA, such as health plans, health care clearinghouses and healthcare providers, and their respective business associates that access protected health information. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates in some cases, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

In addition, in the U.S., numerous federal and state laws and regulations, including state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws, govern the collection, use, disclosure, and protection of health-related and other personal information. For example, in June 2018, the State of California enacted the CCPA, which came into effect on January 1, 2020 and provides new data privacy rights for consumers and new operational requirements for companies. The California Privacy Rights Act (“CPRA”), whose substantive provisions go into effect in 2023, revises and expands the CCPA. While we are not currently subject to the CCPA, we may in the future be required to comply with the CCPA, which may increase our compliance costs and potential liability. Furthermore, the CCPA could mark the beginning of a trend toward more stringent state privacy legislation in the U.S., which could increase our potential liability and adversely affect our business.

Furthermore, the collection, use, storage, disclosure, transfer, or other processing of personal data regarding individuals in the European Economic Area (EEA), including personal health data, is subject to the GDPR, which became effective on May 25, 2018. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors. The GDPR also imposes strict rules on the transfer of personal data to countries outside the EEA, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. In addition, the GDPR includes restrictions on cross-border data transfers. The GDPR may increase our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR, and we may be required to put in place additional mechanisms to ensure compliance with the GDPR, including as implemented by individual countries. Compliance with the GDPR will be a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities.

Further, with the end of the United Kingdom’s transition period to leave the European Union, or the Brexit transition period, on December 31, 2020, there is uncertainty with regard to medical device and data protection regulations as well as other regulations that may apply to our industry in the United Kingdom, including new guidance, rules, and regulations by the Medicines and Healthcare products Regulatory Agency (“MHRA”).

Our research and development processes involve the controlled use of hazardous materials, including select chemicals that may be flammables, toxic or corrosives, which subject us to a variety of federal, state and local environmental and safety laws and regulations. Some of the regulations governing hazardous materials under the current regulatory structure provide for strict liability, holding a party potentially liable without regard to fault or negligence. We could be held liable for damages, remediation costs, and fines as a result of our, or our agents’ or contractors’, business operations should contamination of the environment or individual exposure to hazardous materials occur. We cannot predict how changes in laws or development of new regulations will affect our business operations or the cost of compliance.

For further discussion of the risks we face relating to regulation, see the section titled “Risk factors— Risks Related to our Business— Risks Related to Regulatory and Legal Compliance Matters.”

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Intellectual Property

Patents

We strive to obtain and maintain intellectual protection for our products and technology by using a variety of intellectual property protection strategies, such as patents, trademarks, trade secrets and other methods of protecting proprietary information.

As of December 31, 2025, we owned or held exclusive licenses to thirty six issued U.S. patents, approximately eighty-nine pending U.S. non-provisional patent applications, approximately nineteen pending U.S. provisional patent applications, approximately forty-three granted foreign patents, and approximately one hundred thirty nine pending foreign patent applications, including twenty one international patent applications filed under the Patent Cooperation Treaty (PCT application). Our owned and exclusively licensed patents and patent applications, if issued, are expected to expire between 2026 and 2045, in each case absent any patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity, or other governmental fees.

Our solely owned patents and patent applications contain, among others, claims directed to our core platform technology, such as compositions, methods, and systems directed to identifying and quantifying proteins utilizing probes that can bind different epitopes of the proteins with different degrees of binding non-specificity; reagents and materials; instruments; arrays and other consumables; sample preparation; high throughput decoding algorithms, and algorithms for secondary analysis of proteins and proteomes, amongst other things.

Trade Secrets

In addition to patents, we utilize trade secrets and proprietary know-how to boost our competitive position. Specifically, we rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. We protect trade secrets and know-how by establishing confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and partners. These agreements generally provide that all confidential information developed or made known during the course of an individual or entity’s relationship with us must be kept confidential during and after the relationship. These agreements also generally provide that all inventions resulting from work performed for us or relating to our business and conceived or completed during the period of employment or assignment, as applicable, shall be our exclusive property.

Trademarks

As of December 31, 2025, we owned approximately forty eight registered trademarks covering four different marks in Australia, Brazil, Canada, China, the European Union, India, Israel, Japan, Korea, Mexico, Singapore, and Switzerland. In addition, we have approximately twelve pending trademark applications covering seven different marks in the U.S., Brazil, India, and Korea.

Collaboration Agreements

We have entered into research collaboration agreements with Genentech in December 2020, with The Buck Institute for Research on Aging in February 2025, and with the Michael J. Fox Foundation and Weill Cornell Medicine–Qatar in January 2026, and entered into an agreement with the Allen Institute in July 2025. Under each of these agreements, partners gain early experience with the Nautilus VoyagerTM platform and contribute to application development across diverse biological contexts. These agreements are for research only and are not expected to generate any revenues, however they may provide opportunities for the parties to jointly apply for and secure grants, awards, or other government or non-profit research funding

Scientific Advisory Board

We have assembled a highly qualified scientific advisory board composed of advisors who have deep expertise in the fields of proteomics, medicine, regulatory compliance and data science. Our scientific advisory board is composed of:

Ruedi Aebersold, Ph.D.

Dr. Aebersold is Professor of Systems Biology at the Institute of Molecular Systems Biology in ETH Zurich (IMSB). He is widely considered a pioneer in the field of proteomics and has served as the head of the biology/disease branch of the human proteome project.

Lee Hartwell, Ph.D.

Dr. Hartwell is the President and Director Emeritus of the Fred Hutchinson Cancer Research Center. He is a 2001 Co-recipient Nobel Prize in Physiology and Medicine for his discovery of the protein molecules that control the division of cells.

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Joshua LaBaer, MD, Ph.D.

Dr. LaBaer is the Executive Director of the Biodesign Institute at Arizona State University. He is a leading researcher in cancer and personalized medicine and the inventor of the novel protein microarray technology, Nucleic Acid Programmable Protein Array (NAPPA), which has been used widely for biomedical research.

Emma Lundberg, Ph.D.

Dr. Lundberg is a Professor in cell biology proteomics at KTH Royal Institute of Technology, Sweden, and Professor of Bioengineering and Pathology at Stanford University. Dr. Lundberg also holds the positions of Director of the Cell Atlas of the Human Protein Atlas, an international proteomics and cell mapping project, and was previously Director of the Cell Profiling facility at the Science for Life Laboratory (SciLifeLab) in Sweden.

Employees and Human Capital

As of December 31, 2025, we had 130 employees, all based in the United States, over one-third of whom hold doctorate degrees. Of these employees, 91 were engaged in research and development activities, and 39 were engaged in general and administrative activities. None of our employees are represented by a labor union or covered under a collective bargaining agreement.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

Corporate and Available Information

We were incorporated as a Cayman Islands exempted company in March 2020 as a blank check company under the name ARYA Sciences Acquisition Corp III. On June 9, 2021, we consummated the Business Combination pursuant to the terms of the Business Combination Agreement. Pursuant to the terms of the Business Combination Agreement, on the Closing Date, (i) we changed our jurisdiction of incorporation by deregistering as a Cayman Islands exempted company and continuing and domesticating as a corporation incorporated under the laws of the State of Delaware, upon which we changed our name to Nautilus Biotechnology, Inc.

Our principal executive offices are located at 2701 Eastlake Avenue East Seattle, Washington, 98102, and our telephone number is (206) 333-2001. Our investor relations website is located at https://investors.nautilus.bio/. Information contained on the website is not incorporated by reference into this Form 10-K or any other filings we make with the SEC.

We use our investor relations website to post important information for investors, including news releases, analyst presentations, and supplemental financial information, and as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor our investor relations website, in addition to following press releases, SEC filings and public conference calls and webcasts. We also make available, free of charge, on our investor relations website under “Financial Information—SEC Filings,” our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to these reports as soon as reasonably practicable after electronically filing or furnishing those reports to the SEC.