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Item 1. Business

2026-02-26 compared with 2025-02-27 · 469 added, 466 removed, 295 unchanged (76% of the section changed)

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Concurrently with the execution of the Business Combination Agreement, ARYA entered into Subscription Agreements (each, a “Subscription Agreement”) with certain investors (each, a “PIPE Investor”), pursuant to which the PIPE Investors subscribed for and purchased, and ARYA issued and sold to the PIPE Investors, on the Closing Date, an aggregate of 20,000,000 shares of common stock of New Nautilus (“Common Stock”) for aggregate gross proceeds of $200,000,000 (the “PIPE Financing”).

As of the open of trading on June 10, 2021, the Common Stock began trading on the Nasdaq Global Select Market (“Nasdaq”) under the symbol “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).

We are a development stage life sciences company creating a platform technology for quantifying and unlocking the complexity of the proteome.

Our mission is to transform the field of proteomics by democratizing access to the proteome and enabling fundamental advancements across human health and medicine.

We were founded on the belief that incremental advancements of existing technologies are inadequate, and that a bold scientific leap would be required to radically reinvent proteomics and revolutionize precision medicine.

Our vision is to integrate our breakthrough innovations in computer science, engineering, and biochemistry to develop and commercialize a proteomic analysis technology of extreme sensitivity and scale.

To accomplish this, we have built a prototype of a proteome analysis system, an instrument to perform massively parallel single protein molecule measurements which will be further developed to deliver the speed, simplicity, accuracy, and versatility that we believe is necessary to establish a new gold standard in the field.

The human proteome, the make-up of all the proteins in a human, is among the most dynamic and valuable sources of biological insight in modern-day science.

Unlike the genome, which is largely unchanging throughout an individual’s lifetime, the proteome is an ever-changing source of biological information.

Our proteins directly control and determine the functions of our cells, yet we lack the ability to measure all of them with the ease, breadth and sensitivity that is used to measure DNA today.

We believe that deep characterization of the proteome will have the potential to unveil an entirely new layer of complexity and valuable biological information that may have significant implications across life sciences, healthcare and drug development.

Approximately 95% of FDA-approved drug targets are proteins, and yet today we still lack the ability to routinely read and quantify all of the proteins in our cells, or to fully map the downstream changes and modifications to those proteins which may define their biological function.

By leveraging our novel platform design coupled with advanced machine learning software, we believe our Nautilus platform, which includes our end-to-end solution comprised of the proteome analysis system, consumables, and software, has the potential to rapidly and reproducibly identify up to approximately 95% of proteins in a sample from virtually any organism, and could have the ability to detect and map the diverse landscape of modifications on those proteins.

We believe that unlocking proteomics has the potential to create a long-term transformation of basic science, translational research, and healthcare.

Current proteomics platforms for broadly quantifying the abundance of proteins within samples generally fall into two classes:

affinity-based and mass spectrometry-based methods.

For years, these methods have facilitated novel drug development and improved diagnostics.

As with most technology platforms however, these also suffer from distinct limitations that make simple, high-throughput, ultra-deep characterization of the proteome challenging.

Mass spectrometry approaches have tremendous flexibility and thus have been applied to a wide range of applications, however their use requires a trade-off to be made between either depth or throughput;

meaning that a researcher can either look at one sample in a deep analysis or at many samples in a shallow analysis.

Additionally, challenges in operational complexity and sensitivity have limited the ability of mass spectrometry-based methods from easily, comprehensively, and quickly characterizing the entirety of the proteome.

Affinity-based approaches use the binding attraction of antibodies to proteins to capture and measure protein targets.

Many of these legacy technologies measure only a single-target, or are multiplexed to cover a few specific protein targets per reaction.

Newer technologies have further expanded their multiplexing capability by using a next-generation sequencing readout.

However, affinity-based proteomics is inherently dependent on the availability of high quality, specific and sensitive affinity reagents, which can impact scalability, reproducibility and accuracy.

Consequently, we believe researchers are forced into an unattractive trade-off between the number of samples in a study and the depth and breadth of the analysis.

These trade-offs limit researchers’ ability to advance characterization of the proteome to match the current, and highly valuable, characterization of the genome.

We believe the limitations of both mass spectrometry and affinity-based technologies have prevented progress towards achieving comprehensive proteome characterization, including measurement of the many known modifications to proteins.

If detecting and quantifying the complexity of the human proteome were as simple and easy as detecting an entire human genome, we believe a new set of questions could be asked:

• Down to the very low frequencies of expressed proteins, how are healthy tissue cells different from diseased cells?

• What will a comprehensive map of nearly all proteins by organ tissue type tell us about our biology?

• What specific patterns of protein modifications are present in disease, and why?

• What happens to our proteome when we get sick, and how does it change with treatment?

We believe that our Nautilus platform has the potential to position us to answer these questions, and many others that have not previously been possible to fully investigate.

Due to the extensive applications and broad potential of large-scale proteomic characterization, we believe the proteomics market is currently among one of the largest untapped opportunities in the biological sciences today.

According to BCC Research, the existing proteomics research market is currently estimated to be approximately $27 billion annual spend as of 2022, made up primarily of mass spectrometry and affinity-based quantification methods.

Over the longer-term, the proteomics market is expected to reach approximately $55 billion by 2027, representing a compound annual growth rate, or CAGR, of 15% over the five-year period.

Further, we believe there are substantial adjacent opportunities across translational research in drug target discovery, precision medicine development, clinical diagnostics, and other disciplines such as food and environmental science.

We plan to initially target the life sciences proteomics research market and are currently entering the first phase of our product development and commercialization strategy.

In this first phase, we are focused on developing partnerships with key biopharma companies and leading academic institutions to create a founding group of collaborators that will gain experience with our technology, jointly publish research using our Nautilus platform, and generally help validate our initial applications.

As of the date of filing this Annual Report, we have research collaborations with Genentech, Amgen, The University of Texas MD Anderson Cancer Research Center, and The Buck Institute for Research on Aging.

In the second phase of our product development and commercialization we plan to launch an early access program offering more standardized applications to an expanded group of collaborators.

We believe this growing group of collaborators will become important reference sites and key influencers that will aid in the market adoption of our Nautilus platform, and will help us build a strong value proposition ahead of full commercial launch.

In our third phase of commercialization, we intend to execute a broad commercial launch of our Nautilus platform including the introduction of our proteome analysis system, which is an integrated fluidics and optics system for massively parallel single protein molecule detection, accompanied by consumable reagents and analysis software, in direct sales to customers across academia and industry.

The launch of our proteome analysis system is expected to be done with a multi-year product roadmap of system enhancements and new applications designed to help our future customers achieve their research objectives and expand the utility of our Nautilus platform.

We also plan to leverage our machine learning software to build a data analysis and insights engine that improves over time as we grow our data sources and the analysis learns to deliver better accuracy and identify new potential discoveries.

We believe by following this methodical pathway, we can optimize the development of our Nautilus platform, establish a steady flow of validating publications, appropriately scale our operations, deliver exceptional customer experiences, and help ensure we are delivering long term value and revenue growth.

Since inception in 2016, we have worked diligently to secure a strong intellectual property portfolio, and we have successfully filed and obtained numerous key patents.

Our management team also brings a unique combination of experiences from the fields of technology and life sciences, with a proven track record of building successful businesses based on novel technology.

Our company is a highly interdisciplinary organization with deep subject matter expertise across scientific disciplines in chemistry, molecular biology, physics and bioinformatics, and as of December 31, 2024 over one-third of our employees have a Ph.D.

Our organization is driven by the pursuit of deep, hard science, and our Scientific Advisory Board is comprised of world-renowned scientific leaders that support our vision.

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

“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 Voyager TM 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.

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.

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

• Highly disruptive proteomics technology.

Our Nautilus proteome analysis platform is designed to be a completely novel, single protein molecule analysis technology of extreme sensitivity, high throughput, and ease-of-use.

Leveraging a scalable and flexible system architecture, advanced machine learning and algorithms, we believe our Nautilus platform has the potential to identify substantially all proteins in a sample from almost any organism.

We also believe that by measuring single intact protein molecules, our platform has a highly differentiated and unique ability to also detect and quantify combinations and patterns of post-translational modifications, which are strongly suspected to be critical drivers of biology and have been largely invisible to legacy technologies to date.

• Differentiated proteomics technology platform.

The Nautilus Voyager TM 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 end-to-end solution to decode and quantify approximately 95% of the entire proteome, including the variations and modifications of proteins.

Our Nautilus platform consists of instruments, reagent consumables and software that we believe has the potential to deliver broad proteomic profiling to the market and potentially unlock the vast, dynamic, and valuable biological information contained in the proteome.

With each instrument sale, there is expected to be accompanying recurring revenue comprised of reagent consumable sales, instrumentation service, support, and software that creates a comprehensive proteomics solution.

• Open, flexible and customizable technology platform.

Our Nautilus platform is designed to allow our customers to analyze their samples in a variety of run configurations by utilizing flow cells which each contain 4 discrete and independent lanes, analyzed on an instrument that can be loaded with up to 3 flow cells per run.

Our platform is currently designed to either maximize analysis depth by running all 12 lanes on 1 sample, or maximize analysis throughput by running a single sample per lane.

This design is also highly compatible with molecular barcoding, which may be introduced in the future to multiplex increasingly larger sample numbers per run.

Further, with the introduction of an affinity reagent labeling kit, our platform is also designed to be able to incorporate off-the-shelf affinity reagents that have already been created by biopharma, academia, or commercial affinity reagent manufacturers.

We believe that the ability to customize the type of analysis performed by adding or combining these affinity reagent probes with our Nautilus provided reagent kits could provide a very powerful and desirable analysis for our customers.

• Immense data production capacity coupled with machine learning can unlock new proteomic insights.

We have designed the Nautilus platform to create and process a vast amount of proteomic data.

The Nautilus platform is expected to generate up to approximately 35 terabytes of digital protein data per run, which will then be decoded 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 generated with our Nautilus platform.

We believe that this feedback loop has the potential to deliver future value to our customers through the continuous improvements in our analytics, thereby encouraging the analysis, and re-analysis, of more samples through our Nautilus platform to benefit from these advancements.

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.

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 near-term commercial opportunity of capitalizing on the existing mass spectrometry-based proteomics marketplace estimated at over 16,000 installed systems.

Our price point is expected to be in-line with mass spectrometry system budgets allocated for broad scale 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 specifically address our target customer needs.

• Our Nautilus platform technology could position us as a leader in a large initial life sciences research market and provide a path to the clinical diagnostics.

The global proteomics market is estimated to be approximately $27 billion annually as of 2022 and is expected to grow at an estimated 15% CAGR from 2022 to 2027 according to BCC Research.

Furthermore, we believe our Nautilus platform has the potential to facilitate a broader transformation across life sciences and healthcare, and therefore significantly augment our total addressable market over time.

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.

• Nautilus Voyager TM 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 Voyager TM 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 our Nautilus platform could transfer well into the clinical setting prior technologies have thus far been unable reach.

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.

Several members of the executive team and board of directors held leadership roles at Illumina, Agilent Technologies, and Isilon, and helped to guide strategy and manage execution both before and throughout the rapid growth and success for those

We view the core design thesis behind the Nautilus platform technology development as a non-traditional approach to new product development within life sciences that requires thinking at the intersection of three unique disciplines not often found together—life sciences, computer and data sciences, and physical sciences and engineering.

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.

• Drive adoption of our Nautilus platform by providing the life sciences industry with access to the proteome.

We believe our Nautilus platform has the potential to provide value across the life sciences ecosystem as the first end-to-end solution capable of substantially quantifying the proteome.

The utility and potential applications are expected to be broad and serve basic research and discovery, translational and clinical research, and ultimately enable clinical diagnostic market segments.

We intend to drive adoption of our Nautilus platform through a three-phase commercial strategy that begins with an initial partnership and collaboration phase with biopharma companies (such as our existing relationships with Genentech and Amgen), academic institutions (such as our existing relationship with The University of Texas MD Anderson Cancer Center and The Buck Institute for Research on Aging, and others) and research organizations where we aim to jointly publish data utilizing the first versions of our Nautilus platform, followed by a pre-sales or early access program to drive awareness and demand, and finally culminating in a full commercial launch.

• Continuously innovate and scale our Nautilus platform’s capabilities to enable further advancement of proteomic research.

Through both internal R&D projects and external collaborations with our customers and partners, we plan to continuously innovate and develop new products, applications, workflows, and analysis tools that simplify and accelerate the ability for our customers to generate new sources of proteomic data and drive novel biological insights.

We believe our sustainable advantage could come from a continued stream of development and commercialization of new products and applications using our core technology to help our customers succeed in their research endeavors.

We believe if our customers win, we all win.

• Multiple pathways to build and expand our manufacturing capacity to support our commercial launch and the sustained growth of our business .

Our technology is comprised of many off the shelf component parts that help to create efficient sourcing and manufacturing processes.

We have established a manufacturing process for our technology utilizing a combination of both external contract manufacturers and internal resources based in our San Carlos, CA facility, with the ability to support substantially all of our current core activities during development.

We believe there are many potential options we can use in order to increase the manufacturing and production capabilities for our products, including expanding our outsourced manufacturing and supply to multiple suppliers to ensure our quality and production capacity will meet our commercial plan.

• Build long-term value by leveraging the open design of our Nautilus platform to create an ecosystem of products and services based on our core technology.

Our Nautilus platform is compatible with a wide variety of protein affinity reagents, which we believe will allow us to create a broad menu of applications compatible with our technology.

Our Nautilus platform is also designed to be highly customizable, which we believe will allow us to create an infrastructure that enables our customers to design their own custom solutions and applications.

We believe that commercializing our technology with a set of standard product applications, alongside the ability to maintain a flexible approach for designing new applications with our customers, could potentially lead to an entire ecosystem of products and services leveraging our core technology.

• Expand adoption of our Nautilus platform into new markets.

Our market entry strategy involves identifying markets that are constrained by their inability to access comprehensive proteomic information, which we believe can be addressed by our Nautilus platform.

We recognize that these opportunities extend into ancillary markets across life sciences, including clinical and translational research, and clinical diagnostics, where we believe there are substantial unmet needs our Nautilus platform can address in the future.

We expect to drive expansion into these adjacent markets by developing and validating new product configurations and workflows targeting high impact applications, either by adapting our existing workflows or by partnering with leaders in those markets to develop workflows that address their immediate needs and will provide broader general value for other customers in that market segment.

• 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;

◦ 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.

• Drive adoption through strategic collaborations and phased commercialization.

We intend to drive adoption of the Nautilus Voyager TM 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.

Proteomics is the next step in the study of biological information systems and 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.

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 body fluids.

To date, there has been very 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.

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.

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This complex interplay of factors contributes to the complexity of proteomics research.

However, the detailed and complex information provided from proteomics has the potential to help in identifying novel and causal drug targets and to enable more efficient and effective drug development.

A few examples of the way proteomics may lead to novel insights in research are highlighted below.

However, we believe the detailed and complex information provided from proteomics has the

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 .

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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 directly unlock new insights on their own, but they would also have the potential to increase the value of data and insights generated in related fields such as genetics, gene expression, and metabolism.

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 our Nautilus platform has the potential to be uniquely positioned in the proteomics market.

In our mission to democratize proteomics, we see initial research applications in precision and personalized medicine, with a natural growth path into clinical diagnostics, as well as in machine-learning powered drug discovery.

We believe that the Nautilus Voyager TM 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.

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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 $1.2 billion in 2010 to approximately $2.0 billion in 2019.

The increasing cost, time and complexity of drug development have driven down the rate of return on R&D to less than 2% in 2019 for the 12 leading biopharmaceutical companies analyzed in a 2020 report by the Deloitte Center for Health Solutions.

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.

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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 FDA approval for use with therapies today.

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.

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 the Nautilus platform, we believe researchers will have the power to deeply and comprehensively measure the physical proteins at the root of disease, dramatically increasing the potential to identify more clinically meaningful biomarkers with greater precision in the practice of medicine.

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.

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 enhancing our fundamental understanding of biology and the mechanisms of disease.

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:

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 of biological interactions with important ramifications across the organism that remains coded and hidden within unique protein patterns.

Beyond the genome lies a vast multi-level network

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.

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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 protein-encoding genes, many of which have been well characterized.

However, to coordinate the myriad of processes that occur within organisms at all times, the genome has evolved multiple ways to generate further biological complexity.

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.

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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 governs all biological processes, both healthy and sick, cannot be captured or characterized routinely by current methods.

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 basic protein, known as “proteoforms”.

In total, our original 20,000 protein-coding genes are estimated to produce as many as 6,000,000 different proteoforms, as illustrated in the figure below.

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.

It is strongly suspected that it is within this proteoform space of molecular information that fundamental biological processes are present that govern our cells, and our molecular health.

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

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 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, shortfalls in the ability of bioinformatics to predict the existence as well as the function of genes have further illustrated the need for enhanced protein analysis techniques.

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.

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

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, the global proteomics market was valued at

approximately $27 billion as of 2022.

This encompasses only the fraction of the proteomics market that is currently available to us via mass spectrometry and other quantification methods and does not include diagnostics.

The overall proteomics market is projected to reach approximately $55 billion in 2027, representing a CAGR of 15% for the five-year period.

We believe that as the proteomics market evolves, substantial adjacent opportunities will arise due to the potential applications in not only precision and personalized medicine, clinical diagnostics, and machine-learning powered drug discovery, as well as other disciplines such as food and environmental science.

Within the biomedical sciences, 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.

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.

Existing Proteomics Technologies and Shortfalls

Over the past decade, the importance of proteomics in the field of diagnosis and drug research & development has increased dramatically due to the direct biological relevance of analyzing the interaction of proteins in living organisms.

However, the analysis of the proteome is substantially more complex than the analysis of the genome or transcriptome.

Unlike DNA and RNA, proteins themselves cannot be amplified.

Consequently, measurement tools must address the challenges of sensitively detecting the minute quantities of low frequency expressed targets.

This challenge is exacerbated by the exceptionally large dynamic range of proteins in both cells and in blood spanning more than seven orders of magnitude.

For example, some critical and influential proteins such as transcription factors may be present with only a few copies per cell, whereas abundant proteins such as cytoskeleton or ribosomal proteins may be present in millions of copies per cell.

Quantifying both the low frequency and the abundant proteins within a single sample is very challenging and stands in stark contrast to genome or transcriptome analysis which only contends with a dynamic range of approximately three orders of magnitude.

Furthermore, the biochemical and physical diversity of proteins far exceeds that of DNA or RNA as proteins are created from 20 highly distinct amino acids, whereas genes and transcripts are created from only 4 distinct nucleotides.

These inherent complexities have hampered progress in the development of life science tools that can sensitively and comprehensively quantify the proteome.

Additionally, the ability to identify unique proteoform composition and frequency in a single complex sample is not achievable today.

Currently available tools can be broadly segmented into mass spectrometry-based and affinity-based methods.

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 is a powerful tool for the measurement of proteins and has progressed the field of proteomics immensely, similar to the impact that Sanger sequencing had to the founding of large-scale genomics research.

However, for the powerful data that is generated, current mass spectrometry workflows still remain complex and time consuming.

The mass-spectrometry workflows and processes are not fully automated requiring skilled professionals to prepare samples and operate instruments, which limits the impact of these powerful technologies.

Mass spectrometry is also known to have poor sensitivity to detect proteins present at low frequencies within biological samples, which is where many believe important drivers of biology exist.

Lastly, the most widespread approach called shotgun mass spectrometry, requires proteins are first broken apart into small pieces called peptides in order to measure them.

This detection method can only measure the individual protein fragments, and is therefore unable to identify specific patterns of post-translational modifications and proteoforms visible on intact proteins across a sample.

Despite these challenges, there has still been a strong appetite for protein data given its importance in biology and drug development, and the proteomics research marketplace is estimated to have over 16,000 installed mass spectrometry systems.

Limitations with Affinity-based Approaches

Where mass spectrometry-based approaches have been widely used for broad scale protein discovery applications, affinity-based approaches have generally been used for targeted protein measurements.

Affinity-based protein detection commonly utilizes affinity reagents that are designed to be very specific to an individual protein target that is already known to the researcher.

Additionally, the ability of an affinity reagent to selectively bind to its target may also be impacted by protein specific factors, such as the protein’s folded structure and orientation.

Lastly, affinity-based approaches intended to target more than one protein at once in a sample commonly require a different affinity reagent for each target.

Despite decades of ongoing efforts, there are still nowhere near the number of affinity reagents in existence today to attempt to measure the full proteome.

In general, affinity-based approaches are most useful when the end user has a relatively small pre-defined set of targets they want to measure, and because the affinity reagents themselves only detect a small portion of the intended target, this method is also not capable of resolving unique proteoform patterns at the single protein molecule level today.

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

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 a desire to enable the research community to rapidly and comprehensively access and quantify the proteome, thereby transforming our ability to examine disease mechanisms, and develop new therapeutics and diagnostics.

This mission is guided by a recognition that major advances in proteomics have generally lagged behind genomics, primarily due to a lack of available tools for measuring the proteome as easily or completely as one can measure the genome and transcriptome.

We believe that evolutionary or incremental improvements to existing technologies will not suffice;

that a fundamentally new approach is required to unlock this large opportunity in biological science.

In pursuit of that mission, we are developing our innovative Nautilus platform to be an end-to-end single protein molecule analysis solution composed of instrumentation, reagent consumables, and software that processes a sample and returns valuable and unique biological data and insight.

We have designed the Nautilus platform to enable extreme sensitivity and scale, without compromising on ease of use.

Leveraging a unique architecture and advanced machine learning software, we believe our Nautilus platform has the potential to identify substantially all proteins in a sample from almost any organism.

We view many of the core ideas underlying the Nautilus platform as “counterintuitive”, as it required innovations at the intersection of three distinct disciplines not often found in harmony:

life sciences, computer and data sciences, and physical sciences and engineering.

We have designed the Nautilus platform to integrate a variety of both computational and experimental approaches, diverse measurement modalities, and the best available analytical tools to accelerate biomarker discovery and precision medicine.

Several Nautilus platform technology elements (e.g., cloud computing and machine learning) are disciplines that have now sufficiently matured to create this timely opportunity for Nautilus to pursue the deep, hard science required to bring to market a potentially revolutionary capability that we believe will help democratize access to proteomics data.

Our Nautilus Platform Design Criteria

To achieve our ambitious goals, and to meet the unmet needs of scientists and researchers, we recognized early on that we would need to tackle the deep, hard, novel science required to innovate and commercialize a fundamentally new detection technology capable of reading and quantifying the proteome and associated proteoforms.

As such, we designed the Nautilus platform – from the ground up – to accomplish the following goals:

A core design criterion was that the Nautilus platform needed to be comprehensive.

One of the largest challenges with existing “shotgun” proteomics technologies is that replicate analyses are likely to sample different subsets of the proteome.

Next, the Nautilus platform needed to be ultra-sensitive.

Unlike NGS technologies, where one can leverage natural processes and enzymes (e.g., polymerases) to amplify DNA and RNA, proteins cannot be amplified from the original molecule.

To achieve the goal of measuring the complete proteome, scientists and researchers needed a new analysis method with unprecedented sensitivity.

The Nautilus platform was designed to cover a very large dynamic range in a simple workflow in order to scale to the full proteome.

In addition, the process needed to be reproducible and robust, maximizing the chance that the results derived in one experiment are the same as the results derived in subsequent experiments.

Importantly, the Nautilus platform needed to be fast and able to analyze tens of thousands of samples in a reasonable time period.

It also needed to be sufficiently easy-to-use so that virtually any lab could benefit from using it, not just labs that are explicitly focused on proteomics or analytical chemistry.

In order to fully support the wide-ranging needs of our future customers, the platform can also support multiple run configurations.

Our design accommodates both low throughput and high throughput run configurations, and will also employ in-lane sample multiplexing to enable our customers to meet the high-volume data production needs of large-scale studies or core facilities.

With these objectives identified as our core design criteria, we set out to create a transformative technology with the potential to achieve all of these criteria.

The resulting Nautilus platform has embodied many technical innovations across sample preparation, reagent consumables, instrumentation, and downstream protein analysis.

However, we believe there are four critically important key technical innovations that, when brought together, make the achievement of our Nautilus platform design specifications and benefits possible:

A Single Protein Molecule Flow Cell

The Proteome Analysis System:

An Integrated Multi-cycle Optical and Fluidics Instrument

A Novel Class of Affinity Reagent Probes for Efficient Whole Proteome Analysis

Machine Learning Protein Decoding Analytics

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 Voyager TM 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 Voyager TM 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

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 Voyager TM 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.

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:

Hyper-dense Single-molecule nanoarrays

Integrated Proteomics Platform

Probes for multi-cycle analysis

Machine-learning powered quantification

Key Innovations

Single Protein Molecule Flow Cell

The vast majority of protein analysis tools, such as affinity-based methods like an ELISA (Enzyme-Linked Immunosorbent Assay), typically measure proteins in bulk.

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.

Additionally, going through multiple intermediaries to assess a protein’s concentration (such as protein capture, secondary detection, calibration between fluorescent output and concentration) places limitations on the accuracy, sensitivity, dynamic range and reproducibility.

Genomic studies are able to get around these limitations by amplifying DNA or RNA, but unfortunately, there is no equivalent approach for amplifying proteins available.

Consequently, the limit of detection for most immunoassays has been bounded primarily by the signal-to-noise ratio provided by the instrument used to detect antibody-antigen binding and by non-specific binding, which in a 50uL sample could represent tens-of-thousands of molecules.

Accordingly, the dynamic range of such platforms are typically about 1-order of magnitude, though this can be scaled through dilution at the upper end.

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.

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

To break through these barriers, we have designed our Nautilus platform with a fundamentally different approach:

to measure billions of individual protein molecules at a time, in a massively parallel and efficient workflow.

If one is able to identify each protein molecule, quantification arises simply from counting

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.

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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 by binding them to a much larger nanoparticle scaffold which has been created to hold exactly one protein molecule.

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.

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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.

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

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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 platform is designed to enable extreme sensitivity, which we have observed in our internal testing as shown in the “Nautilus Platform Sensitivity” section below, and the sheer scale of proteins captured enables the measurement of proteins across an exceptionally wide dynamic range.

Flow cells with loaded protein libraries can then be introduced into our proteome analysis system for the analysis and quantitation of the captured protein library.

Nautilus Single Protein Molecule Flow Cell is Designed at Nanometer-Scale to Cover the Information Density Needed to Measure Approximately 95% of the Human Proteome

Our Proteome Analysis System:

An Integrated Multi-cycle Optical and Fluidics Instrument

The single protein molecule nature of the Nautilus Voyager TM 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.

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.

With our platform, 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 and ultimately decode approximately 95% of the proteome.

Nautilus Platform Multi-Cycle Affinity Reagent Probe Binding, Imaging, Washing, and Re-Binding

To achieve extreme sensitivity and scale, we have designed a novel instrument that integrates reagent fluidics with a sensitive high-resolution optical imaging system to cyclically measure all single protein molecules captured on the flow cell.

Our affinity reagent probes are labeled with proprietary fluorescent labels that help improve both the signal-to-noise and speed of our assay chemistry.

The instrument introduces labeled affinity reagent probes into our flow cell, allowing them to briefly incubate, then rinse off unbound molecules, and then rapidly images the entire surface.

During the imaging process, a laser system is used to excite and illuminate the fluorescent labels.

The high-resolution imaging components allow resolution sufficient to characterize each individual protein molecule, generating data as shown in the above illustration.

Once an imaging pass is complete, the instrument then washes the flow cell, leaving the proteins fully immobilized, and rinses out the wash reagent before pursuing additional cycles.

Samples may be multiplexed in a variety of ways to enable higher sample throughput and to reduce the cost per sample.

A typical full scale proteome run will generate approximately 35 terabytes of data, which is then compressed to a digital binding matrix for downstream analysis by our cloud-based software-as-a-service, SaaS, analytics suite.

Multi-Cycle Binding and Detection using Affinity Reagent Probes Enables an Entirely New Way to Detect Proteins and their Modifications

Our Nautilus platform technology is designed with fundamentally different principles of how to use and exploit the properties of affinity reagents compared to prior methods.

Historically, affinity reagents have been qualified for use based on their specificity to a given protein target, and showing the ability to bind strongly to that specific target.

In order to see and measure a single protein target, a researcher would require an affinity reagent of sufficient specificity to detect it.

These higher specificity affinity reagents are commonly used for bulk measurements, and are typically only used for one single bulk measurement event (or cycle) and then discarded.

By using these same high specificity reagents in our multi-cycle system, we believe it is possible to detect each specific protein target now at the single-molecule level, enabling digital quantitation.

We further believe it is possible to expand this concept, and use our Nautilus platform with a wide variety of “off-the-shelf” affinity reagents that are highly specific to multiple individual protein targets.

Also and of particular importance, is these off-the-shelf affinity reagents can often also target very specific sites on the protein itself, such as post-translational modification sites.

Using affinity reagent probes that target very specific locations and features of proteins will allow the Nautilus platform to detect and quantify the different patterns and varieties of post-translational modifications (i.e.

the proteoforms).

In a highly innovative and counterintuitive way, our Nautilus platform has also been designed to exploit low specificity affinity reagents.

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.

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Probes for multi-cycle analysis

The Nautilus Voyager TM 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, each we describe as a “multi-affinity reagent probe”.

While the binding of a single multi-affinity reagent probe is not sufficient to identify a given protein, sequential binding events using a series of multi-affinity reagent probes can create enough information that it is sufficiently powerful to accurately identify an exceptionally broad number of proteins present in a sample.

In this approach, each new multi-affinity reagent probe 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 Protein Identification by Short-epitope Mapping (PrISM).

Our Nautilus platform technology is estimated to achieve the detection of the vast majority of proteins in the proteome using a combination of approximately 300 unique multi-affinity reagent probes.

Nautilus Platform Technology Protein Identification with Increasing Multi-Affinity Reagent Probe Cycles

A theoretical framework for proteome-scale single-molecule protein identification using multi-affinity protein binding reagents.

Egertson, Dan DiPasquo, Alana Killeen, Vadim Lobanov, Sujal Patel, Parag Mallick bioRxiv 2021.10.11.463967.

Machine Learning Protein Identification Software

Among the most unique aspects of our Nautilus platform is the integration of a proprietary machine learning-based protein identification analysis software engineered to work with the type of data our system generates.

As discussed, more typical measurements for high specificity affinity reagent probes can be used in our system to identify, and thereby quantify, each protein from a single binding and imaging step.

These high specificity affinity reagent probes 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 probes and therefore an exceedingly large number of cycles to measure every protein in the proteome.

To enable broad protein identification on our system, we instead use our multi-affinity reagent probes that can bind to hundreds or even thousands of individual proteins in a given cycle.

Protein identification and quantification can be extended to proteoform-resolution by incorporating high specificity affinity reagent probes against protein targets of interest.

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.

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.

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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 probe binding events to uniquely identify a protein.

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.

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

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

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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 platform data sets, it is able to adapt and update its confidence in each protein identification, essentially getting “smarter” over time.

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.

Our Technology Workflow

From the earliest stages of developing the Nautilus platform, we set out to integrate the four key innovations (listed in the above section) into a single, cohesive proteomics workflow, creating an end-to-end solution designed for ease-of-use, speed, scale and performance.

We believed that doing so could unlock the potential to democratize proteomics and make it possible for the broader scientific community to undertake a wider range of new, high-value scientific inquiries, thereby accelerating research and ultimately impacting healthcare and the development of precision medicine.

The Nautilus workflow is designed to consist of five major steps, beginning with sample preparation and concluding with the machine learning analytics that yields high-value proteomic data.

• Step 1 – Sample Preparation

The Nautilus sample preparation process attaches a label to extracted proteins and then attaches them to a proprietary scaffold to isolate them individually, thereby creating a library of single protein molecules.

This process was designed to be simple, robust, and rapid.

Internal tests demonstrate that substantially all of the proteins are attached to the scaffold during the library preparation process, which requires minimal hands-on time over a 2-day protocol.

• Step 2 – Sample Deposition onto the Flow Cell

The protein library is then deposited onto the three flow cells capable of holding up to 10 billion intact single protein molecules.

The landing pads on the flow cell are matched to the size of the protein-attached scaffold, thus allowing only one protein to be deposited per site.

This element of the process was specifically designed to enable massively parallel, rapid, single-molecule sampling of proteins, as shown in the flow cell occupancy figure below.

• Step 3 – Integrated Imaging and Fluidics System Processing Multiple Cycles of Affinity Reagent Probes

Following protein library deposition, the proteome analysis system then initiates the multi-cycle interrogation of each single-molecule bound to the surface of the flow cell.

This process entails introducing fluorescent dye labeled affinity reagent probes into the flow cell, rinsing out the unbound fraction, imaging the surface area, and then stripping and washing the affinity reagent probes away.

This entire process is then repeated sequentially to collect data on the desired number of cycles in the system run, where each cycle is a unique batch of affinity reagent probes intended to identify a set of targets.

• Step 4 – Processing of Digitalized Proteomic Data

After the proteins on the flow cell have been iteratively imaged over the determined number of cycles, the resulting raw images are converted into a coordinate map with corresponding illumination signals indicating positive affinity reagent probe binding events, effectively digitizing up to approximately 35 terabytes of raw image analyzed proteomic data.

• Step 5 – Machine Learning Analytics - Decoding, Protein Identification, and Quantity

In the final step of the workflow, the digital proteomic data is analyzed by our cloud-based machine learning protein identification analysis software.

The data is converted to protein identities during this analysis, evaluating the characteristics of each affinity reagent probe binding event at each location to determine protein identity and quantity.

Nautilus Platform Technology Performance

Simple and Robust Sample Handling

Nautilus’ straightforward sample protein library preparation is designed to convert protein samples into a format optimized for single-molecule deposition on our flow cell.

The process has been designed to be accessible to virtually any life sciences researcher.

In addition, the protocol is highly compatible with standard lab automation equipment and workflows, which is expected to further minimize the effort required while increasing laboratory processing throughput.

Also, unlike existing shotgun proteomics methods, no sample protein digestion is required in our method which in turn makes the workflow very simple.

The result is a process that is expected to effectively prepare a sample into a library ready to load on the flow cell with minimal hands-on time completed over a 2 day period.

A key feature of our Nautilus platform is the large scale (up to billions) of protein molecules that we believe can be measured massively in parallel on our single-molecule flow cells.

An analysis of nearly 1,000 flow cells showed typical sample loading of nanoparticle scaffold libraries yielded near complete flow cell occupancy, which demonstrates the speed and efficiency of our sample handling process.

Nautilus Platform Stability in Multi-Cycle Experiments

We believe we have designed a technology with direct applicability in research use settings as well as having the potential to translate discoveries into healthcare practice.

A critical aspect of any molecular detection technology with translational and clinical potential is robustness and reproducibility.

To understand how stable our measurement process was, we tested the durability of our flow cell with a loaded protein library to ensure that proteins remained present on the surface over multiple cycles in a proteome analysis system run.

In our studies evaluating stability over numerous cycles, we observed substantially less than 1% of proteins were lost from the flow cell.

To examine both the effectiveness of our wash buffer and the ability of proteins to be probed after being washed, we first examined the detection ability of the protein on a first cycle.

We next demonstrated that our wash buffer successfully eliminated remaining signal.

Last, we demonstrated that after extended exposure to washing, and rinsing, that the protein detection remained nearly identical to the initial measurement.

These results suggest that our wash conditions are highly effective and that our

process of reagent cycling does not significantly damage the protein and thereby interfere with the probability of its measurement accuracy.

Protein Library Remains Bound to Flow Cell During Repetitive Affinity Reagent Probe Binding and Wash Cycles

Nautilus Platform Sensitivity

Our Nautilus platform is designed both to be extremely sensitive (by virtue of being a single protein molecule platform) and to have an extremely wide dynamic range of detection (by virtue of measuring a very large number of molecules).

In single protein molecule assays, dynamic range is defined by the total number of molecules measured.

Consequently, a platform measuring a million molecules will have a smaller dynamic range than a platform measuring 10-million molecules.

On our Nautilus platform, we project we will be able to reach sensitivity down to 1 molecule out of 10 billion.

We are also able to use this sensitivity in flexible way, for example we can perform an extremely deep analysis of a single protein library sample across all lanes of a flow cell, or we can perform a multiplexed analysis by processing a batch of samples together (each sample protein library individually barcoded) during one proteome analysis system run.

Development and Characterization of Multi-Affinity Reagent Probes

Multi-affinity reagent probe discovery and development pipelines have been built that generate multi-affinity reagent probe candidates that target short peptides, typically three amino acids in length.

These pipelines employ multiple candidate discovery methods to identify and select antibody, antibody fragment, or nucleic acid based candidate multi-affinity reagent probes.

Promising candidates are further screened in assays to determine EC50 values off-platform (example results for two candidate multi-affinity reagent probes shown below), and then leads are evaluated in detail for their performance on the Nautilus proteome analysis platform.

Multi-Affinity Reagent Probe Discovery and Development Pipeline

Mapping Proteoforms

We believe there are likely millions of different proteoforms that define cellular activity, cellular localization and biochemical function.

With peptide-centric approaches (detecting only small pieces of proteins), such as “shotgun” mass spectrometry, it is simply impossible to differentiate proteoforms.

Using phosphorylation as an example for a post-translational modification of a protein, consider the case of two samples as shown in the figure below.

On the left, one protein sample contains a single protein molecule with a triple phosphorylation (red) and two unmodified proteins versus a second sample on the right, in which each protein molecule contains one phosphorylation each at a single different site.

These two samples would likely appear identical to one another in a shotgun mass-spectrometry analysis.

The Nautilus Platform Detection of Proteoform Patterns

On our Nautilus platform, we are able to use existing commercially available affinity reagents to perform detailed mapping of proteoform patterns at the single protein molecule level.

We do this by measuring individual proteins at each specific post-translational modification site over multiple cycles, each cycle targeting a different specific site or feature of the protein.

Illustrating this concept in the diagram below, during the first cycle we use an anti Tau affinity reagent probe to identify all of the Tau proteins present on the flow cell.

Then over the next 4 cycles we detect each Tau molecule again, only now with a slightly different affinity reagent probe that targets a different isoform or phosphorylation modification on the Tau protein.

In this simple workflow using only 4 position-specific Tau affinity reagent probes, our technology is able to distinguish up to 16 different proteoforms (4 position-specific targets = 2 4 possible forms of Tau based on variation in protein length or site phosphorylation status).

Workflow for the Detection of Tau Proteoform Patterns

The protein counts in the image above are for illustration purposes only.

Nautilus Platform Development Plan Key Areas of Focus

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 Voyager TM 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 our proteome analysis system 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 comprising our Nautilus platform.

Our development plan will build upon the foundational achievements our prototype technology has made in several key areas, with the goal of ultimately allowing us to fully realize the potential of our technology.

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 our proteome analysis system, 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 our proteome analysis system for both broad scale 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 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 proteome analysis system performance.

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

reagents for compatibility with our technology.

APPLICATIONS OF OUR TECHNOLOGY

The Nautilus platform technology is an open platform that is designed to leverage a wide variety of reagents to read and quantify the proteome and proteoforms

We believe that our Nautilus platform technology is designed to represent one of the first truly novel technologies for the detection and quantitation of proteins and proteoforms by leveraging the creation of our single protein molecule flow cell in combination with a broad range of affinity reagent probes.

By design, our Nautilus platform technology 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 our Nautilus 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 reagent probes that will potentially allow us to detect substantially all of the proteome.

On the other end of the spectrum (above right), we believe we can apply high specificity affinity reagent probes that detect and quantify individual target proteins of interest, and the post-translational modifications of these target proteins to detect and quantify the various proteoforms that may exist.

We believe it is

this inherent flexibility of reagent applications on our Nautilus platform that will enable a broad suite of uses across research, discovery, translational and clinical applications.

Because of this inherent flexibility, we also believe our Nautilus platform will spark the creation of new and unforeseen applications, 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 platform creates the opportunity to partner with third-parties on the development and supply of affinity reagent probes for use on our instrument.

Basic Research and Discovery Applications

The Discovery Potential of Our Nautilus Platform

The Nautilus Voyager TM 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 Voyager TM 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 Voyager TM 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.

Our Nautilus 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.

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 our Nautilus platform for these applications broadly.

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 our Nautilus platform technology could experience a similar trajectory of utilization for research and discovery applications, making very large sample size studies that were not feasible using prior proteomic detection methods now practical for our customers to implement.

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.

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 technologies and tools in existence today 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 probe broad protein detection method to enhance the output of our analyses.

Multi-Omic Systems Biology and Proteogenomics

We believe the creation of matched DNA, RNA and protein data sets for integrated multi-omic (DNA, RNA and protein) analyses will enable a more complete understanding of the path of information transfer from gene, to transcript, to protein.

It is estimated that at most only 40% of protein expression can be predicted by gene expression data.

Integrated multi-omic data sets are expected to have far greater potential for better understanding this discordance, its biological origin, and ultimately its impact on cell function with deeper and more complete proteomic data.

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 our Nautilus platform technology.

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.

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 Voyager TM 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.

Our Nautilus 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 our Nautilus platform technology into these studies to leverage matched genomic and proteomic data.

Translational Research and Discovery Applications

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.

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 our Nautilus platform technology 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 our Nautilus 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.

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 our Nautilus platform.

Which drugs work on specific protein drug targets is not just a result of the total number of post-translational modifications, but instead by how combinations of specific post-translational modification are operating together.

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 this will become an essential application of our technology used to investigate important drug targets and molecular disease pathways.

We believe this application has the potential to advance precision medicine by making an entire layer of molecular complexity and information available to researchers for the first time.

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 wellness.

Individual or small panel protein surveillance tools have existed in the healthcare market for decades using traditional assay methods across a range of biospecimen, 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 molecular surveillance tools in oncology 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.

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 changes will be a key area of interest in the future.

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 Applications

Diagnostics, Clinical Research and Drug Development Use Cases

Transitioning from Discovery into Clinical Application

We believe one of the largest and most impactful applications 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.

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.

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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 our Nautilus platform to continue to advance these applications and methods of proteoform pattern biomarker detection from discovery all the way through to future diagnostic 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 our Nautilus platform could have a profound impact on precision medicine.

We believe this presents an opportunity to use the Nautilus Voyager TM 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 broad scale proteomic data across the continuum of preclinical and clinical drug development.

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 our Nautilus platform.

We first expect adoption of our Nautilus platform could occur in the preclinical and clinical retrospective settings, where we believe single-molecule proteomic and proteoform composition and frequency will become essential tools in building a more complete picture of how experimental medicines are interacting in complex molecular pathways.

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.

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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 our Nautilus platform desirable in a research setting can be fully realized.

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 our Nautilus platform design is ideally suited for the quality, stability, and speed required to fully realize the value of accessing deep proteomic profiling data to identify biomarkers that stratify patients for clinical trials and improve drug development.

Our primary business model is anticipated to be focused on the commercialization of our Nautilus platform through the sale of instrumentation, reagent consumables, and software.

Our proteome analysis system is our detection instrument at the center of our product suite, supported by reagent 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.

Proteome Analysis System

Our proteome analysis system is a high-resolution optical imaging system coupled with integrated fluidics and liquid handling sub-systems.

The system is designed to deposit protein libraries onto a flow cell and to process labeled multi-affinity reagent probe 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 system, the remainder of the workflow is automated.

System run reagent kits are comprised of four main components:

sample preparation, flow cell(s), multi-affinity reagent probes, and instrument buffers used to perform multi-cycle analysis runs.

Our proprietary sample 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.

We believe the Nautilus Voyager platform design is ideally suited for the quality, stability, and speed required to fully

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

Our primary business model is anticipated to be focused on the commercialization of the Nautilus Voyager TM 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 Voyager TM Platform

Nautilus Voyager TM 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.

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.

Given the breadth and depth of data output capability planned for our proteome analysis system, it is not expected that additional protein sample enrichment, enhancement or pre-treatments of samples will be required for processing, however we do intend to be compatible with such pre-treated samples.

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.

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 in to each lane for multi-cycle analysis.

Our proteome analysis system is designed to hold and concurrently analyze up to three flow cells in a single system run, for a total of 12

Additional sample throughput may also be achieved by the use of a molecular barcode in our reagent kits that will enable the multiplexing of more than one barcoded sample library together within a single lane for analysis in the future.

Affinity reagent probes will also be included as a reagent kit.

The Nautilus Voyager TM 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 reagent probes for the broad-scale 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.

Additionally, custom affinity reagent probe 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.

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

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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 probe binding profiles are refined and trained across a growing database.

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.

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Commercial Strategy

The primary business model we intend to implement is to directly commercialize our entire end-to-end Nautilus platform technology solution through the sale and installation of our proteome analysis system at customer sites;

the ongoing sale of consumables covering a broad suite of applications run on our system;

a SaaS analytics and insights software subscription to capture long term value created by our machine learning-based analysis enhancements;

and a service warranty plan to maintain our install base and support our customers in the field.

We believe a comprehensive solution could offer a compelling value proposition across multiple market segments due to the substantial enhancements it will create in speed and scale of data creation, single protein molecule quantitation, sensitivity, and reproducibility.

We initially intend to target customers with a history of strong focus in proteomic research, and a substantial annual research budget allocation for proteomics technologies and proteomic data.

We expect many of our customers will already have access to existing proteomic or genomic analysis capabilities including a segment of the greater than 16,000 system install base of mass spectrometry detection systems.

Our early customers are expected to span laboratories focused on basic and translational research in large pharma and biotech research groups, academia, and large-scale commercial and academic multi-omics research laboratories.

As our Nautilus platform becomes established in these customer segments, we further intend to expand our commercialization into clinical settings, where our target customers are expected to include pharma and biotech clinical development groups, contract research organizations, and ultimately, diagnostic laboratories.

Our proteome analysis system is expected to be priced in-line with mass spectrometry peptide detection equipment, or high-throughput NGS equipment, making the capital expense for our system within the budget for our initial customers.

Our consumables are expected be priced at a level that provides comparable market value for full proteome analysis.

The use of multiplexed run configurations will continue to grow over time, which we believe will help to reduce our costs and the price-per-sample of our reagent kits such that we are able to support customers with very high-throughput applications of our systems.

We expect these high-throughput run configurations and economics to accelerate the initiation of large-scale proteomics and multi-omics research projects, and also to be much more compatible with centralized core lab facility operations with requirements for proteomic data generation that can support an entire organization or user base.

Because we believe our unique approach to protein and proteoform detection is a significant deviation from any prior method, we believe it is critical to provide the market with peer reviewed publications describing our technology and its performance capabilities, and to demonstrate its ability to deliver new biological insight.

Our publication strategy is a key component of our overall go-to-market plan, and we expect to spend considerable time and resources building these fundamental proof-sources to accelerate adoption of our proteome analysis system.

We further believe that once our proteome analysis system is launched, key performance indicators of our success would include publications and references to our platform technology.

We intend to track this closely, and we expect to invest both internally and externally to accelerate the pace of new research and publications leveraging our Nautilus platform pre- and post- proteome analysis system launch.

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.

Go-To-Market Strategy

We expect our proteome analysis system technology will be highly disruptive to the current proteomics technology and market landscape, and as a result, we have designed our go-to-market plan with a strategy that combines elements of highly successful mass

spectrometry and NGS platform technology introductions and commercialization.

We also believe that engaging with the market early is a critically important activity in building confidence and awareness of our technology and its capabilities.

Our planned go-to-market strategy is organized into 3 phases:

1) Collaborations & Partnerships

2) Early Access Program

3) Proteome Analysis System Launch & Commercial Scale Up

We have mapped the phases of our go-to-market strategy against specific technology development milestones which we believe will allow us to build the value proposition of our technology early, and to grow it in conjunction with our Nautilus platform enhancements over time.

Our strategy to utilize our Nautilus platform early in its formal development cycle through partnerships is an important component, and in part can be attributed to the inherent flexibility we have to employ commercially available reagents for targeted applications of single-molecule proteomics that drive new and significant discovery value.

Further, as we advance from low-cycle targeted applications towards longer runs with increasing data output, we believe each of the milestones on our development plan are potentially new and unprecedented advancements we can leverage to build commercial momentum.

Collaborations & Partnerships

We believe that directly engaging our future customers early, well before system launch, will have the potential to be a very important differentiator to raise awareness of our platform technology as it matures throughout the formal development process, and to build credibility as we educate the community on our scientific approach.

We believe the most effective way to engage our future customers now is through research collaborations, with the primary purpose of driving new and meaningful biological insights while demonstrating our technology’s performance, unique characteristics, and capabilities.

We continue to maintain a formal program for identifying collaborative research partners and establishing new relationships in specific research areas where we wish to generate data and publications highlighting the value of single-molecule proteomics.

We also believe we can use these collaborations to improve the performance characteristics of our technology during development, and we can shape the system and run parameters to more precisely meet our customer’s needs.

We further intend to target projects within these engagements that will help to define and validate our first launched product applications, which we expect will further aid in the rapid adoption of such applications once directly commercialized as products.

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 Voyager TM platform as it moves toward broader commercialization.

Early Access Program

Following the important Collaboration and Partnership work necessary to lay a foundation of publications describing our technology and the initial product applications, we believe we will have a body of scientific evidence sufficient to start building demand for our technology and the single-molecule proteomic data it generates.

We then intend to initiate our pre-sales activities, which include the launch of an Early Access Program comprised of a service offering that will generate data on customer biological samples using our prototype systems run by Nautilus staff in our facilities.

Using this Early Access Program, we intend to begin building a pipeline of customer engagements, supporting their evaluations of our technology through proof of concept and pilot studies, and giving them access to our data to begin establishing interest in our proteome analysis system leading up to launch.

We further intend to build on the momentum of our Early Access Program by expanding it to include a small group of target customers to evaluate of our first generation proteome analysis system on site at their facilities.

Our goal in the planned proteome analysis system Early Access Program is to establish this influential group of customers as reference sites ahead of our broader commercial launch, and to integrate the learnings from our system performance outside of our own laboratories to improve the performance and robustness of our system and process design.

Proteome Analysis System Launch and Commercial Scale Up

At full commercial proteome analysis system launch, we expect to continue offering our Proteomic Data Early Access Program, and to maintain the laboratory services to continue supporting proof of concept and pilot projects for an extended period of time to continue building our sales funnel.

Our proteome analysis system launch is expected to be coupled with a substantial scale up of our commercial sales and marketing workforce.

We intend to employ a “land and expand” sales model to promote high value cutting edge technology adoption, where we will first establish a presence in key accounts across our customer demographics, then work to broaden and expand our value and contributions across those key account organizations while concurrently growing our customer base through an increasing salesforce.

We expect to commercialize directly in the United States, and in the future to expand commercial operations to the Asia Pacific and European regions.

Following our initial proteome analysis system commercial launch, we expect future system upgrades and enhancements periodically over time that will further drive discovery potential and our business with each incremental advancement.

Our planned commercialization strategy and technology are designed to offer a highly differentiated and defensible position in the market we intend to capitalize on.

We believe we will have significant competitive advantages if we are able to execute on the following opportunities:

• Being first to market with a novel protein and proteoform detection platform;

• Demonstrating the ability to unlock new sources of primary biological information with proteoform mapping and rare protein detection;

• Providing immense data production capacity, driving discovery by enabling large scale studies and building our database to become a strategic asset;

• Implementing a proven commercial model with an efficient direct salesforce;

• Expanding our impact in translational research for clinical applications, precision medicine and diagnostics.

In December of 2020, we signed a research collaboration agreement with Genentech to engage in a pilot study using our technology to investigate proteoforms of the Tau protein, an important biomarker of neurodegenerative disease.

In October 2021, we entered into a research collaboration agreement with Amgen in which the Nautilus platform may be used across a number of projects to investigate proteins and proteoforms of interest to the both organizations.

In October 2021, we signed a research agreement with The University of Texas MD Anderson Cancer Center.

And, in February of 2025, we entered into a research collaboration with The Buck Institute for Research on Aging where the Nautilus platform may be used across a number of projects focused both on proteoform analysis of the Tau protein, as well as new projects and analysis methods exploring other platform applications.

All of the above research collaborations are consistent with our objectives in Phase I of our commercial go-to-market strategy to establish external collaborations and relationships that produce data and publications exploring the utility and strengths of our Nautilus platform technology.

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

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 Voyager TM 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.

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.

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 Voyager TM platform.

Commercial Organization

We plan to build out a world-class commercial organization, focused on delivering value and support through every stage of the sales cycle.

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.

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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 qualified second sources for several of our critical reagents.

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.

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Instrumentation

Our proteome analysis system instrumentation automates the Nautilus assay chemistry concurrent with rapid optical imaging of the flow cell.

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.

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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

Nautilus currently competes with technology and diagnostic companies that supply components, products, and services to customers engaged in proteomics analysis.

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Becton, Dickinson and Company;

Standard Biotools (formerly known as Somalogic ) .

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.

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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 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.

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.

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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 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.

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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 and may involve considerable delay.

Obtaining the requisite regulatory approvals, including the FDA quality system inspections that are required for PMA approval, can be expensive

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.

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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.

However, on October 3, 2014, the FDA issued two draft guidance documents that set forth the FDA’s proposed risk-based framework for regulating LDTs, which are designed, manufactured, and used within a single laboratory.

The FDA 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 in recent years, 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.

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 phases out its enforcement discretion for most laboratory-developed tests (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.

This final rule is being challenged in federal courts.

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, including this LDT final rule.

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 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.

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.

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.

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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 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.

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.

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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.

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”).

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Intellectual Property

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

As of December 31, 2024, we owned or held exclusive licenses to thirty one issued U.S.

patents, approximately sixty pending U.S.

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 twenty five granted foreign patents, and approximately one hundred thirty six pending foreign patent applications, including twenty four international patent applications filed under the Patent Cooperation Treaty (PCT application).

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.

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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.

As of December 31, 2024, we owned approximately thirty four registered trademarks covering four different marks in Australia, Brazil, Canada, China, the European Union, India, Israel, Japan, Mexico, Singapore, Switzerland.

In addition, we have approximately twenty pending trademark applications covering seven different marks in the U.S., Brazil, Canada, China, India, Japan, Korea, and Mexico.

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 Amgen in October 2021, with The University of Texas MD Anderson Cancer Center in October 2021, and with The Buck Institute for Research on Aging in February 2025.

Under each of these agreements, respective research collaboration teams are using prototype versions of the Nautilus platform in pilot projects to learn about it’s capabilities and accelerate the development process to meet the needs of our future

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 Voyager TM 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

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Emma Lundberg, Ph.D.

Lundberg is a Professor in cell biology proteomics at KTH Royal Institute of Technology, Sweden, and Director of the Cell Atlas of the Human Protein Atlas, an international proteomics and cell mapping project.

Lundberg also holds the positions of Director of the Cell Profiling facility at the Science for Life Laboratory (SciLifeLab) in Sweden.

Lundberg is a Professor in cell biology proteomics at KTH Royal Institute of Technology, Sweden, and Professor of Bioengineering and Pathology at Stanford University.

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

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business