Caris Life Sciences, Inc. (CAI) Business

Item 1. Business

Overview

We are a leading, patient-centric, next-generation AI TechBio company and precision medicine pioneer. We develop and commercialize innovative solutions to transform healthcare through the use of comprehensive molecular information and artificial intelligence/machine learning algorithms at scale. Our entire portfolio of precision medicine solutions is designed to benefit patients, with an initial focus on oncology, and serves the clinical, academic, and biopharma markets.

We founded Caris in 2008 with the belief and vision that combining a vast set of consistently generated molecular information with robust data-driven insights could realize the potential of precision medicine for patients. We have spent the last 17 years developing and building our portfolio of comprehensive, proprietary molecular profiling solutions and generating what we believe to be one of the largest and most comprehensive multi-modal clinico-genomic datasets in oncology. As of December 31, 2025, we have performed sequencing on over 1,000,000 cases. Our platform is purpose-built to leverage the convergence of next-generation sequencing (“NGS”), artificial intelligence (“AI”) and machine learning (“ML”) technologies, and high-performance computing. The power of our differentiated Caris platform has enabled us to develop the latest generation of advanced precision medicine diagnostic solutions designed to address the entire cancer care continuum, including early detection, minimal residual disease (“MRD”) tracking, therapy selection, and treatment monitoring, as well as to create molecular signatures and discover and develop novel precision medicine therapeutics. Our Molecular Intelligence product portfolio is currently focused on oncology and consists of: (1) our MI Profile Platform, our whole exome sequencing (“WES”)/whole transcriptome sequencing (“WTS”) tissue-based molecular profiling solutions, (2) our Caris Assure Platform, our WES/WTS blood-based molecular profiling solutions, and (3) our Precision Whole Genome Platform, our whole genome sequencing (“WGS”) blood- and tissue-based profiling solutions.

We believe we are well-positioned to realize the full potential of our vision and enable a transition from intuitive to empirical medicine due to the recent convergence of several advancements in biology, medicine, and technology: the medical community’s understanding and appreciation of the molecular nature of cancer has accelerated in recent years, resulting in a continued increase in molecular profiling of different cancer types and stages; NGS costs have declined, making NGS more accessible to the healthcare ecosystem; cloud-computing architecture has enabled massive scalability, distributed real-time collaboration, and greater cost efficiency for the analysis of previously unmanageable amounts of data; and AI and ML computational capabilities have advanced to allow more effective interrogation of large biological datasets. We believe that our early foresight to generate comprehensive data at scale over the past many years and build a robust, foundational infrastructure have uniquely positioned Caris to leverage the benefits of these biological and technological advances to deliver transformative and advanced innovations in precision medicine and patient care into the future.

Our purpose-built, proprietary multi-omic profiling solutions capture and analyze molecular information from tissue and blood in a comprehensive manner. We provide WES (all 23,000 encoding DNA genes) and WTS (all 61,000 RNA transcripts that encode proteins) or WGS (sequencing across the entire DNA) on every eligible patient sample (a sample provided by ordering physicians that contains sufficient genetic material for profiling). Our in-depth profiling of patient samples has led to our creation of what we believe to be one of the largest and most comprehensive multi-modal clinico-genomic datasets in oncology, including genomic data, clinical data, digitized slide images, and remnant tissue. Leveraging high-powered computing and AI/ML algorithms, we, and our biopharma and research partners who use our data and bioinformatics services, analyze our datasets to determine the key molecular characteristics of a particular disease or dysfunction that drives disease, enabling signature identification and drug target discovery. As a leader in the transition to WES/WTS sequencing through our launch of a WTS solution in 2019, a WES solution the following year, and our anticipated launch of WGS solutions in 2026, we believe we have more molecular data and information than any other company and are well-positioned to make precision medicine widely accessible.

Our molecular profiling solutions and the data generated by our multi-omic technology platform provide value to our biopharma partners, such as Moderna, AbbVie, Xencor, Merck KGaA and Genentech, through partnerships that aim to increase the probability of technical and regulatory success of their therapeutic pipelines. In addition to biopharma, we leverage our datasets to partner with outside academic centers and researchers to further advance precision oncology research. The Caris Precision Oncology Alliance (“Caris POA”), which we established in 2015, is a growing network of leading cancer centers and research consortia across the globe that collaborate to advance precision oncology and biomarker-driven research, with its members working together to establish and optimize standards of care for molecular

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testing through innovative research to improve clinical outcomes for cancer patients. Close connectivity with this valuable network of key opinion leaders (“KOLs”) in oncology clinical care, research, and drug development has enabled us to remain at the forefront of precision oncology and closely attuned to the key needs of the most sophisticated researchers.

Our Molecular Intelligence Platform was purpose-built to leverage the convergence of NGS, AI and ML technologies, and high-performance computing.

The Caris Platform

We are leading a molecular revolution and developing the latest generation of advanced precision medicine information solutions that we believe have applicability across the care continuum for a broad range of conditions. The fundamental differentiation of our business model is the depth, breadth, and scale of data, including how that data is integrated vertically and horizontally across our business, as well as the resulting innovation that it fuels.

Our multi-omic technology platform is built on the following pillars: (1) our Molecular Intelligence solutions; (2) Caris Discovery; (3) Caris Strategic Data; and (4) Caris Infrastructure. These four pillars are designed to work together to create a virtuous cycle that can enable continued innovation and improved impact for patients and physicians. We believe our comprehensive approach to profiling will continue to drive demand for our genomic profiling capabilities, leading to further expansion of our clinico-genomic datasets, which provide additional valuable inputs to develop and enhance our solutions, with the ultimate goal of contributing to improved patient results. We believe this continuing cycle will deepen our competitive advantage and allow us to achieve meaningful innovation and business success in precision oncology, while illuminating a path to precision medicine for other chronic disease states, including cardiology, neurology, and metabolic conditions.

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We believe our growth and competitive differentiation are driven by the four pillars of our platform, each of which are both a product of the upstream data and a foundation to further innovation and data generation across the platform:

•Caris Molecular Intelligence: Our MI Profile, Caris Assure and Precision Whole Genome platforms collectively include both marketed and in development comprehensive WES, WTS and WGS solutions. These solutions span the entire continuum of cancer care, including early detection, MRD tracking, therapy selection, and treatment monitoring.

•Caris Discovery: The combination of our data and our AI enables us to discover previously unknown drug targets for antibody-directed therapies (such as antibody drug conjugates, degrader-antibody conjugates, and T-cell engagers), small molecules, targeted protein degradation, synthetic lethal interactions, and cell therapy. In addition, we believe Caris Discovery is well-positioned for neoantigen discovery for personalized therapy development given our ability to detect variants, insertions, and deletions by WES and to assess gene expression and detect fusions by WTS on every patient’s tumor.

•Caris Strategic Data: To assist us with analyzing the data we generate, we utilize AI/ML tools across our clinical testing, R&D, and biopharma business. We have used our datasets to create many of these algorithms and signatures. The breadth and depth of our data assets, together with our demonstrated ability to use them to create algorithms and discover signatures, represent a deep competitive moat for us.

•Caris Infrastructure: We have a well-developed laboratory, R&D, and sales infrastructure that we believe is foundational to our business.

The Caris Advantage

We believe our approach is differentiated and we have a competitive advantage because:

•We purpose-built our Molecular Intelligence platform to put the patient first and make comprehensive precision medicine a reality. Our patient-centric ethos has guided us since inception. This guiding principle underpins our belief and vision that combining a vast set of consistently generated molecular information with robust data-driven insights would realize the potential of precision medicine, driving superior patient outcomes. Our approach, which includes deep WES, WTS and WGS, maximizes the molecular information generated for each clinical case and enables us to analyze and provide patients and physicians with industry-leading breadth, depth, and accuracy of multi-omic information. By providing a high-quality, individualized molecular blueprint of a patient’s disease, our platform is designed to enable the discovery, development, and application of cutting-edge precision medicine that pushes the boundaries of current science. This differentiated approach has made Caris a destination for KOLs and clinicians seeking the most complete and accurate information available for treating their patients.

•We are a leading provider of tissue-based molecular profiling, including through our FDA-approved companion diagnostic tissue-based profiling solution, MI Cancer Seek. MI Cancer Seek, part of our MI Profile platform, together with associated professional services, consists of a WES and WTS NGS, immunohistochemical (“IHC”) analysis, and AI/ML analysis to identify the origin of a tumor for 90 unique cancer types with approximately 95% accuracy. This comprehensive solution assists clinicians in identifying patients who may benefit from treatment with specific targeted therapies.

•Our novel blood-based profiling solution, Caris Assure, is experiencing rapid adoption in the market. We believe our leadership in tissue molecular profiling uniquely positions us to capitalize on the increased use of blood-based profiling and adoption into clinical practice with Caris Assure, our novel blood-based solution, which includes clonal hematopoiesis (CH) subtraction through plasma sequencing. We built upon the data we have generated to date with MI Profile and believe our data is a significant competitive advantage in the development and clinical utility of Caris Assure.

•Our novel blood-based detection solution, Caris Detect, is expected to launch in 2026. Our Caris Detect early detection assay is a WGS assay that is intended to overcome some of the current limitations faced by other similar assays. Caris Detect is designed to deliver higher sensitivity while maintaining a low false positive rate due to novel library preparation chemistry, deep sequencing, and a proprietary AI/ML algorithm for cancer detection.

•We have built what we believe to be one of the largest and most comprehensive multi-modal clinico-genomic datasets in oncology. Our proprietary oncology clinico-genomics datasets provide insights into the fundamental building blocks of disease, potentially enabling breakthroughs from targeted therapies to truly personalized medicine. Our ever-expanding datasets include data generated from sequencing over 1,000,000 cases as of December 31, 2025, as well as matched clinical outcomes for many of these patients. We also expand and enrich our datasets through partnerships that add real-world evidence, longitudinal patient data, and clinical outcomes. The breadth and depth of our large and growing data assets represents a deep competitive moat for

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us, overcoming which requires significant capital investment, scaled sequencing capacity, acquisition of patient samples, and generation of corresponding clinical outcomes data. These significant data assets enable us to effectively deploy our proprietary AI/ML algorithms to analyze patient information and empower our customers to make better informed diagnoses and treatment decisions.

•Our first mover advantage, specialized commercial channel, robust infrastructure, and deep research collaborations enable our leadership and provide us with the ability to scale for future growth. We believe we will be the first provider to achieve leadership in both solid tumor and liquid biopsy profiling solutions across the entire precision oncology care continuum. To support our sales activity and expansion, we have built a commercial organization specialized in precision oncology, serving over 6,000 ordering physicians in the United States across all major health systems, academic cancer institutions, and community settings.

•We are led by a founder with significant experience building and scaling businesses in the healthcare industry and a management team with scientific expertise. Our management team has deep domain expertise in molecular biology, oncology, artificial intelligence, data science, medicine, and genomics and have a track record of delivering innovative, high clinical utility solutions to the market. Our management team is highly entrepreneurial and has significant experience leading and operating large multi-national organizations and building innovative healthcare companies. In particular, our Founder, Chairman, and Chief Executive Officer, David Dean Halbert, has successfully built and scaled profitable enterprises for approximately 40 years, including AdvancePCS Inc. (acquired by CareMark in 2004 for $7.5 billion) and Caris Diagnostics (acquired by Miraca Life Sciences in 2011 for $725 million), among others.

Our Strategies

As we execute on our vision, we will continue to put the patient first. Our solutions provide physicians and individual patients with actionable information throughout the disease journey, while contemporaneously generating data that can be aggregated and leveraged to unlock academic and biopharma scientific breakthroughs, which may lead to curative therapies for future generations. To achieve our goal of leading a molecular revolution and developing the next generation of precision medicine information solutions for a broad range of conditions across the care continuum, we plan to:

•Drive the continued adoption and use of our tissue-based profiling and expand our blood-based profiling offerings into early detection, MRD, and monitoring.

•Utilize the data generated by our existing solutions to develop new solutions with additional revenue.

•Leverage our platform to provide solutions to biopharma companies to drive advances in personalized medicine and accelerate the development of novel therapeutics.

•Continue to expand and enrich our clinico-genomic datasets to drive breakthrough science and develop new solutions.

•Maximize market reach through our regulatory approval and reimbursement strategy.

•Capitalize on the ultimate potential of Caris Detect, our WGS, blood-based solution in development, and broader innovation platform in other chronic disease states beyond oncology, including in cardiology, neurology, and metabolic conditions.

Our Caris Molecular Intelligence Solutions

Caris Assure—Our WES/WTS Blood-Based Solution

Caris Assure is currently being offered for therapy selection as a laboratory developed test (“LDT”), and we have Medicare reimbursement and various levels of commercial payer adoption and/or reimbursement coverage for Caris Assure for therapy selection across the United States (other than New York State). Caris Assure for therapy selection is available in all U.S. states (other than New York, where we intend to apply for approval from New York State’s Clinical Laboratory Evaluation Program (“NY CLEP”)) and in Puerto Rico. We also offer Caris Assure for therapy selection internationally through distributors and direct contracts with hospital systems, where permitted by applicable regulations. Customers for Caris Assure include treating physicians as well as researchers and biopharma companies. Molecular features we identify using Caris Assure’s WES and WTS data include single nucleotide variants (“SNVs”), insertions/deletions (“INDELs”), structural variants, gene expression, copy number alterations (“CNAs”), tumor mutational burden (“TMB”), and microsatellite instability (“MSI”).

In addition to sequencing cell-free DNA and cell-free RNA isolated from the plasma to identify somatic tumor variants, Caris Assure for therapy selection sequences genomic nucleic acid (gDNA and gRNA) isolated from the white blood cells, or buffy coat, from each sample. Plasma contains a mixture of cell-free variants derived from tumor, blood

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and other cells. These variants cannot be separated based on plasma sequencing alone. Sequencing the buffy coat separately from the plasma allows Caris Assure to identify incidental germline (inherited) mutations as well as CH mutations. CH mutations are somatic mutations that accumulate in the blood with age, occur in a substantial portion of the population, and are not cancer-derived. Caris Assure “subtracts” CH mutations in the reporting of somatic tumor variants. If CH mutations are not distinguished from tumor-derived mutations, it can confound liquid biopsy results and lead to selection of a therapy targeted at a mutation that is present in the white blood cells instead of in the tumor, which is not beneficial for the patient with cancer.

Caris Assure for therapy selection generates a personalized report that provides oncologists with the information to tailor each patient’s treatment plan. This report is built to maximize clinical utility in an easy-to-interpret format. Our technology enables us to report our results for blood-based profiling even quicker than tissue-based profiling, as Caris Assure results are typically reported in approximately seven calendar days from “activation,” the time at which we receive the patient’s samples and required paperwork.

Drawing blood is a routine medical procedure that is much less invasive than a tissue biopsy. Processing of a blood specimen, from collection to isolation, analysis, and reporting, enables faster time to results and potentially earlier start of treatment. Clinical guidelines for molecular profiling in cancer have focused on tissue as the gold standard, but with recent advances in blood-based profiling demonstrating its clinical utility, we believe that evidence and clinical guidelines support complementary usage of both tissue- and blood-based profiling across many major cancer types. We believe that one example of the benefits of blood-based profiling is that cancers frequently become resistant to new targeted therapies by developing genetic mutations that can make drugs less effective and lead to cancer recurrence. When resistance develops, clinicians need an updated molecular profile of the cancer to guide subsequent treatment strategies. At this stage in cancer progression, it is often not feasible to acquire additional tumor tissue to build the updated profile, or the amount or quality of accessible tissue is low. Small quantities or low quality of tissue from an inaccessible biopsy site can lead to a Quantity Not Sufficient (“QNS”) result when NGS fails for lack of input material. Without another way to generate an updated molecular profile of the patient’s tumor, the tools of precision oncology cannot be deployed. Conducting additional tissue biopsies also carries its own health risks, such as tumor seeding, which can occur when cancer cells are unintentionally deposited elsewhere in the body during the biopsy process, and infection. Liquid biopsy is a potential solution to the challenges and risks of tissue biopsies.

Nonetheless, we believe that tissue-based profiling generally remains the gold standard for cancer therapy selection primarily because it is the most mature technology and is broadly supported by analytical validation studies. Microscopic examination of the tumor tissue is necessary for characterization of tumor type and stage and to confirm the presence of key proteins via IHCs. In blood, the variant allele frequencies of tumor biomarkers can be so low that negative results must be confirmed by tissue analysis. However, the tide is turning in clinical guidelines toward acceptance that tissue and liquid biopsy, used in combination, can improve clinical outcomes for patients. For example, the 2024 version of one of the prominent clinical guidelines for non-small cell lung cancer states that: (1) concurrent testing can improve time to test results and should be considered in the appropriate clinical situation, and (2) negative results (meaning absence of definitive driver mutation) by one method suggests the use of a complementary method.

We believe Caris Assure represents the most comprehensive blood-based therapy selection solution on the market, featuring over 23,000 gene coverage, as compared to other blood-based offerings in the market that only assess 500 to 1,000 genes from DNA. Caris Assure performs WES and WTS for every eligible patient blood sample. Additionally, Caris Assure generates sequencing results from both the plasma and the white blood cells, or buffy coat, from each sample. This gives Caris Assure a differentiated ability to distinguish tumor variants, which are relevant for therapy selection, from both incidental germline variants and common age-related mutations that are not related to the tumor and which can confound analysis and therapy selection if not properly distinguished.

Caris Assure for Biopharma

The same benefits that blood-based WES, WTS, and CH subtraction bring to patients in the clinical setting also offer significant and previously unavailable advantages to biopharma companies across the drug development continuum. Caris Assure allows biopharma companies to conduct exploration into biology and address elusive questions around response and resistance with repeat and/or longitudinal biopsies, without the restriction of earlier generation liquid biopsies. This enables biopharma companies to understand the molecular alterations responsible for resistance. In a drug development setting, we believe the only way to get this understanding is through the WES/WTS sequencing technology underlying Caris Assure. Caris Assure can be used in early stage trials to identify and enroll eligible patients that meet inclusion and exclusion criteria, or more broadly to leverage this comprehensive molecular profile of patients for exploratory analyses.

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Caris Assure for Minimal Residual Disease Tracking and Treatment Monitoring

We are also developing Caris Assure for minimal residual disease tracking and treatment monitoring. Caris Assure in the minimal residual disease space utilizes a tumor naïve approach, and therefore does not require a bespoke panel to be created to track the recurrence of a patient’s tumor. This bespoke-free approach is designed to enable faster turn-around-time, enabling patients to be informed of additional therapy sooner to combat their disease. Additionally, because Caris Assure analyzes the entire exome, any tumor-derived alterations including those that may derive from subclones not included in the original tissue biopsy, are also detectable, thus accounting for tumor heterogeneity to help contribute to sensitivity of detection.

We are in the process of conducting studies and analysis to internally validate and refine the Caris Assure for MRD and treatment monitoring in various cancer lineages. We have submitted a technical assessment for Caris Assure MRD for patients with colorectal cancer to MolDX, but cannot provide any assurance on when or if such technical assessment will be accepted. The commercial application of Caris Assure for MRD is subject to further assay development, validation, and reimbursement coverage. Because many of these factors are outside of our control, we cannot be certain when or if Caris Assure for MRD and treatment monitoring markets will become commercially available.

MI Profile—Our WES/WTS Tissue-Based Profiling Solutions

MI Profile is our tissue-based molecular profiling solution for cancer therapy selection, with approximately 170,300 clinical cases in 2025. MI Profile includes MI Cancer Seek, our comprehensive WES/WTS NGS assay, and IHC protein expression testing. Our tissue microdissection process has, to date, resulted in a high success rate in identifying actionable biomarkers.

The information generated from profiling the patient’s tissue is used to create an interpretative report based on our bioinformatics pipeline and recommend individualized therapies for cancer patients. Our goal is to maximize the information generated and corresponding clinical utility for patients from the limited available tumor tissue. The information generated, which further expands our multi-modal datasets, also provides valuable insights to aid drug discovery and development efforts. Customers for MI Profile include treating physicians as well as researchers and biopharma companies.

MI Profile, including our MI Cancer Seek assay and our proprietary clinical molecular signatures GPSai and FOLFIRSTai are available in all U.S. states and in Puerto Rico. We also offer MI Profile internationally through distributors and direct contracts with hospital systems, where permitted by applicable regulations.

We have obtained a PMA approval from the FDA for certain companion diagnostic and tumor profiling indications for MI Cancer Seek, a WES/WTS NGS assay for which we have obtained a Proprietary Laboratory Analyses (“PLA”) code, Current Procedural Terminology (“CPT”) code 0211U, which is covered under the NGS NCD. MI Cancer Seek was commercially launched in January 2025, and we currently market it as the WES/WTS NGS component of our MI Profile Platform.

MI Cancer Seek Report

MI Cancer Seek generates a personalized report that provides oncologists with the information to tailor each patient’s treatment plan. The MI Cancer Seek report was built by oncologists for oncologists and is designed to maximize clinical utility in an easy-to-interpret format. We generally report our results for tissue-based profiling approximately 10 calendar days from activation.

MI Cancer Seek

The current WES/WTS NGS component of our MI Profile Platform is MI Cancer Seek. MI Cancer Seek has obtained FDA approval for use as a companion diagnostic device to identify cancer patients who may benefit from treatment with targeted therapies listed in the accompanying Companion Diagnostic Indications, in accordance with the approved therapeutic product labeling. The companion diagnostic FDA approval currently includes one pan-cancer and five tumor-specific indications that cover numerous FDA-approved therapies. To our knowledge, MI Cancer Seek is the first and only simultaneous WES and WTS-based assay with FDA-approved companion diagnostic indications for molecular profiling of solid tumors. MI Cancer Seek is available for adults and pediatric patients between the ages of one and 22.

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MI Cancer Seek is a WES/WTS NGS-based in vitro diagnostic device using total nucleic acid isolated from formalin-fixed paraffin embedded tumor tissue specimens for the detection of SNVs, INDELs, MSI, TMB in patients with previously diagnosed solid tumors, and CNAs in one gene in patients with breast cancer.

AI Algorithms

Our WES/WTS profiling solutions generate a vast amount of data per clinical case. To interpret this data, we utilize an advanced, AI-powered bioinformatics pipeline. This bioinformatics pipeline includes a sophisticated rules engine, variant calling, fusion calling, copy number prediction, and expression analysis.

MI Profile can also include our proprietary clinical molecular signatures, GPSai and FOLFIRSTai, which were developed by training and clinically validating AI/ML algorithms with our extensive multi-modal clinico-genomic datasets. These molecular signatures, which we currently offer as LDTs, provide clinical utility for molecular diagnosis of cancer and prediction of patient response to treatment.

•GPSai. Our GPSai signature is a molecular disease classifier that utilizes multiple deep neural networks and hundreds of thousands of molecular features to predict a histologic diagnosis and tumor origin directly from the DNA and RNA sequencing data. The result is a probability of the most likely diagnosis, which is then reviewed by a Caris Board-Certified Pathologist in the context of all available clinicopathologic information before report release. The primary indication for GPSai is to determine if the initial diagnosis is correct and serves as a quality control for all patients. In addition, it can be used to help identify the tissue of origin for Cancer of Unknown Primary (“CUP”), cases where the starting point of the cancer is not yet clear, which is a major unmet need in clinical oncology. This tissue of origin prediction is provided along with the comprehensive biomarker data without the need for additional specimen utilization; this tool runs on the MI Profile exome and transcriptome sequencing results. GPSai is also utilized as a quality control metric where it is run on every clinical case and the results reviewed by a pathologist. If the GPSai results do not match the outside pathologic diagnosis of the specimen, our pathologists will do additional work-up, including IHC testing, to support a new diagnosis to provide the best overall service and patient care.

The latest GPSai model was trained and clinically validated by us through retrospective profiling data from over 200,000 clinical cases using the outside pathologist diagnosis as the baseline. In a prospectively run clinical validation study that we conducted and published in the American Association for Cancer Research’s Cancer Research Communications journal, GPSai demonstrated 95.0% accuracy in identifying tumor tissue of origin in

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non-‘Cancer of Unknown Primary’ (“CUP”) cases and successfully reported a tissue of origin in 84.0% of CUP and 96.3% of non-CUP cases during retrospective and prospective validations. The clinical validation of GPSai enables us to offer the solution as an LDT in accordance with the Clinical Laboratory Improvement Amendments of 1988’s (“CLIA”) requirement of clinical validation of a variety of performance characteristics, including accuracy, precision, specificity, sensitivity, reportable range, and reference interval before an LDT is used in clinical testing.

•FOLFIRSTai. Our FOLFIRSTai signature is our first clinically validated, AI-powered molecular predictor of efficacy of oxaliplatin-based chemotherapy combined with bevacizumab in patients with metastatic colorectal cancer (“mCRC”). According to estimates by the ACS, one in 23 men and one in 25 women in the United States will be diagnosed with colorectal cancer in their lifetime. FOLFOX, FOLFIRI, or FOLFOXIRI chemotherapy with bevacizumab is considered standard first-line treatment option for patients with mCRC. Some mCRC patients benefit from one combination chemotherapy regimen over the others, and identifying which patients would benefit from which regimen is a challenge for physicians. FOLFIRSTai is included for all clinical cases with completed WES results and a diagnosis of advanced stage colorectal adenocarcinoma. The FOLFIRSTai results appear in the MI Cancer Seek report as “Increased Benefit” or “Decreased Benefit” with additional detail provided about the results in the report. FOLFIRSTai is broadly accessible to patients and is covered by almost all insurance companies. We clinically validated FOLFIRSTai using a real-world evidence dataset collected from the Caris POA registry, insurance claims data and samples from the TRIBE2 Phase 3 clinical trial, which compared first-line use of FOLFOXIRI and FOLFOX. In a clinical validation study that we conducted, FOLFIRSTai demonstrated that the overall survival of patients treated in a manner consistent with the FOLFIRSTai prediction was 17.5 months longer than the overall survival of patients treated counter to the prediction (representing a 71% difference). This clinical validation of FOLFIRSTai enabled us to offer the solution as an LDT in accordance with CLIA’s requirement of analytical validation of a variety of performance characteristics, including accuracy, precision, specificity, sensitivity, reportable range, and reference interval before an LDT is used in clinical testing.

Molecular Tumor Board Report

We use sequencing data generated by MI Profile to produce the Molecular Tumor Board Report (formerly referred to as QuantumAI report), a research-use-only description of the patient's molecular tumor biology and phenotype characterization using whole exome and whole transcriptome sequencing. The report, which we have analytically validated but not yet clinically validated, contains biological signatures to help oncologists and researchers understand relationships between genetic variations, mutations, and other molecular features and to tailor precision medicine approaches. The report also features AI-powered signatures that leverage whole exome and whole transcriptome data to predict response to specific therapies across multiple cancer types, including glioblastoma, ovarian, breast, pancreatic, and non-small cell lung cancers, as well as the likelihood of brain metastasis. We continue to develop additional predictive signatures and report features.

IHC Testing

We leverage a broad menu of third-party IHC tests to create a customized set of tests for each patient to reveal a more complete molecular blueprint of the patient’s disease. We use IHC testing to complement our WES/WTS profiling both to inform decisions regarding therapy selection as well as to act as confirmatory testing in circumstances where our GPSai algorithm indicates a different diagnosis than that indicated in the patient record prior to our profiling or in CUP cases. We believe we have one of the broadest IHC testing menus available to patients and physicians to provide the most appropriate therapy results and diagnosis.

Testing patient specimens for protein-based biomarkers by IHC is the standard of care for both predictive and diagnostic purposes. For predictive IHCs, we run third-party companion diagnostic IHCs when available to provide therapy associations that cannot be identified through NGS testing. We also utilize a number of third-party diagnostic IHCs to help with refining or changing a diagnosis. Most samples come to us for molecular profiling with a diagnosis in hand. However, WES and WTS provide a broad and deep data set that can help alter or refine a diagnosis. In some cases, we receive patient sample labeled as ‘Cancer of Unknown Primary,’ where it is hoped that molecular profiling will allow a more specific diagnosis to be applied. Once we evaluate the molecular data, including the results of GPSai if applicable, our pathology team will often order diagnostic IHC testing to provide additional support for a specific diagnosis.

MI Profile for Biopharma

Maximizing knowledge and extracting the most information out of every patient sample on a clinical trial reduces the risk of researchers missing potential efficacy or safety signals. Sequencing the whole exome and the whole transcriptome not only yields far more biomarker data from limited specimens, but also allows for the power of such

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comprehensive information to be aggregated and deployed to improve patient outcomes in the future via real-world data analyses. The breadth and depth of data make our methodology fundamentally different from the currently available DNA panels, which are limited by only looking at known biomarkers. We believe that a non-comprehensive, subset panel of genes or DNA-only assay that ignores RNA is an inadequate solution for efficient and successful drug development, and represents the central underpinning for why we believe we are uniquely positioned in the marketplace to be the industry leading innovator and strategic partner of choice for biopharma companies, to jointly bring forward the next generation of novel therapies for patients with cancer. Oncology therapeutics are inevitably shifting from single driver alterations with single biomarkers to more sophisticated and complex biomarkers that can stratify patients such as novel signatures for DNA damage response repair targeting molecules and RNA-based expression for immunotherapies. Our comprehensive WES/WTS NGS tumor assay is optimally positioned to seamlessly validate these novel biomarkers since they are already included in our assay.

Molecular profiling has broad applications for our biopharma partners, including prospective screening, retrospective testing and deep translational analyses, stratification of patients for existing or future trials, and treatment monitoring. When our tissue WES/WTS assay is deployed as an integrated component of early development programs and clinical trials, that same assay is being leveraged for companion diagnostics development and commercial services that we deliver for our partners. Commitment to Caris as registration partner allows early regulatory interactions while minimizing pharma sponsor costs, maintaining flexibility to changing timelines and evolving biomarker strategies. Furthermore, the comprehensiveness of our WES/WTS approach creates a deep competitive moat for us.

In addition to testing of both DNA and RNA, we offer companion diagnostic partners opportunities to use samples sourced from our vast biobank of clinical specimens. This offers partners access to a large selection of fully characterized specimens of known positive and negative biomarker status. This can alleviate one of the most difficult hurdles of companion diagnostic development, namely access to enough biomarker-positive specimens across the minimum number of cancer types required to conduct FDA validation studies. For companion diagnostic projects involving a biomarker with low incidence, we offer partners a significant advantage. Beyond companion diagnostics, our biobank carries significant value for exploratory translational studies. When novel discoveries are made in silico, or based on DNA or RNA, the path to validate these findings requires tissue for proteomic assessments or targets or biomarkers. Having any tissue is valuable however, our tissue biobank is unique because of the scale due to the number of cases and tests we have completed to date, the heterogeneity of tissue types which reflects cancer prevalence, and most importantly because of the amount of WES and WTS information we have generated. In aggregate, our biobank with accompanying data and digital images provides biopharma companies with a unique and highly valuable set of research tools to help validate and derisk the next wave of oncology therapeutics.

Caris MI Clarity—Our Breast Cancer Risk Recurrence Predictor

We are also utilizing our datasets and AI/ML analysis to develop the ability to use digital scans of tissue slides to predict the presence of certain biomarkers, with or without the need for NGS profiling.

We have utilized these tools to develop Caris MI Clarity (formerly called ESPai), an AI-powered multimodal tool for breast cancer recurrence risk stratification. It is developed through research partnerships with ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and NRG Oncology (NRG), to combine Caris comprehensive WES/WTS, whole slide imaging, and advanced ML platforms. The test was developed using tumor specimens and clinical data from the TAILORx (ECOG) and B-42 (NRG) randomized clinical trials. Our internal validation study results demonstrated an ability to predict risk of both early (0-5 years) and late recurrence (5-15 years) of breast cancer.

Across analytic evaluations, the multimodal AI models (one using comprehensive WES/WTS, whole slide imaging, and clinical data, and another using only whole slide imaging and clinical data) demonstrated enhanced prognostic performance compared to existing recurrence-risk assessment methods, highlighting the potential to support more personalized treatment decision-making in early-stage breast cancer. This new diagnostic test for women with HR-positive, HER2-negative, node-negative breast cancer has the potential to help guide physician decisions about the use of chemotherapy and extended endocrine therapy. We are currently evaluating and pursuing reimbursement and launch pathways for Caris MI Clarity, in versions both with and without WES/WTS.

Precision Whole Genome Platform—Our WGS Tissue- and Blood-Based Profiling Solutions

In 2025, based on our belief in the power of comprehensive profiling, we determined to pursue whole genome sequencing for certain of our assays that are under development. These assays include: Caris Detect, our WGS-based multi-cancer early detection ("MCED") solution; Caris WGS MRD, our WGS and digital droplet PCR (polymerase chain

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reaction)-based minimal residual disease solution; and Caris ChromoSeq, our WGS and WTS based assay for therapy selection in hematological (blood) cancers.

We are in the process of conducting studies and analysis to internally validate and refine our WGS assays as LDTs. The commercial application of these assays is subject to further assay development, validation, and reimbursement coverage. Because many of these factors are outside of our control, we cannot be certain when or if each of our WGS assays, including Caris Detect, Caris WGS MRD and Caris ChromoSeq, will become commercially available.

Caris Detect

Caris Detect is our comprehensive blood-based WGS-based MCED assay under development to identify multiple cancer types by analyzing molecular signals circulating in the bloodstream. We have entered into a collaboration agreement with Everlywell to expand access to Caris Detect. We believe that Caris Detect will allow for the detection of cancer at early and more treatable stages, before it can spread, ultimately supporting better outcomes for patients. We expect to launch Caris Detect as an LDT in the first half of 2026. We plan to launch Caris Detect with a self-pay model at a price of $3,500.

We are in the process of validating the performance of Caris Detect for early detection through Achieve 1, an approximately 3,000-subject case-control study of Caris Detect in MCED, that consisted of approximately 66% undiagnosed patients and 33% patients with cancer. We reported an interim readout of results of Achieve 1 in February 2026, and are in the process of completing a blinded validation of nearly 900 samples held out of the initial readout. We are also actively enrolling approximately 25,000 subjects, including non-cancerous subjects, cancerous subjects and subjects with advanced adenomas, in Achieve 2, a subsequent study for Caris Detect in MCED.

We believe that future advances planned for Caris Detect technology have the potential to deliver meaningful innovation in other chronic disease states, including cardiology, neurology, and metabolic conditions.

Caris WGS MRD

We are in the early stages of developing an ultra-low sensitivity, WGS-based, tumor informed assay for MRD in Stage 1, 2, and 3 cancers. This assay utilizes WGS of tumor samples to identify trackers that then can be measured using digital droplet PCR analysis in follow-up testing to track cancer recurrence.

Caris ChromoSeq

Through an exclusive license arrangement with Washington University in St. Louis (“WashU”) that we entered into in October 2024, we are developing Caris ChromoSeq, an assay that detects and analyzes hematological cancers using WGS and WTS. We have internally validated this assay, which is based upon the licensed WGS assay and also includes our WTS technology, and are developing it for commercial launch subject to receipt of reimbursement approval from MolDX. We have submitted a technical assessment to MolDX for Caris ChromoSeq for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). We are also working to expand and validate the assay’s capabilities for hematological cancers beyond AML and MDS and currently intend to seek additional coverage from MolDX for additional hematological cancers.

We believe this assay designed for genomic evaluation of patients with blood cancers would serve as a valuable complement to our existing tissue and liquid assay solutions, which are oriented towards identifying and profiling cancers of solid tumor origin, and enhance our position as a provider of choice for molecular profiling solutions.

Caris Discovery

Caris Discovery is our drug target and therapeutic discovery business. Caris Discovery leverages our profiling solutions, multi-modal clinico-genomic datasets, wet lab facilities, proprietary Adaptive Dynamic Artificial Polyligand Targeting (“ADAPT”) platform, and AI/ML-enabled in silico analyses to identify potential drug targets and develop therapeutics. We launched Caris Discovery in 2022 to partner with biopharma partners to address the lack of novel cancer-specific targets and the herding of biopharma pipelines around a discrete number of lower-risk targets. Caris Discovery is disease- and modality-agnostic and can be applied to any therapeutic modality, including antibody-directed therapies (such as antibody drug conjugates, degrader-antibody conjugates, and T-cell engagers), small molecules, targeted protein degradation, synthetic lethal interactions, cell therapy, and neoantigen discovery for personalized therapy development, among others. In addition to working with biopharma partners, Caris Discovery is developing a wholly owned pipeline of biologics based on our platform.

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An antibody-drug conjugate is a targeted cancer therapy that combines an antibody with a cytotoxic drug. The antibody specifically targets cancer cells, delivering the drug directly to them, which helps minimize the impact on healthy cells. This approach aims to increase the effectiveness of the drug while reducing side effects.

Degrader-antibody conjugates (“DACs”) are an emerging class of therapeutic agents that combine the targeting ability of antibodies with the protein degradation mechanism of degraders. DACs are designed to bind to specific proteins on the surface of cancer cells through the antibody component and then recruit the cell’s degradation machinery to eliminate the target protein inside the cell. This dual action allows for precise targeting and removal of disease-causing proteins, potentially leading to more effective treatments with fewer side effects.

T-cell engagers are a class of artificial engagers that are designed to specifically direct the body’s immune system to target cancer cells. They function by simultaneously binding to CD3 on T cells and to a specific antigen on the tumor cell, thereby bringing the T cells into close proximity with the tumor cells, which can result in the T cells attacking and killing the tumor cells.

A small molecule refers to a low molecular weight organic compound that can regulate a biological process, with a size on the order of 1 nm. In the pharmaceutical industry, small molecules can include drugs that can be orally or intravenously administered and are often used to regulate biological processes. The term contrasts with larger molecules, such as biologics.

Targeted protein degradation is a therapeutic strategy that aims to eliminate disease-causing proteins from cells. It involves the use of small molecules, known as proteolysis-targeting chimeras, or molecular glues, that can bind to specific proteins and tag them for destruction by the cell. This approach is particularly useful for targeting proteins that are difficult to inhibit with traditional drugs or for which no inhibitors exist.

Synthetic lethal interactions in drug discovery refer to a relationship between two genes where the loss of function of either gene alone is survivable by the cell, but the simultaneous loss of both is lethal. This concept is utilized in drug discovery to target cancer cells with specific genetic mutations. By inhibiting the function of a gene that is synthetically lethal to a mutated gene already present in the cancer cell, the cell can be selectively killed without harming normal cells.

Cell therapy is a form of treatment where living cells are injected into a patient to help cure a disease. In the context of cancer treatment, cell therapy can involve the use of immune cells that are either taken from the patient or from a donor, modified in a lab to enhance their ability to fight cancer, and then injected back into the patient. This approach is part of a broader category known as immunotherapy, which aims to harness the body’s immune system to combat cancer.

In addition, we believe Caris Discovery can be leveraged to discover personalized therapies for cancer. A major paradigm-shift in cancer therapy in recent years has focused on harnessing the immune system’s ability to recognize and eliminate cancer cells. One promising approach involves using personalized therapies to stimulate the immune system against tumor-specific antigens also known as neoantigens. Those neoantigens are proteins that are produced by mutations in the DNA of cancer cells and are not present in normal cells. We believe Caris Discovery is well-positioned to be able to discover personalized neoantigens for cancer therapies given our ability to detect variants and INDELs by WES and to assess gene expression and detect fusions by WTS on every patient’s tumor. We also leverage our deep proteomics expertise utilizing mass spectrometry to validate neoantigens using our biorepository of contemporaneous molecular profiled remnant patient tissue that can be predicted by deep ML from our Caris Assure blood and MI Profile tissue sequencing. Furthermore, we can predict who may or may not respond to personalized therapies and who should be excluded from personalized therapy trials due to defects in antigen presentation machinery, such as loss of major histocompatibility complex genes due to mutations or downregulation. We are working with multiple partners that have a personalized therapy in clinical development or clinical trials.

Our proprietary repositories of tissue and data, each of which we believe to be at an unmatched scale, are a resource that could not have been amassed without our underlying commercial profiling business, and as such are a significant differentiator and enabler of our discovery efforts.

We have achieved external validation of our Caris Discovery approach through strategic partnerships with established biopharma companies, such as Genentech, Merck KGaA, and Xencor, to develop therapeutics against novel targets that emanate from our molecular insights and proprietary technology. Our Caris Discovery partnerships are designed to emphasize both near term revenue and the potential upside of successful therapeutics developed against novel targets identified by us, thus aligning our partners’ financial interests with our own. Our proprietary discovery

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proteomics and downstream target validation work is performed, by Caris scientists in our R&D laboratory in Tempe, Arizona, a 59,000 square foot facility that includes a cell culture laboratory and state-of-the-art instrumentation dedicated to drug target discovery.

In Silico Target Discovery Leveraging the Caris Clinico-genomic Dataset

Caris Discovery leverages our multi-modal clinico-genomic datasets to define clinically relevant cohorts of unmet need for drug target discovery. Stratifying cases by molecular profile, histology, and/or clinical features in silico prior to performing our proprietary proteomic work on the profiled cases in our tissue repository is extremely powerful to identify drug targets in highly relevant therapeutic areas. Once potential targets are identified, the clinico-genomic data can be integrated with our proteomics data and can be utilized to filter the initial target pool down to the targets with the highest potential value for further downstream wet-lab validation.

The proteomics work leveraging our in silico discovery work is driven by three complimentary components: (1) our ADAPT Biotargeting, (2) Proximity Labeling, and (3) the Caris Surfacesome.

•ADAPT Biotargeting—Aptamer-Based Proteomics Discovery System. Our ADAPT system uses a broad library of synthetically manufactured molecules called aptamers that bind to a wide range of biological targets and characterize complex biological systems, enabling the profiling of biological samples at a systems-wide scale coupled with affinity purification-mass spectrometry to identify the underlying target proteins. ADAPT is able to simultaneously measure millions of molecular interactions within complex biological systems in their natural states and directly from patient tissue. ADAPT is powered by real world contemporaneous patient samples, including our combined clinico-genomic datasets, thus overcoming the limitations of traditional target discovery approaches, such as comparative genetics, molecular pharmacology of variants, analysis of molecular signaling pathways, cell-based and in vivo disease models, limited panel based proteomics with a defined set of target proteins and traditional proteomics, which result in a high degree of off-target activity, false positives and bias, and lack enrichment of patient enriched cancer proteins. ADAPT allows us to make unbiased identification of unique features of disease state and allows for elucidation of novel biological mechanisms. Actionable drug targets (or molecular markers) include proteins that are present in diseased tissue but low to no detection in normal tissue. Traditional biomarker discovery tools suffer from a signal to noise challenge and require a hypothesis of where to look before being deployed. ADAPT can filter out features shared by both cancer and normal cells and enriches for features specific to cancer cells.

•Proximity Labeling—Antibody-based Proteomics Discovery System. We also apply proximity labeling on molecularly profiled remnant patient tissue to examine protein-protein interactions as well as to identify components that localize to discrete subcellular compartments. This approach enables us to identify actionable drug targets in patient tissue and permits the systemic analysis of spatially restricted proteomes. Applying proximity labeling on our proprietary tissue profiling data has resulted in the discovery of numerous novel drug targets potentially actionable for bispecific antibodies, dual targeting antibody modalities, and cell therapies.

•Caris Surfacesome. Cell-surface proteins are key to antibody-based therapeutics, and we have developed our own cell surfacesome comprising a database of cell surface proteins detected by mass spectrometry. This in-house database comprises genomic, transcriptomic, and proteomic data for multi-omic data analysis in addition to prepared cytosections and live cells instrumental for antibody quality control and wet-lab validation of drug targets discovered from our Aptamer and Antibody-based discovery systems.

Caris Strategic Data

Data and molecular information are at the core of every aspect of our business. Our team of data scientists deploys our proprietary advanced AI/ML algorithms to decipher unique features from our resulting clinico-genomic datasets, helping us decode and further unravel the molecular complexity of disease. Our long history of utilizing AI and ML algorithms, together with the breadth and depth of our clinico-genomic datasets, provide us a significant advantage in sophisticated analysis of cancer, and a foundation that we believe will have applications in additional disease states.

The tremendous amount of data we have generated, which we have deidentified for research use, provides us a differentiated capability to advance precision oncology research through many business models, including training new profiling solutions and signature development, therapy development, and research into new ways to treat and cure disease, including personalized treatments. To assist us with analyzing this data, we utilize AI/ML tools across our clinical testing, R&D, and biopharma business.

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Data for Biopharma

We launched our data licensing business in late 2022. We license deidentified multi-modal datasets, components of which were generated from our clinical profiling business to external researchers, including those with biopharma companies, with the aim of generating insights directly responsible for superior clinical outcomes for patients. As the adoption of our tissue and blood-based profiling solutions continue to grow, this will result in further expansion of our multi-modal datasets, which can provide additional valuable insights to aid biopharma companies’ drug discovery and development efforts to bring innovative therapies to market. We utilize a third-party tokenization process to match deidentified data from various sources to create the multi-modal product. The linked data is then provided to the external researcher. Prior to the tokenization process, we run a series of software solutions through standardized data fields designed to remove and replace any PHI with a randomly generated string of letters and numbers. We then use a third-party expert to certify that the data is deidentified pursuant to 45 CFR §164.514(b)(1) under HIPAA. We contractually require recipients of the data to maintain compliance with laws and regulations. The end customer takes on the contractual responsibility to properly maintain the data, not to attempt to reidentify any patient from the deidentified data set, and to obtain its own expert certification before combining the Caris data with any other data.

To further broaden the applicability and usefulness of our multi-modal datasets for biopharma companies, we have entered into agreements with clinical data partners, such as ConcertAI, Flatiron and COTA, to enable the creation of matched clinico-genomic datasets that can be licensed to biopharma companies for their use in drug discovery. These datasets generally consist of Caris molecular profiling data (and in some cases claims data), together with matched clinical data from our partners. We and our partners have entered into agreements with AbbVie, Moderna, and others to license our datasets for use in drug discovery. Together, our combined multi-modal data create a differentiated capability to advance precision oncology research through novel target identification and discovery, translational sciences, clinical trial design solutions and patient enrollment facilitated by our right-in-time trials network, post-market label expansion, and commercialization insights.

We have a rich pipeline of data opportunities that we believe will deliver new partnerships, as we continue to introduce biopharma companies to this unique data offering. In addition, many of our biopharma-related data initiatives and data partnerships allow for the flow of multi-modal data to our internal research teams, providing further synergies and enabling AI/ML powered research across the broader Caris enterprise.

Data for Clinical Research: The Caris Precision Oncology Alliance

We established the Caris POA in 2015. The Caris POA is a growing network of leading cancer centers and research consortia across the globe that supports research partner engagement, collaboration opportunities, and the advancement of precision oncology research. It consists of members that demonstrate a commitment to precision medicine and work collaboratively toward a common goal: to advance tumor profiling and establish and optimize standards of care for molecular testing through innovative research to improve clinical outcomes for cancer patients.

As of December 31, 2025, the Caris POA was comprised of 99 members, including over 45 National Cancer Institute (“NCI”)-designated comprehensive cancer centers.

POA members participate in the various activities of the Caris POA through the following:

•profiling cancer patients using our comprehensive profiling solutions;

•establishing guidelines to integrate molecular testing into cancer care and patient treatment management;

•participating in research studies and clinical trials, both prospective and retrospective;

•collaborating in molecular tumor boards to advance the institution and industry’s understanding of cancer and the clinical utility of profiling in clinical care;

•tracking longitudinal outcomes and contributing data to the Caris POA; and

•publishing novel research and clinical data.

As part of the Caris POA collaboration, we contribute de-identified molecular data obtained from tumor profiling of cancer patient samples, and our partners have an opportunity to contribute outcome or clinical data for use in joint research projects. Physicians and researchers across the Caris POA network are provided with information from our datasets as part of our mission to give greater access to and disseminate this data in furtherance of creating solutions for oncology. Caris POA members access our datasets through CODEai, a custom interface for our multi-modal clinico-genomic datasets that we launched in 2020. CODEai allows users to explore a cohort of over 484,000 matched datasets and clinical outcomes. CODEai users can define patient cohorts of interest and direct the underlying AI to mine the data, extract cogent information such as molecular markers that correlate with defined patient cohorts, and perform various

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analyses. Working with leading oncologists at Caris POA member sites, we have established a number of tumor-specific working groups comprised of key academic thought leaders and subject matter expertise to assist us in ensuring our profiling components remain clinically up-to-date with the latest important molecular markers and testing threshold criteria.

We also contribute to academic research to advance the understanding of molecular science and further enable the delivery of precision medicines through our collaborations with member institutions within the Caris POA. We routinely collaborate with leading cancer centers to publish and present new learnings with immediate implications on the clinical use and utility of comprehensive molecular profiling.

Data Driving Development of New Clinical Solutions

A significant benefit of generating WES, WTS and WGS results is that the resulting dataset becomes a unique and proprietary resource to fuel the development of new molecular-driven signatures, products, and profiling solution enhancements that are only possible due to the availability of large datasets. Our datasets have also been augmented through agreements with external data providers. We have leveraged our vast datasets to drive the development of AI-based signatures and other enhancements, including hundreds of AI algorithms that are used in our bioinformatics pipelines for our profiling solutions. These solutions are designed to allow us to better leverage our data to improve patient outcomes and significantly differentiate us from our competitors.

We plan to utilize our datasets and molecular profiling knowledge to continue to create proprietary molecular signatures that leverage NGS-based testing results and to utilize digital scans of tissue slides to predict the presence of certain molecular markers without the need for NGS profiling. In addition, we plan to establish patient-level prognosis and prediction of therapeutic benefit, with an initial focus on breast cancer, but that we believe will have therapeutic benefits across all cancer types.

Caris Proprietary Molecular AI/ML Driven Signatures

We plan to utilize our datasets to continue to create proprietary molecular signatures and potentially establish patient-level prognosis and prediction of therapeutic benefit, with an initial focus on breast cancer.

In addition to our two clinically validated proprietary molecular signatures, GPSai and FOLFIRSTai, which can be ordered as part of MI Profile, we have a pipeline of proprietary molecular signatures that we are in the process of refining and validating. For example, we are developing MGMTai, a predictive signature that will help oncologists assess a patient’s risk of developing brain metastases, and other signatures in development include pancreatic cancer response predictors, a predictor of response to checkpoint inhibitor therapy for lung cancer patients, and a predictor of response to platinum-based therapies for ovarian cancer patients. Similar to our FOLFIRSTai signature, we believe these types of multi-omic, ML-driven signatures will add significant and differentiating clinical value to our solutions, positioning our profiling solutions as the most complete and comprehensive for late-stage cancer available.

Our basic strategy for molecular signature development is to utilize our proprietary WES/WTS/WGS and claims data clinical databases for initial signature creation, with validation in external datasets (when advisable), including datasets that have been developed in other prospective clinical trials. These external datasets will, in many cases, be derived from active and ongoing collaborations with cooperative oncology groups or single academic institutions, many of which are active members of the Caris POA.

Our Laboratory Infrastructure

We have built substantial testing capacity with throughput capabilities of over one trillion “reads” per day. We operate two precision medicine laboratories in Phoenix, Arizona, and one R&D laboratory in Tempe, Arizona. Our Arizona laboratories all utilize state-of-the-art genomic sequencing technology, including NovaSeq 6000 and NovaSeq X sequencing systems. We provide high quality, reliable molecular testing services for all stages of the drug development cycle and routine clinical use. From pre-clinical research for compound development efforts to established, commercially available therapies, we provide robust genomic and proteomic testing capabilities across a variety of specimen types and high-throughput technologies.

Our solid tissue clinical laboratory in Phoenix, Arizona is an approximately 66,000 square foot, state-of-the-art laboratory. This laboratory has the following certifications: ISO 15189, ISO 13485, CLIA: CMI 03D1019490, College of American Pathologists (“CAP”): 7195577, and New York State Department of Health.

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Our blood-based clinical laboratory in Phoenix, Arizona is approximately 35,500 square feet. This laboratory started testing operations in February 2022 following the installation of liquid-handling robots and NovaSeq sequencing systems. This laboratory has the following certifications: ISO 15189, CLIA: CMI 03D2210981 and CAP: 9536852.

We also have an approximately 59,000 square foot R&D laboratory in Tempe, Arizona that is utilized for R&D and therapeutic discovery work. This laboratory has an ISO 13485 certification.

We test patient samples on powerful sequencing systems that are built for high throughput sequencing, scalability, and speed, all economically. Our use of high performance NGS sequencing systems improves our throughput efficiencies and lowers our cost of sequencing. In addition to NGS, we employ other technologies in our operations, including liquid handling robotic systems, ultra HD digital image scanning, dynamic light scattering, flow cytometry, fragment analysis, IHC, in situ hybridization, laser capture microdissection, mass spectrometry, Sanger sequencing, pyro sequencing, quantitative polymerase chain reaction, RT-PCR, and surface plasma resonance.

Our Commercialization Strategy

The precision medicine industry is characterized by rapid changes, including technological and scientific breakthroughs, frequent new product introductions and enhancements, and evolving industry standards. Education of customers, both physicians and biopharma companies, remains one of the key barriers to higher adoption of molecular profiling. More than ever, oncologists need a trusted profiling partner to provide reliable, high-quality molecular profiling information to guide precise and individualized treatment decisions. Our relationships across key oncology stakeholders include more than 6,000 ordering physicians and partnerships with many top biopharma companies. We have optimized our systems to provide industry-leading reports, service, and turn-around-time, helping oncologists (1) navigate among therapies with potential benefit, (2) identify therapies that may not have been considered, (3) determine drugs with potential lack of benefit (avoiding unnecessary toxicities and costs), and (4) match patients to clinical trials.

In the United States, we market our solutions to clinical customers through our marketing and commercial sales organizations. Since the end of 2021, the size of our sales organization has generally remained constant, though the team has grown slightly during certain periods and contracted slightly in others. Our sales team members cover the entire U.S. market, focusing on the community setting where the majority of cancer patients are treated.

In addition, we have highly trained Ph.D. or M.D. MSLs who focus on physician and provider education and consultation, enabling us to provide a personalized consultation experience for oncologists. MSLs are responsible for communicating the value of Caris to external stakeholders, such as physicians, nurses, scientists, and other interested parties. This communication primarily involves face-to-face discussions with customers. The MSLs use a variety of opportunities such as molecular tumor boards, educational seminars, and conference participation to act as a conduit of information and feedback between the medical community and us.

Decisions about which profiling services to use have become increasingly “institutionalized,” where cancer center directors and other medical leaders are adopting the approach of designating a “preferred partner” that is a technology and service leader for molecular profiling services. We believe that the Caris POA and our deep, high-quality institutional relationships provide us with an advantage in being selected as a preferred partner, and we expect this trend to continue to accelerate to further drive growth in ordering of our profiling solutions.

We market our solutions to biopharma companies through a separate Biopharma Business Development team. This team is differentiated from traditional sales organizations by recruiting professionals with a diversity of direct biopharma experience and strong scientific backgrounds and business acumen. We believe the credibility that our partnering team brings to discussions with biopharma companies has been well-received, and when combined with our profiling solutions and molecular datasets, has created a strong competitive edge.

We estimate that approximately two-thirds of our top 200 customers based on case volume were either academic medical centers or corporate physician practices.

International Distribution

Globally, we market our solutions through distributors and direct contracts with hospital systems, where permitted by the applicable regulations. Our distributors are generally obligated to obtain required in-country regulatory approvals and comply with in-country regulations. We have a UK-CA mark for both Caris Assure and MI Cancer Seek. We are considering filing for regulatory approvals in Japan and the European Union.

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Competition

The precision oncology industry is highly competitive and subject to rapid change. An increasing awareness of the importance of genetic information to accurately understand cancer and deliver solutions for early detection, MRD tracking, therapy selection, and treatment monitoring is leading to more companies offering services in genomic profiling and sequencing.

Our competitors in tissue-based molecular profiling include Foundation Medicine (Roche) and Tempus. In addition, some academic centers, such as Memorial Sloan Kettering Cancer Center and New York Presbyterian—Weil Cornell, offer profiling to patients in their networks. Our competitors in blood-based early detection include Grail, Freenome, Guardant Health, Exact Sciences, and Delfi Diagnostics, among numerous other companies pursuing the early detection market. Our competitors in blood-based molecular profiling for therapy selection include Guardant Health, Tempus and Foundation Medicine (Roche). Our competitors in blood-based molecular profiling for MRD tracking and treatment monitoring include Natera, Guardant Health, SAGA Diagnostics, Personalis, BillionToOne, Quest Diagnostics and Adaptive Biotechnologies. Our competitors in core biopharma services include Foundation Medicine (Roche), Guardant Health, Tempus, Natera, and Personalis. Our competitors in offering genomic data and AI services include Tempus and Foundation Medicine (Roche). Other companies offering testing in the precision oncology industry include Illumina, NeoGenomics, Myriad Genetics, Laboratory Corporation of America, Quest Diagnostics, and BostonGene.

Some of these companies may have substantially greater financial and other resources than we have, such as larger R&D staff and more established marketing and sales forces, or may operate in jurisdictions where lower standards of evidence are required to bring products to market. In addition, other established diagnostic, medical technology, biotechnology, or pharmaceutical companies may decide in the future to invest heavily to accelerate discovery and development of similar services that could make our solutions less competitive.

We believe that we compete favorably based on the following competitive factors: our patient-first approach that includes deep sequencing of all DNA encoding genes and RNA transcripts utilizing comprehensive WES and WTS, and anticipated sequencing of all DNA using WGS, enables us to provide patients and physicians with industry-leading breadth, depth, and accuracy of multi-omic information; our tissue-based molecular profiling solutions; blood-based profiling solutions; our large and comprehensive multi-modal clinico-genomic dataset; our specialized commercial channel, robust infrastructure, and deep research collaborations; and our highly experienced management team.

Intellectual Property

Protection of our intellectual property is fundamental to our business success. To protect our intellectual property, we use a combination of patents, trademarks, copyrights, trade secrets, license agreements, confidentiality agreements and procedures, employee agreements, and other legal and contractual rights.

Patents

We enter into invention/patent assignment agreements with employees and consultants requiring assignment of inventions developed while working for us.

Our company-owned and in-licensed patents and applications generally fall into the following categories:

•Patents and applications related to our molecular profiling services. As of December 30, 2025, we owned 68 patents (including four allowances) and 77 pending applications, and had an exclusive license to one patent application, which collectively relate to our molecular profiling solutions, including claims directed to early detection of cancer, monitoring disease recurrence, identifying treatments of likely benefit or lack of benefit for cancer patients, and the use of AI and ML for prediction of response to various cancer therapies, prediction of tumor origin, and to assess other characteristics of cancers based on NGS data and/or digital pathology. The Caris-owned patents and applications are assigned to our subsidiary Caris MPI, Inc. and include 18 issued U.S. patents, 21 pending U.S. applications, 50 foreign patents (including four allowances), and 56 pending foreign applications. The in-licensed patent application is a U.S. application and is exclusively licensed to Caris MPI, Inc.

•Patents and applications related to our pharma research and development services. As of December 30, 2025, we owned 121 patents (including one allowance), and 24 pending applications, and had exclusive licenses to 43 patents and applications, which collectively relate to aptamer library screening and uses thereof, including uses in biomarker discovery, as well as cell targeting constructs and therapeutic applications thereof. The Caris-owned patents and applications are assigned to our subsidiary Caris Science, Inc. and include 17 issued U.S. patents and one allowance, five pending U.S. applications, 103 foreign patents, and 19 pending foreign

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applications. The in-licensed patents and applications are exclusively licensed to Caris Science, Inc. and include two issued U.S. patents, one pending U.S. application, 36 foreign patents, and four pending foreign applications.

Patents and applications of particular importance within our portfolio that relate to our commercial molecular profiling services include:

•47 patents (including one allowance) and 11 pending applications directed to systems and methods for comprehensive molecular profiling for cancer patients independent of cancer type. These include 15 issued U.S. patents and two pending U.S. applications, and 32 foreign patents (including one allowance) and 9 pending foreign applications between Australia, Canada, China, Europe, India, Israel, Japan, Mexico, Singapore, South Africa, and South Korea. These patents and applications are Caris-owned and assigned to our subsidiary Caris MPI, Inc., and are expected to expire between 2027 and 2033;

•Two issued patents in Japan, one issued patent in Australia, an allowance in Israel, and 16 pending applications directed to AI/ML systems and methods for predicting cancer type. These include two pending U.S. applications, one PCT application, and 13 pending foreign applications between Australia, Canada, Europe, Israel, Japan, South Korea, and Mexico. These patents and applications are Caris-owned and assigned to our subsidiary Caris MPI, Inc., and are expected to expire between 2040 and 2044; and

•16 patents (including two allowances) and 14 pending applications directed to AI/ML systems and methods for predicting response to platinum compounds, including FOLFOX regimens. These include three issued U.S. patents and two pending U.S. applications, and 13 foreign patents (including two allowances) and 12 pending foreign applications between Australia, Canada, Europe, France, Germany, Ireland, Israel, Japan, South Korea, Mexico, Netherlands, Switzerland, and the United Kingdom. These patents and applications are Caris-owned and assigned to our subsidiary Caris MPI, Inc., and are expected to expire between 2039 and 2040.

Additional patents and applications with varying levels of importance within our portfolio that relate to our commercial molecular profiling services include:

•19 pending applications directed to AI/ML systems and methods for characterizing cancers, including predicting response to various cancer treatments. These applications are Caris-owned and are expected to expire in 2041;

•Seven pending applications directed to AI/ML systems and methods for predicting likelihood of metastasis. These applications are Caris-owned and are expected to expire between 2041 and 2046; and

•One pending application directed to profiling hematological malignancies using whole genome sequencing. This application is exclusively in-licensed and is expected to expire in 2042.

Additional patents and applications with varying levels of importance within our portfolio that relate to our pharma research and development services include:

•38 patents directed to methods for use of microvesicles and microRNA as cancer biomarkers. These patents are exclusively in-licensed and are expected to expire in 2028;

•47 patents and five pending applications directed to methods of sequencing aptamer libraries to detect targets of interest. These patents and applications are Caris-owned and expected to expire between 2028 and 2033;

•56 patents (including one allowance) and six pending applications directed to methods for aptamer library enrichment. These patents and applications are Caris-owned and are expected to expire between 2028 and 2038; and

•18 patents and 18 pending applications directed to compositions and methods related to cell-targeting technologies. These patents and applications are either Caris-owned or exclusively in-licensed and are expected to expire between 2036 and 2044. The expiration dates described above are subject to, in the case of pending applications, our continued prosecution to allowance at the applicable patent offices, and in the case of allowed, issued and granted patents, our payment of applicable issue fees, maintenance fees and annuities. Patent expiration dates are estimates and may be subject to terminal disclaimers and patent term adjustments.

In some instances, we have acquired or in-licensed patent rights developed by third parties to enhance our patent portfolio and competitive advantage. For example, we have acquired patent families related to aptamer technologies and in-licensed patent applications related to cell targeting and hematological cancer assay technologies that are currently under development. Under such license agreements, we would be obligated to pay royalties for future sales in which the patents are used in the product or service sold.

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Trade Secrets

In addition to patent protection, we have determined that certain technologies are better kept as trade secrets, such as aspects of our NGS methodology, bioinformatic analysis techniques, and identity of cancer biomarkers under development. We have a policy to restrict access to our trade secrets to a need-to-know basis. To further mitigate the chance of trade secret misappropriation, we enter into confidentiality agreements with parties who have access to trade secrets, such as our employees, collaborators, outside scientific collaborators, consultants, advisors, and other third parties.

Brand Protection

Our customers and partners recognize us as a leader in the molecular profiling field. Thus, just as patent and trade secret protection is essential to protecting our technology, we believe that it is equally as important for us to protect our brand and identity. We have obtained, and will continue to obtain, trademark protection for our name, logo, and solutions in countries where we operate.

Additional Information

We will continue to pursue intellectual property protection, whether developed in-house or via third parties, that we believe will advance our business objectives. Despite our efforts and vigorous defense, our intellectual property rights in the United States and abroad may be invalidated, circumvented, or challenged in the future. In addition, the laws of various countries where our solutions are distributed may not protect our intellectual property rights to the same extent as the laws in other countries. For additional information, see the section titled “Risk Factors—Risks Related to Intellectual Property.”

Regulatory Strategy

Our regulatory strategy aligns with our overall business objectives. We believe that receiving FDA approval of our diagnostic solutions would positively impact our ability to sell our solutions and enhance our reimbursement efforts with payers, including Medicare. The current marketing status and relevant regulatory approvals obtained, planned, and/or potentially required for each of our solutions is summarized in the table below. We currently market all of our existing solutions, including Caris Assure for therapy selection, MI Tumor Seek Hybrid, GPSai, and FOLFIRSTai, as LDTs and, as required under CLIA, have analytically validated such solutions across a variety of performance characteristics, including accuracy, precision, specificity, sensitivity, reportable range, and reference interval. We have obtained an FDA marketing authorization for MI Cancer Seek, and it is possible that we may seek FDA marketing authorization for Caris Assure for therapy selection and additional solutions in the future. We do not yet have specific plans regarding the timing of an FDA or other regulatory submission, if any, for Caris Assure for therapy selection. For additional information, see “—Government Regulation—U.S. Food and Drug Administration—Laboratory Developed Tests.”

The FDA premarket review process requires significant resources and accurate device descriptions including intended use, indications, target population, performance characteristics, labeling and marketing claims. These factors, combined with device classification and predicate device availability, determine the appropriate submission type and regulatory pathway.

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The FDA encourages participation in the FDA’s Pre-Submission Program and we may have formal meetings with CDRH to obtain non-binding feedback on study designs and regulatory strategy for solutions we intend to submit for premarket review.

We have obtained PMA approval for MI Cancer Seek as a companion diagnostic and tumor profiling device. We market MI Cancer Seek as the WES/WTS NGS component of MI Profile. For additional information, see “Risk Factors—Risks Related to Regulation and Legal Compliance—The marketing authorization processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming, and unpredictable. If we are ultimately unable to obtain any necessary or desirable marketing authorizations, or if such marketing authorizations are significantly delayed, our business will be substantially harmed.”

Key Relationships

Supply Agreement with Illumina

In November 2022, we entered into Illumina, Inc.’s (“Illumina”) “open offer” supply agreement wherein Illumina provides products and services that we use in our laboratory operations for certain research and clinical activities, including certain sequencers, equipment, and other materials (the “Illumina Agreement”).

Under the Illumina Agreement, Illumina grants non-exclusive, non-transferable, personal, non-sublicensable rights to use certain Illumina know-how and technology with Illumina products purchased under the agreement, and we granted Illumina an irrevocable, perpetual, worldwide, fully paid-up, and royalty-free license covering improvements to certain Illumina know-how and technology. The Illumina Agreement does not contain any minimum purchase requirements but provides for volume discounts and other promotions. The Illumina Agreement also contains use limitations, representations and warranties, indemnification, limitations of liability, change notification, audit rights, and other provisions.

The Illumina Agreement is irrevocable by Illumina until its expiration in August 2033. We have a unilateral right to terminate our supply relationship with Illumina at any time and for any reason without termination liability upon 90 days’ prior written notice to Illumina.

Master Supply Agreement with Roche

In July 2024, we entered into a master supply agreement with Roche Diagnostics Corporation (“Roche”), for Roche to provide sequencing probes and other testing supplies and equipment for clinical and research uses in our laboratory operations (the “Roche Agreement”). Under the Roche Agreement, we receive certain pricing levels if we purchase a specified minimum annual quantity of supplies. Under the terms of the Roche Agreement, we also agreed to make rolling forecasts of our expected needs, which forecasts currently become three- and six-month binding purchase commitments for catalog and custom products, respectively. The pricing is fixed for the initial 12 months of the agreement term described below, and subject to increase thereafter. The Roche Agreement also contains negotiated use limitations, representations and warranties, indemnification, limitations of liability, and other provisions.

The Roche Agreement has an initial term through April 2027 and will automatically renew with successive one-year terms unless either party provides 90-day advance notice of non-renewal. The agreement also provides for other customary termination rights, including in the case of material breach by, or insolvency of, either party.

Government Regulation

We are subject to complex and frequently changing national, state, and local laws and regulations that govern various aspects of our business. In many jurisdictions, including the United States, the clinical laboratory and medical device industries must operate in accordance with extensive and complex legal standards, including laws and regulations related to certification, licensing, development, research, testing, manufacturing, laboratory operations, distribution, ordering and billing practices, advertising, promotion, marketing, sales and pricing practices, anti-markup practices, health information privacy and security, and consumer protection and unfair trade practices.

We are subject to complex and evolving U.S. laws and regulations governing diagnostic products. Clinical LDTs are regulated by CLIA and applicable state laws. The FDC Act defines medical devices to include in vitro diagnostic reagents and other articles intended for use in diagnosis, treatment, or prevention of disease. The FDA regulates the research, testing, manufacturing, safety, labeling, premarket clearance or approval, marketing, and distribution of medical devices to ensure they are safe and effective for their intended uses.

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For information on the risks we face related to the regulatory environment and other legal matters, see the section titled “Risk Factors—Risks Related to Regulation and Legal Compliance.”

Clinical Laboratory Improvement Amendments of 1988

CLIA establishes quality standards for U.S. laboratories performing testing on human specimens for diagnosis, prevention, or treatment of disease.

CLIA requires laboratories to obtain federal certification and maintain compliance with operational, personnel, quality control, and proficiency testing requirements. CMS administers the CLIA certification program. For every LDT used in clinical testing, CLIA requires analytical validation of performance characteristics including accuracy, precision, specificity, sensitivity, reportable range, and reference interval. Certified laboratories performing certain testing categories must enroll in approved proficiency testing programs. Failure to comply with CLIA requirements can result in loss of certification or revocation of the laboratory’s CLIA certificate.

We operate two clinical laboratory facilities in Phoenix, Arizona with CAP and CLIA accreditations. CLIA-accredited laboratories are inspected every two years.

Prior to offering new solutions, we must satisfy notification requirements to regulatory and accrediting bodies. CLIA-accredited laboratories are reviewed biannually by CMS-approved accreditation organizations and may be subject to additional inspections.

Non-compliance with CLIA requirements may result in enforcement actions including suspension or revocation of CLIA certification, corrective action plans, monetary penalties, or other sanctions that could materially adversely impact our business.

State Laboratory Licensure Laws

In addition to federal CLIA certification, certain states including Maryland, Pennsylvania, New York, California, and Rhode Island require state laboratory licenses with standards for laboratory operations. CLIA provides that states may adopt more stringent regulations. New York requires premarket approval of certain tests including LDTs.

Our Arizona laboratories have obtained out-of-state licenses where required.

Non-compliance may result in suspension, revocation, financial penalties, or other sanctions that could materially adversely impact our business.

Some states also impose registration/licensing on medical device manufacturers, with violations resulting in denial, suspension, revocation, fines, and penalties.

U.S. Food and Drug Administration

In the United States, laboratory tests are subject to regulation by the FDA under the FDC Act and its implementing regulations, and other federal and state statutes and regulations governing medical device development, testing, manufacture, labeling, storage, premarket clearance or approval, advertising, promotion, and distribution.

Laboratory Developed Tests

IVDs are medical devices used in disease diagnosis. The FDA historically considered LDTs a subset of IVDs designed, manufactured, and used within a single laboratory, historically exercising enforcement discretion.

The FDA issued the LDT Final Rule in May 2024 to phase out enforcement discretion and impose medical device requirements; however, a federal district court vacated this rule in March 2025 and the FDA ultimately rescinded this rule in 2025. It remains uncertain whether or when the FDA may in future exercise, or attempt to exercise, medical device authority over LDTs.

FDA Classification and Premarket Review of Medical Devices

PMA Pathway. The FDA categorizes medical devices into three classes (I, II, or III) based on risk and regulatory controls necessary for safety and effectiveness. Class I devices have lowest risk and require adherence to General

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Controls. Class II devices require General Controls and special controls. Class III devices pose greatest risks and require PMA approval.

Class III devices require PMA approval before marketing. Obtaining PMA approval requires submission of valid scientific evidence, complete analytical and clinical performance data, and device information. The FDA reviews the application, may convene an advisory panel, and inspects manufacturing facilities for Quality System Regulation (“QSR”) compliance. The statutory review period is 180 days, though in practice reviews often take significantly longer. The FDA collects user fees for PMA submissions.

FDA will approve the device if it determines there is reasonable assurance of safety and effectiveness. FDA may approve a PMA with post-approval conditions including restrictions on labeling, promotion, and distribution, or requirements for additional clinical studies or post-market surveillance. Failure to comply with conditions of approval can result in material adverse enforcement action, including withdrawal of approval.

Certain changes to an approved device require submission of a PMA supplement or new PMA depending on the nature and significance of the changes.

510(k) Notification Pathway. To obtain 510(k) clearance, a manufacturer must demonstrate the proposed device is “substantially equivalent” to a legally marketed predicate device. The process usually takes three to 12 months but often takes longer. The FDA may require additional information including clinical data and collects user fees for submissions. If the FDA agrees the device is substantially equivalent to a lawfully marketed predicate device, it grants 510(k) clearance. If not substantially equivalent, the device is designated Class III, requiring PMA approval or a de novo classification request for low to moderate risk devices. Once a de novo classification is granted, the device receives Class I or II classification and may serve as a 510(k) predicate for future devices.

After receiving 510(k) clearance or de novo classification, modifications significantly affecting safety or effectiveness require new 510(k) clearance, PMA approval, or de novo classification. Manufacturers determine whether changes require new submissions, but the FDA may disagree and require the manufacturer to cease marketing until new authorization is obtained.

De Novo Classification Pathway. If no legally marketed predicate can be identified for a new device to enable use of the 510(k) pathway, the device is automatically classified under the FDC Act into Class III, which generally requires PMA approval. However, the FDA can reclassify or use “de novo classification” for a device that meets the FDC Act standards for a class I or class II device, which in turn permit the device to be marketed without PMA approval. To grant such a reclassification, the FDA must determine that the FDC Act’s general controls alone, or general controls and special controls together, are sufficient to provide a reasonable assurance of the device’s safety and effectiveness. If the manufacturer seeks reclassification into Class II, the classification request must include a draft proposal for special controls that are necessary to provide a reasonable assurance of the safety and effectiveness of the medical device. The FDA may reject the classification request if it identifies a legally marketed predicate device that would be appropriate for a 510(k) notification or determines that the device is not low to moderate risk or that general controls would be inadequate to control the risks and special controls cannot be developed. The de novo classification route is generally less burdensome than the PMA approval process.

Investigational Device Exemption Process. Clinical trials are almost always required to support a PMA and sometimes required for 510(k) submissions. All clinical investigations must be conducted in accordance with FDA’s IDE regulations. For significant risk devices, the sponsor must submit an IDE application to the FDA supported by appropriate data showing it is safe to test in humans. The IDE becomes effective 30 days after FDA receipt unless the FDA objects.

Studies must be approved by and conducted under IRB oversight. If FDA and IRB approve, human clinical trials may begin at approved sites with approved patient numbers. For significant risk devices, progress reports must be submitted to FDA and IRBs. For non-significant risk devices, sponsors may begin trials after IRB approval without separate FDA approval but must follow abbreviated IDE requirements. Acceptance of an IDE application does not guarantee FDA will allow the IDE to become effective or that trial data will support device safety and effectiveness.

During a study, sponsors must comply with applicable FDA requirements including trial monitoring, IRB review, adverse event reporting, and record keeping. Clinical investigators must obtain patient informed consent and comply with all reporting requirements. We, the FDA, or the IRB could suspend or terminate a clinical trial at any time if risks to subjects outweigh anticipated benefits.

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Expedited Development and Review Programs. The FDA has established programs including Breakthrough Device designation that offer manufacturers opportunities to interact with the FDA more frequently to expedite commercialization. The program is available to devices that provide more effective treatment or diagnosis of life threatening or irreversibly debilitating diseases and meet certain eligibility criteria.

Postmarket Regulation. After a device is cleared or approved, numerous regulatory requirements continue to apply, including: establishment registration and device listing; QSR compliance; labeling regulations and off-label promotion prohibitions; approval of product modifications; Medical Device Reporting; correction, removal, and recall reporting; post-market surveillance; and Unique Device Identifier requirements.

Manufacturers must comply with QSR requirements and are subject to periodic FDA inspections. Failure to maintain QSR compliance could result in manufacturing restrictions, product recalls, or seizures. Discovery of previously unknown problems with products could result in restrictions on the device, including removal from the market or device recalls.

FDA Enforcement Powers. The FDA has broad regulatory compliance and enforcement powers. If the FDA determines a manufacturer has failed to comply with applicable requirements, it can take various compliance or enforcement actions including: warning letters, fines, injunctions, and civil penalties; recalls or seizures; manufacturing restrictions or shutdowns; refusing or delaying marketing clearances or approvals; withdrawing clearances or approvals already granted; refusing export approvals; or criminal prosecution.

Healthcare Fraud and Abuse Oversight

A variety of federal and state laws prohibit fraud and abuse involving healthcare programs and private insurers. These laws are interpreted broadly and actively enforced by CMS, DOJ, and OIG. Violations may result in significant penalties including administrative and civil fines, criminal penalties, loss of licensure, disgorgement, imprisonment, exclusion from federal healthcare programs, and additional reporting obligations.

Federal and State Physician Self-Referral Prohibitions. The federal Stark Law generally prohibits entities from billing Medicare or Medicaid for designated health services, including laboratory services, when the ordering physician or immediate family member has an ownership interest or compensation arrangement with that entity, unless certain exceptions apply. The Stark Law is a strict liability statute. Sanctions include denial of payment, refunds, monetary penalties, and exclusion from federal healthcare programs. Violations may also serve as the basis for FCA liability. Many states have similar self-referral bans that may extend to all payers.

The Anti-Kickback Statute. The federal AKS prohibits knowingly and willfully offering, paying, soliciting, or receiving remuneration to induce referrals of items or services reimbursable by federal healthcare programs. Remuneration is broadly defined to include anything of value. The AKS contains statutory exceptions and regulatory safe harbors that protect certain arrangements if specific requirements are met. Violations may result in significant penalties including imprisonment, fines, and exclusion from federal healthcare programs, and may also incur FCA liability. Some states have similar AKS laws that may apply to all payers.

Eliminating Kickbacks in Recovery Act. EKRA is an all-payer anti-kickback law that criminalizes paying or offering remuneration to induce referrals to recovery homes, substance use clinical treatment facilities, or laboratories. Although there is overlap between EKRA’s exceptions and AKS safe harbors, compliance with an AKS safe harbor does not guarantee protection under EKRA. DOJ has not yet issued clarifying regulations, and relationships between laboratories and physicians, sales representatives, hospitals, and customers may be subject to scrutiny under EKRA.

False Claims Act. The FCA prohibits knowingly submitting false claims, making false records or statements to secure payment, or knowingly retaining overpayments from the federal government. Claims resulting from AKS violations may constitute false claims under the FCA. Penalties include payment of up to three times actual damages, substantial per-claim civil penalties, and possible exclusion from federal healthcare programs. The FCA’s qui tam provisions allow private individuals to bring actions on behalf of the government and share in recoveries. Several states have similar laws that may apply to any payer, including private insurers. For a discussion of such a proceeding in which we are currently involved, please see “—Legal Proceedings.”

Healthcare Fraud and False Statements. The federal healthcare fraud statute criminalizes knowingly and willfully defrauding any healthcare benefit program. The false statements statute prohibits knowingly and willfully falsifying, concealing, or making materially false statements in connection with healthcare delivery or payment. Violations may result in fines, imprisonment, or exclusion from government healthcare programs.

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Civil Monetary Penalties Law. The federal CMP law prohibits, among other things, offering remuneration to federal healthcare program beneficiaries to influence their ordering decisions, employing or contracting with excluded individuals or entities, billing for services requested by unlicensed or excluded providers, and billing for medically unnecessary services. Penalties include exclusion from federal healthcare programs and substantial fines.

Physician Payments Sunshine Act. The Sunshine Act requires certain manufacturers to collect and report annually to CMS data on payments and transfers of value to U.S. licensed physicians, teaching hospitals, and certain advanced non-physician healthcare practitioners. The Open Payments program is administered by CMS. Several states have similar reporting requirements.

While we intend to comply with applicable fraud and abuse laws, some of our arrangements may become subject to regulatory scrutiny, and we cannot be certain we will be found in compliance following any such review.

Other Potentially Applicable State Laws

Other Potentially Applicable State Laws. States may have additional fraud and abuse laws including fee-splitting restrictions, insurance fraud laws, anti-markup laws, direct billing requirements, prohibitions on waiving patient cost-sharing, prohibitions on providing solutions at no or discounted cost to induce adoption, and corporate practice of medicine prohibitions. Violations may result in civil or criminal penalties and sanctions.

Additional International Regulation and Product Approval

Additional International Regulation and Product Approval. We may have to obtain or submit approvals, markings, notifications, or satisfy other premarket requirements from regulatory authorities in non-U.S. jurisdictions prior to marketing our solutions in those countries and territories. The laws and regulations in other jurisdictions vary from those in the United States and may be more difficult to satisfy, and they are subject to change, in some cases frequently. Certain regulatory authorities regulate LDTs and IVDs differently than the United States, and our solutions may need to satisfy additional requirements to be offered commercially within the jurisdictions.

European Union

The European Union adopted IVDR 2017/746 in May 2017, replacing the IVD Directive in May 2022. IVDR requires notified body involvement for many more IVDs. Transitional provisions allow IVDs with certificates under the IVD Directive to continue until May 2024 at the latest. After transitional periods, only IVDR CE-marked IVDs may be placed on EU markets.

Other Jurisdictions

Expanding into other countries requires compliance with varying healthcare and other laws and regulations that are complex, change frequently, and differ among jurisdictions.

Coverage and Reimbursement

Reimbursement and billing for clinical laboratory services is highly complex. Laboratories must bill various payers including federal healthcare programs (Medicare, Medicaid, TRICARE), Medicare Advantage plans, private insurers, and managed care organizations, each with different billing requirements and audit requirements.

We are currently pursuing and will continue to pursue payment for our solutions through a diverse and broad range of channels, including coverage and reimbursement by government healthcare programs and commercial third-party payers.

A payer’s decision to cover a solution does not guarantee adequate reimbursement. Third-party payers increasingly examine medical necessity and cost-effectiveness of clinical laboratory tests in addition to safety and efficacy. Coverage and reimbursement differ significantly among payers. The coverage determination process is often time-consuming and costly, requiring us to provide scientific and clinical support to each payer separately, with no assurance of consistent coverage or adequate reimbursement. In certain foreign markets, governments control coverage and pricing of healthcare products. The marketability of our solutions may suffer if payers fail to provide adequate coverage and reimbursement. Coverage policies and reimbursement rates may change at any time.

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Coverage and Reimbursement in the United States

In the United States, there is no uniform coverage for clinical laboratory tests, and obtaining coverage for genomic sequencing solutions is particularly challenging. Medicare is the largest healthcare payer in the United States and a significant payer for cancer-related laboratory services. Many U.S. payers look to Medicare policies as a benchmark for their own coverage and reimbursement decisions. Medicare provides traditional fee-for-service coverage and Medicare Advantage coverage administered by private insurers.

Medicare’s NGS NCD, established in 2018 and updated in 2020, provides national Medicare coverage for certain molecular diagnostic tests meeting specified criteria. MACs may provide local coverage of other NGS tests through LCDs. Palmetto GBA administers Medicare’s MolDX, which issues LCDs for molecular diagnostic tests not approved or cleared by the FDA. Our MAC is Noridian, which relies on MolDX for coverage and pricing determinations. To achieve MolDX coverage, a test must demonstrate analytical and clinical validity, and clinical utility. Our MI Cancer Seek solution has Medicare coverage under the NGS NCD. Our MI Tumor Seek Hybrid solution and Caris Assure solution for therapy selection are covered by Medicare under the MolDX Program. MolDX has issued LCDs providing coverage for MRD for CRC, breast cancer, lung cancer, and other indications when applicable coverage criteria are satisfied, and for NGS assays for myeloid malignancies. In order to obtain MolDX coverage for Caris ChromoSeq, we will need to submit, and MolDX will need to approve, a technical assessment.

Coding plays a significant role in reimbursement. CPT codes and PLA codes (maintained by the AMA) are used for medical and laboratory services billing. Z-Code Identifiers are used by certain payers including MolDX to supplement CPT codes for molecular diagnostics tests. In July 2020, the AMA issued PLA code CPT 0211U for our MI Cancer Seek solution. CMS established national pricing at $8,455 under the CLFS. Our MI Tumor Seek Hybrid solution uses CPT code 81479 and unique Z-Code Identifiers. In July 2024, the AMA issued PLA code CPT 0485U for Caris Assure for therapy selection. In November 2024, CMS determined to price Caris Assure using the “Gapfill” method, which resulted in a price under the CLFS of $3,649, effective January 1, 2026. Changes to coverage policies or codes may result in significant changes in reimbursement.

Our early detection solution could be considered a screening test and is not currently covered by Medicare. Medicare coverage for preventive services must be expressly authorized by statute or by CMS under an NCD and historically required specified criteria including United States Preventive Services Task Force ("USPSTF") recommendation with a grade of A or B. Recent legislation enacted as part of the Consolidated Appropriations Act, 2026, creates an alternative pathway for FDA-approved MCED tests beginning in 2028 without requiring USPSTF endorsement. None of our early detection solutions have received an "A" or "B" grade from USPSTF. Under the traditional NCD pathway, the NCD process may take multiple years, and it is possible that our early detection solution Caris Detect will not become eligible for Medicare coverage through that pathway. The alternative pathway would require us to obtain FDA approval for Caris Detect, and any reimbursement may not adequately cover our costs. We do not currently have plans to seek Medicare coverage for Caris Detect. We currently plan to launch Caris Detect as a cash pay only test, however, the scale of adoption of Caris Detect may be impacted by whether coverage is available for Caris Detect or competitor tests.

The Protecting Access to Medicare Act of 2014

The Protecting Access to Medicare Act of 2014 (“PAMA”). PAMA (as amended) requires certain laboratories to report private payer payment rates, test volumes, and HCPCS codes. CMS uses this data to calculate weighted median payment rates to establish revised Medicare CLFS reimbursement rates for CDLTs. The reimbursement rate we receive for newly developed tests may be affected by payment rates from private payers. PAMA codified Medicare coverage rules for laboratory tests and authorizes CMS to consolidate coverage policies among laboratory-specific MACs. The revised reimbursement methodology generally results in relatively lower reimbursement amounts. Reductions are limited to 0% in 2026 and 15% per test per year in 2027 through 2029. Data reporting occurs in three-year cycles, with the next cycle beginning in 2026. Given uncertainties in PAMA’s price-setting process, we cannot predict how payments under the CLFS may change from year to year.

Healthcare Reform

There have been numerous legislative and regulatory changes to the healthcare system in the United States and certain foreign jurisdictions. Changes in healthcare policy could increase our costs, subject us to additional regulatory requirements, decrease our revenue, and adversely impact sales of and reimbursement for our solutions. The ACA, signed into law in March 2010, substantially changed healthcare financing by governmental and private insurers and included provisions governing enrollment in federal healthcare programs, reimbursement adjustments, and fraud and abuse. Since enactment, there have been judicial, Congressional, and executive branch challenges to aspects of the ACA. The Inflation

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Reduction Act of 2022 (the “IRA”) extended enhanced subsidies for ACA marketplace coverage through 2025 and eliminated the Medicare Part D “donut hole” beginning in 2025. Other legislative changes since the ACA include the Budget Control Act of 2011 (reducing Medicare provider payments through 2032), the American Rescue Plan Act of 2021 (requiring additional Medicare payment reductions delayed until 2025), the American Taxpayer Relief Act of 2012 (reducing CMS payments and extending statute of limitations for Medicare overpayment recovery), and the One Big Beautiful Bill Act enacted in July 2025 (imposing significant Medicaid funding reductions). We believe there will continue to be proposals to reduce costs while expanding healthcare benefits. Changes in healthcare policy could increase our costs, decrease our revenue, and impact sales of and reimbursement for our solutions.

Privacy Regulation

Data Privacy and Security Regulation. Numerous federal, state, and foreign laws and regulations, govern the collection, dissemination, use, access to, confidentiality, and security of personal information, including health-related information. In the U.S., data breach notification laws, HIPAA, HITECH, and consumer protection laws apply. We are a HIPAA Covered Entity for healthcare services and a Business Associate for certain services, requiring policies for PHI protection, administrative/physical/technical safeguards, and breach notifications. Many states have healthcare privacy and genetic testing laws requiring patient consent and protecting test results. Privacy and security laws constantly evolve and can result in investigations, penalties, and data processing restrictions. We are subject to Section 4004 of the 21st Century Cures Act and HHS regulations for patient access to EHI and interoperability.

Other International Privacy and Security Regulations. We are subject to evolving global data privacy, security, cross-border transfer, and localization laws. Many governments are implementing or expanding data protection regimes, resulting in additional compliance costs and risks. Laws are subject to change and uncertain interpretation and could result in claims, changes to business practices, penalties, increased costs, or harm to our business.

We rely on IT systems including third-party hosted services storing personal data, creating cybersecurity risk. A cybersecurity incident could result in system unavailability, data loss/misuse/unauthorized disclosure, negative publicity, reputational damage, litigation, and regulatory investigations. Data breach notification laws may require notifying regulators, affected individuals, and other third parties.

Our Employees

As of December 31, 2025, we had 1,846 employees. None of our employees are represented by a labor union or party to a collective bargaining agreement.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing, and integrating our existing and new employees, advisors, and consultants. We believe our success depends on our ability to attract, retain, develop, and motivate diverse highly skilled personnel. In particular, we depend upon the personal efforts and abilities of the principal members of our senior management to partner effectively as a team and to provide strategic direction, develop our business, manage our operations, and maintain a cohesive and stable work environment. We also rely on qualified managers and skilled employees, such as scientists, engineers, and laboratory technicians, with technical expertise in operations, scientific knowledge, engineering skills, and quality management experience in order to operate our business successfully.

Our compensation programs are designed to retain, motivate, and attract highly qualified personnel, including through the granting of stock-based and cash-based compensation awards, in order to increase shareholder value and the success of our Company by motivating such individuals to perform to the best of their abilities and achieve our business objectives.

Corporate History

We were founded in 2008 when we entered the field of precision oncology through our acquisition of Molecular Profiling Institute, a Delaware-incorporated molecular life sciences company. We were incorporated under the laws of the Cayman Islands in October 2011 as Caris Life Sciences, Ltd. and in July 2020, we changed our name to Caris Life Sciences, Inc. and re-domiciled to be incorporated in Texas.

Available Information

Our website address is https://www.carislifesciences.com. At our Investor Relations website, https://investor.carislifesciences.com, we make available free of charge a variety of information for investors, including our

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Annual Report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and any amendments to those reports, as soon as reasonably practicable after we electronically file that material with or furnish it to the Securities and Exchange Commission (the “SEC”). We intend to use our Investor Relations website as a distribution channel of material information about the Company and for complying with our disclosure obligations under Regulation FD. The information we post on our Investor Relations website may be deemed material. Accordingly, investors should subscribe to our investor alerts, in addition to following our press releases, SEC filings, public conference calls and webcasts. The SEC also maintains a website that contains our SEC filings at www.sec.gov. Information contained on, or connected to, these websites does not and will not constitute part of this Annual Report on Form 10-K, or any other filings with, or any information furnished or submitted to, the SEC.