BillionToOne, Inc. 10-K

Item 1. Business Unless context requires otherwise, references to “we,” “us,” “our,” “BillionToOne,” or “the Company” here refer to BillionToOne, Inc. Overview BillionToOne is transforming healthcare by redefining molecular diagnostics. Our revolutionary single molecule next-generation sequencing (smNGS) platform achieves what was once thought impossible—detecting and precisely quantifying genetic targets with single-molecule sensitivity. At the heart of this technological breakthrough lies our patented Quantitative Counting Templates (QCTs), enabling measurements at the physical limit of detection—the single DNA molecule. This leap forward addresses a fundamental limitation in healthcare—the inability to detect sparse but clinically crucial disease signals in cell-free DNA (cfDNA). Our superior technology platform has enabled us to build category-defining prenatal and oncology products. Our products reveal actionable insights from a simple blood draw that are fundamentally changing how diseases are diagnosed and treated, leading to a paradigm shift in personalized medicine, overcoming the technical noise that restrains the traditional next-generation sequencing (NGS) testing methods used by other diagnostic companies. We believe our novel smNGS platform technologies combined with our AI-enhanced integrated workflow, allows us to push the technology frontier forward and deliver on the full promise of non-invasive liquid biopsy. Founded with the mission to remove the fear of the unknown through powerful and accessible smNGS-based diagnostics, we have swiftly transitioned from an R&D-focused company to a proven commercial organization. In 2019, we launched our first prenatal product, UNITY. UNITY is the first NIPT that uses cfDNA to provide fetal risk assessment for recessive conditions such as sickle cell disease and cystic fibrosis without requiring a paternal sample or invasive procedures such as amniocentesis. Since then, we have established ourselves as a leader, based on revenue and American College of Obstetricians and Gynecologists (ACOG) practice advisory guidelines, in the prenatal testing market and expanded our UNITY offering to cover comprehensive prenatal genetic needs from a single maternal blood draw. While some competitors have launched competing NIPTs for recessive conditions, we believe the differentiation of our smNGS technology, as well as five years of accumulated data and publications, will allow us to maintain our competitive advantage as this type of testing becomes the standard of care and significantly improves patient outcomes. In the oncology setting, ultrasensitive tests with real-time insights are required to effectively detect, diagnose, and treat patients with a diverse range of mutations and solid tumor types across the cancer care continuum. In 2023, we successfully leveraged our smNGS platform to launch two complementary pan-cancer liquid biopsy tests – Northstar Select and Northstar Response. Our Northstar Select test is used to guide therapy selection and has been shown to detect over 50% more actionable solid tumor mutations than conventional liquid biopsies, when compared to comparator products in the aggregate. Based on our knowledge of all widely available tests, Northstar Response is the only methylation-based assay that quantifies the amount of cancer (tumor burden) at the single molecule level without requiring a tissue biopsy, enabling real-time monitoring of patient response to therapy with unprecedented precision. Our Northstar tests give physicians extraordinary visibility into cancer profile and treatment response, enabling more informed and earlier treatment decisions that can fundamentally alter patient outcomes. Backed by our commitment to continued innovation and high-quality execution, we aim to lead the next wave of advancements in precision diagnostics, delivering profound benefits to patients, providers, and the broader healthcare system. Our Four Pillars of Differentiation At BillionToOne, we are building a different type of molecular diagnostics company, backed by our four pillars of differentiation described below. We believe these competitive advantages are difficult for others to replicate and uniquely position us to redefine the industry. Our breakthrough technology platform. Our revolutionary platform achieves absolute quantification at the single molecule level, enabling us to: (i) accurately quantify genetic targets by using our QCTs as amplification 5 Table of Contents controls to detect and eliminate biases and errors that would otherwise be introduced from PCR amplification during library preparation for NGS; (ii) precisely measure and analyze intermediate biochemical reactions to optimize the performance of our assays; and (iii) reduce sequencing costs by obtaining a higher quality signal at each genomic location analyzed by significantly reducing total reads required per sample. Moreover, we believe our design-based R&D approach allows us to harness this quantitative technology to mathematically model and accurately predict the clinical performance of a novel assay before testing a single patient sample, which we believe accelerates time-to-market and significantly improves our commercial launch success rate. Collectively, these platform capabilities enable us to build better products while we simultaneously decrease costs. Our category-defining products. As demonstrated in multiple analytical and clinical studies, as well as peer reviewed publications, we have leveraged our smNGS platform to create differentiated prenatal and oncology products with 10 times greater precision versus other available tests. For example, our UNITY test has extended NIPT from detecting one million-plus base pair conditions to single base pair conditions. This advancement is already starting to impact the treatment options for babies affected by these severe recessive conditions. In addition, our Northstar Select and Response tests deliver superior sensitivity and precision, respectively, and can generate clinically relevant insights for late-stage cancer therapy selection and response monitoring that may otherwise have been missed or delayed through conventional liquid biopsy tests and/or imaging tools. We believe that each of our products has the potential to become the standard of care in its respective market. Furthermore, we believe our competitive moat will strengthen over time as we continue to enhance and expand our portfolio of ultrasensitive tests. Our ability to deliver rapid growth at scale. The differentiated nature of our products and our relentless commitment to improving the patient and provider experience have resulted in recurring use of our tests with extremely low customer churn. Our existing accounts have created a stable and growing revenue base with increasing penetration, and we see similar adoption trends in new clinics, as we continue our expansion within existing and new territories. We believe this market setup, along with our scaling business, provides a significant opportunity for us to grow over the near and long-term horizon. Our superior efficiency. We believe our capital efficiency and emerging profitability set us apart from other molecular diagnostics companies especially at our scale. Since inception we have produced a track record of cost efficiency. Going forward, our financial discipline will continue to be integral to our innovation efforts. By prioritizing efficiency, we have been able to consistently invest in R&D and commercial expansion while reducing losses over time and achieving profitability as measured on both income from operations and net income basis. In doing so, we believe we have established a differentiated financial profile that positions us for sustainable value creation. Background on cfDNA and the limitations of traditional NGS technologies cfDNA represents one of the most promising biomarkers in modern precision medicine. cfDNA is continuously shed from all tissues into the bloodstream and has a short half-life of approximately one to two hours. This transient nature gives cfDNA a unique capability to provide a real-time snapshot of cellular turnover and can be used to diagnose and monitor disease, as both genetic and epigenetic properties of cfDNA directly reflect the originating tissue. Despite its potential, the detection of cfDNA is fundamentally challenging due to its limited quantity in blood and short half-life. Certain conditions that stem from large scale genetic changes or generate abundant quantities of cfDNA in the bloodstream can be identified by previous testing approaches. However, other serious conditions may have lower DNA shedding rates which can result in very few relevant DNA fragments in the blood. These conditions are nearly undetectable with previous cfDNA detection techniques. For example, even in a late-stage cancer patient, there may only be one mutated cell-free tumor DNA molecule found in one tube of blood. While traditional NGS has revolutionized genomic medicine over the past decade, it faces inherent limitations when applied to the analysis of cfDNA. Conventional NGS technologies are primarily limited to presence or absence detection. For example, within germline testing, which includes nearly unlimited input DNA material, the clinically relevant changes are detected at around 50% additional disease burden. However, in cfDNA applications, these clinically relevant changes can be at the level of 0.01% of cfDNA in blood. These applications require ultrasensitive quantification at the single molecule level that we believe is only possible with our smNGS platform. Further complicating the challenge, cfDNA samples undergo numerous enzymatic, amplification, and other biochemical steps prior to sequencing. Each of these steps introduces technical noise that makes it harder for traditional sequencing technologies to accurately quantify the absolute and relative abundance of cfDNA sequences in the biological specimen, resulting in lower sensitivity and specificity. 6 Table of Contents Our Proprietary Single-Molecule Next-Generation Sequencing Platform (smNGS) We have developed a transformative technology platform that redefines the possibilities of cfDNA analysis. In the past, the significant advancements from polymerase chain reaction (PCR) to Sanger Sequencing to NGS expanded molecular diagnostics from being limited to infectious disease testing and human genome mapping to now becoming standard of care for genetic screening. The cornerstone of our platform is its ability to resolve and quantify individual DNA molecules with absolute precision. This single-molecule resolution provides extraordinary visibility into the biological signals present in a sample, even when the target DNA represents just one molecule among billions. Beyond mere detection, our technology enables absolute quantification of cfDNA, eliminating the reliance on relative measurements that has constrained previous approaches. This quantitative foundation allows us to transform every aspect of our operations in a measurable way, from research and development to clinical testing and quality control. While traditional diagnostic approaches have often relied on trial-and-error experiments to screen for incremental improvements, our smNGS platform does not. The quantitative nature of the data that our smNGS platform generates is critical to our success in creating ultrasensitive, differentiated molecular diagnostics. Perhaps most significantly, we believe our smNGS technology transcends the precision-versus-scale tradeoff that has limited legacy diagnostic methods. Conventional genetic analysis techniques, such as NGS and digital droplet PCR (ddPCR), typically sacrifice either sensitivity or multiplexing, i.e., ability to interrogate many genomic loci at the same time, forcing compromises in clinical utility. We believe our platform eliminates this constraint, delivering both high sensitivity and broad genomic coverage simultaneously. This unique capability allows us to provide physicians and patients with more actionable information from cfDNA that was previously possible only with more invasive diagnostics. Our smNGS platform is powered by several patented technologies, most notably the use of synthetic DNA fragments, called QCTs. QCTs encode the molecular information in sequencing data which are subsequently decoded using proprietary machine learning and bioinformatic algorithms, enabling us to precisely quantify cfDNA. The precision and multiplexability of QCT-powered assays make them ideal for addressing clinically significant challenges where sensitivity of rare-variant detection or quantification necessary for longitudinal measurements is essential. The power of QCTs is best exemplified when the clinical problem itself is quantitative, as in the case of fetal risk assessment of recessive conditions during pregnancy and monitoring of response to therapy in a cancer patient. QCTs and our other smNGS technologies also serve as the backbone of our technical operations. We leverage this quantitative foundation to track samples throughout our workflows, to drive continuous operational improvement, and to support robust quality controls. For instance, QCTs detect cross-contamination down to the level of <0.001% and thereby enable the creation of carefully constructed and automated end-to-end laboratory workflows, including special laboratory infrastructure, that prevent such cross-contamination that could otherwise be a bottleneck on sensitivity and specificity of an assay. The financial impact of our technology platform is substantial. We believe the ability to quantify biomarkers enables us to rationally design and engineer superior diagnostic tests optimized for clinical performance, scalability, and cost of goods sold (COGS). Our smNGS platform therefore drives our differentiated financial performance both by enabling the development of unique products and by de-risking clinical studies before dedicating significant resources. Our platform is a key differentiator versus our peers in the molecular diagnostics space and is protected by a robust and growing collection of patents and proprietary know-how. Our Solution & Suite of Products Our product portfolio of ultrasensitive tests touches everyone from the beginning of life, with prenatal genetic testing, to the end of life, with cancer therapy selection and response monitoring. We launched our initial prenatal product, UNITY, in 2019. Today, we believe it is becoming the new standard of care, as evidenced by two recent ACOG practice advisory changes that cited our publications in support of the change. With UNITY, we have leap-frogged the resolution of cfDNA testing from one million base-pair chromosomal abnormalities to single base-pair recessive conditions. In this highly competitive market with increasing commoditization, our differentiated UNITY Fetal Risk Screen remains the only cfDNA test for these conditions. with peer-reviewed clinical publications. 7 Table of Contents We have more recently entered the oncology market, initially focusing on addressing the highest unmet need areas of therapy selection and response monitoring in late-stage cancer patients. To date, we have launched multiple products in these markets, which are described below. Prenatal products Traditional prenatal screening focuses on assessing a fetus’ risk for larger chromosomal changes. However, many common and severe conditions are the result of much smaller genetic changes, in single base pairs. These recessively inherited conditions, including sickle cell disease (SCD), alpha thalassemia, beta-thalassemia, cystic fibrosis (CF), and spinal muscular atrophy (SMA), are collectively more common than aneuploidy conditions like Down syndrome. Yet these conditions cannot be directly tested with traditional NIPT since each condition requires the precise quantification of fetal cfDNA. Given the technical challenges of directly assessing the fetal risk for these conditions, current medical guidelines recommend that every pregnant patient is offered carrier screening, with father screening then required if the mother is found to be a carrier. However, studies estimate that fewer than half of fathers complete the recommended screening due to barriers related to cost, availability, and willingness. As a result, approximately 58% of pregnancies affected by these recessive conditions are undetected by traditional screening workflows. Our UNITY Fetal Risk Screen directly addressed these challenges and is the first test that uses cfDNA to provide precise fetal risk assessments for recessive conditions without requiring a paternal sample. In addition, it reports fetal aneuploidy and 22q11.2 microdeletion, enabling complete genetic insights from a single maternal blood draw. Our UNITY Complete portfolio Our UNITY prenatal testing portfolio includes the first sgNIPT that uses cfDNA to achieve precise fetal risk analysis without requiring a paternal sample – a breakthrough that enhances accessibility, ease of use, and adoption across patient populations. In 2020, we added Aneuploidy and RhD NIPT to create our UNITY Complete offering. In 2022, we added other fetal red blood cell antigens for alloimmunized pregnancies at risk for HDFN without requiring a paternal sample or invasive procedures such as amniocentesis. Our portfolio delivers unmatched clinical insights through the screening for recessive conditions, aneuploidies, and fetal antigens using a single maternal blood draw. We believe our offering provides the most comprehensive view of fetal health available today. UNITY Fetal Risk Screen In 2019, we launched UNITY Fetal Risk Screen as the first sgNIPT that uses cfDNA to provide fetal risk assessments for recessive conditions. This breakthrough approach addresses a major gap in traditional carrier screening and enhances accessibility, speed, and accuracy for all pregnant patients. In May 2025, we expanded UNITY Fetal Risk Screen’s testing menu to include up to 14 conditions, further enhancing its clinical impact. The first step of the UNITY Fetal Risk Screen involves determining the maternal carrier status. If the mother is identified as a carrier, cfDNA analysis is performed on the same blood sample to assess fetal risk. We believe directly measuring fetal risk through a single maternal blood draw is only possible with the precision and sensitivity provided by our smNGS technology. Within two weeks, the information provided to the clinician and patient includes: • Maternal carrier status and any information about the specific variant that may be identified; 8 Table of Contents • A personalized fetal risk score on each condition for which the pregnant mother is a carrier, ranging from <1 in 5,000 to 9 in 10, providing clear, actionable information for clinicians and patients; and • Whether the risk is classified as low or high risk. UNITY Fetal Risk Screen’s accuracy has been validated in multiple peer-reviewed studies. A 2023 study published in Prenatal Diagnosis demonstrated 100% of “9 in 10” risk pregnancies were confirmed to be affected pregnancies. Because UNITY Fetal Risk Screen does not rely on paternal testing, which is often not completed, it detects up to three times as many affected pregnancies for these recessive conditions compared to traditional carrier screening. UNITY Aneuploidy Screen In 2020, we launched our UNITY Aneuploidy Screen, which we believe has become the most performant assay for aneuploidies. Compared to many competing tests, our test overcomes the significant challenge of low fetal cfDNA levels in the mother’s blood, which often produces inconclusive results. This issue can be particularly pronounced for single nucleotide polymorphism-based NIPTs, which tend to have a higher fetal fraction cutoff to provide conclusive results. Our smNGS platform provides a critical signal boost that is especially noticeable at lower fetal fractions, significantly reducing inconclusive results. In addition to robust performance above 99.7% sensitivity and 99.9% specificity for common trisomies, UNITY Aneuploidy NIPT uniquely leverages smNGS technology to enhance 22q11.2 Microdeletion Analysis, addressing a critical gap in competing prenatal screening tests. As the most common microdeletion disorder, 22q11.2 deletion syndrome (DiGeorge Syndrome) has historically resulted in low positive predictive values (PPV), reducing clinical confidence and resulting in patient anxiety. smNGS enables >95% sensitivity and >99.9% specificity, which results in an industry-leading PPV of 80% in average risk pregnancies. More than 75% of UNITY Aneuploidy orders now include 22q11.2 optional add-on testing. UNITY Fetal RhD NIPT Approximately 15% of pregnant individuals in the United States are RhD-negative, putting them at risk of RhD alloimmunization if they are carrying an RhD-positive fetus. To prevent this, the standard of care has been the administration of Rho(D) immune globulin (RhIG) (e.g., RhoGAM) at 28 weeks’ gestation and postpartum. However, this approach lacks precision, as 40% of RhD-negative pregnancies do not require RhIG because the fetus is also RhD-negative. Administering RhIG to these pregnancies is unnecessary, costly, and limits supply availability for those who need it most. This is because RhIG availability can be limited given it is a blood product derived from human donors. To address this issue, we launched UNITY Fetal RhD NIPT in 2020 to detect fetal D antigen. While other tests for fetal RhD detection were launched in 2024, UNITY Fetal RhD NIPT remains the only test that can accurately detect fetal RhD status when the pregnant individual has RhD and RhD-CE-D hybrid genes, which are prevalent in Black (45%) and Asian (>10%) populations. Other fetal RhD NIPTs are limited in their ability to detect these genetic complexities. UNITY Fetal RhD NIPT addresses these limitations through our revolutionary smNGS platform. Since launching, UNITY Fetal RhD NIPT has been ordered for over 150,000 patients, with data published in peer-reviewed studies demonstrating 100% concordance with neonatal outcomes and sensitivity/specificity of >99.9%. UNITY Fetal Antigen NIPT Alloimmunization occurs when a pregnant individual’s immune system produces antibodies against fetal red blood cell (RBC) antigens. This can happen when an RhD negative pregnant mother carrying an RhD positive fetus does not receive RhIG. This can also happen with other rare RBC antigens are present, such as Kell, especially due to a blood transfusion prior to the pregnancy. This can lead to HDFN, a condition that can cause severe anemia, hydrops fetalis, or fetal demise. Managing these pregnancies is challenging. The current methods to determine fetal antigen status, such as amniocentesis, are often invasive. These invasive procedures could cause maternal and fetal blood to mix, which would exacerbate HDFN. As a result, many patients experience undue anxiety, unnecessary and expensive weekly monitoring, frequent antibody titer checks, and intensive surveillance. In approximately 65% of these pregnancies, the fetus is negative for the antigen and therefore there is no fetal risk. To address this issue, we launched UNITY Fetal Antigen NIPT in 2022. Our UNITY Fetal Antigen NIPT addresses a critical gap in managing alloimmunized pregnancies and detects key fetal RBC antigens, including D, C, c, E, K (Kell), and Fya (Duffy), helping to guide clinical decisions and reduce unnecessary monitoring. As 9 Table of Contents the only commercially available test for fetal antigen screening in the United States, UNITY Fetal Antigen NIPT not only solves a previously unmet clinical need but has deepened our relationships with Maternal-Fetal Medicine (MFM) specialists. UNITY Fetal Antigen NIPT’s clinical accuracy has been validated in multiple peer-reviewed publications, including a Scientific Reports study demonstrating 100% concordance between test results and neonatal antigen status. UNITY Fetal Antigen NIPT offers 100% sensitivity and specificity while maintaining a no-call rate of <0.1%, ensuring highly reliable results. In 2024, ACOG issued two clinical guideline updates, referencing UNITY Fetal RhD NIPT and UNITY Fetal Antigen NIPT data: (i) acknowledging the role of fetal RhD NIPT in triaging anti-D immunoglobulin (e.g., RhoGAM) use, particularly amid shortages, and (ii) endorsing UNITY Fetal RhD NIPT as a reasonable alternative for guiding management of alloimmunized patients who decline invasive testing. These clinical guideline updates recognized comparable performance of our assay to invasive diagnostic testing while avoiding complications. They not only validated the clinical utility of our UNITY Fetal RhD NIPT and UNITY Fetal Antigen NIPT but also further highlighted their critical role in enhancing patient care and ensuring effective management of patients across diverse populations. In February 2026, we announced the launch of our expanded Red Blood Cell (RBC) Fetal Antigen NIPT and a first-and-only Platelet Fetal Antigen NIPT. Available exclusively through the UNITY Aneuploidy™ Screen, these offerings represent the first-and-only non-invasive prenatal tests in the U.S. designed to determine fetal antigen status across both red blood cell and platelet antigens in pregnancies affected by or at risk for HDFN and FNAIT. These conditions together affect or place at risk approximately 1.5-2.5% of pregnancies in the U.S., a rate higher than the genetic burden of aneuploidies. UNITY Fetal Antigen CTA NIPT In December 2023, we announced a global partnership with Johnson & Johnson to provide our UNITY Fetal Antigen clinical trial assay (CTA) in their AZALEA Phase 3 clinical trial of nipocalimab in pregnancies at risk for severe HDFN. In April 2023, the FDA granted an Investigational Device Exemption (IDE) for the assay’s use in the trial. Final FDA approval of the companion diagnostics indication is dependent on the success of the Johnson & Johnson AZALEA Phase 3 clinical trial. We have also received regulatory clearances from health authorities in certain European and Latin American countries for the use of the assay in a global clinical trial. We believe that a successful completion of this Phase 3 trial may enable our test to be the first NIPT that is granted a companion diagnostics indication. Our comprehensive customer experience and commitment to quality and innovation beyond our tests UNITY Complete is more than just a test, it is a fully integrated, end-to-end experience that delivers a seamless workflow for both patients and providers. Over the years, we have developed various software tools to support the entire testing workflow for providers and patients, which has fueled the rapid growth of the UNITY Complete portfolio. We continuously refine our workflow to address the evolving needs of obstetric providers, in an effort to maximize efficiency, accessibility, and ease of adoption for both patients and providers. By combining unique clinical testing with workflow enhancements, we believe UNITY Complete has established a highly scalable infrastructure that streamlines every step of the journey, further solidifying that UNITY Complete is becoming the new standard in prenatal care. Oncology products 10 Table of Contents Precision oncology continues to be a focus in the global fight to cure cancer. However, despite significant advancements and growth in the field, cancer continues to rank as the second leading cause of death worldwide, with persistently high mortality rates. Liquid biopsies, or blood-based tests that interrogate ctDNA, cfDNA released from a tumor cell, for therapy selection or disease monitoring have recently become available for clinical practice as non-invasive, rapid and readily available alternatives to traditional tissue-based biopsies. Despite the increase in uptake, current liquid biopsies developed using standard NGS methods present shortcomings, including undetected actionable mutations and delays in detection of response and progression. In 2023, we entered the oncology market with two complementary products that leverage our smNGS platform to address these unmet needs. Northstar Select, our ultrasensitive liquid biopsy test, provides insights into appropriate therapies for stage III or IV cancer patients. We simultaneously launched Northstar Response, the only tissue-free, pan-cancer, smNGS-based liquid biopsy test that precisely measures thousands of genomic loci uniquely methylated in cancer to provide insight into dynamic changes in therapy response. The clinical value of our oncology portfolio is validated by physician adoption. More than 95% of oncologists who ordered our tests in 2025 utilized both Northstar Select and Northstar Response in tandem, highlighting their complementarity in guiding cancer care. Our Northstar portfolio Our Northstar portfolio for oncology consists of smNGS-based pan-cancer liquid biopsy tests that provide comprehensive therapy selection (Northstar Select) and therapy monitoring (Northstar Response) for late-stage, solid tumor cancer patients. Using a blood-only approach with a focus on sensitivity and precision, we are committed to pushing the limits of cfDNA testing to ensure patients are getting the most advanced profiling and monitoring tools available, while maintaining the convenience of a single blood draw. Northstar Select In January 2023, we launched Northstar Select, which is an ultrasensitive liquid biopsy test using smNGS. Northstar Select can provide insight into what therapies may be appropriate for a patient with stage III or IV cancer. Our Northstar Select test has demonstrated industry-leading performance, including two to five times lower limit of detection (LOD), which results in more than 50% more actionable mutations identified than comparator products. In 2025, the MolDX Program, which is administered by Palmetto GBA, a Medicare administrative contractor, determined Northstar Select meets the coverage requirements under LCD L38043. The MolDX Program’s thorough review process confirms Northstar Select’s clinical validity and utility and enables reimbursement for Medicare and Medicare Advantage beneficiaries who are receiving the test. In the future we may seek FDA approval for certain of our tests, in particular, Northstar Select, which could provide us with competitive advantages such as including enhanced reimbursement through Advanced Laboratory Diagnostic Test (ALDT) pricing; however, it would also subject us to additional regulatory requirements, which can be costly. Northstar Select achieves a significantly lower limit of detection than other liquid biopsy products Liquid biopsy tests are dependent on finding tumor molecules circulating in blood that are shed from tumor cells. The tumor shedding rate is highly variable, with many cancers shedding very little ctDNA. This poses a sensitivity challenge for liquid biopsies, especially for variants at low levels, and can lead to potential false-negative results and missed treatment opportunities. The amount of a particular SNV or alteration compared to normal DNA detected by liquid biopsy tests are measured as a variant allele fraction (VAF), with over half of all treatable alterations occurring at a VAF <0.5%, and approximately one fourth occurring at <0.2%. The ability to reliably detect more alterations at a lower VAF is a significant area of unmet clinical need for ctDNA-based testing and an opportunity for technological improvement. The limit of detection (LOD) is the lower bound limit of an assay’s ability to reliably detect alterations at a specific VAF, at a 95% sensitivity. First generation liquid biopsy tests have an LOD that ranges between 0.25%—0.50%, whereas Northstar Select has demonstrated an LOD of 0.15%, representing a 2-fold higher sensitivity than these other assays. Since most treatable mutations occur at very low VAFs and studies have shown that even mutations found at <0.20% VAF respond to therapy, Northstar Select uncovers more treatment options for patients. The sensitivity of other liquid biopsies is even more problematic for copy number variants (CNVs). During a cancer’s development and evolution, certain genes may replicate in number, driving uncontrollable growth. CNVs are increasingly recognized as hallmarks of cancer. While there are therapies that target these CNVs, 11 Table of Contents CNVs are very difficult to detect in plasma due to amplification bias inherent in standard NGS approaches. smNGS-based Northstar Select solves this problem and achieves an LOD that is approximately five to eight times lower than other liquid biopsies. Northstar Select detects >50% more actionable mutations than comparator assays In a head-to-head clinical validation study, we compared the performance of Northstar Select against commonly used first-generation ctDNA comprehensive genomic profiling assays. Northstar Select found superior detection rates with 51% more actionable SNVs and Indels, and 109% more CNVs than conventional liquid biopsies. Moreover, the study results showed that variants detected at VAF below 0.20% were overwhelmingly detected by Northstar Select only, demonstrating Northstar’s superior sensitivity. In practice, finding more actionable variants can help oncologists more effectively plan treatment for their patients, improving overall patient care. Northstar Response In January 2023, we launched Northstar Response, a pan-cancer smNGS-based liquid biopsy test that precisely measured more than 500 genomic loci uniquely methylated in cancer, achieving single-molecule level quantification, without the need for an upfront tissue-sample. In May 2025, along with other improvements, we updated the assay to include more than 2,200 genomic loci. The new version of the assay has a significantly lower LOD, achieving 0.01% LOD. Northstar Response provides epigenomic insight into dynamic changes in a patient’s response to therapy and, based on our knowledge of all widely available tests, is the only tissue-free methylation-based assay that quantifies tumor burden with single molecule precision. We believe Northstar Response offers a convenient and more precise method to accurately monitor the molecular changes occurring during a patient’s treatment course, which can enable real-time treatment decisions for physicians and patients. Northstar Response is complementary to standard of care radiographic imaging The ability to monitor a tumor’s response to therapy and rapidly adjust treatment strategy when necessary is pivotal to improving patient outcomes, especially in late-stage cancers. Today, the most common and accepted method to assess treatment response is by measuring changes in tumor size through radiographic imaging (e.g., CT, MRI, and PET scans). Radiation exposure, infrequent scans, pseudo-progression with immuno-oncology therapy, and inability to precisely quantify changes, highlight some of the limitations of an anatomic-only based approach in treatment monitoring. Our Northstar Response test is complementary to traditional imaging and introduces real-time, single-molecule quantification to treatment monitoring with a Tumor Methylation Score (TMS). TMS is a quantitative metric that measures the extent of cancer-specific DNA methylation signal that is present in blood and reflects whether the tumor is growing or shrinking in a cancer patient when measured longitudinally. Using a DNA methylation-based approach in conjunction with our smNGS platform, we bring a new level of precision that can help determine molecular progression or therapy response at multiple time-points over the course of a patient’s treatment. Northstar Response is highly accurate at measuring changes in tumor burden across cancer types Our pan-cancer Northstar Response assay has been analytically validated across more than 10 tumor types and has been evaluated in several clinical studies. In one study, we demonstrated that our assay could detect minute changes in cfDNA burden as small as 0.02% (e.g., an elevation of tumor fraction from 0.02% to 0.04%) demonstrating high sensitivity for a tissue-free, blood only test. The assay also achieves a coefficient of variation (CV) of less than 10% for a typical sample with 1% tumor fraction, which is at least two times lower than conventional tumor-naive, targeted-panel methods that measure VAF. It has demonstrated a strong correlation with clinical outcomes in patients with lung, colorectal, and pancreatic cancers. We also collaborated with the University of California, San Diego on a study involving immunotherapy and immuno-chemotherapy treated advanced non-small cell lung cancer patients. In that study, which involved 60 samples from 51 patients, Northstar Response’s changes in TMS measured four to ten weeks after starting treatment significantly predicted real-world progression free survival (rwPFS, p < 0.0001), compared to standard imaging assessments which did not reach statistical significance (p = 0.55). The p-value is used to determine the probability as to whether the difference between two data sets is due to chance. The smaller the p-value, the more likely the differences are not due to chance alone. In general, if the p-value is less than or equal to 0.05, the outcome is considered statistically significant. The study also showed that the test often detected treatment response and progression earlier than standard of care CT scans, with high concordance between TMS and clinical outcomes. 12 Table of Contents In collaboration with Allegheny Health Network (AHN), a separate pan-cancer validation cohort of 54 advanced stage cancer patients (lung, melanoma, and six other solid-tumor cancers) treated with immunotherapy regimens, TMS-based molecular responders had significantly better progression free survival (PFS) (HR=0.26) and OS (HR=0.18) than molecular non-responders. This was particularly remarkable given that the separation between responder and non-responder was made within the first 90 days from baseline and was predictive of durable outcomes years in advance. Molecular responders at day 90 had a significantly improved median overall survival of over two years longer compared to patients who were found to be molecular non-responders. In addition to the aforementioned studies, we are further engaged in multiple prospective clinical validation studies spanning all solid tumor and therapy types. Our flagship NORTH study is a multi-site study with over 500 late-stage (stage III/IV) solid tumor cancer patients undergoing systemic therapies. We completed enrollment of the study in early 2025 and expect to complete sample and data collection by the end of 2025. We expect the initial results to be available in 2026. The NORTH study, along with other ongoing clinical studies, has the potential to generate sufficient clinical validity evidence for our MolDX submissions for Medicare coverage. We have also engaged with academic key opinion leaders in specific disease areas to provide more insights into the validity and utility of Northstar Response. In collaboration with University of Florida, we are conducting a 100-patient prospective study examining the clinical validity of Northstar Response focusing specifically on advanced gastrointestinal tumors. The study completed enrollment in March 2025. In collaboration with University of Miami, we are engaging in a clinical utility study to identify metastatic pancreatic ductal adenocarcinoma (mPDAC) patients who may benefit from ctDNA informed switching to second line chemotherapy based on early measures of response at four weeks following first line treatment initiation. We have also sponsored an investigator-initiated study at the Fred Hutch Cancer Center to assess the clinical validity of Northstar Response in quantifying therapy response in appendiceal and metastatic peritoneal tumors, which are more difficult to assess by imaging modalities. Additional opportunities in oncology We are actively developing additional diagnostic products to address critical needs across the cancer care continuum. For example, in January 2026, we launched Northstar PGx, and in February 2026 we launched Northstar Select CH. Northstar PGx and Northstar CH are add-on applications for Northstar Select, and expand the Northstar platform beyond genomic profiling to address chemotherapy safety (PGx) and clonal hematopoiesis (CH) — two critical decision points in selecting the right therapy for patients. Our current development efforts focus on MRD detection, leveraging our platform’s exceptional sensitivity to identify trace amounts of tumor DNA following curative-intent surgery in earlier stage cancers. We are developing a tissue-free, pan-cancer MRD test, which we expect to be commercially available in the fourth quarter of 2026. Longer term, we believe that our smNGS-based technology could address the sensitivity challenges of early-stage cancer detection. While we have not yet started development in this area, the research work that we have done for Northstar Response and MRD is a necessary precursor for early detection development. We also believe that there is significant potential for our smNGS platform to accommodate products in this area. We believe the molecular information provided by our tests can assist in predicting the diagnostic pathway that can confirm the presence and tissue of origin of cancer. As a part of our five-year strategic plan, we have included the necessary R&D funding for development of an early detection test that builds upon our earlier work. Our vision of powering AI-enabled personalized medicine for all Healthcare today stands at an inflection point, poised for transformation through the convergence of unprecedented molecular insights and AI. Despite significant advances in precision medicine, particularly in oncology where treatments have evolved from being organ-based to increasingly being mutation-based, response rates for many marketed targeted therapies can be as low as single-digit percentages in their indicated patient populations. Similarly, pregnancy care follows one-size-fits-all standardized protocols despite unique patient biology. Even with broader technological advances, clinicians still cannot reliably predict or prevent major complications like preterm birth, preeclampsia, and gestational diabetes. This sobering reality underscores a fundamental challenge: many current approaches to precision medicine often rely on single biomarkers that fail to capture the full complexity of disease biology and individual patient variation. We believe that these important problems can be addressed in the future with the combination of AI and smNGS technology. We believe AI-enabled personalized medicine can revolutionize healthcare delivery across all specialties. Truly personalized medicine requires the (i) characterization of the disease specific to each patient beyond the presence of the single mutation marker to quantification of disease biology of individuals at the single-molecule 13 Table of Contents level, and (ii) integration of this characterization with multi-modal clinical history, powered by AI. We have already built products for this characterization, and we are starting to integrate our diagnostics with this multi-modal clinical history. Our approach to building AI-enabled precision medicine will begin with our ability to generate extraordinarily precise molecular data. As we continue to generate unique data via our smNGS platform, we are building a differentiated and clinically actionable genomics dataset. Our advantage stems from two key factors: first, our biomarker measurements achieve single-molecule precision and sensitivity, capturing the key disease-causing molecular signatures in cfDNA; and second, our response monitoring assay provides an objective measurement of how a patient is responding to a therapy. AI has recently unlocked widespread access to and analysis of multimodal patient clinical history data. This powerful combination positions us to harness AI for identifying distinct patient subgroups based on their specific biomarker profiles and for predicting how each subgroup will respond to different therapeutic approaches. By mapping these response patterns with extraordinary granularity, we believe we will be able to deliver personalized treatment recommendations based on each person’s unique biology that maximize efficacy while minimizing adverse effects — moving precision medicine from aspiration to clinical reality. Our Technology Our smNGS platform leverages proprietary and patent-protected technologies that allow us to detect previously undetectable diseases and support physicians developing and managing treatment plans for patients. Our platform integrates our patented QCTs, proprietary machine learning algorithms embedded in sophisticated bioinformatics systems, and a quantitative, iterative, engineering-oriented assay design. We developed our smNGS platform specifically to address the fundamental challenge of cfDNA scarcity. cfDNA is the extracellular DNA found in blood plasma that is released by all tissues as a part of both normal and pathological cellular processes. cfDNA offers non-invasive windows into the genetic make-up and disease status of different tissues throughout the body. However, the concentration of cfDNA is typically very low, and the amount of cfDNA from any given source, such as a fetus or a tumor, is even lower. For a pregnant patient, typically only 2% to 15% of the cfDNA in a standard blood draw is of fetal origin. For a cancer patient, approximately between 0.01% to 1% of the cfDNA is derived from a tumor, depending on cancer stage. Notably, there is often only one cfDNA molecule present in a sample for any given genomic location associated with disease, even in advanced cancer patients. Breakthrough performance capabilities Our smNGS platform performs absolute quantification of different DNA species down to the level of a single DNA molecule. In addition, smNGS can interrogate thousands of loci simultaneously on the same sample. The cumulative number of cfDNA molecules corresponding to disease can then be summed across all of these loci, thereby amplifying the scarce disease signal by thousands. This capability is especially important for applications such as tissue-free response monitoring and MRD. In contrast, traditional methods are only able to achieve modest relative quantification, far from single molecule level, precluding any applications that require precise quantification. In comparison to other DNA analysis methods, smNGS uniquely combines precise measurements with a high degree of multiplexing, as depicted in the figure below. ddPCR, the only other established method of performing absolute quantification, is limited to multiplexing no more than one to four probes, making it impractical for clinical testing that requires interrogating more than one hundred loci to cover even a few genes of interest. Traditional NGS methods have transformed many areas of clinical testing due to their ability to multiplex across thousands of loci, such as enabling a single clinical test to cover multiple genes. However, these NGS methods face significant limitations when applied to cfDNA analysis. The scarcity of cfDNA necessitates amplification by a factor of millions before it can be sequenced. This amplification occurs at different rates across different genomic loci, which introduces significant biases that challenge traditional NGS methods, even for relative quantification. Moreover, these NGS methods struggle with the easiest copy number analyses, such as the ability to distinguish one copy of a gene versus two copies, as may be needed for a standard germline or carrier testing. Consequently, the gold standard for clinical testing of copy number analysis is pre-NGS technologies, such as microarray and multiplex ligation-dependent probe amplification. The identification of these copy number changes in cfDNA requires detecting a change that is more than 100 times smaller, since the fraction of cfDNA that is derived from the fetus or the tumor can constitute less than 1% of the total cfDNA. Only our smNGS platform can detect CNVs in cfDNA at these levels today. Similarly, smNGS is needed for determining 14 Table of Contents fetal risk in single-gene recessive conditions and precisely quantifying response to therapy, as these problems require absolute quantification of a low cfDNA signal against a high background originating from other tissues. The components of our platform Our smNGS platform seamlessly integrates several tools and patented technologies, which are further described below. Quantitative Counting Templates (QCTs) QCTs are the foundation of our smNGS technology. They are artificial DNA fragments that we design and synthesize to mimic the properties of the human DNA loci that are being interrogated in an assay. A specific identifier is embedded into the sequence that flags the QCTs as synthetic controls, and a randomized embedded sequence ensures that each QCT is unique. QCTs are added to the biological sample at the start of the testing process so that they are subject to the same laboratory processes, including amplification and sequencing, as the disease-associated genetic molecules that the assay targets. Importantly, QCTs amplify at the same rate as the genetic targets. We can then precisely calculate the amplification and sequencing biases that were introduced during the sample processing and remove their effects from the data to absolutely quantify the number of cfDNA molecules that are present in the sample. The precise number of QCT molecules added to each specimen is calculated bioinformatically through the counting of the number of diversity regions in the sequencing data. This method is therefore “calibration-free” and does not require the exact measurement and titration of spike-in DNA concentrations, a feature that is particularly advantageous for quantitative assessments across multiple timepoints in longitudinal monitoring contexts. QCTs are compatible with almost all NGS library preparation methods and can be used to measure both genetic and epigenetic changes, such as methylation. Our ability to absolutely quantify methylation across genomic loci allows us to combine signals from thousands of genomic loci to reduce the amplification and sample processing noise to negligible levels, thereby converting a 0.01% signal to the equivalent of a 10+% signal. QCTs are used in our testing workflow with the following steps: 1. Add an aliquot of traceable and specific QCTs into the patient’s blood sample, which contains an unknown number of DNA fragments of interest (m1) among a vast background of the patient’s genome. The precise number of QCT molecules (n1) is also unknown at this stage but is determined in a subsequent step. 2. Amplify the cfDNA fragments of interest using PCR at the same, unknown amplification rate as QCTs. 3. Count the number of clusters of sequences with identifier tags (i.e., the number of distinct QCTs with different diversity regions), which is equal to the number of QCTs that were added to the sample (n1). 4. Determine the amplification multiplier (x) by dividing the number of total sequencing reads that map to QCTs by the number of QCTs (n1). 5. Remove bias by dividing the total number of sequencing reads that map to cfDNA fragments of interest by x to find the absolute number of molecules in the cfDNA sample (m1). We believe that QCTs provide unprecedented insight into disease biology across the human genome. We have developed custom machine learning models to analyze the tiny, individualized variations across hundreds of thousands of patients, uncovering novel patterns of disease biology. These insights are incorporated into our assays to significantly improve performance. We continuously refine our understanding of disease biology to support existing and future diagnostic products. Custom bioinformatics with machine learning Due to the vast amounts of data generated by genetic sequencing, robust bioinformatics are required to analyze the data and identify mutations of interest. Our smNGS platform requires the use of proprietary bioinformatics to further analyze the data generated by the genetic sample and QCTs to accurately quantify the presence of disease. A selection of proprietary bioinformatic tools enabling the single-molecule sensitivity of smNGS includes the following: 15 Table of Contents • Our bioinformatic tools implement numerous quality control metrics that enable single molecule sensitivity, for instance, the QCTs’ ability to identify cross-contamination between samples down to a 0.001% level. • Our bioinformatic models enable us to effectively combine signals across thousands of loci, enabling unprecedented sensitivity. • The close collaboration between our clinical and bioinformatics teams enables us to curate personalized reports for patients. For example, there are more than 500 types of results that our fetal risk screen can provide with a vast repertoire of risk assessment. • Our custom bioinformatic tools enable design-based approaches to assay development, significantly reducing the time and cost of building a novel assay. Specialized and scalable infrastructure Our smNGS platform leverages specialized and scalable infrastructure that we have spent years building and refining. Our laboratory infrastructure has been custom designed from the ground up to support the single molecule sensitivity of our assays. The scalability of our tests has been built over time through automation, which has enabled us to maintain single molecule sensitivity while driving down COGS. While the vast majority of our laboratory processes are now fully automated, it was accomplished through a deliberate step-by-step approach of continuous implementation. In addition to the smNGS technology that we have developed, we believe that the current scalability of our assays also gives us a multi-year advantage. For example, it took an entire year to automate one single step of our sgNIPT assay, automated cfDNA extraction with the same yield as manual column-based extraction, to maintain the same single molecule sensitivity. Once a sample is received at one of our facilities, it is processed through a single-directional workflow across four separate labs, each with strictly separated and segregated airflows and air filtration systems. Every step in the laboratory process is designed to optimize yields and support a high-quality testing process. By leveraging smNGS techniques and strictly controlling the workflow and environment, we can detect sample cross-contamination at the single molecule level and even determine the exact point in the process where the contamination occurred, including potentially at the clinic where the sample was collected. Even if QCTs were deployed in a traditional NGS lab, post-PCR contamination that is typically found in such labs would preclude the single molecule sensitivity, absent a complete redesign of not only the assays and bioinformatics, but of the entire laboratory infrastructure. We have also utilized automation and AI throughout our infrastructure to reduce errors and increase laboratory throughput. By automating our labs, we are able to build uniformity into sample processing and can rapidly identify and triage problems as they occur. Each individual lab contains specialized equipment with bespoke programming to drive specific processes and to progress the sample through the testing workflow. In addition, we also integrate third-party large language models and AI to improve our laboratory workflows. For example, we completely redesigned and automated our biological sample accessioning process by incorporating AI and computer vision that automates labor-intensive clerical tasks. This allowed us to redeploy our laboratory personnel to higher impact areas. While our current laboratory space is already sufficient for at least four times more growth, our process engineering and automation teams continue to work on creative solutions to further scale our laboratory capacity and decrease our COGS. IP and know-how Our smNGS platform is protected by a suite of patents and proprietary technological know-how. Our patented technologies differentiate us from our competitors and support improved quality controls, enable nimble product iteration, and drive rational assay design that allow us to build novel products with attractive gross margin. We have multiple issued patents for our core technologies and our ancillary technology in the United States and internationally. Our core patents cover various approaches to using synthetic molecules to provide accurate counting of target molecules, which is our QCT technology, as well as protecting the following technologies: • Dilution tagging is a novel method to quantify the abundance of targeted DNA molecules across a dynamic range of many orders of magnitude. This technology enables low-cost sequencing of cfDNA samples with rare sequences without the loss of quantitative information. For example, this can reduce sequencing costs by 10-50x for sequencing intensive applications, such as immune receptor repertoire profiling and single cell RNA sequencing. • Spike-in technology refers to synthetic DNA controls custom-made for each assay and added to every patient sample. These DNA controls enable the calculation of relative abundance of targeted DNA molecules at a low cost. 16 Table of Contents • qSanger technology combines spike-in technology with custom-built, proprietary signal processing and applies it to Sanger sequencing and capillary electrophoresis, bringing the power of quantification to previously qualitative technologies. This approach brings NGS-level precision to easy-to-deploy technologies and enables their use as low-cost and high-throughput diagnostic tools. Beyond these patented technologies, we have developed substantial proprietary techniques and know-how throughout our organization that are critical to our R&D and commercial success. We protect our IP through a comprehensive strategy including patents, trademarks, copyrights, trade secrets, confidentiality agreements, and other contractual protections. For further details on our IP portfolio, including issued and pending patents, see Part 1, Item 1 “Business—Intellectual property.” Engineering biology approach Our focus on quantification fundamentally transforms our R&D approach. We believe, by leveraging the precise molecular measurements enabled by our smNGS platform, we significantly reduce biological and clinical risks in our diagnostic pipeline. When designing new assays, we build mechanistic models that mathematically predict clinical performance with high confidence, transforming diagnostic development from a biology-driven trial-and-error process with inherent uncertainties into an engineering challenge with clear, solvable parameters. We believe this engineering biology framework delivers exceptional capital efficiency. While many competitors invest heavily in exploratory biological research with uncertain outcomes, our quantification-first approach enables us to predict diagnostic performance based on biomarker measurability rather than speculative biology. We believe this targeted strategy accelerates time-to-market and significantly improves our success rate in developing category-defining products, creating substantial value for patients and shareholders alike. We have complemented these technological advantages with an innovative organizational structure inspired by Bell Laboratories, Inc. Our R&D model organizes core scientists into focused teams reporting directly to our CEO and CTO, eliminating bureaucratic layers and accelerating decision-making. Each scientist has end-to-end responsibility across the biochemistry and bioinformatics technology stack and is empowered to drive new products from conception through commercialization. This structure enables rapid iteration with minimal resources. We believe this combination of technological foundation and organizational design will create compounding advantages that widen the gap between BillionToOne and our competitors over time. Future uses of artificial intelligence Productivity improvements We have already begun to harness the transformative potential of AI to drive productivity improvements across our operations. For example, AI has significantly reduced the time required on sample accessioning, reimbursement, and healthcare operations, while substantially improving software programming productivity. These early applications represent just the beginning of our AI integration strategy. We envision an organization where AI augments virtually every functional area, creating a continuous cycle of productivity enhancement and financial performance improvement. By progressively automating routine tasks, we expect to increasingly redirect our exceptional talent toward high-value, creative activities that drive innovation and competitive differentiation. We believe this will further strengthen our differentiated financial profile by continuously improving the ratio of revenue to operating expense. Personalized medicine We believe that our smNGS platform is building a uniquely valuable genetics dataset due to its ability to detect single molecules at scale. We have processed over one million tests to date and our dataset continues to grow rapidly. AI can reduce medical chart extraction costs by over 90%, enabling the synthesis of smNGS molecular data and AI-extracted longitudinal clinical data for each patient. This powerful combination creates the potential for us to increasingly provide more actionable and personalized clinical reports of treatment strategies while minimizing adverse effects for patients, making our products increasingly more valuable. Industry Background The strengths and challenges of precision-based diagnostic solutions Precision diagnostics has emerged as one of the most critical components of healthcare in improving patient outcomes across multiple therapeutic areas. Through the identification of actionable unique biomarkers, diagnostic tests can offer critical information for the diagnosis and treatment of diseases. Historically, directly 17 Table of Contents obtaining a sample from the fetus or the tumor for analysis has been the standard of care for prenatal and oncology diagnostics, but such procedures are highly invasive and can lead to inconclusive results. More recently, many areas of care, including prenatal and oncology, have been transformed by cfDNA diagnostics. Both genetic and epigenetic properties of cfDNA reflect the originating tissue and can be used to diagnose and monitor disease. However, while powerful, the extremely limited availability of cfDNA in blood poses significant challenges to traditional diagnostics. The fraction of cfDNA that is of fetal or tumor origin can be as low as 0.01% to 1.0% of the total cfDNA, and often there is only a single molecule that corresponds to the particular mutation of interest within a tube of blood. To address this challenge, the DNA sample must be amplified during laboratory processing by a factor of millions, which adds significant errors and biases that are then difficult to differentiate from the actual targeted mutations. It also makes quantification extremely challenging, as the original signal can be orders of magnitude smaller than these errors and biases. The need for comprehensive prenatal testing solutions In 2023, the U.S. Center for Disease Control and Prevention (CDC) reported approximately 3.7 million births in the United States, with about one in every 33 infants affected by congenital anomalies. These anomalies can be due to chromosomal abnormalities or single gene inherited disorders. While commonly-used cfDNA prenatal tests can detect chromosomal abnormalities, they are unable to screen for these inherited single gene conditions, such as sickle cell disease, cystic fibrosis, alpha-thalassemia, beta-thalassemia and spinal muscular atrophy (SMA). These five recessive conditions are common, clinically actionable, and recommended for universal screening by ACOG, with one in six pregnant individuals in the United States being a carrier for recessive conditions. Inherited single gene conditions can be identified through carrier screening of the parents, followed by invasive diagnostic procedures such as amniocentesis. One of the most significant problems with traditional carrier screening is the requirement for both maternal and paternal blood draws. Obtaining the paternal blood sample is logistically challenging in an obstetricians-gynecologists (OB-GYN) setting. As reported in studies by independent publications, in at least 58% of cases when the mother is identified as a carrier, the father’s carrier test is not performed, resulting in the majority of affected pregnancies to be undetected. The significant prevalence of genetic disorders underscores the critical need for safe and effective prenatal screening methods. By identifying these disorders prenatally, we can significantly improve patient outcomes through earlier therapeutic interventions. For instance, SMA is a progressive and debilitating disorder that causes irreversible damage to affected newborns every day following birth. Administering therapy within the first six weeks of life can be the difference between lifelong physical disability and meeting age-appropriate physical milestones. Prenatal detection of SMA is critical when considering the timelines for newborn screening, confirmatory molecular diagnostics and insurance authorization for expensive therapies. Similarly, there are an increasing number of case reports where specialists prescribe therapeutics to carrier pregnant mothers with affected CF fetuses, which significantly improved newborn outcomes. In addition, novel diagnostics enable the development and use of novel therapies. We have a global exclusive partnership with Johnson & Johnson in which a therapy for preventing HDFN is administered only to those at-risk pregnancies that we identify through our non-invasive fetal testing. We have two strategic partnerships with Johnson & Johnson. The first relates to our UNITY fetal antigen clinical trial assay in Johnson & Johnson’s AZALEA Phase 3 clinical trial of nipocalimab in HDFN. The second is governed by a development and commercialization agreement we entered into with Johnson & Johnson on July 11, 2025 (as amended, the Commercialization Agreement), which governs our collaboration on a companion diagnostic product for nipocalimab. The Commercialization Agreement sets forth the roles and responsibilities, including development activities, to be performed by each party; the timelines for development activities and associated milestone payments; and target specifications for the companion diagnostic product. Under the Commercialization Agreement, Johnson & Johnson made an initial payment to us, with subsequent payments due upon achievement of specific milestones, including submission of the companion diagnostic product to the FDA for marketing approval by January 2028, and FDA approval of the companion diagnostic product, by the later of (i) December 2029 and (ii) one year after Johnson & Johnson obtains regulatory approval for nipocalimab. The cumulative amount of upfront fees, milestone payments, expenses and costs payable to us under the Commercialization Agreement will not exceed $13 million. The Commercialization Agreement will remain in effect until such time as Johnson & Johnson ceases the development and commercialization of nipocalimab. While we expect to make the FDA submission of the companion diagnostic product by January 2028, the exact timing of FDA approval will depend on the approval timeline of the associated Phase 3 clinical 18 Table of Contents trial of nipcalimab. The timing and conduct of the Phase 3 clinical trial, including submissions to the FDA, are the responsibility of Johnson & Johnson and its affiliates, as the sponsor of the trial. The market demand for more sensitive and precise oncology tests Cancer is the second leading cause of death according to the CDC. Despite the breadth of therapeutic options, treatment response rates can be as low as single-digit percentages due to differences in genetic and epigenetic patient profiles. Enabling more personalized cancer treatments and better outcomes requires more sensitive and precise tests to (i) select the best therapy regimen and (ii) monitor the patient’s response to that treatment. The gold standard for cancer therapy selection has been a tissue biopsy, which can be sequenced to determine the tumor profile. However, tissue biopsies can be invasive, challenging to obtain, and can lead to inconclusive results and quality control failures from the extracted DNA. They may also miss mutations due to tumor heterogeneity. In addition to tissue biopsies, non-invasive liquid biopsy tests are a rapidly growing approach to analyze tumor DNA. Faster and more convenient blood-based tests may allow earlier treatment; however, they also have lower sensitivity due to very low amounts of circulating tumor DNA (ctDNA) shed by tumors. This challenge has meant traditional liquid biopsies often miss targetable tumor mutations at lower ctDNA fractions. Our Northstar Select test addresses these challenges by capturing tumor-specific variants with high sensitivity at low variant allele frequencies (VAF). In essence, our test enables physicians to detect mutations in cancers that other diagnostic tests might miss. The detection of these mutations can enable better, more targeted therapies that their patients would otherwise not receive. We have demonstrated the analytical and clinical validity, as well as the clinical utility, of our Northstar Select test through rigorous reviews. Analytical validity refers to how accurately and reliably the molecular diagnostic test measures the specific DNA, RNA, protein, or other molecular target it is designed to detect. Clinical validity refers to the accuracy with which a molecular diagnostic test correctly identifies the presence or absence of a specific genetic variant, biomarker, or molecular target associated with a disease or condition in the intended patient population. Clinical utility refers to the likelihood that a test will, by prompting an intervention, result in an improved health outcome. In February 2025, these reviews resulted in the decision to grant Medicare coverage for the Northstar Select test for eligible beneficiaries with advanced solid tumors who meet the Molecular Diagnostics Services program (MolDX) coverage criteria. The clinical validation data submitted as part of the MolDX evaluation included a head-to-head concordance study, directly comparing the utility of our test to that of our leading competitors. The results demonstrated the superior sensitivity of Northstar Select by identifying 51% more single nucleotide variants (SNVs) and 109% more copy number variants (CNVs), most of which were found below the comparator assays’ 95% limit of detection. While the number of cancer treatment options continues to expand, determining whether a specific treatment is working for an individual patient remains a significant challenge that relies too heavily on subjective assessments. Currently, doctors use medical imaging (e.g., computed tomography (CT) scans, magnetic resonance imaging (MRIs), and positron emission tomography (PET) scans) as the primary tool to evaluate a patient’s cancer status. However, this approach has important limitations affecting both accuracy and reliability. Tumors often contain diverse cell populations that respond differently to treatment, making overall assessment difficult. Some patients receiving immunotherapy experience “pseudoprogression,” where imaging temporarily shows growth even though the treatment is working. Scar tissue forming around tumors can be hard to distinguish from active cancer. Certain areas of the body, like bones and the abdominal cavity lining, naturally provide poor contrast on imaging, making cancer changes difficult to see. Lastly, interpreting scans involves significant human judgment, introducing inconsistency between different radiologists’ assessments. The practical limitations of imaging also create problems. Most patients undergo scans only every few months, leading to critical delays in determining whether a treatment is effective. These delays can result in patients continuing ineffective therapies longer than necessary or missing opportunities to begin alternative treatments sooner. While increasing scan frequency might seem like a solution, patients face real-world barriers including limited availability of imaging equipment (especially in rural areas), the physical and financial burden of traveling to specialized imaging centers, and substantial costs that might not be fully covered by insurance. These limitations create an urgent need for better tools that can assess treatment response more accurately, consistently, and frequently to help doctors make timely and informed decisions about patient care. Northstar Response is designed to solve these problems. Northstar Response is a tissue-free, pan-cancer, smNGS-based liquid biopsy test that precisely measures more than 2,200 genomic loci uniquely methylated in cancer. Based on our knowledge of all widely available tests, Northstar Response is the only methylation-based 19 Table of Contents assay that quantifies tumor burden with single molecule precision and provides insight into dynamic changes in a patient’s response to therapy. In validation studies, Northstar Response showed a consistent ability to detect quantitative changes in tumor fraction across more than 10 different cancer types, in some cases as much as six months earlier than indicated by imaging scans. Northstar Response has been analytically and clinically validated in three peer-reviewed publications, including in collaborations with the University of California, San Diego and the University of Florida. Northstar Response is now undergoing further validation through our large flagship study: NORTH (Northstar Oncology Response Monitoring Test Hallmark). NORTH is a multi-site study with over 500 Stage III and IV solid tumor cancer patients undergoing systemic therapies. Enrollment of the study, as well as sample and data collection, were completed in 2025, and we expect results to be available in 2026. The NORTH study, along with other ongoing clinical studies, have the potential to generate sufficient clinical validity evidence for our MolDX submissions for Medicare coverage. Beyond late-stage cancer testing, we recognize there is a significant need for more powerful early-stage cancer testing. We are developing additional oncology products for these cancer patients, including MRD testing. Current standard of care for early-stage cancer is the surgical removal of the tumor. However, a small number of cancer cells may remain and can lead to future metastasis. MRD testing post-surgery enables healthcare providers to administer adjuvant therapy when needed and can also be used to monitor cancer recurrence over time. There are two approaches to MRD testing today, tumor-informed and tumor-naive. Tumor-informed approaches involve sequencing the cancer tissue to identify mutations which can then be tracked in blood at subsequent points in time. Tumor-informed approaches can have up to 40% failure rates due to the limited amount of tissue that can be obtained in early-stage cancers or tissue sequencing failing to identify a sufficient number of variants that can be used for MRD tracking. Moreover, the mutations that are tracked may not represent the evolution of the tumor, resulting in false negatives. Tumor-naïve approaches measure the levels of ctDNA in a patient’s blood and do not require an upfront tissue sample, but to date, their lower sensitivity has been a limiting factor in their adoption. We believe that our smNGS platform will allow our planned MRD test to address the sensitivity challenges of existing tumor-naïve assays. Publications and collaborations We have extensive publications on our smNGS platform and products. Our UNITY Fetal Risk Screen clinical publication in Genetics in Medicine was selected for the Top 10 publications in Genomic medicine year in review 2023 by AJHG. Our hallmark publications in the Obstetrics & Gynecology journal (the Green Journal) demonstrated 100% sensitivity and specificity in approximately 860 patients for fetal RhD and other fetal RBC antigen detection, ultimately leading to the ACOG practice guideline changes. The analytical and clinical validity of our Northstar products have also been demonstrated in peer-reviewed publications. The analytical validation of Northstar Response was published in January 2025 in Scientific Reports while additional clinical studies of the assay performance in lung and liver cancer cohorts were published in Clinical Lung Cancer and the Journal of American College of Surgeons, respectively. The analytical and clinical validation of Northstar Select, including the head-to-head comparison against other on-market assays published in August 2025, demonstrated Northstar Select’s superiority in detection of SNV and CNVs as relative to commercially available competitors. Beyond peer-reviewed journal publications, we have published posters and abstracts at various medical conferences including AACR, AACR LBx, ASCO, and the International Society of Liquid Biopsy. Commercialization We commercialize our UNITY and Northstar tests in the United States through our direct sales force targeting physicians in the prenatal and oncology markets, respectively. As of December 31, 2025, our clinician-focused sales organization included 231 sales representatives, with 177 in prenatal and 54 in oncology. In comparison, we had a total of 137 sales representatives at the end of 2024, 120 in prenatal and 17 in oncology. We plan to continue to expand our field sales force systematically, as our prenatal sales force is less than one-third the size of our largest competitor and our oncology sales force is very small relative to many other liquid biopsy companies. Our sales representatives in prenatal are engaged in educating OB-GYNs, MFMs, genetic counselors (GCs) and others about the existence, uniqueness and clinical utility of our offerings. Our sales representatives in oncology conduct similar commercial and educational activities and primarily engage with oncologists. We have supplemented our direct sales team with medical science liaisons (MSLs) who are generally genetic counselors in prenatal and PhDs in oncology, as well as adding other support staff to help onboard clinics and to manage the physician and patient experiences. 20 Table of Contents Our sales force achieved an annualized revenue run-rate of $2.2 million per sales representative in the year ended December 31, 2025. We believe our high sales efficiency is driven by the combination of our differentiated products and our ability to provide a seamless, end-to-end solution that enhances both the patient and provider experience and significantly reduces churn. Our cohort analysis indicates that the net test retention, as defined by the total number of tests that are received from a cohort of clinics first onboarded in a particular quarter, even after accounting for any account or provider churn, is over 100% after a year for the majority of quarterly cohorts. Our sales efficiency has also increased over time, and we believe this efficiency will be maintained or further increase as we systematically grow our sales team. We also drive physician awareness of our products by actively participating in industry conferences, publishing in relevant scientific journals, and driving dialogue with key opinion leaders and physician organizations. These efforts have already resulted in practice advisory changes within the prenatal field, including for RhD and fetal antigen NIPT. Across both prenatal and oncology, we believe that our ongoing and planned studies will help drive increased guideline expansion. Through our extensive digital marketing, we also engage directly with motivated patients, and this can lead to access to physicians in clinics that typically do not otherwise allow sales representative presence. In international markets, which represented less than 1% of our revenue for the year ended December 31, 2025, we primarily sell through distributors, which collect and send samples to our laboratories in the United States. In these markets, the patient bears the full cost of the testing, which limits the adoption. In the future, we believe that the health economics of our tests will enable nationwide coverage via single-payor agreements. However, this is often predicated on the tests being performed locally within the country, requiring capital investments in international markets. While we believe that international expansion could significantly expand our total addressable market, we are currently focusing on expansion opportunities in the United States. Prenatal commercialization We sell our UNITY products through direct targeting of OB-GYNs, GCs, MFMs and others in the United States. Our penetration in prenatal is often executed via a “land-and-expand” strategy in which the adoption of UNITY by one physician in a larger clinic often leads to increased access and broader adoption of our tests by other physicians in the clinic. This approach enables us to first access clinics and then expand within those clinics by providing an excellent end-to-end service. Our high client satisfaction is evidenced by our low churn, which is an important factor in our rapid growth. Our tests are typically ordered during the first trimester, starting as early as nine weeks into the pregnancy, and help physicians and patients assess risk across a variety of conditions. We have simplified billing process that consolidates all tests ordered into one claim and one bill. Our dedicated clinical support staff aids in our commercial and education efforts by providing workflow implementation, patient and payor billing, and report interpretation. We also have a global partnership with Johnson & Johnson in the AZALEA Phase 3 clinical trial of nipocalimab in pregnancies at risk for severe HDFN, in which UNITY Fetal Antigen CTA is exclusively used for determining patient eligibility, and a related U.S.-specific partnership regarding development of a companion diagnostic product. Exclusivity of this arrangement is another proof point of the unique capabilities of our products. We believe this partnership and potential future partnerships or collaborations with other partners can boost awareness and adoption of our tests, while also providing us with access to patients who can benefit from our products. We will also continue to increase the size of our direct sales force to better penetrate existing markets and to cover new territories in the United States. Our sales team was built with proven performers, and we have designed a robust training infrastructure to continue our leading sales efficiency as we continue to grow the team. Oncology commercialization Our oncology strategy is dedicated to the cross-selling of both Northstar Select and Northstar Response. These complementary products support physician decision-making on initial therapy selection, monitoring patient response to treatment, and informing treatment modification when necessary. The head-to-head study that showed significantly higher numbers of actionable mutations that Northstar Select found versus competing assays is an important factor in our ability to persuade oncologists to start using our tests. Each Northstar Select test is often accompanied by a Northstar Response test for the baseline measurement, followed by 21 Table of Contents additional Northstar Select and Response tests in certain cases as physicians monitor and adapt treatment plans. As of December 31, 2025, approximately 95% of our ordering providers utilize both Northstar Select and Northstar Response tests in tandem for the same patient’s care. Higher reimbursement and existing Medicare coverage of our Northstar Select tests allow us to broaden the use of Northstar Response without incurring significant losses. If we were to receive increased coverage and reimbursement for Northstar Response, it would lead to a significant increase in our revenue as the adoption of the test will have already been established. Outside of our direct sales efforts in oncology, we have signed collaboration agreements with a select number of pharmaceutical companies and institutions to support clinical development of novel precision oncology therapeutics. These collaborations utilize our existing Northstar products, as opposed to developing new assays that are specifically tailored to each agreement. Our Growth Strategy We are driving and leading a paradigm shift within precision diagnostics. Our vision is to leverage our novel single-molecule next-generation sequencing (smNGS) platform to develop ultrasensitive diagnostic tests that enable personalized solutions and enhance patient outcomes. Our growth strategy to achieve this goal includes the following elements: • Drive increased adoption of our existing products in the prenatal and oncology markets. Healthcare professionals have increasingly incorporated our UNITY tests into their clinical practices to adopt what we believe will be the new standard of care. There are three main opportunities to expand our market penetration of our UNITY prenatal products. First, we believe that we have a significant opportunity for footprint expansion and are continuing to invest in increasing our sales team size to cover new geographies, with aggressive recruiting targets. Second, we believe that our current sales team has only just begun to penetrate their existing territories and, over time, more clinics will adopt our tests in an existing sales territory. Finally, we typically see significant growth once we have gained adoption in a clinic, as additional physicians in those clinics adopt our tests. We are in the early stages of executing the same sales strategy in oncology. We will continue to drive adoption of our tests by working closely with physicians, medical societies, payors, and patient advocacy groups to educate them on the benefits of our products. We also believe that our commitment to quality customer experience, through patient education, patient self-service, streamlined testing, and patient-friendly billing, will help maintain and enhance usage of our tests. With our Northstar product line, our commercial efforts have just begun, with our field sales team covering only a fraction of the geography. We have significant room to grow, via more geographical expansion, more penetration within existing sales territories, as well as within existing clinics. • Build beyond our extensive library of clinical evidence to support favorable coverage and reimbursement. In prenatal, our carrier and aneuploidy tests are broadly covered by most major insurance providers, and we have broad reimbursement for the tests we provide. In addition, we have contracts with payors that account for more than 250 million covered lives in the United States as of December 31, 2025, which generally include our oncology products. We are continuing to generate persuasive clinical utility data that we believe can lead to additional payor contracts and justify guideline inclusion. While we believe we have industry-leading ASPs for our prenatal products, as we contract with more payors and as certain aspects of our tests are more broadly covered due to guideline inclusions, we believe that our ASP will continue to increase. In oncology, we have already secured Medicare and Medicare Advantage coverage for Northstar Select. For Northstar Response, our flagship study, NORTH, along with other ongoing clinical studies, has the potential to generate sufficient clinical validity evidence for our MolDX submissions for Medicare coverage. • Utilize our smNGS platform and R&D capabilities to efficiently expand and improve our portfolio of category-defining molecular diagnostic tests. Our foundational smNGS platform fundamentally reduces the biological and clinical risks in our product development process. Because it achieves single molecule level sensitivity and precision at the physical LOD, we can accurately predict clinical performance in advance when designing new smNGS assays. This is complemented by our lean and innovative R&D structure which further enables efficient and high-impact product development. As a result, we are able to rapidly convert R&D investment into differentiated products. In the prenatal 22 Table of Contents market, we started with one UNITY Fetal Risk Screen and then developed multiple tests and add-ons, including UNITY Aneuploidy Screen and UNITY Fetal Antigen NIPT. In oncology, we are extending our portfolio beyond our commercial products focused on therapy selection and response monitoring. We are also developing a tissue-free, pan-cancer MRD test, which we expect to be commercially available in 2026. Longer-term we believe that our smNGS-based technology could address the sensitivity challenges of early-stage cancer detection, among other applications. • Continue to deploy AI across our entire organization, including laboratory operations, to improve efficiency and productivity. The integration of AI across our operations has been and will continue to be a critical driver of efficiency and productivity. We have been an early adopter of AI, and every function across the company uses AI in some capacity. By continuing to automate labor-intensive processes, we expect to continue to reduce costs and significantly increase productivity across our organization. • Leverage our growing clinical dataset with AI to improve the utility of diagnostics and enable personalized medicine. Our advanced diagnostics platform generates rich biomarker data as we test patients that can be integrated with multimodal patient clinical information such as medical records. By leveraging AI algorithms to analyze these large datasets, and combining them with our unique Northstar Response results, we believe we will be able to identify distinct patient subgroups with unique biomarker profiles and predict therapeutic response patterns with unprecedented precision. This capability will enable us to provide clinicians with personalized treatment recommendations tailored to each patient’s unique biology. We believe this approach will significantly improve therapeutic outcomes by maximizing efficacy while minimizing adverse effects. As we continue to expand our clinical data repositories and refine our AI models, we expect to further enhance our competitive advantage and accelerate the transition of precision medicine from aspiration to clinical reality across our diagnostic portfolio. Competition Healthcare delivery continues to focus on becoming more patient-centered with personalized solutions. This evolution is leading to more companies and product offerings in the molecular diagnostics market. As a result, each of our products faces competition from a number of established and emerging companies. In the prenatal market, our main competitors offering NIPTs include Illumina, through its subsidiary Verinata, Laboratory Corporation of America Holdings (Labcorp), Myriad Genetics, Inc. (Myriad), Natera, Inc. (Natera), and Quest Diagnostics Incorporated (Quest). We also compete with companies providing carrier screening tests such as Fulgent Genetics, Labcorp, Myriad, Natera, and Quest. Each of these companies offers comprehensive carrier screening panels. While we know of competitors, in particular Natera and Myriad, that have been working on creating competing products to UNITY that also assess fetal risk for recessive conditions non-invasively, we believe that our smNGS platform will allow us to maintain clear clinical and technical superiority as this type of testing becomes the standard of care. In addition, while product launches by our competitors can create heightened competition in our prenatal market, we also believe that it can lead to increased awareness, acceptance, and adoption of this modality of testing by both providers and medical guidelines. In the oncology market, our main competitors for our therapy selection and response monitoring tests include Caris Life Sciences, Inc., Foundation Medicine, Inc., which was acquired by Roche Holdings, Inc., Guardant Health, Inc., NeoGenomics Laboratories, Inc., and Tempus AI, Inc. As we expand our oncology offerings into applications such as MRD testing, as well as potentially testing for early detection in the future, we anticipate facing competition from a broader universe of companies, including Exact Sciences, Grail, Haystack, which was acquired by Quest, and Natera. Our competitors may offer oncology tests for therapy selection that encompass a broader range of genes, thereby positioning their products as more comprehensive. While we believe that these larger panels result in reduced sensitivity for identifying actionable variants, their expanded gene coverage enables selection of a wider array of therapies—including some that are not yet approved or immediately actionable. As the number of approved therapies continues to increase, necessitating the addition of new genetic targets and revalidation of our assays, we may incur higher costs and risk losing customers to competitors if updates to our tests are delayed. 23 Table of Contents Many of our competitors, either alone or with their collaborators, may have greater financial and/or other resources than we do, including larger and more established manufacturing capabilities and marketing, sales, and support functions. Other competitors are in the process of developing novel technologies which may lead to products that rival or replace our products. While we cannot assure you how the market will evolve, we believe our four pillars of differentiation provide competitive advantages that are difficult for others to replicate. These statements regarding our competition are subject to a number of risks, uncertainties, factors and assumptions described under Part I, Item 1A, “Risk factors—Risks related to our business and strategy.” Intellectual Property The long-term success of our business depends on securing protection of our intellectual property through patent, trade secret, trademark, and other intellectual property rights. We also utilize non-disclosure agreements and proprietary information and inventions assignment agreements with employees, consultants, contractors and other third parties and maintain physical security of our premises and physical and electronic security of our information technology systems in order to strengthen the protection of our intellectual property. As of December 31, 2025, we held nine U.S. issued patents, which expire between August 2038 and March 2043, and 45 foreign patents, which expire between August 2038 and September 2041. Additionally, we had 14 pending U.S. patent applications and 31 foreign patent applications. We also held 4 U.S. registered trademarks and 13 foreign registered trademarks as of December 31, 2025. Our patent strategy is focused on seeking robust coverage for our core molecular counting technology (covered by U.S. Patent No. 11,629,381, with a pending U.S. divisional application, granted patents in Australia, Brazil, China, Europe Hong Kong, India, Japan and South Korea (validated in 17 countries), and pending applications in Canada, Israel, Singapore, Japan (divisional), Europe (divisional), and Hong Kong (divisional), our dilution tagging technology (covered by U.S. Patent No. 12,071,651, with a pending U.S. continuation, and issued patent in Canada and pending foreign applications in China, Europe, and Hong Kong), our custom-made Synthetic DNA controls (covered by U.S. Patent Nos. 11,646,100 and 12,176,066, with a pending U.S. continuation, an issued patent in Canada, and pending applications in China, Europe, and Hong Kong), and our proprietary signal processing technology (covered by U.S. Patent Nos. 11,430,543 and 12,183,437, also granted in Brazil, Japan, Singapore, South Korea, Israel, Canada, Australia and Europe, and pending in China, Hong Kong, and India), all of which is used to maximize readings taken from single blood draws. We have also recently filed several unpublished patent applications covering a range of techniques for improving the efficiency and accuracy of DNA sequencing-based assays. In addition, we file for patent protection in connection with our ongoing research and development activities, particularly those related to early-stage cancer detection. Our patents and applications generally fall into three broad categories: • detecting and monitoring cancer and other diseases by determining genetic variations and other biomarkers in biological samples; • methods for preparing and sequencing cfDNA, techniques for enriching nucleic acid samples, identifying cfDNA, and detecting epigenomic variations (such as DNA methylation) in biological samples; and • precision diagnostics, including biochemical and analytical techniques for obtaining and analyzing genetic information to detect genetic abnormalities in relatively small complex samples, such as fetal cfDNA using reflex single-gene noninvasive prenatal screening. The following table includes our U.S. patents granted and U.S. patent applications published as of December 31, 2025, along with the status in other jurisdictions (excluding divisional and continuation patents and applications). All patents are utility patents. We have additional patent applications that have not yet published as of December 31, 2025. BillionToOne Patent Portfolio 24 Table of Contents Patent Family Patent Name Summary U.S. Patent Number U.S. Exp. Date Other Jurisdictions P01 Dilution Tagging for Quantification of Biological Targets Method for accurate determination of biological target abundance that can include generating a first set of molecules associated with a target sequence that includes dilution tags associated with a relative concentration profile; generating a second set of molecules including dilution tags; generating a dilution tagged mixture; amplifying the dilution tagged targets; generating a modified dilution tagged mixture from the amplified subsets; determining, for the biological sample, a count of the distinct molecules including the target sequence. 12,071,651 3/19/2041 Issued/Allowed: CA Pending: CN, EP, HK P02 Target-Associated Molecules for Characterization Associated with Biological Targets A method and/or system for facilitating characterization of one or more conditions that can include: generating a set of target-associated molecules; generating a reference-associated set of molecules; facilitating generation of a spike-in mixture; determining abundance metrics based on an analysis of the spike-in mixture; and facilitating the characterization of the conditions based on the abundance metrics 11,646,100 3/5/2042 Issued/Allowed: CA Pending: CN, EP, HK P03 Sequencing Output Determination and Analysis with Target-Associated Molecules in Quantification Associated with Biological Targets A method and/or system for generating a set of target-associated molecules (e.g., spike-in molecules) associated with biological targets; generating spike-in mixtures based on processing the set of target-associated molecules with samples including the biological targets; performing Sanger sequencing operations on the spike-in mixtures; determining abundance metrics based on chromatogram-related outputs from the Sanger sequencing operations; and/or facilitating characterization of medical conditions based on the abundance metrics. 11,430,543 6/24/2041 Issued/Allowed: AU, BE, BR, CA, DE, EP, ES, FR, IL, IT, JP, KR, NL, SG, EP, GB Pending: CN, HK, IN, SG P04 Quality Control Templates for Ensuring Validity of Sequencing-Based Assays A method and/or system for generating a set of quality control template (QCT) molecules; determining a set of QCT sequence read clusters based on the set of QCT molecules, such as based on variation regions of the set of QCT molecules; and based on the set of QCT sequence read clusters, determining a sequencing-related parameter, such as a contamination parameter and/or molecule count parameter, associated with the at least one of sequencing library preparation and sequencing. 11,629,381 2/17/2042 Issued/Allowed: AU, AT, BE, BR, CN, CY, DE, DK, EP, FI, FR, GR, HK, IN, IR, IE, IT, JP, KR, LI, NL, NO, PT, ES, SE, CH, GB Pending: CA, EP, HK, JP, SG 25 Table of Contents Patent Family Patent Name Summary U.S. Patent Number U.S. Exp. Date Other Jurisdictions P05 Homologous Genomic Regions for Characterization Associated with Biological Targets A method and/or system for generating a co-amplified mixture based on co-amplifying a set of nucleic acid molecules (e.g., cell-free nucleic acids, etc.) from the biological sample, wherein the set of nucleic acid molecules includes a genomic region of interest associated with the medical condition; and a homologous native genomic region with partial sequence similarity to the genomic region of interest; sequencing the co-amplified mixture; determining an abundance metric for the genomic region of interest and an abundance metric for the homologous native genomic region; and/or facilitating the characterization of the medical condition based on the abundance metric for the genomic region of interest and the abundance metric for the homologous native genomic region. 11,519,024 3/25/2040 Pending: CA, EP P08 Fragment Analysis for Quantitative Diagnostics of Biological Targets Methods of detecting the presence or absence of diseases using quantitative approaches, including methods for determining the abundance of endogenous targets and determining the presence or absence of an aneuploidy. Pending N/A Pending: CA, EP P09 Molecule Counting of Methylated Cell-free DNA for Treatment Monitoring Methods to quantify methylation in a DNA sample that include treating the sample to encode the presence or absence of DNA methylation, adding to the sample a set of synthetic molecules (e.g., quality control template (QCT) molecules), generating a co-amplification mixture, sequencing the co-amplification mixture, and determining a number of methylated molecules in the sample based on the number of methylated reads from the sample and a number of reads from the set of synthetic molecules. 12,043,873 3/21/2043 Pending: AU, CA, CN, EP, HK, JP, KR P10 Non-Invasive Prenatal Testing at Early Stage of Pregnancy A highly accurate non-invasive prenatal testing methodology that allows accurate fetal rhesus determination and fetal DNA fraction measurement in a single assay is provided. The disclosed testing may be administered as early as at week 10 of pregnancy and can be conveniently combined with prenatal genetic disease testing and detection. 11,946,104 7/7/2040 Issued/Allowed: EP, FR, DE, IT, NL, ES, CH, GB Pending: CA, EP 26 Table of Contents BR = Brazil CN = China IN = India PT = Portugal CA = Canada CY = Cyprus IE = Ireland ES = Spain CH = Switzerland DE = Germany IT = Italy SE = Sweden DK = Denmark EP = Europe LI = Liechtenstein SG = Singapore FR = France FI = Finland NL = Netherlands GB = United Kingdom IL = Israel HK = Hong Kong NO = Norway To date, we have not been engaged in patent infringement lawsuits or any other material intellectual property disputes. However, we may in the future become subject to or initiate intellectual property litigation. Moreover, our ability to compete effectively depends to a large extent on our ability to develop proprietary products and technologies and to maintain adequate protection of our intellectual property in the United States and other countries. We pursue intellectual property protection to the extent we believe it would advance our business objectives. Notwithstanding these efforts, there can be no assurance that we will adequately protect our intellectual property or provide any competitive advantage. For more information regarding risks relating to our intellectual property, see Part I, Item 1A, “Risk factors--Risks related to our intellectual property.” Payor Coverage and Reimbursement Reimbursement is a critical component of our business strategy and financial success. We approach reimbursement through a comprehensive framework addressing coding, coverage, and contracting to maximize access to our tests and optimize ASP. More than 90% of our revenue in 2025 stemmed from reimbursement of our prenatal and oncology tests in the United States, making our payor strategy central to our financial performance. While the vast majority of the carrier and aneuploidy tests we offer are covered under existing policies, we initially operated primarily out-of-network with commercial third-party payors. Our in-network coverage included 250 million covered lives as of December 31, 2025. We anticipate our covered lives will continue to increase over time, which we expect will drive progressively higher ASPs. Reimbursement sources and status We receive reimbursement from several distinct sources: • Commercial third-party payors, including insurance companies and health maintenance organizations; • Government payors, state Medicaid programs, and Medicare; • Employee benefits health plans; and • Individual patients, who represent a small amount of our revenue. Commercial third-party payors We have significantly expanded our in-network status with commercial insurers, including several of the largest national payors. We expect this in-network expansion to continue driving higher ASPs and enhance revenue predictability, due to the contracts establishing agreed-upon rates. Beyond our contracted rate agreements, we submit claims for reimbursement and receive associated payments from commercial insurers on a non-contracted basis as necessary. The amount of reimbursement allowed and collected outside of network contract rates with commercial insurers is subject to greater variability and less predictability. In prenatal, our carrier and aneuploidy tests are broadly covered by most major insurance providers, and we have broad reimbursement for tests we provide. Our sgNIPT and fetal antigen NIPT have variable coverage, with certain payors providing reimbursement, creating opportunities for ASP growth as coverage expands. For our oncology products, Northstar Select has gained coverage from several commercial insurers. Northstar Response, while newer to market, is already reimbursed by certain commercial insurers, achieving a level of ASP that already provides positive contribution margins. Medicare We have obtained Medicare coverage for both our prenatal and oncology testing services. In April 2025, our Northstar Select test received a positive coverage decision and Z-code through the MolDX program administered by Palmetto GBA. 27 Table of Contents For our prenatal tests, Medicare provides coverage for patients who meet the Medicare eligibility criteria; however, this represents a very small portion of our prenatal test volume given the demographics of pregnant patients. For our oncology portfolio, Medicare coverage is crucial given the higher prevalence of cancer in the Medicare-eligible population. We continue to advance our evidence development strategy for Northstar Response, which requires additional clinical validity and utility data for Medicare coverage. Our flagship “NORTH” study, along with other ongoing clinical studies, is designed to generate the evidence necessary for Medicare coverage, initially focusing on immunotherapy and immunotherapy-combination therapy applications. Medicaid We have enrolled in over 40 state Medicaid programs across the United States. These enrollments are critical for our prenatal test ASPs. We plan to expand our Medicaid participation as our geographical footprint continues to grow, ensuring access to our tests for underserved populations. While Medicaid broadly covers carrier and aneuploidy tests, reimbursement rates vary significantly across state Medicaid programs. Moreover, various managed Medicaid payors may not have any out-of-network benefits, resulting in non-payments until they agree to contract with our laboratory, creating variability in our reimbursement from this payor segment. In addition, our carrier screen test is not covered by Alabama, Michigan, or Nevada, and our aneuploidy test is not covered by Nebraska or Utah. State Medicaid coverage for our RhD and fetal antigen tests is currently uncommon. Our oncology tests are covered at the federal level by Medicare. Medicaid coverage for our oncology tests is less relevant, as the vast majority of cancer patients do not have Medicaid coverage. Billing and claims processing Laboratory tests are classified for reimbursement purposes under a coding system known as Current Procedure Terminology (CPT), which we and our customers must use to bill and receive reimbursement for our diagnostic tests. Once the American Medical Association (AMA) establishes a CPT code, the Centers for Medicare & Medicaid Services (CMS) establishes payment levels and coverage rules under Medicare, while state Medicaid programs and commercial health plans establish rates and coverage rules independently in accordance with applicable rules. A Proprietary Laboratory Analyses (PLA) code is part of the CPT code set and may be assigned to tests that are not covered by standard CPT codes. We utilize a combination of established CPT codes and recently obtained PLA codes for billing and reimbursement of our tests. We use established CPT codes for certain tests, including our aneuploidy NIPT, for which CMS had a pricing rate of $759 per test as of December 31, 2025. For other proprietary tests, we use PLA codes, including our carrier panel which CMS had a pricing rate of approximately $1,825 per test as of December 31, 2025. We have also obtained PLA codes for our Northstar Select and Northstar Response tests, for which CMS had pricing rates of approximately $2,920 per test and $1,644 per test, respectively, as of December 31, 2025. The transition from miscellaneous codes to specific PLA codes has enhanced our reimbursement clarity and is expected to continue to improve our ASPs as these codes are increasingly recognized by commercial third-party payors. Despite favorable coding and high coverage rates for many of our tests, we face reimbursement challenges in certain scenarios. For example, for out-of-network claims with Managed Medicaid plans, we may receive no reimbursement. Even for commercial insurances with out-of-network benefits, the percentage of allowed amounts that are paid may be a small fraction of the CMS rate. Challenges related to reimbursements are more fully discussed in the Part I, Item 1A, “Risk factors—Risks related to our reimbursements” included elsewhere in this Annual Report. As a result of these challenges and rates negotiated with contracted payors, our Overall ASP is lower than the reimbursement amounts suggested by the codes. We maintain a systematic approach to appeals for denied claims, with variable success rates depending on the payor and reason for denial. Our appeals process is supported by our internal reimbursement team, who analyze denial patterns and optimize appeal strategies accordingly. Moreover, as our test volume increases, we believe this will improve our ability to secure network contracts with more commercial insurers, which should decrease claim denials and increase ASPs. In addition, we have built a robust revenue cycle management infrastructure to optimize reimbursement for our tests, which includes internal and external resources, as well as AI-based automation for processing payor communications and streamlining claims management. Patient access and financial assistance 28 Table of Contents We provide comprehensive patient support services, including pre-authorization support where required by payors, patient-focused education about potential financial responsibilities and personalized financial assistance for patients who indicate an inability to afford out of pocket charges. We use a combination of robotic process automation and AI for reimbursement, including sorting thousands of pages of correspondence we receive from payors on a daily basis, and submitting reconsiderations or appeals for thousands of claims that are initially denied. Reimbursement expansion strategy We are actively generating additional clinical validity and utility evidence to expand coverage of our tests. For our prenatal products, we continue to build evidence demonstrating improved outcomes and cost-effectiveness compared to traditional approaches. In oncology, our NORTH study and other ongoing clinical studies aim to demonstrate the clinical utility of Northstar Response in early therapy response assessment across multiple cancer types and treatment modalities. In addition, inclusion in clinical practice guidelines is a key element of our reimbursement strategy. Recent ACOG practice advisory changes have cited our publications in support of new approaches to testing. Additionally, inclusion of our specific tests, such as sgNIPT, or broader adoption of testing categories like 22q11.2 microdeletion screening in ACOG guidelines could significantly increase coverage and ASPs. Moreover, our publication strategy prioritizes studies that address key questions relevant to clinical guideline development. We continuously pursue strategic initiatives to enhance our reimbursement landscape, including: • Expansion of in-network coverage. As we increase test volumes and publish additional evidence, we expect to secure additional in-network contracts with commercial third-party payors. • Medicare coverage expansion. We are working toward Medicare coverage for Northstar Response, beginning with applications in immunotherapy response monitoring where the clinical utility is most established. • Clinical guideline incorporation. We actively engage with professional societies to support the inclusion of our testing methodologies in clinical practice guidelines. • Test menu optimization. We evaluate reimbursement potential when developing new tests or expanding existing test menus to ensure alignment with payor policies. • Payor education. We maintain active engagement with medical directors at key payors to ensure understanding of our unique technology and clinical value proposition. Future reimbursement landscape The reimbursement landscape for molecular diagnostics continues to evolve, with increasing emphasis on demonstrated clinical utility and economic value. We believe our approach to evidence generation, combined with our unique technology platform and differentiated products, positions us favorably for continued improvements in reimbursement. As we expand our menu of tests and geographical reach, we anticipate further strengthening our reimbursement profile through various initiatives, including increasing in-network coverage with commercial and Managed Medicaid payors; adding additional Medicaid participation across states, and obtaining Medicare coverage for Northstar Response. We believe these initiatives will support continued growth in our realized ASPs and gross margin over time. Government Regulations Our business is subject to and impacted by laws and regulations in the United States (at both the federal and state levels) and internationally that are subject to change. Some of these laws and regulations are particular to our laboratory business while others relate to conducting business generally and billing and reimbursement practices. In addition, we are subject to site inspections, claims audits, and other inquiries by certain federal and state governmental agencies. Food and Drug Administration In the United States, medical devices are subject to extensive regulation by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (FDC Act) and its implementing regulations, and other federal and state statutes and regulations. The laws and regulations govern, among other things, medical 29 Table of Contents device development, testing, labeling, storage, premarket clearance, de novo classification or premarket approval, post-market requirements, labeling, advertising and promotion and product sales and distribution. Unless subject to an exemption, to be commercially distributed in the United States, medical devices must receive from the FDA prior to marketing, clearance of a 510(k) premarket notification submission, grant of a request for de novo classification, or approval of an application for premarket approval (PMA). An in vitro diagnostic product (IVD) is a type of medical device that is intended for use in the diagnosis of diseases or conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. IVDs comprise reagents, instruments, and systems intended for use in the collection, preparation and examination of specimens from the human body. IVDs can be used to detect the presence of certain chemicals, genetic information or other biomarkers related to health or disease. IVDs include tests for disease prediction, prognosis, diagnosis, and screening (e.g., carrier screening). A subset of IVDs are known as analyte specific reagents (ASRs). An ASR is a single reagent (e.g., antibody, specific receptor protein, ligand, nucleic acid sequence) that, through specific binding or chemical reaction with substances in a specimen, is intended for use in a diagnostic application for the identification and quantification of an individual chemical substance in biological specimens. Most ASRs are exempt from the premarket review processes but must comply with general controls, as described below, including applicable provisions of the quality system regulation (QSR). Device classifications The FDC Act classifies medical devices into one of three categories based on the risks associated with the device and the level of control necessary to provide reasonable assurance of safety and effectiveness. • Class I devices are deemed to be low risk and are subject to the fewest regulatory controls. Many Class I devices are exempt from FDA premarket review requirements. • Class II devices, including some software products to the extent that they qualify as a device, are deemed to be moderate risk, and generally require 510(k) clearance. • Class III devices are generally the highest risk devices and are subject to the highest level of regulatory control to provide reasonable assurance of the device’s safety and effectiveness. Class III devices typically require a PMA by the FDA before they are marketed. A clinical trial is almost always required to support a PMA application and is sometimes required for 510(k) clearance. All clinical trials of investigational devices must be conducted in compliance with any applicable FDA and Institutional Review Board requirements. Devices that are exempt from FDA premarket review requirements must nonetheless comply with post-market general controls as described below, unless the FDA has chosen otherwise. FDA premarket clearance and approval requirements 510(k) clearance. To obtain 510(k) clearance, a manufacturer must submit a premarket notification demonstrating to the FDA’s satisfaction that the proposed device is substantially equivalent to a legally marketed predicate device. The FDA’s 510(k) clearance pathway usually takes from three to 12 months from submission, but it can take longer, particularly for a novel type of product. PMA. The PMA pathway requires valid scientific evidence demonstrating to the FDA’s satisfaction the safety and effectiveness of the device for its intended use. The PMA pathway is costly, lengthy, and uncertain. The PMA review process typically takes one to three years from submission but can take longer. De novo. If no predicate device can be identified, a device is automatically classified as Class III, requiring a PMA application. However, the FDA on its own initiative or at the request of a manufacturer can reclassify as low- or moderate-risk device for which there is no predicate through the de novo classification process. The de novo route is intended to be less burdensome than the PMA process. The de novo route has historically been used for many IVD products. Post-market general controls. After a device, including a device exempt from FDA premarket review, is placed on the market, numerous regulatory requirements apply. These include: the QSR, labeling regulations, registration and listing, the Medical Device Reporting regulation (and the Reports of Corrections and Removals regulation. 30 Table of Contents The FDA enforces compliance with its requirements through inspection and market surveillance. If the FDA finds a violation, it can institute a wide variety of actions, ranging from issuing a Form 483 Notice of Inspectional Observations or sending an untitled or public warning letter, to enforcement actions such as fines, injunctions, and civil penalties; recall or seizure of products; operating restrictions, partial suspension or total shutdown of production; refusing requests for 510(k) clearance, de novo classification, or PMA approval of new products; withdrawing PMAs already granted; and criminal prosecution. Research use only. Research use only (RUO) products are exempt from FDA medical device requirements provided their manufacturers comply with specified labeling and restrictions on distribution and promotion. The products must bear the statement: “For Research Use Only. Not for Use in Diagnostic Procedures.” Manufacturers of RUO products cannot make any claims related to safety, effectiveness or diagnostic utility, and RUO products cannot be intended by the manufacturer for clinical diagnostic use. An RUO product promoted for diagnostic use may be viewed by the FDA as adulterated and misbranded under the FDC Act and the manufacturer of such product could be subject to FDA enforcement activities. Our LDTs use instruments and reagents labeled as RUO. Laboratory-developed tests. Each of our genetic tests is an LDT. The FDA considers LDTs to be tests that are designed, developed, validated and used within a single laboratory. The FDA had historically taken the position that it had the authority to regulate LDTs as medical devices under the FD&C Act but exercised enforcement discretion until it recently rescinded LDT regulations indicating that it does not have the authority to require clearance, de novo classification, or approval of LDTs prior to market release. As a result, our molecular diagnostic products are not subject to FDA approval requirements. Clinical Laboratory Improvement Amendments of 1988, College of American Pathologists, and state regulations Clinical Laboratory Improvement Amendments (CLIA) As a clinical laboratory, we are required to hold certain federal and state licenses, certifications or permits to conduct our business. As to federal certifications, the Clinical Laboratory Improvement Amendments of 1988 (CLIA) establishes rigorous quality standards for all commercial laboratories that perform testing on human specimens for the purpose of providing information for the diagnosis, prevention, or treatment of disease or the assessment of the health or impairment of human beings. CLIA requires such laboratories to be certified by the federal government and mandates compliance with various operational, personnel, facility, administration, quality and proficiency testing requirements intended to ensure the accuracy, reliability and timeliness of patient test results. CLIA certification is also a prerequisite to be eligible to bill state and federal health care programs, as well as many commercial third-party payors, for laboratory testing services. Our laboratories located in Menlo Park and Union City, California, are CLIA certified and must comply with all applicable CLIA regulations and standards. If a clinical laboratory is found to be out of compliance with CLIA standards, CMS may impose sanctions; suspend, limit or revoke the laboratory’s CLIA certificate (and prohibit the owner, operator or laboratory director from owning, operating, or directing a laboratory for two or more years following license revocation); subject the laboratory to a directed plan of correction, on-site monitoring, civil monetary penalties, civil actions for injunctive relief, criminal penalties; or suspension or exclusion from the Medicare and Medicaid programs. CLIA provides that a state may adopt laboratory licensure requirements and regulations that are more stringent than those under federal law and requires compliance with such laws and regulations. A number of states have implemented their own more stringent laboratory regulatory requirements. State laws may require the laboratory to obtain state licensure and/or laboratory personnel to meet certain qualifications and obtain professional licensure, specify certain quality control procedures or facility requirements, or prescribe record maintenance requirements. Moreover, several states impose the same or similar state requirements on out-of-state laboratory testing specimens collected or received from, or test results reported back to, residents within that state. Therefore, we are required to meet certain laboratory licensing requirements for those states in which we offer services or from which we accept specimens, and that have adopted laboratory regulations beyond CLIA. College of American Pathologists (CAP) The College of American Pathologists (CAP) maintains a clinical laboratory accreditation program. While not required to operate a CLIA-certified laboratory, many private insurers require CAP accreditation as a condition to contracting with clinical laboratories to cover their tests. In addition, some countries outside the United States 31 Table of Contents require CAP accreditation as a condition to permitting clinical laboratories to test samples taken from their citizens. Our two laboratories have each been accredited by CAP, which means that our laboratories have been certified as following CAP standards and guidelines in operating the laboratory facility and in performing tests that ensure the quality of our test results. In order to maintain CAP accreditation, we are subject to survey for compliance with CAP standards every two years. Failure to maintain CAP accreditation could have a material adverse effect on the sales of our tests and the results of our operations. California laboratory licensing In addition to federal certification requirements for laboratories under CLIA, we are required under California law to maintain a California state license for both our Menlo Park and Union City clinical laboratories, and to comply with California state laboratory laws and regulations, because our laboratories are located in California, and both facilities test specimens originating from California. Similar to the federal CLIA regulations, the California state laboratory laws and regulations establish standards for the operation of a clinical laboratory and performance of test services, including the education and experience requirements of the laboratory director and personnel (including requirements for documentation of competency), equipment validations, and quality management practices. All testing personnel must maintain a California state license or be supervised by licensed personnel, and our laboratory director must maintain an additional license issued by the California Department of Public Health (CDPH). Clinical laboratories are subject to both routine and complaint-initiated on-site inspections by the state. If a clinical laboratory is found to be out of compliance with California laboratory standards, the CDPH may suspend, restrict or revoke the California state laboratory license to operate the clinical laboratory (and exclude persons or entities from owning, operating, or directing a laboratory for two years following license revocation), assess civil money penalties, and/or impose specific corrective action plans, among other sanctions. Clinical laboratories must also provide notice to CDPH of any changes in the ownership, directorship, name or location of the laboratory. Failure to provide such notification may result in revocation of the state license and sanctions under the CLIA certificate. Any revocation of a CLIA certificate or exclusion from participation in Medicare or Medicaid programs may also result in suspension of the California state laboratory license. New York laboratory licensing In order to test specimens in our laboratories originating from, and return test results to, New York State, both of our laboratories are required to obtain a New York state laboratory permit and comply with New York state laboratory laws and regulations. We maintain a valid permit in the state of New York for the prenatal molecular genetic testing services furnished by our Union City laboratory and we are in the application process to obtain a permit in the state of New York for the oncology molecular genetic testing services furnished by our Menlo Park laboratory. The New York state laboratory laws, regulations and rules are equal to or more stringent than the CLIA regulations and establish standards for the operation of a clinical laboratory and performance of test services, including education and experience requirements of a laboratory director and personnel, physical requirements of a laboratory facility, equipment validations, and quality management practices. The laboratory director(s) must maintain a Certificate of Qualification issued by the New York State Department of Health (DOH) in the permitted test categories. Under the New York state requirements, our clinical laboratory in Union City is, and our clinical laboratory in Menlo Park will be, subject to proficiency testing and on-site survey inspections conducted by the Clinical Laboratory Evaluation Program (CLEP) under the DOH. If a laboratory is found to be out of compliance with New York’s CLEP standards, the DOH may suspend, limit, revoke or annul the New York laboratory permit, censure the holder of the license or assess civil money penalties. Statutory or regulatory noncompliance may result in a laboratory’s operator, owners and/or laboratory director being found guilty of a misdemeanor under New York law. Clinical laboratories must also provide notice to the CLEP of any changes in ownership, directorship, name or location of the laboratory. Failure to provide such notification may result in revocation of the state license and sanctions under the CLIA certificate. Any revocation of a CLIA certificate or exclusion from participation in the Medicare or Medicaid programs may result in suspension of the New York laboratory permit. The DOH also must approve each LDT before the test is offered to patients located in New York. Our Union City clinical laboratory has received approval from New York’s CLEP to offer most of our prenatal tests that are performed in Union City. We are in the application process to obtain approval from New York’s CLEP to offer our Northstar Select test that is performed in our Menlo Park laboratory. 32 Table of Contents Other state laboratory licensing laws In addition to New York and California, certain other states require licensing of out-of-state laboratories under certain circumstances. We have obtained licenses in the states that we believe require us to do so based on our current operations, and believe we are in compliance with applicable state laboratory licensing laws, including Maryland, Pennsylvania, Rhode Island and the District of Columbia. Potential sanctions for violation of state statutes and regulations can include significant monetary fines, the rejection of license applications, the suspension or loss of various licenses, certificates and authorizations, and in some cases criminal penalties, which could harm our business. CLIA does not preempt state laws that have established laboratory quality standards that are more stringent than federal law. State genetic testing and privacy laws Many states have implemented genetic testing and privacy laws imposing specific patient consent requirements and protecting test results. Under some state laws, we are prohibited from conducting genetic tests without appropriate documentation of patient (or parental/guardian) consent from the physician ordering the test. For example, Texas enacted legislation limiting use of genetic data applicable to companies offering direct-to-consumer (without health care provider involvement) genetic testing or collect, use, or otherwise analyze genetic data derived from individuals using such products or services, but exempt genetic data collected or generated by an entity subject to HIPAA. While we rely on physicians to obtain the required patient consent to perform genetic testing, the regulatory burden may be deemed to be our responsibility and such consents, or our compliance with applicable laws and regulations, could be challenged. Requirements of these laws and penalties for violations vary widely from state to state. Federal and state health care laws As a clinical laboratory, we are subject to certain federal and state laws and regulations relating to delivery of diagnostic healthcare. To meet the requirements of these laws and regulations, we have developed and operate a compliance program modeled after the general and specific guidance issued by the Office of Inspector General of the U.S. Department of Health and Human Services (HHS) and grounded in our company ethics and values. Although we believe that our compliance program and company culture support compliance with the various laws and regulations applicable to our business, we cannot ensure that government regulators will not identify potential deficiencies or violations in the conduct of our business activities. The Federal Civil Penalties Inflation Adjustment Act Improvements Act of 2015 provides for an annual, automatic adjustment of civil monetary penalties authorized under the Social Security Act to account for inflation, which are published in the Federal Register annually. Federal physician self-referral prohibition We are subject to the federal physician self-referral prohibition (42 U.S.C. §1395nn), commonly known as the Stark Law, and to comparable state laws. Together these restrictions generally prohibit us from billing a patient or governmental or private payor for certain designated health services, including laboratory test services, when the physician ordering the service, or a member of such physician’s immediate family, has a financial relationship with our company, such as an ownership or investment interest in or compensation arrangement with us, unless the relationship meets an applicable exception. Several Stark Law exceptions are relevant to many common financial relationships involving clinical laboratories and referring physicians, including: fair market value compensation for the provision of certain laboratory items or services; payments by physicians to a laboratory; space and equipment rental arrangements, and personal services arrangements that satisfy certain criteria. No clinical laboratory may submit claims to the Medicare or Medicaid programs for items or services furnished in violation of the Stark Law. These prohibitions apply regardless of any intent by the parties to induce or reward referrals or the reasons for the financial relationship and the referral. Penalties for violating the Stark Law include significant civil penalties, such as the return of funds received for all prohibited referrals, fines, civil monetary penalties, exclusion from the federal healthcare programs, integrity oversight and reporting obligations. Any person who presents or causes to be presented a claim to the Medicare or Medicaid programs in violation of the Stark Law may be subject to civil monetary penalties – up to $30,868 as of 2024 – per claim submission, an assessment of up to three times the amount claimed, and exclusion from participation in any federal health care program. A person who engages in a scheme to circumvent the Stark Law’s referral prohibition may be fined – up to $205,799 as of 2024 – for each such arrangement or scheme. Claims submitted in violation of the Stark Law may not be paid by Medicare or Medicaid, and any person collecting any amounts with respect to any such prohibited claim is obligated to refund such amounts. In addition, knowing 33 Table of Contents violations of the Stark Law may also serve as the basis for liability under the federal False Claims Act (FCA), which may result in additional civil penalties. Federal Anti-Kickback law The federal Anti-Kickback Statute (42 U.S.C. §1320a-7b), commonly known as AKS, makes it a felony for a person or entity, including a clinical laboratory, to knowingly and willfully offer, pay, solicit or receive any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce business that is reimbursable under any federal health care program. A person or entity does not need to have actual knowledge of the statute or specific intent to violate the AKS to have committed a violation if there is the requisite intent to commit the act. A violation of the federal Anti-Kickback Statute may result in imprisonment for up to ten years and/or criminal or civil fines – up to $104,330 (or $27,894 for each wrongful act) as of 2024 – and exclusion from participation in federal health care programs. Claims submitted in violation of the federal Anti-Kickback Statute may not be paid by a federal health care program, and any person collecting any amounts with respect to any such prohibited claim is obligated to refund such amounts. Although the AKS applies only to items and services reimbursable under any federal health care program, a number of states have passed statutes substantially similar to the AKS that apply to any payor. Penalties for violations of such state laws may include imprisonment and significant monetary penalties. Generally, courts have taken a broad interpretation of the scope of the AKS, holding that the statute may be violated if merely one purpose of a payment arrangement is to induce referrals or purchases. In addition to statutory exceptions to the AKS, regulations set forth in 42 C.F.R. § 1001.952 provide for a number of safe harbors for defined payment arrangements that will not be deemed improper remuneration. An arrangement must fully comply with each element of an applicable safe harbor to qualify for protection. Failure to meet the requirements of the safe harbor, however, does not render a payment arrangement per se illegal. Rather, the government must evaluate such arrangements on a case-by-case basis, taking into account all facts and circumstances. In addition, a knowing violation of the AKS constitutes a false or fraudulent claim under the FCA, which is discussed in greater detail below. False Claims Act The federal False Claims Act (31 U.S.C. §§ 3729-3733), commonly known as FCA, prohibits, among other things, a person from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment or approval and from making, using, or causing to be made or used, a false record or statement material to a false or fraudulent claim to secure payment or retain an overpayment by the federal government. Violation of the federal False Claims Act may result in fines of up to three times the actual damages sustained by the government, plus mandatory civil penalties – up to approximately $28,619 in 2025 – per false claim or statement, imprisonment or both, reimbursement of the whistleblower’s attorneys’ fees, and possible exclusion from any federal health care programs. The penalties will continue to be adjusted, increasing each year to reflect changes in the inflation rate, pursuant to the 2015 Bipartisan Budget Act. In addition to actions initiated by the government itself, the statute authorizes actions to be brought on behalf of the federal government by a private party having knowledge of the alleged fraud. Because the complaint is initially filed under seal, the action may be pending for some time before the defendant is even aware of the action. If the government intervenes and is ultimately successful in obtaining redress in the matter or if the plaintiff succeeds in obtaining redress without the government’s involvement, then the plaintiff will receive a percentage of the recovery. Finally, the Social Security Act includes its own provisions that prohibit the filing of false claims or submitting false statements in order to obtain payment. Several states have enacted comparable false claims laws which may be broader in scope and apply regardless of payor. Civil Monetary Penalty Law The Civil Monetary Penalty Law (42 U.S.C. § 1320a-7a), commonly known as CMPL, imposes penalties against any person or entity that, among other things, is determined to have presented or caused to be presented a claim to a federal health care program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent. In addition, a person who offers or provides to a Medicare or Medicaid beneficiary any remuneration, that the person knows or should know is likely to influence the beneficiary’s selection of a particular provider, practitioner or supplier of Medicare or Medicaid payable items or services may be liable and subject to civil monetary penalties. A violation of the federal Civil Monetary Penalty statute may result in maximum civil fines – up to $124,732 in 2024 – plus treble damages and exclusion from participation in any federal health care program. Eliminating Kickbacks in Recovery Act 34 Table of Contents The Eliminating Kickbacks in Recovery Act of 2018 (18 U.S.C. §220), commonly known as EKRA, prohibits knowingly and willfully soliciting or receiving any remuneration (including any kickback, bribe or rebate) directly or indirectly, overtly or covertly, in cash or in kind, in return for referring a patient or patronage to a laboratory; or paying or offering any remuneration (including any kickback, bribe or rebate) directly or indirectly, overtly or covertly, in cash or in kind, to induce a referral of an individual to a laboratory or in exchange for an individual using the services of that laboratory. EKRA was enacted under the SUPPORT Act for the legislative purpose to help reduce opioid-related fraud and abuse. However, EKRA defines the term “laboratory” broadly and without reference to any connection to substance use disorder treatment. Moreover, EKRA applies to claims submitted to both government and commercial third-party payors. Violation of EKRA carries potential penalties of up to $200,000 in fines and imprisonment of up to ten years for each occurrence, and potential exclusion from participation in any federal health care program. The law includes a limited number of exceptions, some of which closely align with corresponding AKS safe harbors, and others that materially differ. Currently, there is no regulation interpreting or implementing EKRA, nor any guidance released by any federal agency regarding the scope of EKRA. The only case law issued to date involves decisions interpreting the EKRA as it applies to compensation of laboratory sales personnel hired as independent contractors, and the courts differ on interpretation and application of the law. These decisions are currently on appeal in the federal court of appeals. We cannot assure you that our relationships with physicians, hospitals, customers, or sales personnel will not be subject to scrutiny or will survive a challenge under EKRA. If imposed for any reason, sanctions under EKRA could have a negative effect on our business. Because we operate a laboratory facility located in California and licensed by California’s DHS, California law is applicable to our business arrangements. California’s state anti-kickback statutes, Business and Professions Code Section 650 (which applies to all categories of payors) and Insurance Code Section 754, and its Medi-Cal anti-kickback statute, Welfare and Institutions Code Section 14107.2, are analogous to, and have been interpreted by the California Attorney General and California courts in substantially the same way as the federal government and the courts have interpreted, the federal Anti-Kickback Statute. A violation of Section 650 is punishable by up to one year of imprisonment, a fine up to $50,000, or both imprisonment and a fine. A violation of Section 14107.2 is punishable by imprisonment and fines of up to $10,000. The California Insurance Code includes similar prohibitions against any consideration for the referral or procurement of patients if a claim is submitted to a commercial insurer, CA Ins. Code § 750, which is punishable by criminal penalties mirroring those that apply to violations of Business and Professions Code Section 650. Because each of our laboratories holds a New York CLEP permit, we must comply with New York state laboratory statutes and regulations, which include anti-kickback provisions, Public Health Law Section 587, and Medicaid anti-kickback provisions, 18 NYCRR Section 515.2, related to laboratory services. The New York DOH may suspend, limit, revoke or annul the New York laboratory permit or otherwise discipline the permit holder for a violation. Data Privacy and Security We are, or may become, subject to numerous federal, state, local and foreign laws, regulations, standards, and guidance regarding data privacy and security. The federal Health Insurance Portability and Accountability Act of 1996 (HIPAA) created federal criminal statutes relating to privacy of personal data. HIPAA imposes privacy, security and breach reporting obligations with respect to individually identifiable health information upon “covered entities” (health plans, health care clearinghouses and certain health care providers), and their respective business associates, individuals or entities that create, received, maintain or transmit protected health information in connection with providing a service for or on behalf of a covered entity. HIPAA mandates the reporting of certain breaches of health information to HHS, affected individuals and if the breach is large enough, the media. Entities that are found to be in violation of HIPAA, including as the result of a breach of unsecured protected health information (PHI), a complaint about privacy practices or an audit by HHS, may be subject to significant civil, criminal and administrative fines and penalties and/or additional reporting and oversight obligations if required to enter into a resolution agreement and corrective action plan with HHS to settle allegations of HIPAA non-compliance. HIPAA also prohibits knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services. Like the AKS, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation. 35 Table of Contents HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH) and their respective implementing regulations, impose obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information. Additionally, HITECH created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in U.S. federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions. Even when HIPAA does not apply, failing to take appropriate steps to keep consumers’ personal information secure may constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act, 15 U.S.C § 45(a). The FTC expects a company’s data security measures to be reasonable and appropriate in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and reduce vulnerabilities. Personally identifiable health information is considered sensitive data that merits stronger safeguards. The FTC’s guidance for appropriately securing consumers’ personal information is similar to what is required by the HIPAA Security Rule. In addition, certain state laws govern the privacy and security of personal information, including health information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. Many states are considering similar laws. Failure or perceived failure to comply with these laws, where applicable, can result in material adverse effects to our business, including the imposition of significant civil and/or criminal penalties and private litigation. As a health care provider, we are also subject to Section 4004 of the 21st Century Cures Act, or Cures Act, and regulations promulgated by HHS related to patient access to electronic PHI, or EHI, to promote interoperability and to ensure the access, exchange, or use of EHI. Various U.S. states have implemented similar restrictive requirements regulating the use and disclosure of health information and other personal information that are not necessarily preempted by HIPAA or that regulate different information than HIPAA. The California Consumer Privacy Act (CCPA), which went into effect January 1, 2020, and California Privacy Rights Act of 2020 (CPRA), which went into effect on January 1, 2023, which created additional obligations with respect to certain data relating to consumers, significantly expands the CCPA, is an example of the increasingly stringent privacy laws at the state level in the United States. The CCPA also created a private right of action with statutory damages for certain data breaches, thereby potentially increasing risks associated with a data breach. However, the CCPA and CPRA include an exemption for HIPAA covered entities such as our laboratory. The California Confidentiality of Medical Information Act, which protects the confidentiality of individually identifiable medical information obtained by health care providers and their contractors, is much broader than HIPAA and the data protected is also broader than HIPAA. In addition, numerous other states’ legislatures have passed or are considering similar laws that will require ongoing compliance efforts and investment. For example, Virginia passed the Virginia Consumer Data Protection Act, and Colorado passed the Colorado Privacy Act, both of which differ from the CPRA and became effective in 2023 and the Texas Data Privacy and Security Act became effective in 2024. These state privacy laws dictate how we can collect, use, store, sell, share, analyze or process personal identifying information and/or consumer or health data received or generated by our business operations. Outside the United States, there are an increasing number of laws and regulations governing the collection, use and processing of personal data. For example, the European Union’s General Data Protection Regulation (EU GDPR) applies to any company established in the European Economic Area (EEA), and to companies established outside the EEA that process personal information in connection with the offering of goods or services to data subjects in the EEA or the monitoring of the behavior of data subjects in the EEA. These regulations are often more restrictive than those in the United States and may restrict transfers of personal data from the EEA to the United States and other countries unless certain requirements are met. The EU GDPR provides that EU member states may make their own further laws and regulations limiting the processing of genetic, biometric or health data, which could limit our ability to use and share personal data or could cause our costs to increase, and harm our business and financial condition. Further, the United Kingdom’s decision to leave the European Union has created uncertainty with regard to data protection regulation in the United Kingdom. As of January 1, 2021, we are also subject to the UK General Data Protection Regulation and UK Data Protection Act of 2018, which retains the GDPR in substantially similar form in the United Kingdom’s 36 Table of Contents national law. Failure to comply with any of these obligations could expose us to material adverse effects, including significant fines. It is possible that state, federal (including legislative and executive branch initiatives), and foreign healthcare reform measures may be adopted in the future. Employees and Human Capital Our culture and values BillionToOne was founded on the mission of removing the fear of the unknown by providing molecular diagnostics that are accurate, fast, and accessible. To fulfill our mission, we are dedicated to fostering a high-performance culture where every individual, regardless of level or position, feels empowered to solve significant problems and make a notable impact. Our vision is to challenge the status quo that makes healthcare opaque and financially out of reach for many. We are focused on building a corporate culture that nurtures innovation, creative problem solving, and a strong sense of purpose with patient and caregiver mindsets at the forefront. Talent development, compensation and retention We focus on attracting, retaining, and cultivating highly-talented employees, with the goal of hiring the top 1% from the application pool. Due to our highly technical and competitive industry, we believe recruiting and retaining highly-talented personnel is key to our ability to execute our business strategy and maintain competitive margins. We offer our employees competitive pay, equity compensation, a retirement savings package with company matching, and other benefits such as four months of paid time off at full salary for parental or family leave, as well as incentive plans. The principal purposes of these plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives. Our values-based culture and our employees are a critical component of our success. We strive to create a supportive and professional environment for our employees. We expend considerable management time and attention, and financial resources, to attracting, retaining, and motivating exceptional individuals at our company. As of December 31, 2025, we had 713 employees, all of which were full-time employees. Of these employees, 125 were engaged in research and development activities and the remaining employees are engaged in laboratory operations, sales or administrative activities. None of our employees are represented by a labor union or covered by collective bargaining agreements, and we believe our relationship with our employees is good. Human capital resources Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees. The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of stock-based compensation awards and cash-based performance bonus awards. Available information Our website is located at https://www.billiontoone.com/. Information on our website is not part of this Annual Report on Form 10-K or any of our other securities filings unless specifically incorporated herein or therein by reference. Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including their exhibits, proxy and information statements, and amendments to those reports filed or furnished pursuant to Sections 13(a), 14, and 15(d) of the Securities Exchange Act of 1934, as amended, are available through the investor relations page of our website free of charge as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. We use the investor relations page on our website, press releases, public conference calls, public webcasts, our X handle (@BillionToOneInc) and our LinkedIn feed for purposes of compliance with Regulation FD and as a routine channel for distribution of important information to investors. In addition, our filings with the SEC may be accessed through the SEC’s Interactive Data Electronic Applications system at http://www.sec.gov. All statements made in any of our securities filings, including all forward-looking statements or information, are made as of the date of the document in which the 37 Table of Contents statement is included, and we do not assume or undertake any obligation to update any of those statements or documents unless we are required to do so by law.