BillionToOne, Inc.

Overview

BillionToOne develops and commercializes ultrasensitive, single-molecule next-generation sequencing (smNGS) solutions for molecular diagnostics. Its core technology is Quantitative Counting Templates (QCTs), synthetic DNA controls that enable absolute, single-molecule quantification of cell-free DNA (cfDNA) with high target multiplexing and low technical noise. The company focuses on prenatal testing (non-invasive fetal testing) and oncology (therapy selection and real-time monitoring), with ongoing development in additional oncology applications and future early-detection efforts. Its approach combines quantification-first assay design with algorithmic data interpretation and an AI-enabled, integrated workflow to deliver sensitive, specific tests from a single blood draw.

Products and portfolio

Prenatal — Unity family

• Unity Fetal Risk Screen: sgNIPT using cfDNA to report maternal carrier status and fetal risk for recessive conditions without a paternal sample; expanded to up to 14 conditions as of May 2025.
• Unity Aneuploidy Screen: high sensitivity and low inconclusive rates for common trisomies; improved performance at low fetal fractions; strong 22q11.2 microdeletion (DiGeorge) testing enabled by smNGS.
• Unity Fetal RhD NIPT: fetal RhD antigen detection with >99.9% sensitivity and specificity in published data; effective across RhD hybrid genes with extensive published concordance data.
• Unity Fetal Antigen NIPT: detects fetal RBC antigens (D, C, c, E, Kell, Fya) to guide alloimmunization management; peer-reviewed studies report 100% sensitivity and specificity with <0.1% no-call rate. Expanded RBC and, in 2026, Platelet Fetal Antigen NIPT options are marketed under Unity Aneuploidy Screen.
• Unity Fetal Antigen CTA NIPT: global collaboration with Johnson & Johnson to support the nipocalimab trial in pregnancies at risk for severe HDFN; IDE clearance in 2023 and regulatory clearances in some regions.
• Unity Complete: end-to-end workflow with software tools to streamline testing, reporting, and payor/billing processes to support adoption and retention.
• Market impact: Unity Fetal Risk Screen and related tests have influenced clinical guidelines and practice advisories (ACOG-referenced publications).

Oncology — Northstar portfolio

• Northstar Select: ultrasensitive liquid biopsy for therapy selection in late-stage solid tumors with single-molecule sensitivity and approximately 2× lower LOD than older ctDNA tests; head-to-head analysis shows >50% more actionable SNVs/Indels and >100% more CNVs versus comparator tests. Palmetto GBA MolDX coverage decision (L38043) in 2025 supports Medicare reimbursement.
• Northstar Response: tissue-free, pan-cancer assay that quantifies tumor burden via methylation signals in cfDNA across more than 2,200 genomic loci (expanded from 500+); LOD of 0.01% with single-molecule precision; designed for real-time therapy monitoring and validated in multiple studies. The NORTH multi-site study enrolled and expects results in 2026.
• Northstar PGx and Northstar Select CH (launched Jan–Feb 2026): add-on applications for chemotherapy pharmacogenomics and clonal hematopoiesis to inform therapy choices.
• MRD (Minimal Residual Disease): tissue-free MRD test in development, targeting commercialization in Q4 2026 to detect trace disease after curative-intent surgery across multiple cancers.
• Clinical validation and utility: Northstar products have an expanding body of clinical literature and ongoing prospective validation studies (e.g., NORTH, GI cancer-focused trials) to support coverage and guideline development.

Technology, data, and analytics

• Proprietary platform that integrates QCTs, machine learning/bioinformatics, and engineering-focused assay design to achieve single-molecule resolution and high multiplexing.
• Quantification advantages: absolute counts of cfDNA, cross-sample contamination detection down to 0.001%, calibration-free quantification (no spike-in titration required), and consistent longitudinal measurements.
• Custom bioinformatics and quality controls support data integration across thousands of loci and tailored patient reports, enabling design-based assay development and rapid iteration.
• Infrastructure: specialized, scalable laboratory operations designed to preserve single-molecule sensitivity with largely automated workflows and AI-enabled process improvements (for example, automated accessioning and payor communications).

Scale, customers, and reach (as of Dec 31, 2025)

• Employees: 713 full-time employees.
• Field sales: 231 sales representatives (177 prenatal; 54 oncology).
• Tests processed: over one million tests to date.
• Revenue mix and reimbursement: more than 90% of 2025 revenue derived from U.S. reimbursement; in-network coverage expanded to 250 million covered lives as of 12/31/2025.
• Revenue per salesperson: annualized revenue run-rate of $2.2 million per sales representative for the year ended December 31, 2025.
• Market and guideline impact: ACOG practice advisory changes reference Unity publications; Northstar Select has a Medicare/MolDX coverage decision; international activity is conducted mainly through distributors with varying patient payment models.

Business model and geography

• Commercial model: direct U.S. sales teams for prenatal and oncology testing; international distribution primarily via partners.
• Payor strategy: coding and contracting approach that includes use of PLA codes for some tests and efforts to increase in-network contracts to improve average selling price and predictability.
• Customer relationships: high physician adoption and low churn reported in prenatal; Northstar’s turnkey approach supports cross-selling between therapy selection and response monitoring, with about 95% of ordering oncologists using both Northstar Select and Northstar Response for the same patient in 2025.

Intellectual property and regulatory status

• IP: nine U.S. issued patents (expiry window 2038–2043) and 45 foreign patents, plus 14 U.S. and 31 foreign patent applications. Core coverage includes QCT technology, dilution tagging, spike-ins, QCT-based methylation assays, and sequencing-related innovations, including methods for counting and quantifying methylation and quality control templates.
• Regulatory posture: CLIA-certified laboratories (Menlo Park and Union City, CA) and CAP-accredited; state licensing where applicable (California, New York, Maryland, Pennsylvania, Rhode Island, DC). Tests operate as laboratory-developed tests (LDTs) under current FDA enforcement discretion, with prospective regulatory filings and coverage pathways pursued for select products.
• Data privacy and security: compliance with HIPAA and related privacy regimes, and consideration of HITECH, CCPA/CPRA, and GDPR requirements for international data.

Strategic partnerships and collaborations

• Johnson & Johnson: global collaboration on UNITY Fetal Antigen CTA and a separate development/commercialization agreement for a companion diagnostic for nipocalimab (AZALEA trial). The agreement includes upfront and milestone payments capped at $13 million, with an FDA submission milestone targeted for January 2028.
• Academic and clinical collaborations: partnerships with institutions such as UC San Diego, University of Florida, University of Miami, and Fred Hutch to validate Northstar Response and other applications, generating evidence to support coverage and guideline adoption.

Positioning and outlook

BillionToOne positions itself as a high-sensitivity molecular diagnostics platform focused on cfDNA with single-molecule precision, delivering tests for prenatal genetics and oncology. The company is expanding its portfolio (Northstar PGx/CH, MRD, additional fetal antigen testing, and early-detection concepts) and investing in AI-enabled data integration to advance personalized medicine. It maintains a growing U.S. commercial footprint with a reimbursement-focused strategy and strategic partnerships to broaden clinical adoption and utility.