BillionToOne's Northstar Select® Demonstrates Superior Sensitivity in Prospective Head-to-Head Validation Study Publication

Powered by proprietary single-molecule next-generation sequencing (smNGS) technology, Northstar Select sets a new standard in sensitivity for non-invasive, blood-based comprehensive genomic profiling of advanced solid tumor cancers by uncovering over 50% more clinically actionable alterations compared to other tests

MENLO PARK, Calif., Aug. 26, 2025 /PRNewswire/ -- BillionToOne, Inc., a molecular diagnostics company with a mission to create powerful and accurate tests that are accessible to all, today announced publication of Validation of a liquid biopsy assay with increased sensitivity for clinical comprehensive genomic profiling¹. The study validates Northstar Select, BillionToOne's highly sensitive comprehensive genomic profiling (CGP) liquid biopsy assay, demonstrating superior performance in detecting more clinically actionable alterations in circulating tumor DNA (ctDNA).

The prospective head-to-head comparison included 182 patients with more than 17 solid tumor types enrolled from six community oncology clinics and one large hospital from across the United States. Researchers directly compared Northstar Select against six commercially available liquid biopsy assays from four CLIA/CAP laboratories, with assay panel sizes ranging between 73 and 523 genes. Results demonstrated Northstar Select's clear superiority: the assay detected 51% more pathogenic single nucleotide variant (SNV)/Indels and 109% more copy number variants (CNVs) than available comparators, with 45% fewer null reports. When comparing matched CNV coverage between assays, Northstar Select detected almost 40% more CNVs, while the overall comparison across all tested genes showed 109% more, reflecting Northstar Select's broader coverage of copy number losses. The superior sensitivity was validated through orthogonal testing with digital droplet PCR (ddPCR), demonstrating 98% concordance with Northstar Select results and further evidence that the additional alterations found where comparators missed variants were confirmed true positives. Even in central nervous system cancers – where detection rates in plasma liquid biopsy are notoriously tough – Northstar Select detected alterations in 87% of cases, more than the current reported detection rates which range from 27-55% (including variants of unknown significance, or VUS) with other platforms. 

Notably, 91% of the additional clinically actionable variants detected by Northstar Select were found below 0.5% variant allele frequency (VAF), where other assays typically fail to reliably detect alterations. The assay demonstrated exceptional analytical performance across all variant classes, achieving greater than 99.9% specificity. Importantly, the enhanced sensitivity was not a result of detecting false positives due to clonal hematopoiesis (CH). Matched buffy coat testing identified CH variants in both Northstar Select and comparator assays at similar rates, confirming that CH was not the source of Northstar Select's superior detection performance.

"Current liquid biopsy assays often fall short in detecting clinically relevant alterations, especially in patients with low-shedding tumors," said Dr. Gary Palmer, Chief Medical Officer, Oncology at BillionToOne. "Northstar Select's superior sensitivity means we can identify more actionable treatment options for significantly more patients, including those with challenging tumor types where liquid biopsy has traditionally been limited by sensitivity constraints and where tissue sampling may be challenging or contraindicated."

Northstar Select delivers ultrasensitive detection of key cancer biomarkers in plasma and its clinically focused panel design optimizes sensitivity while maintaining actionability, covering 84 actionable and guideline-aligned genes with comprehensive coverage across SNV/indels, CNVs (including amplifications and losses), gene fusions, and microsatellite instability high detection (MSI-H). The assay achieved a five-fold better 95% limit of detection (LOD95) for CNVs² —2.1 copies for amplifications and 1.8 for losses—compared to many first-generation liquid biopsies. With an unprecedented LOD95 of 0.15% VAF for SNVs, Northstar Select uncovered clinically actionable alterations below the limit of detection for other tests.¹ This peer-reviewed head-to-head data establishes this test as the most sensitive therapy selection assay for late-stage solid tumor cancers, addressing one of the most critical limitations in liquid biopsy testing.

Another advantage of Northstar Select is its unique ability to differentiate focal copy number changes from aneuploidies. Most existing assays miss CNV losses and cannot reliably differentiate between clinically actionable focal "driver" amplifications from broad chromosomal aneuploidies, which lack specific therapeutic targets. Northstar Select overcomes these limitations by combining insights from over one million cfDNA tests for fetal aneuploidy with its patented QCT™ technology, which is a core component of BillionToOne's smNGS technology, to address this critical unmet need in oncology. As cancer testing grows more complex, BillionToOne's smNGS platform offers distinct advantages to continually innovate and enhance diagnostic detection and treatment decisions for cancer patients.

In part based on this head-to-head study, Northstar Select has recently met Medicare coverage criteria established by Palmetto GBA, a Medicare administrative contractor that administers the Molecular Diagnostics Services program (MolDx) following rigorous review of evidence demonstrating the test's analytical validity, clinical validity, and clinical utility, ensuring that more patients with advanced cancer can benefit from uncovering more personalized treatment approaches.

"The enhanced sensitivity we have achieved with Northstar Select is beneficial for all advanced cancer patients, but is particularly meaningful for patients that harbor clinically actionable alterations that fall below the limits of detection for other tests, which represent nearly a quarter of all cancer patients," said Dr. Oguzhan Atay, Co-founder and CEO of BillionToOne. "For these patients, our improved detection capability could mean the difference between identifying life-changing treatment options or missing them entirely."

For more information about Northstar Select, visit northstaronc.com.

About BillionToOne
Headquartered in Menlo Park, California, BillionToOne is a precision diagnostics company on a mission to make molecular diagnostics more powerful, efficient, and accessible for all. The company's patented Quantitative Counting Templates™ (QCT™) molecular counting platform is the only multiplex technology that can accurately count DNA molecules at the single-molecule level. For more information, visit www.billiontoone.com.

Media Contact: [email protected] 

¹ Bower, X., Wignall, J., Varga, M. G., Zhu, J., O'Sullivan, M., Searle, N. E., ... & Zhou, W. (2025). Validation of a liquid biopsy assay with increased sensitivity for clinical comprehensive genomic profiling. The Journal of Liquid Biopsy. https://doi.org/10.1016/j.jlb.2025.100322.
² Internal data on file. Comparator assays have published LOD95% for CNVs that range from 2.46-3.83 copies for amplifications and ≥20%-30.4% tumor fraction for losses.

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SOURCE BillionToOne