Company: BLLN
Filing Date: 2025-09-17
Form Type: DRS/A
Source: 0001193125-25-206347
Chunk: 217

Company: BillionToOne, Inc.
Filing Date: 2025-09-17
Form: DRS/A
Chunk 217
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. (2025). Validation of a liquid biopsy assay with increased sensitivity for clinical comprehensive genomic profiling. The Journal of Liquid Biopsy, 100322.            |

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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. Above 0.5% VAF Below 0.5% VAF Below 0.2% VAF 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-foldhigher sensitivity than these other assays. 62Since 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