Company: BLLN
Filing Date: 2025-10-17
Form Type: S-1/A
Source: 0001193125-25-242632
Chunk: 225

Company: BillionToOne, Inc.
Filing Date: 2025-10-17
Form: S-1/A
Chunk 225
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0.15%, representing a 2-foldhigher sensitivity than these other assays. 66Since 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, 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.

Single Nucleotide Variants (SNV) 0.5% 0.4% 0.3% 0.2% 0.1% Other Common 0.25% -0.50% Assays Copy Number Variants (CNV) 3.00 copies 2.75 Other Common Assays 2.50 -2.87 2.50 lower 0.15% level of detection 2.25 NORTHSTAR SELECT 2.00 2.11 NORTHSTAR SELECT lower level of detection baseline

| 66 |     | Deveson, I.W., Gong, B., Lai, K. et al. (2021). Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology. Nature Biotechnology, 39(9), 1115–1128. |

155

Northstar Select detects >50% more actionable mutations than comparator assays 67 In a head-to-headclinical 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. 68Moreover, 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. 364 Superior detection rates for SNVs, indels, and CNVs 51% more SNVs/Indels