Company: BLLN
Filing Date: 2025-10-07
Form Type: S-1
Source: 0001193125-25-233697
Chunk: 230

Company: BillionToOne, Inc.
Filing Date: 2025-10-07
Form: S-1
Chunk 230
---
. Continuing with monotherapy IO alone, TMS increased above 100,000, which prompted the provider to increase treatment intensity by adding chemotherapy. Dramatic molecular response was observed, with the TMS dropping below
10,000. After the next cycle, TMS rebounded to over 71,000, prompting the physician to switch therapy strategy and treat with encorafenib + cetuximab, the approved treatment for the BRAF V600E mutation that Northstar Select had detected.

The patient’s follow-up response demonstrated a significant decrease down to a TMS of 200, a decrease of more than
99.9% of the tumor burden compared to the pre-treatment time point. While undergoing a perioperative treatment hold for a planned ileostomy reversal procedure, scans showed radiographic stable disease while
TMS demonstrated molecular progression and a rise in TMS to 2,800. Molecular progression detected by Northstar Response enabled better surgical treatment planning, and the patient resumed targeted therapy to control disease burden, indicated by a
falling TMS down to 670 at the latest collection date.

In this case, longitudinal sampling and observed changes in TMS via Northstar Response offered real-time
insights into the patient’s treatment response, while comprehensive profiling from the same blood draw by Northstar Select helped optimize the therapeutic strategy at several key time points. This case highlights how the synergistic use of
Northstar Select and Response can enable a physician to pivot to an alternative therapy expeditiously.

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Longitudinal Tumor Methylation Score (TMS) 100,000 10,000 1,000 100 25 Day 0 196 301 329 84 210,000 100,000 71,000 2800 670 PROGRESSIVE DISEASE PROGRESSIVE DISEASE STABLE DISEASE Treatment pembrolizumab pembrolizumab + FOLFOX encorafenib + cetuximab encorafenib + cetuximab Key Insights from Northstar Baseline Started pembrolizumab Profiling Northstar Select BRAF V600E mutation, MSI-high TMS Increase Added FOLFOX TMS Increase Started encorafenib + cetuximab TMS Increase Resumed encorafenib + cetuximab TMS Decrease

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