Company: BLLN
Filing Date: 2025-10-17
Form Type: S-1/A
Source: 0001193125-25-242632
Chunk: 235

Company: BillionToOne, Inc.
Filing Date: 2025-10-17
Form: S-1/A
Chunk 235
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%) Treatment Implication Elacestrant (FDA approved in indication)

Northstar patient case study: Synergistic use of Northstar Select and Response demonstrated true precision oncology and personalized medicine

A patient with metastatic colorectal cancer, awaiting first-line treatment with pembrolizumab
monotherapy, presented with a baseline TMS of 210,000, indicating a very high tumor burden. After the first cycle of treatment, initial molecular response was observed and TMS decreased by over 50%, while therapy profiling with Northstar Select
identified a druggable BRAF V600E mutation. 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

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the synergistic use of Northstar Select and Response can enable a physician to pivot to an alternative therapy expeditiously.

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 pembrol