James Hadfield, Director ctDNA & Epigenomics Oncology Translational Medicine at AstraZeneca, shared a post on LinkedIn:
“Functional Liquid Biopsy: going beyond ctDNA detection
Last night I mentioned functional liquid biopsy (FLBx) on the DeciBio panel with John Simmons and Neel Talwar – I thought I’d share more about this emerging space.
There are at least 3 companies offering cfChIP-Seq as a FLBx: Precede Biosciences, Aqtual, Inc., and SENSEERA – if you know of others let me know in the comments.
Developers of cell-surface targeted drugs like ADC’s need to understand target heterogeneity and resistance bypass mechanisms. Traditional ctDNA LBx only tracks burden and that’s where FLBx comes in.
All use cfChIP-seq to analyse the circulating nucleosomes. By capturing specific histone modifications (e.g., H3K4me3 for active promoters, H3K27ac for enhancers), they can non-invasively infer the transcriptional status of the tumor (ChIP-Seq was one of the coolscience methods in the early days of NGS when we only had 1M 35bp single-end reads on Illumina’s GA – see comments for one of the coolest papers I was involved with).
A word of caution: these assays, and fragmentome approaches like DELFI Diagnostics, only work at higher tumor fraction so are more suitable for advanced cancers or high-shedding disease. But, advanced disease often lacks tissue, or it is old and not representative of the current biology – so FLBx can offer insights you can’t get without biopsy.
The Technological Landscape: While Precede is currently the most oncology-focused, the lineage of this technology includes other key innovators:
Senseera (The Pioneer): The first to publish the foundational method (Sadeh ’21, Nature Biotech), they focus on “cell-state” signatures, particularly in liver disease (MASH) and immuno-oncology studies.
Aqtual: Aqtual has a focus on Rheumatoid Arthritis, and are using cfChIP-seq to understand synovial tissue pathology to guide therapy selection between different classes of biologics.
Precede Biosciences: Precede is the leader for oncology translational research. They have demonstrated the ability to accurately infer the expression of primary ADC targets (e.g., HER2, TROP2, DLL3) and longitudinal monitoring of antigen “drift” without repeat tissue biopsy as well as lineage plasticity e.g. to detect neuroendocrine transdifferentiation in prostate and lung cancer resistance. Here are some Precede publication highlights: they have released several datasets at major oncology conferences, specifically focusing on how their platform can detect the expression of drug targets and the biological pathways that lead to treatment resistance. Berchuck ’25 (ASCO) quantifying PSMA expression from blood. Beagan ’25 (ASCO) ADC resistance in breast cancer. Barrett ’25 (ESMO) SCLC subtyping and target expression. Verjee ’25 (AACR) & APEX preprint, inferring genome-wide expression across 2500 genes. Morganti ’24 (SABCS/ASCO) classifying HER2 status.
Are you considering using Functional Liquid Biopsy – tell me what you think it’s good for in the comments.”