• Analytical framework establishes a clinically meaningful performance assessment of blood-based early detection tests
• Methodology enhances cancer signal detection, boosts specificity and predictive value
• Presentations further validate the HarbingerHx platform and its utility in early cancer detection

Harbinger Health, a biotechnology company championing the detection of early cancer, announced the presentation of two late-breaking studies at the American Association for Cancer Research (AACR) Annual Meeting, taking place in Chicago until Wednesday (April 30).

The new data describe advances that improve both the analytical framework and laboratory methodology for assessing Harbinger’s blood-based multi-cancer early detection (MCED) tests.

Harbinger Health is developing approaches that combine insights into the earliest stages of cancer biology with artificial intelligence and advanced screening technologies. Its platform aims to support the development of diagnostic and screening products for multiple cancer types across various clinical settings.

“While innovations in cancer therapy have revolutionized the treatment landscape, the tools to detect and diagnose it early, when survival rates are highest, have lagged behind,” said Hutan Ashrafian, chief medical officer at Harbinger Health.

“Our mission is to disrupt conventional cancer detection approaches that either lack an appropriately high diagnostic accuracy for clinically impactful outcomes or only provide detection for a single cancer at a time. By pioneering blood-based tests based on DNA methylation signatures with novel applications including sequential reflex testing and individualized analyses, we aim to provide solutions that give physicians highly accurate and reliable information to get their patients on the right treatment pathways, right away.

“The data presented today underscore our commitment to setting a new standard in quantifying test performance, with the ultimate goal of adequately informing earlier clinical intervention and improving outcomes for patients across a wide spectrum of cancers.”

The Cancer ORigin Epigenetics-Harbinger Health (CORE-HH) study underpins this work. It enrolled a diverse cohort of individuals with and without cancer to evaluate the diagnostic accuracy of Harbinger’s proprietary assay and its ability to determine the tissue of origin for detected cancers. Data from this study formed the basis for the presentations at AACR 2025.

One presentation, titled Sharpening the signal: Enhancing liquid biopsy specificity through intra-individual methylation analysis, outlined a new methodology based on Harbinger’s proprietary methylation biomarkers. The approach used a paired intra-individual analysis (IIA), comparing plasma-derived cell-free DNA (cfDNA) to matched white blood cell (WBC)-derived genomic DNA (gDNA) to differentiate circulating tumor DNA (ctDNA) from background noise. Harbinger developed a two-tier system combining a cfDNA-based machine learning classifier (MLX) with a patient-specific intra-individual classifier (IIX). Together, these approaches improved specificity compared to either method alone. When targeting a specificity of 98.5%, the system achieved 63.7% sensitivity, 99.5% specificity, and a positive predictive value (PPV) of 54.8%. At a higher target specificity of 99.5%, the sensitivity was 55.1%, specificity 99.89%, and PPV 80.7%.

The second presentation, Novel performance quantification of MCED testing to aid clinical decisions: Analysis of a sequential reflex blood-based methylated ctDNA test, introduced a new framework for assessing MCED performance. Applied to CORE-HH data, this approach quantified actionable metrics relevant to real-world utility. The test demonstrated a specificity of 98.6%, an important benchmark for population-level cancer screening by minimizing false positives and associated diagnostic burden. Results showed strong detection capability for cancers lacking established screening programs, including pancreaticobiliary and hepatobiliary cancers. Particularly high PPVs were observed for upper gastrointestinal (91%), colorectal (77%), and hepatobiliary (73%) cancers, indicating a favorable risk-benefit balance for clinical application.

Overall, Harbinger Health’s findings highlight the potential of its platform to address critical unmet needs in early cancer detection and screening.