ANGLE plc presented compelling new data at the European Association for Cancer Research (EACR) Congress in Lisbon, showcasing significant advances in liquid biopsy technology through two innovative approaches: DNA dual analysis for comprehensive tumor profiling and androgen receptor expression monitoring in prostate cancer.
Breakthrough in DNA Dual Analysis Reveals Hidden Tumor Mutations
The company's most significant presentation demonstrated the power of combining circulating tumor cell DNA (CTC-DNA) and circulating tumor DNA (ctDNA) analysis from a single blood sample. This dual analysis approach, developed in collaboration with Illumina, revealed substantial differences between the two analytes in a study of 27 lung cancer patients.
The results showed that 53% of mutations were found exclusively in CTCs, 36% in ctDNA alone, and only 11% in both analytes. This finding challenges the current reliance on ctDNA-only approaches and demonstrates that critical therapeutic targets are being missed without comprehensive analysis.
"This study demonstrates the unique value of ANGLE's DNA dual analysis approach, which combines sequencing of CTC-DNA and ctDNA from the same blood sample to uncover critical differences in tumor biology," said Karen Miller, ANGLE's Chief Scientific Officer.
The study utilized ANGLE's Parsortix system alongside a 79-gene lung cancer panel on the Illumina NextSeq2000 platform. Initial validation using contrived samples with defined cancer cell levels (0, 2, 5, 10, and 20 cells) confirmed high sensitivity, with druggable mutations such as BRAF, EGFR, and TP53 consistently detected.
Importantly, the dual analysis identified numerous druggable targets found exclusively in CTC-DNA, including CHEK2 (targeted by olaparib from AstraZeneca and Merck, and talazoparib from Pfizer), ESR1 (targeted by elacestrant from Menarini), NTRK1 (targeted by larotrectinib from Bayer and entrectinib from Roche), and RET (targeted by selpercatinib from Eli Lilly and pralsetinib from Blueprint Medicines).
Novel Androgen Receptor Assay Addresses Prostate Cancer Treatment Monitoring
ANGLE's second major presentation focused on a newly developed assay for monitoring androgen receptor (AR) expression in metastatic prostate cancer patients. This innovation addresses a critical unmet need in a disease area with at least 130 ongoing clinical studies and a projected AR inhibitor market value of $9.8 billion by 2032.
The AR plays a central role in driving prostate cancer growth and progression, with changes in AR expression leading to treatment resistance and the development of metastatic castration-resistant prostate cancer (mCRPC). ANGLE's new Portrait AR workflow enables sensitive, real-time monitoring of AR expression from a simple blood draw.
In validation studies using blood spiked with prostate cancer cells exposed to increasing AR drug concentrations, the assay demonstrated clear, statistically significant reduction in AR expression as drug concentration increased—from over 80% AR-positive cells in untreated samples to under 20% at the highest drug level.
Clinical Validation in Prostate Cancer Patients
The AR assay was subsequently validated in blood samples from 20 patients with mCRPC. Results showed that 50% of patients were CTC-positive, and all CTC-positive patients had AR-positive CTCs, enabling assessment of AR expression levels. Notably, CTC clusters, which are known to be up to 100 times more metastatic, were observed in 80% of CTC-positive patients.
All detected CTCs were mesenchymal or undergoing epithelial-mesenchymal transition (EMT), highlighting the importance of using the marker-independent Parsortix system in this patient population.
Technology Platform and Commercial Applications
Both innovations leverage ANGLE's FDA-cleared Parsortix PC1 System, which uses microfluidic technology to capture cells based on size and deformability rather than surface markers. This marker-independent approach enables capture of CTCs that might be missed by traditional antibody-based methods.
The company's technology platform has been validated in over 100 peer-reviewed publications and offers complete downstream analysis capabilities including whole cell imaging, proteomic analysis, and full genomic and transcriptomic molecular analysis.
Miller emphasized the clinical utility of these advances: "The androgen receptor assay development programme has successfully been completed, and we are excited by its potential to repeatably monitor drug response and resistance in prostate cancer trials. Sharing this data at EACR reflects our ongoing commitment to advancing precision oncology with innovative, real-world solutions."
The AR assay is now available as part of ANGLE's assay menu to support pharmaceutical customers with longitudinal biomarker assessment in AR-targeted clinical trials, while the DNA dual analysis workflow offers biopharma partners a valuable tool for identifying resistance, stratifying patients, and improving trial outcomes.
