Trinity Delta A fuller picture from dual CTC-DNA and ctDNA analysis

A fuller picture from dual CTC-DNA and ctDNA analysis

Lighthouse | 30 January 2025

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ANGLE has successfully developed a workflow with Illumina for the simultaneous analysis of ctDNA (circulating tumour DNA) and CTC-DNA (circulating tumour cell DNA). Initial data from a lung cancer study highlight the potential role of liquid biopsy and ctDNA/CTC-DNA analysis in personalised cancer care. An overview of the approach, and data, will be presented at the European Association for Cancer Research (EACR)-Illumina webinar entitled ‘Complementary insights: Exploring the dual analysis of circulating tumour cells and circulating DNA’ on 6 February.
Having overcome technical challenges, ANGLE has developed a complete end-to-end solution for simultaneous analysis of ctDNA and CTC-DNA from a single blood tube. It involves ctDNA isolation from plasma, followed by isolation and harvesting of CTCs using ANGLE’s Parsortix system, with the ctDNA and CTC-DNA then analysed using Illumina assays and its NextSeq 2000 NGS platform.
Analysis of CTC-DNA and ctDNA (obtained from the same blood tube) from 27 lung cancer patients using Illumina’s 79-gene lung cancer panel indicates that dual analysis improved the identification of clinically relevant mutations. Overall, dual analysis found twice as many cancer mutations, with biomarker information from CTCs complementing that from ctDNA. 100% of treatment-naïve patients (n=8) and 90% of previously treated patients or those currently on therapy (n=19) had mutations identified only in the CTC-DNA and not in the ctDNA. Both groups also had mutations in ctDNA that were not seen in CTCs. This new lung cancer study validates earlier findings from a 47-pt pilot study across four cancers using a dual analysis workflow based on a third-party assay kit with Illumina’s NGS platform.
Cancer mutations are potential biomarkers that could guide targeted therapy, with liquid biopsy playing a central role by allowing minimally invasive and repeatable sampling, unlike tissue biopsy. The Parsortix system can augment this through harvest of CTCs which can provide additional biomarkers not found in ctDNA. Not only does this complementary information provides a more comprehensive profile of a patient’s cancer compared to information derived from either ctDNA or CTC-DNA analysis alone, but the harvesting of intact cancer cells (rather than DNA fragments from dead cells) also offers the potential for RNA and protein sequencing using Illumina platforms, which is not possible with ctDNA.

Trinity Delta view: ANGLE’s collaboration with Illumina, the global leader in next-generation sequencing systems and assays, has significant potential to expand the Parsortix commercial opportunity. Liquid biopsy centred on ctDNA analysis is already widely adopted and these recent studies confirm that Parsortix-enabled dual CTC-DNA and ctDNA analysis can provide additional complementary information for cancer diagnosis and longitudinal monitoring. Establishing an optimised end-to-end workflow for simultaneous analysis is a key step towards supporting Illumina’s customers and offering CTC analysis for DNA dual analysis NGS. In our view, these developments should also help secure new Pharma Services contracts – a key strategic objective for ANGLE – by providing these customers with a sample-to-answer solution that delivers comprehensive molecular insights across many cancers to help guide targeted therapy. Our ANGLE valuation is £155m, equivalent to 48p per share.

Lighthouse

30 January 2025


Price	15.00p
Market Cap	£48.4m
Primary exchange	AIM London
Sector	Healthcare
Company Code	AGL

Corporate client	Yes

Company description

ANGLE is a specialist diagnostics company. Its proprietary Parsortix technology can capture and harvest very rare cells, including CTCs (circulating tumour cells), from a blood sample. Parsortix has received FDA clearance for its clinical use to guide precision cancer care.

Analysts

Lala Gregorek
lgregorek@trinitydelta.org
+44 (0) 20 3637 5043

Philippa Gardner
pgardner@trinitydelta.org
+44 (0) 20 3637 5042

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