TEST:

Parsortix Liquid Biopsy

Preclinical evidence from NSCLC models showed that cell damage caused by cisplatin activates the SDF-1/CXCR4 axis, leading to the recruitment of metastasis initiating cells (MICs), a prometastatic cell subset co-expressing the stemness marker CD133 and CXCR4 (SDF-1 receptor)... CTCs may represent a novel biomarker for monitoring chemotherapy efficacy in NSCLC. An increased number of CTCs baseline and after pb-NACT, as well as after surgery represent a negative prognostic factor for survival. A higher number of CXCR4+CTCs at baseline correlated with inferior response outcomes after pb-NACT, prompting consideration for treatment intensification in pts with higher baseline levels of this CTC subtype.

"ANGLE plc...announce its participation at the European Association for Cancer Research (EACR) Liquid Biopsies Conference being held in Lyon, France from 12 to 14 November 2024."

"ANGLE plc...is pleased to announce its participation at the European Association for Cancer Research (EACR) Liquid Biopsies Conference being held in Lyon, France from 12 to 14 November 2024...ANGLE presented two posters at the EACR Liquid Biopsies Conference...This poster presentation reports on the utility of combining ANGLE's Parsortix® system for CTC capture with the Portrait®+ CTC staining kit for CTC detection and phenotypic characterisation...This proof-of-concept study demonstrates that using amplitude-based multiplexing with QIAGEN's Qiacuity dPCR system can increase the number of genes that can be assessed simultaneously in a Parsortix-enriched CTC sample."

"ANGLE plc...announce the publication of research investigating a panel of known prostate cancer gene transcripts in CTCs, undertaken by the Comprehensive Cancer Center at the Medical University of Vienna...Researchers used the Parsortix®system to isolate and harvest CTCs from 38 localised and metastatic prostate cancer patients. CTCs were then analysed using a range of molecular techniques which enabled multiple biomarkers to be simultaneously analysed."

We successfully developed a non-invasive assay to detect cCAFs in pts with mPDAC and other GI tumors. In our study, high cCAF and HA levels were both associated with significantly worse OS in mPDAC. Both analytes could therefore serve as a negative prognostic biomarker, although a larger cohort should be studied prospectively.

In advanced HGSC (III, IV), there was no statistical difference in peripheral CTC count per 7.5mL blood or PTS, although a trend towards higher peripheral CTC count and smaller PTS was observed in stage III versus stage IV. CTCpos HGSC ovarian vein samples had significantly smaller PTS than HGSC ovarian vein CTCneg patients (p=0.0121). HGSC ovarian vein CTC count also inversely correlated with PTS (r=-0.7356, p=0.0128).

"ANGLE plc...is pleased to announce the publication of the 100th peer-reviewed journal article using the Parsortix® system for the isolation, harvest and analysis of CTCs...The journal article is published by researchers from a leading international referral centre for the treatment and study of cancer, the Fondazione IRCCS - Istituto Nazionale dei Tumori Di Milano (Italy)."

"ANGLE plc...is delighted to announce that it has signed an agreement with the cutting-edge genomics and molecular diagnostics company, NuProbe USA, Inc...to use its proprietary pan-cancer next generation sequencing (NGS) panel...Combining the Parsortix system with comprehensive DNA molecular analysis opens up a broad range of pharma services opportunities."

RNA ISH offers the advantage of confirming these markers at the single cell level. Employing the clinically relevant marker PSMA, our CTC approach can be used for diagnostic purposes to screen patients profiting from PSMA-directed PET-CT or PSMA-targeted therapy.

"ANGLE plc...is pleased to announce that it has signed an agreement with Recursion Pharmaceuticals, Inc...New pharma agreement for Parsortix CTC analysis...The agreement is being initiated with a fully funded pilot study."

"ANGLE plc...is pleased to announce the publication of one of the Company's clinical studies that was submitted to the FDA for De Novo regulatory clearance of the Parsortix® PC1 system...This study, undertaken at ANGLE's UK laboratory, the University of Rochester, US, and the MD Anderson Cancer Center, US, reports that the Parsortix system successfully captured and harvested CTCs from metastatic breast cancer (MBC) patient blood samples for downstream analysis using immunofluorescence (IF) and cytological evaluation."

The presence of epithelial cells in subjects without diagnosed disease has been previously described, with their significance being unclear. Interestingly, a high proportion of the identified CTCs did not express EpCAM, highlighting the limitations of using EpCAM-based approaches.

"ANGLE plc...is pleased to announce the results of an independent study in melanoma patients comparing gene mutations in tumour tissue, circulating tumour DNA (ctDNA) and CTCs...The study, from Dr Laura Keller's team at the Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany, used the Parsortix® system to isolate CTCs from melanoma patient blood samples. The CTCs were analysed alongside tumour tissue and ctDNA samples using PCR (for gene amplification) followed by mass spectrometry."

Furthermore, we demonstrated that the Parsortix® PR1 in-cassette staining method is capable of isolating heterogeneous single CTCs and cell clusters from patient samples. The Parsortix® PR1 in-cassette staining, capable of isolating different phenotypes of CTCs as either single cells or cell clusters with consistent recovery rates, is considered optimal for CTC enrichment for lung cancer, albeit needing further optimization and validation.

Additionally, we isolated single patient-derived CTCs and identified genomic aberrations associated with treatment response and clinical outcome. Thus, this workflow provides a readily scalable strategy for analysis of single CTCs, applicable for use in monitoring studies to identify genomic variations important for guiding clinical therapy decision.

EpCAM-IMS seems to be a better method for CTCs isolation in MTC patients with DM and/or BPD. Expression of VIM in most of our patients advocates towards an epithelial to mesenchymal transition (EMT) process possibly occurring in progressive MTC. CALCA and CXCR4 expression in CTCs, along with other epithelial and mesenchymal markers, should be studied in larger patients’ series and for longer follow-up periods.

Notably, when MDA-MB-231 cells spiked (i.e. supplemented) into DLA aliquots were processed using DanioCTC, cell dissemination patterns remained consistent. Successful xenografting of CTCs from a MBC patient revealed their primary localization in the head and trunk regions of zebrafish embryos.DanioCTC represents a major step forward in endeavors to study the dissemination of individual and rare patient-derived CTCs, thereby enhancing our understanding of metastatic breast cancer biology and facilitating the development of targeted interventions in MBC.

"ANGLE plc...is pleased to announce its participation at the 2024 Annual Congress of the European Association for Cancer Research (EACR 2024) being held in Rotterdam, Netherlands from 10 to 13 June 2024."

In the prostate cancer cohort, the presence of DDR+ CTCs was associated with response to treatment in 50% of the cases as reported at the time of blood draw, compared to 22% for DDR- CTCs (p<0.0001). A similar correlation was not observed in the ovarian cohort (p=0.69).Conclusion This research study demonstrates the ability to determine DDR status of CTCs isolated from a liquid biopsy using the Parsortix® system, highlighting it as a non-invasive tool to provide valuable insight into the efficacy of cancer therapies.

This study identified potentially actionable biomarkers in CTCs enriched using the Parsortix system, from cancer patient samples. Analysing the genetic profile of both CTCs and cfDNA, concomitantly, has the potential to better guide personalised treatment selection and monitoring of therapeutic response outcomes.

PD-L1, PIM-1 and AXL expression in CTCs indicate a potential benefit of targeted therapies for NSCLC patients who relapse following οsimertinib treatment.Conclusion Our results indicate the importance of complementary information obtained through parallel analysis of CTC and ctDNA. Comprehensive LB analysis efficiently represents the heterogeneous molecular landscape and provides prominent information on subsequent treatments for NSCLC patients progressing with osimertinib based on different druggable molecular alterations.

"ANGLE plc...is delighted to announce the publication of a study using the Parsortix® system to identify markers present in CTCs harvested from metastatic mutant-p53 platinum-resistant ovarian cancer (PROC) patients. The study was conducted as an offshoot of the European multi-centre GANNET53 Phase II clinical trial (NCT02012192) funded by the EU 7th Framework Programme (Grant agreement ID: 602602). The study investigated the efficacy of ganetespib in combination with paclitaxel vs. paclitaxel alone. Patients were enrolled across 12 clinical centres in Germany, Belgium, France, and Austria."

"ANGLE plc...is delighted to announce that it has signed a supplier agreement to develop a Parsortix-based Androgen Receptor1 (AR) detection assay for use in prostate cancer studies. The supplier agreement reported here is with AstraZeneca...This follows an earlier agreement to develop a methodology for CTC micronuclei detection using the Company's DNA Damage Response (DDR) assay, announced on 24 April 2024."

"ANGLE plc...has signed a supplier agreement with the global biopharmaceutical company, AstraZeneca PLC, to develop and validate a methodology leveraging ANGLE's existing DNA damage response ('DDR') assay for the detection of micronuclei in CTCs as a measure of DDR."

"ANGLE plc...announce its participation at the American Association for Cancer Research (AACR) Annual Meeting, San Diego, US between 5 to 10 April 2024...ANGLE is presenting a poster entitled the 'Development and analytical validation of a novel assay for HER2 assessment on circulating tumor cells harvested using the Parsortix® system and incorporating BioView imaging technologies'."

"ANGLE plc...is pleased to announce its participation at the 14th European Breast Cancer Conference (EBCC) being held in Milan, Italy on 20 to 22 March 2024...ANGLE presenting two posters highlighting the utility of the Company's new Portrait+ CTC Staining Kit and Portrait HER2 assay"

The commercially available Oncolipsy PD-L1 kit can be used for the quantification of PD-L1 transcripts in CTCs. Expression of PD-L1 in size-based enriched CTCs can predict response to PD-1/PD-L1 blockade therapy.

Cisplatin-induced cell damage has been shown to activate the SDF-1/CXCR4 axis in preclinical models of NSCLC, resulting in the recruitment of a cell subset co-expressing the stemness marker CD133 and CXCR4 (SDF-1 receptor) at distant sites... Out of the 61 enrolled patients, 34 had available CTC data for analysis. In this population, DCR was 64.7%, and the ORR 29.4%. Surgery was performed in 14 pts (41.2%).

The assay enables the identification of both HER2 protein and gene copy information from each target cell with minimal cell loss, with the potential for minimally invasive patient monitoring during treatment and better classification of patients who may qualify and benefit from HER2-targeted therapies. An added value of the assay is the practicality of utilizing preserved blood samples, allowing streamline batch shipping of clinical samples.

Our results show that the PR1 system can successfully capture CTCs from the blood of patients with resectable LC. Monitoring CTC counts post LC surgery may have prognostic relevance and could have an application in the clinical setting, but future research is required.

HER2+ CTCs were also detected in tissue HER2- patients, indicating further investigations are warranted into the clinical significance of HER2+ CTCs. High CTC counts were associated with an increase in PLR, NLR and PAI-1 levels indicating that high CTC trafficking in MBC is associated with an altered inflammatory response which may aid in metastatic dissemination.

Successful xenografting of CTCs from a MBC patient revealed their primary localization in the head and trunk regions of zebrafish embryos. DanioCTC represents a major step forward in endeavors to study the dissemination of individual and rare patient-derived CTCs, thereby enhancing our understanding of metastatic breast cancer biology and facilitating the development of targeted interventions in MBC.

We report that with the use of CTCID markers, single and clusters CTCs can be isolated from ovarian cancer patients with prognostic significance. CTCs isolated from the ovarian vein during surgery are indicative of precursor oligoclonal metastasizing HGSC. Actionable HGSC mutations were found in ctDNA, and may have clinical utility in predicting residual disease, monitoring treatment response, and prognosis in the adjuvant setting.

CTCs were detected across all assessed time points. Regular and dynamic liquid biopsies are essential to assess the clinical relevance of CTCs across the subtypes of EOC. Ongoing follow-up investigation within this patient cohort continues, and further longitudinal sampling is ongoing.

P=N/A; N=60 --> 90 | Trial completion date: Sep 2024 --> Feb 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

No abstracts available

"ANGLE plc...is pleased to announce the publication of a peer-reviewed paper in a special issue of the journal - 'Current Issues in Molecular Biology' Special Issue: Advanced Solutions for Cancer Therapy...This peer-reviewed article brings together supporting evidence for the additional and complementary information that can be obtained from CTCs using the Parsortix® system, demonstrating the value of a dual analyte approach for both CTCs and ctDNA."

Herein, we review the literature in which the microfluidic, label-free Parsortix system is utilised for CTC capture, harvest and analysis, alongside the analysis of ctDNA from a single blood sample. This detailed summary of the literature demonstrates how these two analytes can provide complementary disease information.

Enumerating CTCs throughout treatment in EOC is imperative to assess their clinical significance. Ongoing follow-up and longitudinal sampling of this patient cohort continues.

Dynamic and frequent blood sampling is essential to assess the clinical significance of CTCs across the subtypes of EOC. Ongoing follow-up investigation within this patient cohort continues, and further longitudinal sampling is underway.

CTCs isolated from the ovarian vein during surgery are indicative of precursor oligoclonal metastasizing HGSC. Actionable HGSC mutations were found in ctDNA, and may have clinical utility in predicting residual disease, monitoring treatment response, and prognosis in the adjuvant setting.

"ANGLE plc...is delighted to announce breakthrough results from DNA molecular analysis of cancer patient blood samples that provide a unique insight into the progression of each patient's cancer and how this may be treated...Combined DNA Next Generation Sequencing of CTCs and ctDNA from the same blood sample highlights potential for the Parsortix system to identify key variants (DNA mutations) missed by other approaches to help guide treatment decisions..."