Parsortix used in research paper from ETH Zurich

New treatment strategy provides 'uncharted opportunity' to target metastasis responsible for the vast majority of cancer deaths

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company with innovative circulating tumour cell (CTC) solutions for use in research, drug development and clinical oncology, is delighted to announce the publication of breakthrough research from Professor Nicola Aceto's team at the research university ETH Zurich, Switzerland, in the journal Nature Medicine.

The publication reports on an interventional multi-centre Phase 1 clinical trial using the repurposed, FDA approved drug, digoxin, to treat metastatic breast cancer patients. The Parsortix® system played a critical role in selecting patients for this targeted treatment by identifying those who were positive for CTC clusters (two or more tumour cells travelling together in the bloodstream). This enabled researchers to enrol only patients who might benefit from digoxin treatment, which has been shown to dissociate highly metastatic CTC clusters in preclinical studies1.

The primary endpoint for the trial was successfully achieved with a significant reduction in CTC cluster size reported in the treatment group. This proof-of-principle study paves the way for the development of a novel class of drugs that prevent or suppress the development of metastasis. The Parsortix system is already well established in the Aceto Lab and Professor Aceto has co-founded the company PAGE Therapeutics (pagetherapeutics.com) to develop novel compounds which are highly effective at disassociating CTC clusters. It is anticipated that the Parsortix system will play a crucial role in the pre-clinical and clinical development of these compounds, including dose finding and selection of the most appropriate patients for clinical trials.

Professor Nicola Aceto, Aceto Lab, ETH Zurich, commented:

"Given that the spread of cancer accounts for the vast majority of cancer-related deaths, the effective prevention and suppression of metastasis is an elusive goal for clinicians worldwide. Standard-of-care treatments are typically developed based on their cytotoxic activity and are not necessarily designed to interfere with metastasis-relevant mechanisms. Consequently, there is an uncharted opportunity for the development of targeted agents that disrupt the causes of metastasis themselves.

While clinical outcomes were not assessed in this proof-of-concept study, the trial provides first-in-class evidence that supports the development of novel treatments targeting the metastatic process."

ANGLE's Chief Scientific Officer, Karen Miller, commented:

"We are delighted to report on this first-in-class treatment approach reported by the Aceto Lab which has the potential to significantly reduce the burden of metastatic disease and improve patient outcomes. Given its unique design and ability to capture CTC clusters, we anticipate that the Parsortix system will be a crucial component for the development of drugs targeting the metastatic cascade by facilitating the selection of patients who are most likely to respond to treatment and allow continuous monitoring to determine the pharmacodynamic effects of the drugs. Alongside our ongoing collaboration with ETH Zurich, we look forward to working with PAGE Therapeutics to support their development drugs targeting metastatic spread."

The peer-reviewed publication is published in the journal Nature Medicine and available for review at https://angleplc.com/resources/publications/

Background information

CTCs are intact, living cancer cells circulating in the blood and are well established as the precursors of metastasis. Whilst individual CTCs face formidable obstacles in the bloodstream, including attack by immune cells and disruptive fluid shear forces, the aggregation of cells into clusters has been shown to enhance metastatic potential by up to 100 times through enhanced immune evasion, proliferative advantage and increased cell adhesion which supports metastatic seeding. Furthermore, CTC clusters have been found to exhibit increased resistance to cancer drugs, making them harder to treat.

With the vast majority of cancer deaths caused by the metastatic spread of the primary cancer to other organs, such as bones, liver, lungs and brain, a targeted treatment to disassociate CTC clusters could enable CTCs to be targeted by the body's own immune system and increase the effectiveness of existing cytotoxic treatments. This could result in a profound improvement in treatment success and patient survival across all solid tumours.

The patented Parsortix system enables highly sensitive, marker-independent CTC isolation from a standard blood sample. It is a unique system, capable of harvesting large CTC clusters for downstream analysis which remain intact, and with their associated immune cells, for visualisation and analysis enabling the development and implementation of a completely new method for suppressing cancer metastasis.

Using ANGLE's Parsortix system, the Aceto lab has demonstrated that, in mouse models, disassociation of CTC clusters using an ATPase inhibitor (like the FDA cleared cardiac drug, digoxin, used to treat heart failure and atrial fibrillation) leads to a near total elimination of metastatic cancer spread with treated animals showing 80x less metastasis compared with untreated animals (peer-reviewed publication in the journal Cell https://angleplc.com/wp-content/uploads/2023/05/PIIS009286741831571X.pdf). The new study, demonstrating CTC cluster disassociation in breast cancer patients, opens up the potential to evaluate reduction in cancer metastasis and increased overall survival in breast cancer patients with a new class of drugs under-pinned by the assessment of CTC clusters using the Parsortix system.

• Gkountela et al. Circulating tumor cell clustering shapes DNA methylation to enable metastasis seeding. Cell (2022)

For Research Use Only. Not for use in diagnostic procedures.