AGL Angle Plc

ANGLE plc ("the Company")

Novel findings USING the PARSORTIX SYSTEM DEMONSTRATE ROLE OF CTC:B CELL CLUSTERs IN driving CANCER progression

Findings may enable the development of novel drugs to target B cell and CTC cluster interactions to suppress cancer metastasis

This pivotal work is likely to stimulate further interest in the Parsortix system to investigate metastasis and drive clinical trials

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 novel research by Professor Dario Marchetti's team at the University of New Mexico Comprehensive Cancer Center, United States. The study used the Parsortix^® system to investigate CTC and B cell^* clusters in clinical and pre-clinical models of melanoma brain metastasis, and their ability to target additional organs during the spread of cancer ("metastasis of metastasis").

This pivotal work is likely to stimulate further interest in using the Parsortix system to investigate the process of metastasis and drive clinical trials to develop new drugs to suppress metastasis, powered by the Parsortix system.

By employing a newly developed humanised mouse model, the Marchetti team demonstrated that the aggregation of B cells with CTCs, in CTC clusters, enables cancer cells to be masked from the immune system enhancing their metastatic potential. This finding increases our understanding of cancer progression and may allow for the development of new treatments to suppress cancer metastasis.

Notably, in an additional experiment, the researchers found a significantly higher number of CTC:B cell clusters in blood samples from early stage clinical melanoma patients that later progressed to develop metastatic disease, compared to patients with existing metastasis. They hypothesised that these CTC:B cell clusters may enhance the metastatic process and amplify treatment resistance to immunotherapies. This could be of profound clinical importance in determining which patients have aggressive disease and in assessing their likely response to immunotherapy.

A second major finding of the study was to show that a specific gene signature within CTC clusters acts like a postcode to guide CTCs from the brain to the liver, thereby forming secondary liver metastasis which is associated with poor patient outcomes. The discovery of a melanoma brain-liver axis, and by implication similar axes for other sites in the body, could have important clinical consequences for treating metastatic melanoma and identifying novel drug targets for treatment.

The Parsortix system played an instrumental role in this research, demonstrating another pivotal discovery made possible by ANGLE's unique, marker-independent system which enables the collection of live CTC clusters for downstream analysis.

Professor Dario Marchetti, The University of New Mexico Comprehensive Cancer Center, commented:

"We are delighted to publish these novel findings which provide further insight into the metastatic cascade as culmination of tumour progression. The clinical potential of understanding how and why CTC clusters co-opt B cells to cause fatal metastasis is of unique relevance to patient care and may lead to new treatment options. The study of CTC clustering with immune cells has allowed the discovery of a 'postcode' that tells us which organ the metastasis will target next. This is the first evidence that the direction of metastasis from primary to secondary disease has been reported and could enable the development of a novel class of compounds to target the metastatic spread of cancer.

The unique features of the Parsortix system have enabled my team to undertake pioneering research in this promising field. We consider the Parsortix system to be the best and most suitable technology to capture and interrogate homotypic and heterotypic CTC clusters, from patient blood samples and preclinical models of cancer, and the most advanced technology capable of harvesting large numbers of CTC clusters. We are excited to build on this discovery and its importance for developing treatment strategies which can predict, and/or prevent metastatic disease."

Chief Scientific Officer, Karen Miller, commented:

"We are delighted to see another CTC cluster-based discovery shedding light on the metastatic cascade that was fundamentally made possible by the Parsortix system. We share Professor Marchetti's excitement for this innovative and impactful work and congratulate his team on these novel findings. Furthermore, we are extremely proud to see the Parsortix system playing an instrumental part in such pioneering discoveries in cancer research and the implications for drug discovery. We anticipate that interest in the Parsortix system will increase as commercial and academic research into the metastatic pathway continues to build."

The peer-reviewed publication is published in the journal Cancer Research Communications, a premiere journal of the American Association for Cancer Research and available for review at https://angleplc.com/resources/publications/

* a B-cell is a type of white blood cell and part of the patient's immune system

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

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Notes for editors

About ANGLE plc

ANGLE is a world-leading liquid biopsy company with innovative circulating tumour cell (CTC) solutions for use in research, drug development and clinical oncology using a simple blood sample. ANGLE's FDA cleared and patent protected CTC harvesting technology known as the Parsortix^® PC1 System enables complete downstream analysis of the sample including whole cell imaging and proteomic analysis and full genomic and transcriptomic molecular analysis.

ANGLE's commercial businesses are focusing on clinical services and diagnostic products. The clinical services business is offered through ANGLE's GCLP-compliant laboratories. Services include custom made assay development and clinical trial testing for pharma. Products include the Parsortix system, associated consumables and assays.

Over 100 peer-reviewed publications have demonstrated the performance of the Parsortix system. For more information, visit www.angleplc.com

Any reference to regulatory authorisations such as FDA clearance, CE marking or UK MHRA registration shall be read in conjunction with the full intended use of the product:

The Parsortix^® PC1 system is an in vitro diagnostic device intended to enrich circulating tumor cells (CTCs) from peripheral blood collected in K₂EDTA tubes from patients diagnosed with metastatic breast cancer. The system employs a microfluidic chamber (a Parsortix cell separation cassette) to capture cells of a certain size and deformability from the population of cells present in blood. The cells retained in the cassette are harvested by the Parsortix PC1 system for use in subsequent downstream assays. The end user is responsible for the validation of any downstream assay. The standalone device, as indicated, does not identify, enumerate or characterize CTCs and cannot be used to make any diagnostic/prognostic claims for CTCs, including monitoring indications or as an aid in any disease management and/or treatment decisions.