Angle Regulatory News (AGL)

ANGLE plc ("the Company")

BREAKTHROUGH CLINICAL RESULTS PROVIDE A UNIQUE INSIGHT INTO THE PROGRESSION OF EACH PATIENT'S CANCER

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

The new DNA sample-to-answer molecular solution combining CTC and ctDNA analysis is expected to be a driver of product and pharma services sales

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company with innovative circulating tumour cell (CTC) diagnostic solutions for use in research, drug development and clinical oncology, 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.

Expansion of the Parsortix system downstream analysis into DNA molecular analysis utilising leading third party Next Generation Sequencing (NGS) systems has been a longstanding objective for ANGLE and the results now achieved will allow ANGLE to expand both its product sales and pharma services offerings.

ANGLE has developed sample-to-answer solutions for real-time NGS DNA analysis of both ctDNA (fragments of DNA released mainly by dying cells) and CTCs (living cancer cells) from a single tube of patient blood. Results announced today come from forty-seven patient samples in breast, lung, prostate and ovarian cancers analysed for both ctDNA and CTC-DNA using a pan-cancer panel run on an Illumina NGS system.

Widely accepted actionable DNA variants (cancer mutations) were identified in CTCs that were not present in the ctDNA from the same blood draw in 70% of breast cancer patient samples, 70% of lung cancer patient samples and 60% of ovarian cancer patient samples. Furthermore, the actionable variants identified in the CTCs that were not present in the ctDNA included variants targeted by widely used FDA approved drugs for cancer care.

ANGLE believes that molecular profiling of CTC-DNA alongside ctDNA from the same patient blood sample has the potential to revolutionise the way that cancer is treated. Ultimately, such combined profiling may enable oncologists through routine repeat blood tests to track the clonal evolution of the patient's cancer, informing on treatment decisions, monitoring response to treatment, highlighting drug resistance mechanisms, and signalling disease progression. This will serve to improve patient outcomes and to focus healthcare expenditure by supporting the best therapy choices and maximising the likelihood that treatment will be successful.

ANGLE will start using the clinical results announced today to support the offer of sample-to-answer DNA molecular solutions to pharma services customers using the combined CTC-DNA and ctDNA analysis.

ANGLE will also be working with key opinion leaders (KOLs) and clinicians to expedite the clinical adoption of the combined molecular profiling approach, including the formal establishment of performance under analytical conditions, and through carefully designed clinical studies to build on the promising patient cohort data presented.

ANGLE Chief Scientific Officer, Dr Karen Miller, commented:

"This new clinical evidence highlights the strength of the Parsortix system to provide the best possible sample for analysis, enabling DNA profiling of both the living CTCs and ctDNA released from dead cells from the patient's cancer. We are particularly excited about finding such high levels of additional variants in the CTCs that are not present in ctDNA, as this provides potentially additional information for the clinicians on which to base their treatment options."

ANGLE Chief Executive Officer, Andrew Newland, commented:

"Today's breakthrough is the critical next step post the FDA clearance to show in a sample-to-answer format the potential clinical value of NGS molecular analysis on a repeat basis of living cancer cells harvested from patient blood samples. ANGLE is committed to delivering transformational benefits to cancer patients through a simple blood test. This is a major step in this process and I am enormously proud of the ANGLE team in achieving this."

Technical background information

Utilising its Parsortix system, ANGLE has now pioneered the combined analysis of ctDNA (DNA fragments released from dead cancer cells into the blood) and CTCs (living cancer cells in the blood involved in the active metastasis of the cancer as it spreads to secondary cancer sites) from the same tube of blood using the same NGS molecular analysis. This process enables real time analysis of the progression of cancer in both living and dead cancer cells simultaneously, providing additional potentially clinically relevant information over and above that obtained for each analyte alone. ANGLE's Parsortix system combined with NGS DNA analysis gives a completely new insight into cancer clonal evolution not currently available to researchers or oncologists.

Key elements of the results to date are that:

1) The process involved extraction of the plasma for ctDNA analysis in accordance with standard industry approaches ahead of processing the blood cellular component on the Parsortix system to harvest CTCs for analysis. The plasma extraction has been demonstrated to have no impact on the CTC analysis and does not impair any Parsortix downstream analysis that may be chosen. This is critical as ANGLE's aim is to demonstrate the additional benefit to analysing CTCs alongside ctDNA utilising the same NGS molecular analysis techniques already developed for ctDNA allowing the industry to easily adopt the expanded approach.

2) DNA variants were identified in every patient sample processed and passed the quality control criteria.

3) Both the CTCs and the ctDNA were sequenced using identical protocols. The CTC analysis provided additional information beyond that which could be obtained from ctDNA alone. Some variants were found only in ctDNA, the hypothesis being that the therapy and/or immune system dealt with these. Some variants were found in both ctDNA and CTCs, the hypothesis being that the therapy was partially effective but remaining tumour cells with the potential to seed metastases remained in the blood. Some variants were found in the CTCs but not in the matching ctDNA fraction, in particular for the lung and breast cancer patients, the hypothesis being that these represent clonal evolution, which has not been addressed by either the immune system or the therapy, highlighting the important additional information that can be generated by profiling CTCs, and opening up new treatment options for the benefit of patients.

4) Actionable variants identified in our patient cohort in the CTCs that were not present in the ctDNA included variants targeted by widely used drugs from many large pharma companies, for example:

· PIK3CA (E545K): Alpelisib (Piqray®) marketed by Novartis

· EGFR (T790M): Tagrisso (Osimertinib®) marketed by Astra Zeneca

· ESR1 (K303R): Elacestrant (Oserdu®) marketed by Menarini

· MTOR (T1977K): Everolimus (Afinitor®) marketed by Novartis

· ERBB2 (R678Q): Trastuzumab, Pertuzumab, Neratinib, Afatinib marketed respectively by Astra Zeneca, Roche Genentech, Puma Biotechnology, and Boehringer Ingelheim

5) As well as the unique insight provided by DNA analysis of the CTCs harvested by the Parsortix system, the CTC sample offers the potential to extend the analysis from DNA to RNA, protein, and morphological analysis of CTCs and CTC clusters, all of which together make the intact living cancer cell (CTC) the best sample for repeat non-invasive testing to drive personalised care for cancer patients.

ANGLE is engaging with Illumina, leading KOLs and oncologists to seek their input and consideration of the benefits of the combined ctDNA / CTC-DNA approach giving a new and unique insight into cancer clonal evolution. The early stage responses have been encouraging.

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Notes for editors

About ANGLE plc

ANGLE is a world-leading liquid biopsy company with innovative circulating tumour cell (CTC) diagnostic solutions for use in research, drug development and clinical oncology using a simple blood sample. ANGLE's FDA cleared and patent protected circulating tumour cell (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 diagnostic products and clinical services. Diagnostic products include the Parsortix® system and associated consumables. The clinical services business is offered through ANGLE's GCP-compliant laboratories. Services include custom made assay development and clinical trial testing for pharma.

Over 90 peer-reviewed publications have demonstrated the performance of the Parsortix system. For more information, visit www.angleplc.com