CDH2

Abcuro on Thursday announced that it raised $155 million in Series B financing that will be used to complete a Phase II/III registrational trial of ABC008 for the treatment of inclusion body myositis (IBM). The investment was co-led by Redmile Group and Bain Capital Life Sciences, with other participants including RA Capital Management, Samsara BioCapital and Sanofi Ventures.The anti-KLRG1 antibody ABC008 has been designed to treat diseases mediated by highly cytotoxic T-cells, including IBM, T-cell large granular lymphocytic leukaemia (T-LGLL) and mature T-cell malignancies. The pivotal study in IBM, which began in April, aims to recruit around 230 patients and investigate the efficacy of ABC008 as measured by the IBM Functional Rating Scale (IBMFRS) at week 76."Targeting the depletion of cytotoxic T-cells that express KLRG1 with ABC008…has generated exciting early data in patients with IBM," remarked chief medical officer H. Jeffrey Wilkins. The company previously highlighted data from a Phase I trial showing that at the ABC008 dose levels being used in the Phase II/III study, 97% depletion of blood target cells was observed at 28 days post injection.Abcuro is also evaluating the antibody in a Phase I/II trial for T-LGLL, while plans are under way for a Phase I/II study in T- and NK-cell lymphomas. Meanwhile, the company, which closed a $42 million Series A-1 financing in 2021, has a monoclonal antibody dubbed ABC015 in preclinical development. The therapy is designed to interrupt the interaction of KLRG1 with E- and N-cadherin on the surface of cancer cells.

Researchers led by Osaka University report the development of INCIDER, a fluorescent sensor system that enables high-contrast microscopic imaging of temporal changes in cellular interactions mediated by the N-cadherin molecule. This sensor system, which emits much brighter fluorescence than the currently used system while detecting these interactions, is expected to have a wide range of applications in developmental biology, neuroscience, and other fields. Cells tend to get themselves in and out of "sticky situations" on a regular basis, as they make and break functional connections with each other. Monitoring intercellular interactions is essential for gaining deeper insights into the complex human physiology. Now, researchers from Japan have developed a new way to track some of these adhesive interactions in real time. In a recent article published in Communications Biology, researchers led by SANKEN (The Institute of Scientific and Industrial Research) at Osaka University have reported the development of a new fluorescent sensor system for imaging a key protein involved in interactions between cells. The human body is made up of millions of cells that need to work together to keep everything functioning normally. In order for cells to work well together, they need to stick together, and they do this through the use of adhesion molecules such as neural cadherin (NCad). "Due to a lack of appropriate detection techniques, it remains unclear when and where NCad interactions occur," says lead author of the study Takashi Kanadome. "Conventional sensor molecules have a low resolution and irreversible properties, which makes it challenging to detect dynamic changes in cell-cell interactions." To design a better way to visualize NCad-dependent interactions between cells, the researchers started with a set of two sensors that only let off a bright fluorescent signal when they are right next to each other. They inserted each of these sensors into different copies of NCad to generate INCIDERs (fluorescent indicators for the detection of NCad interactions) and then monitored the interactions between cells expressing the new sensor proteins. "The results were striking," explains senior author Tomoki Matsuda. "We observed bright fluorescence on the surfaces of interacting cells, indicating that the fluorescent sensors were appropriately activated by cell-cell adhesion." Treating the cells with calcium to disrupt the interaction between the paired INCIDER sensor proteins resulted in a decrease in fluorescence, and washing out the calcium increased the fluorescence, showing that this system is reversible and can therefore be used to image dynamic changes in cell interactions. In addition, the fluorescence signal was 70 times stronger than that of the only system that is currently available to detect these kinds of interactions. "Our study demonstrated that, using the INCIDER system, it is possible to perform high-contrast microscopic imaging of temporal changes in cell-cell N-cadherin interactions," says Matsuda. Given that NCad-mediated intercellular adhesion is crucial to a wide range of cells and cellular processes, the INCIDER system is expected to be useful in the fields of developmental biology, neuroscience, and more. In the future, this fundamental technology could be expanded to image interactions between other types of intercellular adhesion proteins.

ANGLE plc STUDY USING PARSORTIX DEMONSTRATES IMPORTANCE OF BIOMARKER-INDEPENDENT CTC ISOLATION IN HEAD AND NECK CANCER EMT status of CTCs found to provide additional insight to tumour tissue biopsy Potential role of CTC EMT biomarkers as therapeutic targets GUILDFORD, UK / ACCESSWIRE / September 28, 2022 / ANGLE plc ("the Company") (AIM:AGL)(OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the University of Birmingham has published the results of a study undertaken in head and neck squamous cell carcinoma (HNSCC) which characterised the epithelial-mesenchymal transition (EMT) status of circulating tumour cells (CTCs). EMT is clinically significant due to its role in tumour progression and invasion, the development of metastasis, metabolic reprogramming, immune evasion, and resistance of cancer cells to therapy. The study used the Parsortix® system to harvest CTCs from peripheral blood samples from 20 treatment-naïve HNSCC patients at baseline prior to surgery. The researchers performed flow-cytometry EMT characterisation of CTCs as compared to EMT gene expression in tumour tissue and investigated expression correlation with respect to clinical outcomes. The expression of EpCAM and N-cadherin were utilised to characterise CTC status as epithelial or EMT. CTCs were detected in 65% of patients and 77% of positive samples included CTCs undergoing EMT. The research demonstrated that EMT status of CTCs was almost exclusively associated with advanced stage (III-IV) disease. In this small patient cohort CTC enumeration alone was not reported to be prognostic with respect to overall survival and progression free survival. However, CTC EMT status was found to be independent to that of tumour tissue, highlighting the potential clinical utility of CTC EMT biomarkers as a complementary analyte to tumour tissue biopsy or as therapeutic targets. Head and Neck Cancer (HNC) is a broad term used to group oral cavity, pharynx, larynx, salivary gland and nose and sinus cancer, with 90-95% of HNCs being squamous cell cancers. Globally, HNC accounted for over 930,000 new cases and over 460,000 deaths in 2020. In head and neck squamous cell carcinoma, 5-year survival rates are in the region of 50%, depending on cancer type and stage, but largely static for several decades. Common risk factors of this cancer include gender, ethnicity, age, poor oral hygiene, tobacco and alcohol use. The toxicity associated with current treatment regimens for this cancer results in a significant impact upon quality of life. Therefore, early diagnosis and effective targeted treatment options are urgently required to improve patient outcomes. A liquid biopsy, in particular analysing CTCs, is one potential avenue to define such therapeutic biomarkers. Professor Hisham Mehanna, the Chair of Head and Neck Surgery, and Director of the Institute of Head and Neck Studies and Education (InHANSE) at the Institute of Cancer and Genomic Sciences, University of Birmingham, commented: "The successful characterisation of EMT CTCs in HNSCC sheds light on the potential adaptive EMT response to stimuli within the circulation of blood, providing an important and unique insight into metastasis. Prospective clinical trials are needed to answer the question regarding the predictive utility of a CTC liquid biopsy (for example CTC immune checkpoint expression directing personalised treatment), especially in recurrent/metastatic patients not amenable to repeat tissue biopsies." ANGLE Founder and Chief Executive, Andrew Newland, commented: "ANGLE is pleased to report on the use of the Parsortix system as a tool for HNSCC EMT classification. Evidence continues to grow supporting the potential clinical utility of CTC enrichment to provide clinical information beyond the scope of tissue biopsy. This research provides further evidence for the role that EMT CTCs play in the metastatic cascade and the clinical importance of biomarker independent CTC isolation methods which capture all subsets of CTCs. In drug discovery, this may enable the identification of drugs that are better able to target cancer cells known to be the precursors of metastasis. As metastasis is responsible for 90% of cancer deaths, this could be transformative for cancer care and patient outlook." The research has been published as a peer-reviewed publication in the Journal Head and Neck and is available online at . ANGLE plc +44 (0) 1483 343434 Andrew Newland, Chief Executive Ian Griffiths, Finance Director Andrew Holder, Head of Investor Relations Berenberg (NOMAD and Joint Broker) Toby Flaux, Ciaran Walsh, Milo Bonser +44 (0) 20 3207 7800 Jefferies (Joint Broker) Max Jones, Thomas Bective +44 (0) 20 7029 8000 FTI Consulting Simon Conway, Ciara Martin Matthew Ventimiglia (US) +44 (0) 203 727 1000 +1 (212) 850 5624 For Frequently Used Terms, please see the Company's website on Notes for editors About ANGLE plc ANGLE is a world leading liquid biopsy company with sample-to-answer solutions. ANGLE's proven patent protected platforms include a circulating tumor cell (CTC) harvesting technology known as the Parsortix® system and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins. ANGLE's Parsortix® system is FDA cleared for its intended use in metastatic breast cancer and is currently the first and only FDA cleared medical device to harvest intact circulating cancer cells from blood. Intended use 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. The Parsortix system enables a liquid biopsy (a simple blood test) to be used to provide the circulating metastatic breast cancer cells to the user in a format suitable for multiple types of downstream analyses. The system is based on a microfluidic device that captures cells based on a combination of their size and compressibility. The system is epitope independent and can capture all phenotypes of CTCs (epithelial, mesenchymal and EMTing CTCs) as well as CTC clusters in a viable form (alive). CTCs harvested from the system enable a complete picture of a cancer to be seen; as being an intact cell they allow DNA, RNA and protein analysis as well as cytological and morphological examination and may provide comparable analysis to a tissue biopsy in metastatic breast cancer. Because CTC analysis is a non-invasive process, unlike tissue biopsy, it can be repeated as often as needed. This is important because cancer develops and changes over time and there is a clear medical need for up-to-date information on the status of a patient's tumor. In addition, the live CTCs harvested by the Parsortix system can be cultured, which offers the potential for testing tumor response to drugs outside the patient. The Parsortix technology is the subject of 26 granted patents in Europe, the United States, China, Australia, Canada, India, Japan and Mexico with three extensive families of patents are being progressed worldwide. In the United States, the Parsortix® PC1 system has received a Class II Classification from FDA for use with metastatic breast cancer patients. FDA clearance is seen as the global gold standard. ANGLE's Parsortix system is the first ever FDA cleared system for harvesting CTCs for subsequent analysis. ANGLE has applied the IVD CE Mark to the same system for the same intended use in Europe. ANGLE has also completed two separate 200 subject clinical studies under a program designed to develop an ovarian cancer pelvic mass triage test, with the results showing best in class accuracy (AUC-ROC) of 95.1%. The pelvic mass triage assay has undergone further refinement and optimisation and a 200 patient clinical verification study has now completed enrolment. ANGLE's technology for the multiplex evaluation of proteins and nucleic acids of all types is called the HyCEADTM platform and is based on a patented flow through array technology. It provides for low cost, highly multiplexed, rapid and sensitive capture of targets from a wide variety of sample types. A proprietary chemistry approach (the HyCEAD method) allows for the capture and amplification of over 100 biomarkers simultaneously in a single reaction. The HyCEAD system is extremely sensitive and is ideal for measuring gene expression and other markers directly from Parsortix harvests and was used in the ovarian cancer pelvic mass triage test to achieve best in class accuracy (AUC-ROC) of 95.1%. ANGLE's proprietary technologies can be combined to provide automated, sample-to-answer results in both centralised laboratory and point-of-use cartridge formats. ANGLE has established formal collaborations with world-class cancer centres and major corporates such as Abbott, Philips and QIAGEN, and works closely with leading CTC translational research customers. These Key Opinion Leaders (KOLs) are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies. The body of evidence as to the benefits of the Parsortix system is growing rapidly from our own clinical studies in metastatic breast cancer and ovarian cancer and also from KOLs with 69 peer-reviewed publications and numerous publicly available posters from 31 independent cancer centres, available on our website. ANGLE has established clinical services laboratories in the UK and the United States to accelerate commercialisation of the Parsortix system and act as demonstrators to support product development. The laboratories offer services globally to pharmaceutical and biotech customers for use of Parsortix in cancer drug trials and, once the laboratories are accredited and tests validated, will provide Laboratory Developed Tests (LDTs) for patient management. This information is provided by Reach, the non-regulatory press release distribution service of RNS, part of the London Stock Exchange. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact rns@lseg.com or visit . SOURCE: ANGLE plc View source version on accesswire.com: