For Immediate Release

23 July 2014

 

 

ANGLE plc

("ANGLE" or "the Company")

 

Preliminary Results for the year ended 30 April 2014

 

CE MARK AWARDED AND SYSTEM DEPLOYED WITH KEY OPINION LEADERS

 

ANGLE plc (AIM: AGL), the specialist medtech company, today announces audited preliminary results for the year ended 30 April 2014. During the year, ANGLE made significant progress with its patented Parsortix system for harvesting circulating tumour cells (CTCs), foetal cells and other rare cells from blood for analysis. 

 

Highlights

 

·     Balance sheet strengthened by sale of Geomerics to ARM Holdings plc for up to £6.2 million in cash with £5.5 million received to date

 

·     Parsortix system successfully deployed with key opinion leaders

 

·     Specialist manufacturer appointed with the necessary quality systems and capacity to support commercialisation 

 

·     CE Mark authorisation secured for use of Parsortix system as an in vitro diagnostic device in clinical use (the treatment of patients) in the European Union and FDA 510(k) submitted in the US         

 

·     Partnership established with the Medical Research Council's Cancer Unit at the University of Cambridge to establish a Cambridge Parsortix Laboratory

 

·     Intellectual property further strengthened, increasing the breadth and duration of patent coverage, and the range of medical applications covered

 

·     Loss for the year of £1.2 million (2013: loss £1.0 million) and cash balance at 30 April 2014 of £3.9 million (30 April 2013: £1.8 million)

 

Continued progress post the year end

 

·     Cancer Research UK Manchester Institute completed full report confirming key competitive advantages of the Parsortix system including:

-  applicability to multiple types of cancer cells including mesenchymal cells

-  applicability to multiple types of cancer

-  easy harvesting of cells for molecular analysis

-  low level of background white blood cell contamination of harvested cell samples 

 

Garth Selvey, Chairman, commented:

 

"ANGLE has made significant progress with commercialisation of Parsortix during the year and is now strongly focused on establishing the use of the system in clinical practice.  To achieve this, the top priority is the establishment of collaborations with key opinion leaders at world class research centres.  These key opinion leaders are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies.  We believe that we are on the right path to unlocking the multi-billion dollar market worldwide available to ANGLE and its potential strategic partners."

 

 

Details of analyst meeting and webcast

 

A meeting for analysts will be held at 10.00am on the morning of the results at the offices of Buchanan, 107 Cheapside, London EC2V 6DN. Please contact Buchanan on 020 7466 5000 for details.

 

There will be a live webcast of the analyst meeting. To listen to the webcast, please log on to the following web address approximately 5 minutes before 10.00am on the day of the results:  http://mediaserve.buchanan.uk.com/2014/angle230714/registration.asp  

 

 

For further information:

 

ANGLE plc	01483 685 830
Andrew Newland, Chief Executive Ian Griffiths, Finance Director
Cenkos Securities Stephen Keys, Christopher Golden (Nominated adviser) Andy Roberts, Christian Hobart (Sales)	020 7397 8900
Buchanan Mark Court, Fiona Henson, Sophie Cowles	020 7466 5000

 

These Preliminary Results may contain forward-looking statements. These statements reflect the Board's current view, are subject to a number of material risks and uncertainties and could change in the future. Factors that could cause or contribute to such changes include, but are not limited to, the general economic climate and market conditions, as well as specific factors including the success of the Group's research and development and commercialisation strategies, the uncertainties related to regulatory clearance and the acceptance of the Group's products by customers. 

CHAIRMAN' S STATEMENT

 

Introduction

 

During the year, ANGLE made significant progress on product development and the deployment of the Parsortix system with key opinion leaders for research use. ANGLE also successfully disposed of its investment in Geomerics, strengthening the balance sheet and substantially completing its refocusing as a specialist medtech company.

 

Results

 

During the year, planned investment principally relating to Parsortix was £3.0 million (2013: £2.5 million). This comprised operating costs of £2.8 million (2013: £1.6 million) and capitalised expenditure of £0.2 million (2013: £0.9 million).

 

The loss for the year of £1.2 million (2013: loss £1.0 million), reflected operating costs of £2.8 million (2013: £1.6 million) offset by a fair value gain on investments of £1.3 million (2013: £0.5 million) and other income of £0.3 million (2013: £0.1 million).

 

The cash balance was £3.9 million at 30 April 2014 (30 April 2013: £1.8 million). 

    

Sale of Geomerics

 

During the year, ANGLE's investment in Geomerics was sold for a cash consideration of up to £6.2 million to ARM Holdings, the world's leading semiconductor intellectual property supplier. £5.5 million has been received and the balance of £0.7 million is being held as a retention, receivable on 12 December 2015.

 

Product development and market introduction

 

During the year, ANGLE progressed the development of its Parsortix system for harvesting rare cells from patient blood for analysis.  The system is designed for use both in the research market and, where authorised, the clinical market for patient treatment.

 

The automated harvesting capability of ANGLE's system enables the harvest of very rare circulating tumour cells (CTCs) in cancer patient blood for DNA and other analysis.  The resulting "liquid biopsy" means that the Parsortix system has the potential, through a simple blood test, to address a major new market for personalised cancer treatment. 

 

During the year, a specialist, large scale manufacturer was appointed to manufacture the Parsortix system with the necessary quality systems and capacity to support the roll out into the research and clinical markets.

 

The product was introduced at the 4th Annual Circulate conference in Berlin in February 2014. This generated significant awareness among key opinion leaders, potential customers and partners.  There is now a growing momentum of interest in the product as key opinion leaders and potential customers appreciate the combination of key operational advantages of the Parsortix system for CTC analysis including:

 

·     Antibody independent so works with all types of cancer cells (not just those with a particular cell surface marker)

·     Easy harvesting of cancer cells out of the system for molecular analysis (unlike other systems where the cells may be trapped in the device)

·     Low level of background white blood cell contamination so that the cells can be directly analysed without the need for a separate single cell extraction step

·     Easy to use, plug and play automated separation system without the need for blood preparation steps

 

Intellectual Property

 

The intellectual property (IP) patent portfolio underpinning the Parsortix system has been further extended during the year.  We have also filed new submissions which, if granted, will provide further patent coverage to late 2033.  The current issued US Patent provides cover until 2026.

 

The new patents cover key new operational aspects as follows: 

·     Cell harvesting method - this covers the method by which the Parsortix system can harvest cells (recover them from the system) for mutational and other medical analysis

·     Cell measurement method - this covers the technique of using the structure and markings in the Parsortix cassettes to determine the sizes of captured cells as part of their identification and analysis

·     Multifold design of Parsortix cassette - this covers the use of an elongated step front (undulating ribbon) providing increased separation capacity within the cassette 

 

Regulatory authorisation

 

Regulatory authorisation is a requirement before the Parsortix system can be sold for use in the clinical market (treatment of patients), although earlier sales will be made into the research market.

 

During the year, ANGLE secured the CE Mark for the use of the Parsortix system as an in vitro diagnostic device in the European Union.

 

Achievement of this key milestone confirms that the clinical use of the Parsortix system, the Parsorter PC1, meets the Essential Requirements of the European Union In Vitro Device Directive (98/79/EC), a prerequisite for the product's use in clinical applications throughout Europe.

 

ANGLE also made an FDA 510(k) submission in March 2014 for clinical use of the Parsortix system in the United States. The timing of approval is dependent on the FDA's review and responses to our submission.  

 

System deployment and sales

 

ANGLE is working to develop the sales platform needed to establish the Parsortix system in the very large clinical market, which is emerging as medical research is undertaken utilising CTCs to determine improved cancer patient treatment. The Strategic Report sets out how this will be achieved.

  

Crucial to securing substantial sales is to ensure that key opinion leaders utilise the system and adopt it as standard.  The adoption by key opinion leaders has been a priority this year and the decision was taken to focus on wider research sales only after this adoption has been established.  This has had a number of key advantages as follows:

 

·     Resources have been prioritised towards adoption by key opinion leaders

 

·     We have received expert feedback from the first wave of users, which has enabled us to refine our product and further differentiate our competitive position

 

·     We now have a highly influential group of world-leading cancer experts who are excited about our system and are actively looking for ways to use it

 

 

The key opinion leader programme is now going well and we have more joining our programme.  Speed of access to the clinical market will remain our overwhelming priority. As applications of the Parsortix system become established in practice by key opinion leaders, we will instigate commercial sales for the research market. 

 

Clinical sales will take longer to develop and are expected to be modest initially.  However, as each clinical application becomes supported by peer reviewed clinical data from key opinion leaders, we expect sustained revenue growth for that application.  We intend to amplify this growth by developing key strategic and research relationships with major international medtech and pharmaceutical companies.  

 

Key Opinion Leaders

 

As stated above, endorsement of the Parsortix system by key opinion leaders (world leading cancer research centres) is crucial in identifying and proving clinical applications, and providing credentials for other users. Key opinion leaders with whom we are working have reported encouraging results from their work and the Parsortix system has been well received.

 

The University of Surrey Oncology Group    

 

The University of Surrey Oncology Group in conjunction with the Royal Surrey County Hospital completed their validation of Parsortix technology. Using colorectal cancer patient blood, they demonstrated that the Parsortix system had twice the sensitivity of currently accepted clinical practice for CTC capture.

 

The University of Surrey Oncology Group then used the Parsortix system to undertake a study of metastatic liver cancer patients and successfully demonstrated that there was a higher prevalence of CTCs in the patients' hepatic blood than in their peripheral blood.  This is under further investigation and may have significant implications for liver cancer surgery in the future.

 

Cancer Research UK Manchester Institute

 

During the year, the Cancer Research UK Manchester Institute, previously known as the Paterson Institute for Cancer Research, in conjunction with The Christie (Europe's largest cancer hospital), reported key clinical advantages for the Parsortix system and has included Parsortix in its ongoing efforts to deliver personalised medicine.  

 

After the year end, Cancer Research UK Manchester Institute completed a full report confirming key competitive advantages of the Parsortix system including:

·     Applicability to capture multiple types of cancer cells including mesenchymal cells

·     Applicability to multiple types of cancer (for example prostate, breast, lung, colorectal, melanoma, liver etc)

·     Easy harvesting of cells for molecular analysis

·     Low level of background white blood cell contamination of harvested cell samples allowing direct analysis 

 

Medical Research Council's Cancer Unit at the University of Cambridge  

 

During the year, ANGLE entered into an agreement with the Medical Research Council's Cancer Unit at the University of Cambridge in conjunction with Addenbrooke's hospital to establish a Cambridge Parsortix Laboratory.  This cancer unit is a leading and highly influential institution which has had access to a Parsortix system since June 2013. The establishment of the Cambridge Parsortix Laboratory will allow the unit's research team, and the wider scientific community at the University of Cambridge and Addenbrooke's hospital, to have improved access to the Parsortix system. It is an important recognition of the Parsortix system that this stand-alone Parsortix laboratory is being established in Cambridge. Pilot studies being considered include colorectal and oesophageal cancer.

 

Scientific Advisers

 

During the year, two additional Scientific Advisers were appointed to help guide the Parsortix non-invasive cancer diagnostic technology to market. 

 

Dr Harold Swerdlow is a world-leading expert in next-generation sequencing (NGS), which is becoming the premier technique in genetic and genomic analysis.  Previously Head of Research and Development for the Wellcome Trust Sanger Institute, he has recently been appointed VP of Technology Innovation at the New York Genome Center.  Dr Swerdlow invented core technology relating to NGS and commercialised this at Solexa Ltd., which was acquired by Illumina for US$600 million.

 

Dr Clive Stanway is an expert in the drug discovery and development process, with worldwide contacts with major pharma development groups.  He is Chief Scientific Officer of Cancer Research Technology (CRT), the technology development and commercialisation arm of Cancer Research UK.

 

ANGLE now has four Scientific Advisers with knowledge between them of key aspects of CTC investigation for personalised cancer care:

·     Prof Adrian Newland, Barts Health NHS Trust - haematology, cancer diagnostics and National Institute for Clinical Excellence (NICE)

·     Dr Clive Stanway, Cancer Research Technology - cancer drug development and major pharma

·     Dr Harold Swerdlow, New York Genome Center - next-generation sequencing

·     Prof Ashok Venkitaraman, Medical Research Council's Cancer Cell Unit- cancer cell biology and personalised cancer care

 

Directors

 

David Quysner, non-executive director, has advised me of his intention to retire at the Annual General Meeting.  David has been a member of the ANGLE board for over ten years.  On behalf of the board and the whole company, I thank him for his clear views and opinion and many contributions to the development of the business during that time.  We wish him much happiness in his retirement.

 

Outlook

 

ANGLE has made significant progress with commercialisation of Parsortix during the year and is now strongly focused on establishing the use of the system in clinical practice.  To achieve this, the top priority is the establishment of collaborations with key opinion leaders at world class research centres.  These key opinion leaders are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies.  We believe that we are on the right path to unlocking the multi-billion dollar market worldwide available to ANGLE and its potential strategic partners.

 

 

 

 

 

Garth Selvey                                                           

Chairman                                            

STRATEGIC REPORT

 

 

 

 

 

Introduction

 

ANGLE is a specialist medtech company commercialising a platform technology that can capture cells circulating in blood, such as cancer cells, even when they are as rare in number as one cell in one billion blood cells, and harvest the cells for analysis.

 

ANGLE's cell separation technology is called Parsortix and is the subject of a granted US patent and three extensive families of patents being progressed worldwide.  The system is based on a microfluidic device that captures cells based on a combination of their size and compressibility.

 

The analysis of the cells that can be harvested from patient blood with ANGLE's Parsortix system has the potential to deliver profound improvements in clinical and health economic outcomes in the treatment and diagnosis of various forms of cancer. 

 

As well as cancer, the Parsortix technology has the potential for deployment with several other important cell types in the future.

 

Cancer medical applications

 

The treatment of cancer is highly problematic primarily because of the heterogeneity of cancer in multiple dimensions:

 

·     Each cancer patient may have different mutations from other patients with the same type of cancer

 

·     Each cancer patient may have several different types of cancer cell mutation within a particular tumour

 

·     Each patient's cancer may mutate and change its mutations over time

 

In order to treat patients effectively, doctors need to deploy drugs that target the individual patient's cancer mutations at that point in time.  This approach is called "personalised cancer care" and in recent years has become accepted worldwide as the most likely way to improve patient outcomes in the long run.

 

There is therefore a crucial need for ongoing information as to the patient's cancer mutational status.  Initially, where the cancer tumour can be accessed, this is currently achieved through a solid biopsy, for example through a breast cancer lumpectomy.  The tissue excised is analysed and the oncologist makes a decision on therapy based on the analysis, for example in breast cancer if the patient is HER2 positive they may receive Herceptin or a similar drug but otherwise they will not.

 

The use of the solid biopsy where it can be applied is effective and the current "gold standard" in treatment.  However it is invasive and relatively costly compared with a blood test. Even more importantly it cannot always be used effectively in difficult to access tumours, such as pancreatic cancer, lung cancer and brain cancer.

 

Crucially, whether or not a solid biopsy can be taken when the patient presents, biopsy of the primary tissue cannot be repeated at a later date when the tissue concerned has already been excised and is no longer there.

 

Primary cancers shed cancer cells into the patient's bloodstream.  These cells circulate in the blood and are known as circulating tumour cells or CTCs.  The CTCs can then land in another part of the body and initiate a secondary cancer.  If they can be harvested for analysis, the CTCs have the potential to provide, through a simple peripheral blood test as is routinely used in medical application, crucial medical information regarding the changing metastatic and mutational status of the patient's disease.

 

It is widely agreed that a non-invasive liquid biopsy that could harvest CTCs for analysis would have a profound impact in understanding the patient's current cancer status and ensuring the optimum treatment is deployed for that individual patient at that particular time.

 

Economics of cancer patient treatment

 

Treatment of cancer patients can be very expensive.  For example a single chemotherapy drug prescribed may cost in excess of £50,000 for a course.  Such drugs are prescribed because they are thought to be the best option available to treat patients, whilst in reality they will be beneficial to only a proportion, perhaps one in three, of patients.

 

In this example, two thirds of the drug cost may be wasted on patients who have no medical benefit from the treatment.  Worse still these drugs are toxic and, regardless of whether they receive any benefit from the drug, patients will often experience severe side effects.

 

Furthermore, it is often the case that without specific information on the individual patient's cancer a cocktail of drugs are prescribed where the doctors know that several will be ineffective for that patient but they do not know which ones.

 

ANGLE's aim is to demonstrate the Parsortix system's capability to harvest CTCs for an analysis that will enable a determination of which patients will benefit from which drug.

 

This will not only improve patient treatment and reduce unnecessary side effects but dramatically reduce overall patient treatment costs allowing more efficient and effective deployment of medical resources.  This approach will support the efforts of NICE in the UK, and similar organisations elsewhere in the world, to ensure effective use of medical resources.

 

Market size

 

ANGLE's ultimate objective is the widespread adoption of the Parsortix system in the diagnosis and treatment of cancer patients. According to the World Health Organisation, there were an estimated 14 million new cancer cases worldwide in 2012, a marked rise on the 12.7 million cases in 2008.  In 2012, there were an estimated 32.6 million people living with cancer.  

(Source: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx)

 

The incidence of cancer continues to grow as a result of demographic, lifestyle and environmental factors and it is estimated that one in three people in the UK will get cancer during their lifetime. 

 

There are a wide range of potential applications for harvested CTCs including diagnosis, prognosis, mutational analysis and drug selection, drug development, assessment of treatment effectiveness, and remission monitoring.  We estimate that this represents a potential global market for ANGLE's Parsortix system worth in excess of £8 billion per annum.

 

ANGLE's major focus is on the cancer market.  There is also a substantial market available in non-invasive foetal diagnostics, harvesting foetal cells from the pregnant mother and analysing for Down's Syndrome and many other chromosomal and genetic conditions through a simple blood test.

 

 

Commercialisation

 

ANGLE has a clear strategy to commercialise its Parsortix technology.

 

The cell capture and harvesting technology has been developed together with an automated machine to run blood samples through the cell separation cassette and extensive intellectual property protection of the system is being prosecuted. 

 

A great deal of work has been completed to ensure the system is robust, operates reproducibly and can run patient samples efficiently.  Optimisation of the system is ongoing for particular applications and to ensure it operates effectively with existing medtech platforms for cell analysis.

 

Successful evaluation of the system by major cancer research centres as key opinion leaders for the market has already been achieved and a major part of ANGLE's current efforts relate to further deployment with key opinion leaders.

 

Regulatory authorisation for the clinical use of the system in patient treatment in the EU has already been achieved and the process is ongoing with the FDA for the USA.

 

Widespread adoption of the Parsortix system in the clinical market crucially depends on ongoing work with key opinion leaders to:

 

·     Undertake successful pilot studies demonstrating patient applications with clear medical utility (patient benefit)

 

·     Select key medical applications with clear medical utility

 

·     Undertake successful patient studies providing fully documented evidence of how the system should be used for particular patient applications in routine treatment

 

·     Convert key opinion leader support and peer reviewed publications into widespread adoption of the Parsortix system in routine patient care

 

Major areas of work currently in progress are described below.

 

Competitive differentiation

 

Major competitive differentiators of the system successfully achieved so far include:

 

·     Epitope independence with no requirement for the use of an antibody to capture cells. The Parsortix system has key advantages over antibody based systems that rely on the expression of a cell surface protein (such as EpCAM) including: 

·     the system is able to capture CTCs that have undergone the epithelial mesenchymal transition during the process of metastasis (and are no longer EpCAM positive)

·     the system is able to capture CTCs in cancer types, such as ovarian cancer, which only have weak or no EpCAM expression

·     the system is versatile and may be used for other cell types such as foetal cells

·     the harvest is clean and does not contain immuno-magnetic beads or other additives needed for the antibody based cell capture systems, which may compromise analysis of the cells

 

·     Easy harvest of cells from the system for molecular analysis, unlike many other systems where cells may be captured but can get stuck in the separation system so that they cannot be harvested for analysis

 

·     Low level of background white blood cell contamination thereby allowing either single cell analysis or direct analysis of the harvested cells containing both the CTCs and a low number of white blood cells.  Competing systems may have far more background white blood cell contamination thereby making analysis of target cells more difficult

 

·     Simplicity and cost effectivenessso that both the one-time use consumable, the Parsortix cassette, and the automated machine that runs the blood through the cassette are simple, easy to use, straightforward in training and cost competitive 

 

·     The Parsortix system is easily deployed at customer sites in stark contrast to many competing systems which, as a result of their size and complexity, the need for expert operators and difficulty in securing regulatory authorisation, may be forced to rely on a CLIA (certified laboratory) approach where the customer has to send the patient sample for analysis at a remote laboratory and cannot process it near the patient

 

Optimising the system

 

ANGLE continues to undertake a great deal of work on the Parsortix system with the aim of ensuring that it is robust, operates reproducibly and can run patient samples efficiently. 

 

During the year, ANGLE successfully completed extensive work in key areas of functionality including:

 

·     Developing protocols to ensure the blood is preserved prior to separation for up to 72 hours thereby enabling transportation, shipping and processing without losing the capability to process the sample

 

·     Developing, testing and then automating the harvesting protocols to allow harvesting of cells from the Parsortix system for molecular analysis

 

·     Developing and refining protocols to reduce the level of background white blood cell contamination of the harvested cells.  This enables the analysis of the harvested cells directly without the need for a separate single cell separation step, although this may still be useful in some applications

 

The main areas of work that are currently taking place include:

 

·     Optimising the speed of flow of blood through the separation system

 

·     Developing interface protocols for the existing molecular analysis platforms deployed by some of the world's largest medtech companies

 

·     Investigating how best the Parsortix system can be used by major pharma companies for  cancer drug development and as a "companion diagnostic" to determine the suitability and effectiveness of drugs for individual patients

 

Successful evaluation of the system by major cancer research centres

 

The Parsortix system is being evaluated by multiple world-leading cancer research centres as key opinion leaders and receiving positive results.

 

Cancer Research UK Manchester Institute, previously known as the Paterson Institute for Cancer Research, is one of the world's foremost authorities on personalised cancer care and specifically CTCs.  As such they have worked extensively with CTC systems and published on the various approaches available to capture CTCs.

 

Leading research scientists at Cancer Research UK Manchester Institute have worked extensively with the Parsortix system over the past 18 months and are now pursuing clinical research work with the Parsortix system in colorectal and pancreatic cancer. 

 

Key advantages of the Parsortix system identified by the Clinical and Experimental Pharmacology group at Cancer Research UK Manchester Institute are as follows:

 

·     Based on spiked cell experiments, the system provides a "very high level of capture" of cells (80-100%) and a "high level of harvest" of cells (60-100%)

 

·     The system is marker independent thus does not require the use of capture antibodies to enrich CTCs. The potential advantages include ability to capture CTCs with weak cell marker expression as well as mesenchymal cells and cell clusters that may be important in dissemination and metastasis

 

·     The Parsortix system can maintain a good rate of harvest while also delivering a low level of background white blood cell contamination (<200 white blood cells independent of sample volumes). The harvest can be used for the extraction and analysis of single CTCs.  Alternatively the exceptionally low background white blood cell contamination means that the harvest is sufficiently concentrated to allow direct genetic analysis of the Parsortix harvest without further processing. This latter point represents a major step forward and has not been possible with other CTC capture and enrichment technologies tested by the team at Manchester so far

 

·     the Parsortix system does not require pre-separation steps such as removal of red blood cells, is compatible with blood preservation collection tubes, allows plasma collection from the same sample and is straightforward to use with minimal user intervention

 

Secure regulatory authorisation

 

In order to be able to sell the Parsortix system for use in treating patients in the clinical market, it is necessary to secure regulatory authorisation for the clinical use of the system in patient treatment in each geographic region.

 

During the year, ANGLE successfully secured CE Mark authorisation for the use of Parsortix as an in vitro diagnostic device in the European Union in the treatment of patients.

 

ANGLE also made an FDA 510(k) submission in March 2014 for clinical use of the Parsortix system in the United States. The aim is to secure an early FDA regulatory acceptance though the timing is dependent on the FDA's review and responses to our submission.  

 

There are no FDA authorised systems for harvesting CTCs for analysis of which we are aware and only one system authorised for the capture and counting of CTCs, which is antibody-based.  Securing FDA authorisation will be another major competitive differentiation for ANGLE.

 

Pilot studies by key opinion leaders

 

A critical element in progressing commercialisation of the Parsortix system is ensuring key opinion leaders undertake successful pilot studies to demonstrate patient applications with clear medical utility.  This involves working closely with key opinion leaders to encourage and support, with both human and financial resources, their investigative work using the Parsortix system.

 

A great deal of effort is being deployed in this area at present as described in the Chairman's report.  The following key opinion leaders are already working with our system under formal agreements:

 

·     The University of Surrey Oncology Group - immunotherapy and colorectal cancer

 

·     The Cancer Research UK Manchester Institute - colorectal and pancreatic cancer

 

·     The Medical Research Council's Cancer Unit at the University of Cambridge - colorectal cancer and oesophageal cancer.

 

Summary

 

ANGLE has a well differentiated patent-protected product addressing a large developing medical market with a clear strategy to secure a substantial market share.

 

Effective execution of the strategy has the potential to deliver significant financial returns for ANGLE's shareholders, profoundly improve the outcome for cancer patients, and reduce healthcare costs.

 

 

 

 

 

Andrew Newland

Chief Executive

On behalf of the Board

 

22 July 2014

 

 

Explanation of frequently used terms in connection with the Parsortix system

 

Biopsy	Process by which cancer cells are removed from the tumour for molecular analysis
Capture	Process for capturing target cells from sample
Capture efficiency	Proportion of target cells captured
CD45	The CD45 antibody recognises the human CD45 antigen, also known as the leukocyte common antigen.  WBC are CD45+ whereas CTCs are CD45-.  Staining with CD45 often used as a negative confirmation that CTCs are not WBC.
Cell-free DNA	Genomic DNA found in the plasma
Cell labelling	Technique involving the staining of target cells with fluorescent and chromogenic markers for cell identification
Cell lines	Cultured cells
CE Mark	Regulatory authorisation for the sale of products for clinical use in the European Union
Circulating tumour cell	Cancer cell that is circulating in the patient blood
CTC	Circulating tumour cell
CTC labelling	CTCs are often labelled with three markers and are formally identified as CTCs if they are CK+, CD45-, DAPI+
CK	Cytokeratin
CK+	A cell positive for the presence of cytokeratin protein or mRNA with the presence of distinct cytokeratins often used to identify epithelial cells
Clinical application	Use in treating patients
Clinical samples	Patient samples usually blood
Clinical use	Use in treating patients
Cultured cells	Cultured cells grown in the laboratory from human-derived cells used for experimental work
Cytokeratin	Cytokeratins are family of intracytoplasmic cytoskeleton proteins with members  showing tissue specific expression
DAPI	A nuclear stain that is often used to identify the nucleus in a cell
DEPArray	A commercial single cell isolation system
DNA	Deoxyribonucleic acid (DNA) the molecule that encodes the genetic instructions used in the development and functioning of all known living organisms and many viruses
Downstream technologies	Technologies used to undertake molecular analysis of harvested cells after the separation has taken place
EGFR	The epidermal growth factor receptor a signalling molecule which is typically present on the cell surface and can cell activity including cell proliferation. Mutations in EGFR or deregulation have been associated with a number of cancers including ~30% of all epithelial cancers
Enrichment	Generic term for concentrating target cells or molecules in a starting heterogeneous mixture
EpCAM	The EpCAM protein is found spanning the membrane that surrounds epithelial cells, where it is involved in cell adhesion
EpCAM+ cells	Cells that express EpCAM.  CTCs can be either EpCAM+ or EpCAM-
Epithelial cells	Cells that line the surfaces and cavities of the body
Epithelial CTCs	CTCs that are epithelial often based on EpCAM+
Epithelial-mesenchymal transition	Process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is thought to occur as part of the initiation of metastasis and is often responsible for cancer progression
EMT	Epithelial-mesenchymal transition
FDA	U.S. Food and Drug Administration responsible for authorised medical products in the United States
FDA 510(k)	A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device that is not subject to Premarket Approval. Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalency claims
Genome	Genetic material of an organism. The genome includes both protein coding and non-coding sequences
Harvest	Process for recovering captured cells from the separation system to allow molecular analysis
Harvest efficiency	Proportion of target cells harvested
Harvest purity	The number of target cells (such as CTCs) in the harvest as a proportion of the WBC. The minimum purity from which downstream analysis is currently possible is 0.5%.  Analysis of one target cell therefore requires no more than 200 WBC be in the harvest
HER2	A member of the epidermal growth factor receptor (EGFR/ERBB) family. Amplification or overexpression of HER2 has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. In recent years the protein has become an important biomarker and target of therapy for ~30% of breast cancer patients
HNV	Healthy normal volunteer
HT29	Cultured colorectal cancer cell line
In-cassette labelling or in-situ labelling	CTC labelling for cell identification undertaken inside the separation system
KRAS	A signalling molecule frequently mutated in the development of many cancers
Leukocytes	White blood cells
Liquid biopsy	Term used for the process of obtaining cancer cells (or cell-free DNA) from a blood sample.  Unlike solid biopsy, liquid biopsy is non-invasive and repeatable
Mesenchymal CTCs	CTCs generally lacking epithelial markers with mesenchymal features
Metastasis	Spread of a cancer from one site to another
Molecular analysis	Analysis of DNA, RNA and protein often used to determine the mutational status of a patient
mRNA	Messenger RNA used to direct the synthesis of proteins
Off-chip labelling	CTC labelling for cell identification of harvested cells undertaken outside the separation system
Paired samples	Two related samples often used to compare different systems
Personalised cancer care	Treating a patient individually based on their personal data often including mutational and disease status
Plasma	Pale-yellow liquid component of blood obtained following removal of cells
Pre-labelled cell lines	Cells which are labelled often with a fluorescent label to facilitate identification during analysis or enrichment
RNA	Ribonucleic acid performs multiple vital roles in the coding, decoding, regulation, and expression of genes. Together with DNA, RNA comprises the nucleic acids, which, along with proteins, constitute the three major macromolecules essential for all known forms of life
Separation	Term used for processing of a sample through the Parsortix system
Single cell analysis	Extraction of a single target cell from the harvest for analysis
Solid biopsy	Standard process for surgically excising (cutting out) cells from a solid tumour when that tumour is accessible
Spiked cell experiments	Experiments where cultured cells are added (spiked) to HNV blood to assess the capture and harvest efficiency of the system
WBC	White blood cells
WGA	Whole genome amplification
Whole genome amplification	Method for amplification of an entire genome necessary for the picogram amounts of genomic DNA present in a single cell

 

ANGLE PLC

CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME

FOR THE YEAR ENDED 30 APRIL 2014

 

 

	Note	2014		2013
		£'000		£'000
Revenue	5	801		969
Change in fair value	5	1,334		514
Operating costs	5	(3,485)		(2,555)
Operating profit/(loss)		(1,350)		(1,072)
Net finance income/(costs)		112		41
Profit/(loss) before tax		(1,238)		(1,031)
Tax	6	-		-
Profit/(loss) for the year		(1,238)		(1,031)
Other comprehensive income
Items that may be subsequently reclassified to profit or loss
Exchange differences on translating foreign operations		(96)		14
Other comprehensive income/(loss)		(96)		14
Total comprehensive income/(loss) for the year		(1,334)		(1,017)
Profit/(loss) for the year attributable to:
Owners of the parent		(1,064)		(866)
Non-controlling interests		(174)		(165)
Profit/(loss) for the year		(1,238)		(1,031)
Total comprehensive income/(loss) for the year attributable to:
Owners of the parent		(1,198)		(841)
Non-controlling interests		(136)		(176)
Total comprehensive income/(loss) for the year		(1,334)		(1,017)
Earnings/(loss) per share	7
Basic and Diluted (pence per share)		(2.74)		(2.54)

 

ANGLE PLC

CONSOLIDATED STATEMENT OF FINANCIAL POSITION

AS AT 30 APRIL 2014

 

	Note	2014		2013
		£'000		£'000
ASSETS
Non-current assets
Non-controlled investments	8	-		2,361
Other receivables	8	601		-
Property, plant and equipment		139		138
Intangible assets	9	1,142		1,080
Total non-current assets		1,882		3,579
Current assets
Non-controlled investments	8	-		1,600
Inventories		52		62
Trade and other receivables		328		454
Cash and cash equivalents		3,898		1,828
Total current assets		4,278		3,944
Total assets		6,160		7,523
EQUITY AND LIABILITIES
Equity
Issued capital	10	4,524		4,524
Share premium		18,414		18,414
Share based payments reserve		432		370
Other reserve		2,553		2,553
Translation reserve		(122)		12
Retained earnings		(19,777)		(18,673)
ESOT shares		(102)		(102)
Equity attributable to owners of the parent		5,922		7,098
Non-controlling interests		(407)		(311)
Total equity		5,515		6,787
Liabilities
Non-current liabilities
Controlled investments - loans		-		132
Total non-current liabilities		-		132
Current liabilities
Trade and other payables		645		604
Total current liabilities		645		604
Total liabilities		645		736
Total equity and liabilities		6,160		7,523

ANGLE PLC

 

CONSOLIDATED STATEMENT OF CASH FLOWS

FOR THE YEAR ENDED 30 APRIL 2014

 

	2014		2013
	£'000		£'000
Operating activities
Profit/(loss) before tax from continuing operations	(1,238)		(1,031)
Adjustments for:
Depreciation of property, plant and equipment	57		19
(Profit)/loss on disposal of property, plant and equipment	13		-
Amortisation and impairment of intangible assets	99		308
Exchange differences	9		13
Net finance (income)/costs	(112)		(41)
Change in fair value	(1,334)		(514)
Share based payments	62		71
Operating cash flows before movements in working capital:	(2,444)		(1,175)
(Increase)/decrease in inventories	22		(62)
(Increase)/decrease in trade and other receivables	131		(88)
Increase/(decrease) in trade and other payables	56		(67)
Net cash from/(used in) operating activities	(2,235)		(1,392)
Investing activities
Purchase of property, plant and equipment	(83)		(140)
Purchase of intangible assets	(270)		(941)
Purchase of convertible loans	-		(257)
Provision of short term loans	(511)		(63)
Proceeds on disposal of investment	5,160		-
Proceeds from settlement of Other receivables	-		154
Interest received	11		19
Net cash from/(used in) investing activities	4,307		(1,228)
Financing activities
Net proceeds from issue of share capital	-		3,326
Net cash from/(used in) financing activities	-		3,326
Net increase/(decrease) in cash and cash equivalents	2,072		706
Cash and cash equivalents at start of year	1,828		1,121
Effect of exchange rate fluctuations	(2)		1
Cash and cash equivalents at end of year	3,898		1,828