Transforming cancer care with a liquid biopsy based on a simple blood test
Annual Report and Financial Statements
31 December 2020
Introduction / We are ANGLE plc
Who we are
ANGLE plc
is a commercially driven medical diagnostics company that has developed pioneering products and services in cancer.
ANGLE's Parsortix® system has the potential to deliver profound improvements in clinical and health economic outcomes in the diagnosis and treatment of cancer.
Our purpose
To revolutionise cancer diagnosis and treatment
Mission
To enable personalised
cancer care by providing the
complete picture of the patient's cancer from a simple blood test
Vision
To make precision medicine a reality
Visit our website for more information at:
www.angleplc.com
@parsortix | ANGLEplc | angleplcParsortix |
The Annual Report and Financial Statements 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 impact of the COVID-19 pandemic, the general economic climate and market conditions, as well as specific factors including the success of the Group's research and development activities, commercialisation strategies, the uncertainties related to clinical study outcomes and regulatory clearance, obtaining reimbursement and payor coverage, getting into national guidelines and the acceptance of the Group's products by customers.
At a glance
Liquid biopsy improving patient outcomes and reducing healthcare costs
The Parsortix system captures circulating tumour cells (CTCs) which cause cancer metastasis and harvests them for analysis.
Tissue biopsy is the current standard of care but has many shortcomings (see over) and is challenged by:
- the frequent lack of tissue availability (too ill for surgery, tumour inaccessible, insufficient tissue)
- tumour heterogeneity as only samples one site, and
- the dynamic nature of the cancer response to treatment meaning the original biopsy information is out-of-date
Obtaining cancer tissue for analysis
Solid biopsy
Liquid biopsy
Solid tissue biopsy
Tumour tissue is cut out from the cancer site through an invasive procedure
Tissue samples
Tissue is specially prepared so sections can be examined - usually formalin-fixedparaffin-embedded (FFPE) samples
Liquid biopsy
Cancer tissue is obtained from a simple blood test Non-invasive, repeatable, real time, cost effective
CTCs | Circulating tumour |
Living cancer cells shed | DNA (ctDNA) |
from a tumour into the | DNA from fragments |
bloodstream in the process | of dead cells shed into the |
of metastasis | bloodstream can contain |
cancer-related mutations |
Benefits of Parsortix CTC solution
Solid tissue biopsy | Liquid biopsy | ||||||
Source | Primary tumour | Metastatic site | CTCs1 | ctDNA2 | |||
Sample type | Intact cells | Intact cells | Intact cells | Fragmented DNA | |||
Procedure | Invasive | Invasive | Non-invasive3 | Non-invasive3 | |||
Sample accessibility | Not always accessible | Less accessible | Accessible using Parsortix4 | Accessible | |||
Tumour heterogeneity | Site of biopsy sampling | Site of biopsy sampling | Multi-site sampling | Multi-site sampling | |||
Patient recovery time | Varies | Longer | None | None | |||
Test costs | Varies | Higher | Lower | Lower | |||
Test turnaround time | Varies | Longer | Shorter | Shorter | |||
Difficult | Very difficult | Easy | Easy | ||||
Longitudinal monitoring5 | |||||||
Molecular | DNA | Yes | Yes | Yes | Yes | ||
analysis | RNA | Yes | Yes | Yes | Difficult | ||
Protein | Yes | Yes | Yes | No | |||
Live cells | Cell culture | Yes | Yes | Yes | No | ||
Xenograft | Yes | Yes | Yes | No | |||
Standard of care | Proven | Proven | Not yet proven | Not yet proven |
- CTCs (circulating tumour cells) are live cancer cells circulating in the blood
- ctDNA is cell-free circulating tumour fragments of DNA from dead cells, which may be found in the plasma component of the blood
- Tissue obtained from simple peripheral blood test
- Access to CTCs from blood is technically challenging given the low number of CTCs present and historically has been very difficult. ANGLE's Parsortix system has been specially designed to address this issue
- Solid tissue biopsy information is a one-time snapshot and rapidly becomes outdated and does not reflect response to treatment and current mutational status. Liquid biopsy information is dynamic as tests can be repeated to provide real time information to monitor changes over time
The challenge
Cancer: a significant and growing problem
What is cancer?
Cancer is a disease in which abnormal cells divide without control and can invade nearby tissues.
Cancer starts when gene changes make one cell or a few cells begin to grow and rapidly multiply. This may cause a growth called a tumour.
How cancer spreads
The main reason that cancer is so serious is its ability to spread in the body. Cancer cells can spread locally by moving into nearby normal tissue or spread regionally, to nearby lymph nodes, tissues, or organs. It can also spread to distant parts of the body via the blood circulation. When this happens, it is called metastatic cancer.
The process by which cancer cells spread to other parts of the body is called metastasis.
How many people are affected?
40-50%
Of the population will be diagnosed with cancer in their lifetime1,2
Why is metastasis so serious?
90%
Metastasis causes ~90% of cancer deaths3
The "stage" of cancer at diagnosis is extremely important to survival. Cancer staging is a way of describing the size of a cancer and how far it has spread and is important in helping determine treatment. If the cancer is "early" stage and just in one place then a local treatment, such as surgery or radiotherapy, may be sufficient. If the cancer is "later" stage and has spread through the body to other organs (metastasis) then treatment is needed that also circulates throughout the whole body such
32%
The number of new cancer diagnoses in the US per year is increasing, and has risen by more than 32% since 19993,4
1.8m
In 2020, an estimated 1,806,590 new cases of cancer will be diagnosed in the US and 606,520 people will die from the disease1
as chemotherapy, hormone therapy or targeted cancer drugs. Once cancer spreads it can be hard to control and whilst some types of metastatic cancer can be driven into remission with treatment, most cannot.
There is also a huge variation in survival between cancer types. Some cancers have screening programmes or more obvious symptoms and can be detected earlier (e.g. breast, colorectal, cervical, skin) and others may have mostly slow growing cancers which may remain early stage (e.g. prostate) and therefore have higher survival rates. Other cancers may
- www.cancer.gov/about-cancer/understanding/statistics- USA (40%)
- www.cancerresearchuk.org/about-cancer/what-is-cancer- UK (50%)
- www.ncbi.nlm.nih.gov/pmc/articles/PMC3597235/
- https://gis.cdc.gov/Cancer/USCS/DataViz.html
have no obvious symptoms and/or are aggressive and may be detected late once they have already spread (e.g. brain, ovarian, pancreatic) and therefore have lower survival rates.
What are the challenges to treatment?
During cancer treatment, particularly of secondary (metastatic) cancer disease, there are many challenges which can arise leaving both physicians and therefore patients with unanswered questions such as:
1 How do we know which drug will work most effectively for a patient?
2 | How can we track |
whether drugs are |
in fact working and having a positive impact?
3 | How do we |
monitor patients |
in remission
to assess any risk of the disease returning?
Tissue biopsy shortcomings
The standard test for cancer cells is to undertake a solid tissue biopsy. This approach has many shortcomings compared to a liquid biopsy:
Expensive to perform and requires a lot of hospital resources
Requires invasive | Frequent lack of | Difficult to repeat |
procedure and | tissue availability | so missing the |
can cause adverse | from difficulty | dynamic nature |
events | in accessing some | of cancer response |
Patients experience | tumours (pancreatic, | to treatment |
lung, brain, liver | Only samples one | |
a longer recovery | ||
and bone cancers) | ||
time which may | site and may not | |
delay treatment | fully reflect tumour | |
heterogeneity | ||
Which sample type?
CTCs provide the complete picture
CTCs Complete DNA, RNA and proteins
CTCs are living cells, often resistant to drug therapy and the cause of metastasis. Targeting these cells will improve patient outcomes.
ctDNA DNA fragments only
ctDNA is derived from dead cells and may not be indicative of how cancer is developing.
Multiple DNA abnormalities | Multiple DNA abnormalities | |
RNA expression | ||
Circulating | Circulating | |
Tumour | Tumour | |
Protein expression | Cell | DNA |
(CTC) | (ctDNA) | |
Blood sample | ||
In vitro and in vivo culture |
Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) can be measured concurrently from a single blood draw to provide complementary information for clinical decision making.
This includes early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment and potentially an early warning for relapse.
Genome
Between
RNA
20k-25k
Genes
Genes (units of DNA) code for proteins. Abnormalities in certain genes can result in cancer development and growth.
Transcriptome
Approximately
100,000
Transcripts
DNA is copied to RNA in the nucleus and exported to the cytoplasm
DNA
Protein
Cell Nucleus
Cell Cytoplasm
RNA is translated into protein at ribosomes
To make proteins, genes must first be transcribed into messenger RNA (mRNA). Different sections of a gene can either be included or excluded from the mRNA transcript, producing multiple different transcripts from a single gene that result in related but different proteins.
Proteome
Estimated more than
1,000,000
Proteins
After mRNA transcripts are translated into proteins, proteins undergo modifications that affect their activity and how long they are present in a cell. Protein abundance, diversity and function could hold the key to understanding why genomic-based therapies may not work as expected.
The cancer genome atlas has transformed the development of targeted treatment, however many patients who are matched to therapy based on their DNA fail to respond to targeted treatment or do not have a sustained response.
Key information about the biology of the tumour is missing from looking at the genome alone. The effect of mutations on the cell can only be understood fully by looking at protein expression, the proteome.
Understanding proteins is critically important when developing drugs, selecting treatments, and predicting treatment response. Integration of proteomic information is the next step in precision oncology.
National Cancer Institute, August 2020
Source: Molecular Diagnostics for Cancer Treatment: Expanding beyond the Genome published by the National Cancer Institute, August 2020
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Disclaimer
ANGLE plc published this content on 02 June 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 04 June 2021 14:20:07 UTC.