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:

  1. the frequent lack of tissue availability (too ill for surgery, tumour inaccessible, insufficient tissue)
  2. tumour heterogeneity as only samples one site, and
  3. the dynamic nature of the cancer response to treatment meaning the original biopsy information is out-of-date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

  1. CTCs (circulating tumour cells) are live cancer cells circulating in the blood
  2. ctDNA is cell-free circulating tumour fragments of DNA from dead cells, which may be found in the plasma component of the blood
  3. Tissue obtained from simple peripheral blood test
  4. 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
  5. 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

  1. www.cancer.gov/about-cancer/understanding/statistics- USA (40%)
  2. www.cancerresearchuk.org/about-cancer/what-is-cancer- UK (50%)
  3. www.ncbi.nlm.nih.gov/pmc/articles/PMC3597235/
  4. 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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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.