ANGLE : Annual Report December 2021

Transforming cancer care with

biopsy simple

Annual Report and

Financial Statements

31 December 2021

Introduction / We are ANGLE plc

WHO WE ARE

ANGLE plc

is a world-leading liquid biopsy company that has developed the revolutionary Parsortix® system for harvesting intact cancer cells (known as CTCs) from a patient's blood sample for subsequent analysis.

By enabling repeat liquid biopsies to assess cancer status, ANGLE's Parsortix® system has the potential to deliver profound improvements in clinical

and health economic outcomes in the diagnosis and treatment of cancer.

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, acceptance into national guidelines and the acceptance of the Group's products by customers.

Our purpose

To revolutionise cancer diagnosis and treatment

Mission

To enable personalised cancer care by providing intact cancer cells as the best sample for a complete picture of the patient's cancer from a simple blood test

Vision

To make precision medicine a reality

ANGLE plc Annual Report and Financial Statements 2021

Strategic Report

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 genetic changes make one cell or a few cells begin to grow and multiply rapidly. This may cause a growth called a tumour.

How many people are affected?

In the US, cancer is responsible for 21% of all deaths and 9.3m Person-Years of Life Lost in 20181.

~40-50%

Of the population will be diagnosed with cancer in their lifetime2,3

50% increase

The number of annual cancer cases is increasing, and in the US has risen by 50% in the last two decades2,5

1.9m new cases

In the US in 2021, an estimated 1.9m new cases of cancer were diagnosed and 0.6m people died from the disease2 There are a further 16.3m people living with cancer2

1. https://seer.cancer.gov/csr/1975_2018/browse_csr.php
2. https://seer.cancer.gov/statfacts/html/all.html - USA (40%)
3. www.cancerresearchuk.org/about-cancer/what-is-cancer- UK (50%)
4. www.ncbi.nlm.nih.gov/pmc/articles/PMC3597235/
5. https://pubmed.ncbi.nlm.nih.gov/11577478/

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 tissue or spread regionally, to nearby lymph nodes, tissues or organs. It can also spread to distant parts of the body from tumour cells released into 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.

Why is metastasis so serious?

90%

Of cancer deaths are caused by metastasis4

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 into the surrounding tissues or other sites in the body (metastasis). Staging is important in helping determine treatment. If the cancer is "early" stage and just in one site then surgery or radiotherapy may be sufficient. If the cancer is "late" stage and has metastasised then treatment is needed that also circulates throughout the whole body such 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 significant variation in stage at diagnosis and 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 are mostly slow growing cancers which may remain early stage (e.g. prostate) and therefore have higher survival rates. Other cancers may have no obvious symptoms or are aggressive and often detected at a late stage once they have already spread (e.g. lung, ovarian, pancreatic) and therefore have lower survival rates.

What are the challenges to treatment?

During cancer treatment,	1	How do you know	2	How do you track	3	How do you
particularly of secondary	which drug will work	whether drugs are	monitor patients
(metastatic) cancer, there		most effectively?		working and continue		in remission to
are many challenges which				to be effective?		assess any risk
can arise leaving both						of the disease
physicians and therefore						returning?
patients with unanswered
questions such as:

Tissue biopsy shortcomings

The standard diagnostic test for cancer 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 an invasive procedure and can cause adverse events

Patients experience a longer recovery time which may delay treatment

Poor tissue availability due to inaccessibility of tumour (pancreatic, lung, brain, liver and bone cancers)

Difficult to repeat so unable to track the changes in the cancer over time and development of drug resistance

Only samples one site and may not reflect tumour heterogeneity

Strategic Report

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 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 rapidly out-of-date

Obtaining cancer tissue for analysis

Obtaining cancer tissue for analysis

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 cells or cell fragments are obtained from a simple blood test. Non-invasive, repeatable, real time, cost effective

CTCs

Living intact cancer cells shed from a tumour into the bloodstream which can cause metastasis

Circulating tumour DNA (ctDNA) DNA from fragments of dead cells shed into the bloodstream can contain cancer-relatedmutations

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
Longitudinal monitoring5		Difficult	Very difficult		Easy	Easy
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. Sample obtained from simple peripheral blood draw
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

ANGLE plc Annual Report and Financial Statements 2021

Strategic Report

WHICH SAMPLE?

CTCs provide the complete picture

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.

CTCs Complete DNA, RNA and proteins

CTCs are living cells that cause metastasis and are often also resistant to drug therapy. Identifying and targeting these cells will improve patient outcomes.

ctDNA DNA fragments only

ctDNA is derived from dead cells and provides little insight into how the cancer might develop in the future e.g. emerging drug resistance.

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

The cancer genome atlas has revolutionised cancer diagnosis and treatment. Aided by this knowledge and advances in genomic sequencing technology, oncologists are increasingly selecting therapies based on the specific genomic abnormalities identified in a patient's tumour.

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.

That may be, in part, because key information about the biology of the tumour is missing from looking at the genome alone. While the presence of mutations can be determined from sequencing a tumour's genome, the effect of mutations on protein function cannot be fully understood without interrogating the proteome, including the many modifications that occur to proteins in

a tumour. Changes that normally occur in proteins after they are made (post-translational modifications) can affect how proteins function or how long they are present in a cell.

With sustained investments in proteogenomics research, doctors will, in the future, be able to assemble a more complete picture of a patient's tumor, one that informs diagnosis and treatment and improves outcomes.

NIH Annual Plan & Budget Proposal for Fiscal Year 2022

What is the genome, transcriptome and proteome?

Genome

Between

20,000-25,000 genes

Genes are units of DNA that code for proteins. Abnormalities in certain genes can result in cancer development and growth.

Transcriptome

Approximately

100,000 transcripts

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 targeted therapies may not always work as expected.

Molecular Diagnostics for Cancer Treatment: Expanding beyond

the Genome published by the National Cancer Institute, August 2020

ANGLE plc Annual Report and Financial Statements 2021