ADVANCED ONCOTHERAPY

COST-EFFECTIVE PROTON THERAPY

* The LIGHT Proton Therapy System is still subject to conformity assessment by Advanced Oncotherapy's Notifi ed Body as well as clearance by the USA-FDA

Introduction

Advanced Oncotherapy is set to deliver disruptive proton therapy technology in the treatment of cancer. Its innovative LIGHT Proton Therapy Solution* has been designed to offer clinically superior treatments for cancer patients, as well as operational advantages for hospitals and clinics.

Cancer

Cancer is the second leading cause of death globally, according to the World Health Organisation.

But treatment of cancer is developing rapidly, with far greater emphasis now on precision cancer medicine and treatment, with the aim of delivering treatment as safely and efficiently as possible.

Medical professionals are beginning to view cancer as a chronic, manageable disease; the focus for oncology providers is to deliver new, targeted treatments with reduced side effects and limited impact on the quality of life for patients.

Radiotherapy

Each year, millions of people worldwide undergo treatment for cancer using beams of high-energy X-rays – external beam radiotherapy. Radiotherapy is one of the three main modalities for treating cancer, alongside surgery and chemotherapy.

Radiation is effective in cancer treatment because it can kill cancerous cells by breaking their DNA strands, but it can also affect healthy tissue. For this reason, the radiation must be directed very carefully. Significant effort has, therefore, been directed to the development of new radiation therapies, which improve targeting and limit unwanted side effects. This is best exemplified through the successful development of proton therapy.

Proton Therapy

X-ray based radiotherapy ionises cells along the entire trajectory of the X-ray beams, including healthy cells, leading to potentially serious side effects. This problem is exacerbated when cancer is located near a critical organ.

Proton therapy is an alternative radiotherapy modality that spares 60% more healthy tissue. A proton beam has a radiation dose profile with most of the dose delivered at its stopping point (the Bragg peak), sparing the patient’s healthy cells. The most significant difference between proton and X-ray or gamma-ray treatments is, therefore, that the proton field has no exit dose.

Proton therapy, a form of particle therapy, would be the preferred approach in most patients with localised tumours. Proton therapy can treat tumours in a more precise manner and can provide radiation dose deposition that better matches the actual three-dimensional shape of tumours, such that surrounding

2

tissues typically receive two to three times less radiation. Side effects can then be reduced to a minimum.

As growing tissues are more sensitive to radiation, proton therapy is the therapy of choice in childhood cancers.

However, despite clinical benefits, the high cost of proton therapy has hindered its uptake. Many hospitals do not have the budget required to invest in highcost treatment options. There are approximately 14,000 radiotherapy systems in use, equating to roughly 1.9 systems per million people. By contrast, there are approximately 90 proton therapy systems globally or 0.2 systems per million people.

Dose (%)

0 Bragg Peak

X-rays (Photons)

Focussing the proton radiation e ect to the tumour's location

Protons

10

Tumour

20 30 40

Depth (cm)

1 Radiation can damage DNA through two mechanisms: direct hits and through free radical formation | 2 Signifi cant radiation dose in healthy tissue in the upper example (Intensity Modulated Radio-Therapy), compared to proton treatment in the lower example. In both treatments of endometrial cancer, the patient receiving IMRT will experience notable discomfort during treatment, due to the dose to the bowel

X-rays

3 Far less irradiation with protons to healthy tissue in front of tumour (red ellipse) and almost none behind it, where the critical spinal cord is located | 4 LIGHT accelerator, beam transfer line and treatment room Advanced Oncotherapy’s disruptive technology is expected to substantially alter this picture and make proton therapy far more accessible.

Advanced Oncotherapy

Current proton therapy systems, where protons are accelerated in a circular fashion, have cost and clinical limitations. Advanced Oncotherapy is developing a solution based on a linear accelerator, which provides more flexibility at a significantly lower cost. The prototype system was assembled on the Research and Development facility that is located on the CERN campus.

Separately, the first medical system is being assembled at the Science and Technology Facilities Council at STFC's Daresbury Laboratory, where Advanced Oncotherapy established its assembly and testing centre. Through these partnerships, Advanced Oncotherapy can benefit from the knowledge of experienced physicists and engineers in the development of its technology.

LIGHT

Advanced Oncotherapy’s LIGHT (LINAC Image Guided Hadron Technology) system is designed to provide next-generation solutions to patients and hospitals alike. It stands apart from existing proton therapy systems in that, at its heart, is a linear proton accelerator. This fact has profound implications for the way it operates.

The LIGHT system is designed to o‡er:

Superior eciency –LIGHT has a transmission of more than 95%. In contrast, the transmission of a circular accelerator is less than 50%. This feature directly allows to decrease the insulation, and therefore the footprint, of sites equipped with LIGHT;

Greater adjustability of energy – Electronic energy modulation at high repetition rate is important and an essential feature of the LIGHT system, with one pulse of protons delivered every 10ms. In contrast, legacy systems can change the energy only once or twice per second. This is particularly relevant when treating moving organs;

Much smaller beam size, at 0.3mm per pulse vs 3mm for competing systems – This brings significant advantages for patients in terms of conformality. Put it simply, the deposition of the radiation is significantly more precise, which is important when treating moving targets and treating the “edge” of the tumours.

These technical features are expected to result in improved clinical outcomes, reduced treatment-related side-e‡ects and lower costs associated with the extensive shielding requirements. The shielding and building costs contribute to the high cost of buildings in proton projects (two-thirds of the upfront investment).

A major expected clinical advantage for LIGHT is the superior ability to deliver FLASH therapy with protons. Still in its experimental phase, FLASH could prove to be the delivery method to decrease treatment costs the most.

What it means for patients

– Non-invasive treatment; – More accurate tumour targeting; – Reduced side e‡ects; – Safer treatment

What it means for operators

– A complete, compact, turn-key solution with minimal footprint; – Enhanced e™ciency; – Operational excellence

The London Clinic – On 11th February 2020, Advanced Oncotherapy and The London Clinic announced a partnership for the site located in Harley Street.

Queen Elizabeth Hospital Birmingham – On 20th February 2020, Advanced Oncotherapy and University Hospitals Birmingham (left) announced a research collaboration, as well as a lease for installing LIGHT in Birmingham.

The Mediterranean Hospital of Limassol – On 17th February 2020, Advanced Oncotherapy and the Mediterranean Hospital (Cyprus) announced a €50m purchase order.

Operators are very sensitive to the fl exibility o ered by Advanced Oncotherapy and its LIGHT system. Between December 2019 and February 2020, four partnerships were announced:

London – Harley Street

Advanced Oncotherapy’s fi rst site for the innovative LIGHT system is the worldrenowned Harley Street Medical Area. Harley Street provides an ideal location:

− It is a centre of medical excellence; − It has medical practitioners with expertise across the full range of disciplines; − Provides access to advanced treatments and services; − Operates like one large virtual hospital, with referrals across clinics and hospitals; − Situated in central London, with its amenities and attractions.

West Midlands – University Hospitals Birmingham NHS Foundation Trust

University Hospitals Birmingham (UHB) and Advanced Oncotherapy have reached an agreement to install a LIGHT system on the UHB premises. As part of the collaboration, Advanced Oncotherapy and UHB will also work together on various research and development activities associated with the use of LIGHT to increase the awareness of proton therapy for the treatment of cancer.

UHB is one of the largest teaching hospital trusts in England and one of the largest regional centres for nonsurgical cancer treatment serving a regional, national and international population. The hospital group sees and treats more than 2.2 million patients every year across its sites.

Cyprus – The Mediterranean Hospital of Limassol

The Mediterranean Hospital of Limassol has agreed to purchase a LIGHT system for €50 million. The installation of the three-treatment room system is due to commence before the end of 2023, to coincide with the completion of construction works being carried out at the hospital.

The Mediterranean Hospital of Limassol is the fi rst health centre integrated with the newly created National Health System (NHS) of Cyprus, the ambition of which is to modernise and upgrade the health sector into a more streamlined and cost-e ective system, bringing Cyprus on a par with its European peers in terms of e¢ cient and a ordable public healthcare.

For further information on Advanced Oncotherapy and its innovative LIGHT system, please get in touch.

Website: www.avoplc.com Telephone: +44 (0)20 3617 8728 Email: info@avoplc.com Post: Advanced Oncotherapy plc, Third Floor, 4 Tenterden Street, London W1S 1TE