Advanced Oncotherapy Regulatory News (AVO)

11 January 2021

ADVANCED ONCOTHERAPY PLC

("Advanced Oncotherapy" or the "Company")

Technical update

Advanced Oncotherapy (AIM: AVO), the developer of next-generation proton therapy systems for cancer treatment, releases the following update on recent developments and accomplishments regarding its LIGHT system.

Highlights since previous technical update released in September 2020:

· Infrastructure in place to support assembly and testing activities --> ongoing conditioning of high-power radio-frequency (RF) accelerating units.

· Optimal RF phase and amplitude stability reached --> system now capable of supporting the delivery of a proton pulse every 5 milliseconds.

· Maximum intensity of the proton beam achieved during the initial conditioning phase --> now ready to support more efficient treatment plans and delivery.

· Integration of the full medical software suite --> previously a key roadblock for clinical users, now overcome.

· Further studies presented at the American Society for Radiation Oncology (ASTRO) --> demonstrating the superiority of the proton beam generated by LIGHT.

· Successful re-certification of ISO 13485 --> supporting the operational activities at the installation and integration site in Daresbury.

The Company remains on track to have a fully operational LIGHT system with a 230MeV beam, which is the beam energy needed to treat patients, during 2021 and the Board currently expects this to be in the second half of 2021. Actual treatment of patients, which is anticipated shortly after the LIGHT machine is fully operational, remains dependent on the Company's clinical partner, University Hospital Birmingham NHS Trust.

The following table summarises the key deliverables for 2021:

While the Company continually monitors the potential impact of the ongoing COVID-19 pandemic lockdown enforced by the UK Government, it remains confident on the completion of its key deliverables set out for 2021 with work currently continuing as planned and the team deemed as "essential workers" and allowed to continue working on site at Daresbury.

Nicolas Serandour, CEO of Advanced Oncotherapy, commented:

"We have continued to make good progress with the set-up of our assembly site in Daresbury, a stepping stone in our plan for the commercial roll-out of LIGHT, and remain committed to our operational plan and key deliverables set out for 2021 despite COVID-19. We are on track to have a fully operational LIGHT system in 2021. As part of the integration and conditioning of our first commercial LIGHT system, we have achieved excellent results which support the differentiated and versatile profile of our LIGHT offering."

Infrastructure in place to support assembly and testing activities --> ongoing conditioning of high-power radio-frequency (RF) accelerating units

The purpose of the site located at Daresbury, Cheshire, UK is to assemble and test the various units of the LIGHT system so that the proton beam meets the relevant medical, health and safety requirements and standards. All the relevant infrastructure is now in place; this required the seamless integration of various disciplines and specialties, most notably Environmental Health and Safety, radiation safety, electromagnetic compatibility and electromagnetic interference, beam dynamics, electrical engineering, electronics, mechanical engineering, vacuum technology, magnet technology, RF technology, power converters, IT, radiation protection, cooling and ventilation, survey and alignment, electrical networks, and civil and structural engineering.

Critical parts completed since September 2020 regarding the infrastructure needed for the assembly and testing of future LIGHT systems comprise, amongst others:

· Successful set-up of three test stands used for high-power RF conditioning: As part of the certification process, data related to the testing, commissioning and maintainability of the radio-frequency equipment of LIGHT must be recorded. In order to test the accelerating structures that have various sizes and specifications, three test stands have been successfully installed with the ability to perform parallel tests and characterise the LIGHT system. The conditioning of the accelerating units is ongoing and has already allowed the Company to optimise key parameters which will be integrated into the medical software and used to prepare the relevant treatment plan for patients.

· Implementation of an ultra-high vacuum environment: Protons must be accelerated throughout the LIGHT accelerating units at ultra-high vacuum. The vacuum pumps have now been installed and integrated with cables, cooling pipes and gauges and are supported by position adjustment systems, which are required to satisfy the stringent alignment tolerances that are necessary for the optimal performance of the LIGHT accelerator.

· Implementation of the cooling system: The chillers, pumps, gages and flow control devices are installed and integrated to the control system to support optimal operation of the LIGHT accelerator.

· Building of fixed and temporary shielding walls: These shielding walls have been built based on the radiation protection standards and can be removed, in such a way that parallel operations can be undertaken, both at the accelerator and in the treatment room areas.

· Installation of instruments needed for the testing phase: These instruments, which are key for a smooth integration process, are now part of the fully functioning repositionable test benches and include quadrupole magnets which are used to measure the beam emittance, spectrometers which measure the beam energy and phase probes which measure the arrival time of the beam bunches.

Optimal RF phase and amplitude stability reached --> system now capable of supporting the delivery of a proton pulse every 5 milliseconds

The LIGHT accelerator has the capability of varying the proton beam energy continuously from 70 MeV to 230 MeV in only five milliseconds which the Board believes is a significant breakthrough in the Company delivering a superior medical treatment compared to other systems on the market which have a significantly slower energy modulation. This is done by acting on both the power provided to the accelerating units of the LIGHT accelerator and the phase of the radio-frequency signal that is used to accelerate protons. Consequently, achieving the right phase stability and radio-frequency amplitude of the proton beam are critical parameters in the commissioning of the LIGHT system. After a series of tests performed in cooperation with Advanced Oncotherapy's previously announced partner, ScandiNova, these have been achieved, which provides the Company with continued confidence for the future successful commercial deployment of LIGHT.

Maximum intensity of the proton beam achieved during the initial conditioning phase --> now ready to support more efficient treatment plans and delivery

In the current clinical routine, the goal is to deliver a homogeneous, curative dose to the target whilst minimising the dose delivered to the surrounding tissues. This is why an important algorithm in the treatment plan in proton therapy is the ability to change the number of protons per pulse, a parameter also called intensity. During the initial conditioning process, the full intensity of 300 µA as per the design has been reached. This is a key step forward in the integration process and provides the basis for an optimised treatment plan as the higher the intensity, the more versatile the LIGHT system can be, and the wider the spectrum of efficient treatment plans and delivery which can become available for clinical users.

Integration of the full medical software suite --> previously a key roadblock for clinical users, now overcome

One of the significant challenges faced by users of proton therapy systems to date has been the lack of an integrated control software suite. The Company has been working in partnership with RaySearch Laboratories AB to develop a seamless software suite customised for the LIGHT system which will support personalised precision proton therapy.

The software suite provides users with a single interface for patient preparation, treatment and follow-up processes, which limits potential risks and facilitates a better user experience for clinicians and healthcare workers. The Company has been using the new integrated software suite at its R&D facility in Geneva, Switzerland and expects to install the software in its clinical system in Daresbury during H1 2021.

The Notes to Editors section below provides further details on the various medical software packages.

After its successful factory acceptance testing, the patient positioning system has been delivered to the assembly site in Daresbury and is ready for installation. The patient positioning system includes the diagnostic quality CT scanner used to scan patients in a seated position; the real-time X-ray verification system which enables continuous imaging of moving tumours; and the robotic chair which can move and rotate the patient with high accuracy and precision.

Further studies presented at ASTRO --> demonstrating the superiority of the proton beam generated by LIGHT

The Company recently presented two posters at the ASTRO conference further demonstrating the potential treatment advantages of the proton beam generated by the LIGHT system:

· Smaller proton spot sizes have been shown to improve conformity to treatment targets. Due to its small constant spot size, the LIGHT beam demonstrated in a modelling study[1] to be more conformal to clinical targets than the cyclotron beam while at the same time sparing more healthy tissues. Significantly, the study showed that the LIGHT scanning beam spot size is constant across the 150-230 MeV energy range, which is advantageous for all clinical cases evaluated and in particular for the brain and prostate tumour cases.

· The delivery of an ultra-high level of radiation in a very short time, a technique known as FLASH, could change cancer treatment by treating patients in possibly one single visit to the hospital. Calculations have shown[2], that the LIGHT system will be able to deliver variable high doses of protons within 0.5 second pulses[3] and that the spot size can be varied from one to six millimetres, which are both essential in delivering a highly differentiated, faster and optimised FLASH treatment with improved conformality.

Successful re-certification of ISO 13485 --> supporting the operational activities at the installation and integration site in Daresbury

In January 2019, the Company obtained ISO 13485:2016 certification, the internationally recognised quality standard to ensure the consistent design, development, production, installation and sale of medical devices that are safe for their intended purposes. 

A subsequent external audit was performed in December 2020 by Lloyd's Register which was focused on installation, integration and product safety management operations. The review confirmed that the design and development and the manufacturing control activities were in compliance with the highest standards for safety and product performance. This result provides a strong platform for the continued integration of the LIGHT system. It further highlights the importance placed on the quality of the LIGHT system and the need to have robust processes in accordance with the stringent requirements associated with medical devices.

- ENDS -

Notes to Editors

The software suite includes the following components:

· Machine parameter verification: Software that compares intended settings with actual machine settings to ensure proper proton treatment delivery.

· Oncology information system: Software integrated with the treatment planning system that offers managed workflows and enables patient treatment to be modified daily.

· Treatment planning system: Software used by clinicians to prepare a proton therapy treatment for each patient.

· Treatment session manager: Software that prepares the daily proton treatment for patient delivery.

· Spot map visualisation: Software that shows a graphic display to the staff of the scanning proton spots during operation.

About Advanced Oncotherapy Plc www.avoplc.com

Advanced Oncotherapy, a UK headquartered company with offices in London, Geneva, The Netherlands and in the USA, is a provider of particle therapy with protons that harnesses the best in modern technology. Advanced Oncotherapy's team "ADAM," based in Geneva, focuses on the development of a proprietary proton accelerator called, Linac Image Guided Hadron Technology (LIGHT). LIGHT's compact configuration delivers proton beams in a way that facilitates greater precision and electronic control.

Advanced Oncotherapy will offer healthcare providers affordable systems that will enable them to treat cancer with innovative technology as well as expected lower treatment-related side effects.

Advanced Oncotherapy continually monitors the market for any emerging improvements in delivering proton therapy and actively seeks working relationships with providers of these innovative technologies. Through these relationships, the Company will remain the prime provider of an innovative and cost-effective system for particle therapy with protons.