These interviews highlight the depth and range of experience within Advanced Oncotherapy’s Board and Executive management teams. They also proffer insight into the goals, challenges and opportunities ahead in the commercialisation of LIGHT.

Following the new appointment at Advanced Oncotherapy Plc (LON:AVO) as Senior Independent Non-Executive Director, Mr Hans von Celsing talks about his past experience, the present and his thoughts on the future of the company.

Q: Hans, could you tell us about your experience in radiotherapy and how that relates to your role as an adviser to Advanced Oncotherapy?

A: I have spent most of my career in radiotherapy and have been involved in this market since the mid-80s. I joined Elekta in the early stages of its development and helped grow the business to a global radiotherapy company with a market capitalisation of 30 billion Swedish kroner. I was also involved in the development and promotion of the Gamma Knife, with the aim of creating radiotherapy systems for neurological indications with more accurate tumour targeting and in advanced imaging/3-D positioning systems.

Q: And in addition to Elekta?

A: I was also involved with Mevion at an early stage and helped it in its international development effort. Mevion technology was an important step in making proton therapy systems clinically affordable on a broader scale.

Q: So you have seen the full spectrum of radiotherapy applications and systems: from small start-ups to big corporations and from state-of-the-art radiotherapy systems with advanced treatment room facilities to one-room proton therapy systems?

A: That’s correct.

Q: So you must have seen a lot of changes and evolution in the field of radiotherapy?

A: Absolutely! When I started out in the 80’s, radiotherapy was not a favourable treatment choice. Patients treated by radiotherapy were generally very sick and were some of the worst cancer cases. Radiotherapy had many side effects and outcomes were often not that favourable.

Q: Why was this the case?

A: One of the biggest issues was accuracy of beam delivery and tumour targeting. The imaging systems and computing power used to deliver radiation beams to the tumour site were considerably less accurate by today’s standards. Excessive doses could be delivered to healthy surrounding tissue, with consequential and unwanted side effects.

I am pleased to say there have been many advances in beam targeting and improvements in this area will lead to more accurate dose delivery and improved patient outcomes. The LIGHT system has the potential to provide a further leap forward in the accuracy of tumour targeting.

Q: So Elekta, then Mevion, and now you’re helping Advanced Oncotherapy. Why AVO?

A: AVO and its LIGHT system is amazing technology and offer a great opportunity for the advancement of proton and particle therapy technology. AVO is developing a Linac–based (linear accelerator) proton therapy system; all other competing proton therapy systems use cyclotrons, synchrocyclotron or synchrotron accelerators. This group originated from physics laboratory experiments. A Linac system is designed specifically for medical use and lends itself extremely well to cancer therapy. I also see much of the excitement at AVO that I did when Elekta and Mevion were at similar stages of their development.

Q: So what are some of the key features of LIGHT?

A: One is the ability to electronically control the energy delivered to the tumour site. This energy can be changed rapidly both in terms of energy amount and energy positioning without the need for physical absorbers or other methods. The required dose can be delivered to the exact site many, many times per second.

LIGHT is also an integrated system. An all-in-one or integrated solution, which provides a system for beam production, treatment planning and accurate beam delivery reduces the risk of errors arising in interoperability between different systems. The treatment planning software and solution that is being developed is, I believe, state-of-the-art. It is simple and its one-touch, one-screen panel will enable radiotherapists and radiation oncologists to devise the best treatment solutions for their patients. The ability to serve multiple treatment rooms is another key feature; the LIGHT system can power up to five treatment rooms, thereby reducing the incremental cost for each room.

Q: Ok. So what’s the significance of this in relation to the potential take-up of LIGHT?

A: The economics of any treatment are critical in many healthcare decisions. It is also not just the incremental cost of each room which is relevant. By virtue of being linear, compact and modular, LIGHT lends itself to easier installation and, hence, lower building/installation costs.

Q: What do you think the future holds in store for Advanced Oncotherapy plc? What should they do next?

A: Essentially what they are already doing. Sticking to their plan of building their first machine, with first installation due at Harley Street, London, integrate imaging for adaptive therapy planning and to continue to generate interest globally for the LIGHT Proton Therapy system.

Michel Baelen, head of Regulatory Affairs at Advanced Oncotherapy plc (LON:AVO), talks about the attraction of joining AVO, his past roles and how this experience benefits the company, work done to date and Michel’s plans for regulatory and quality control going forward.

Q: Michel, what attracted you to join AVO?

A:The development of the proton beam therapy system LIGHT, with its innovative and clinically superior approach to the treatment of cancer.

Q: So how does the position fit to what you have done previously?

A: I have a background in electronic engineering and was responsible for IBA’s regulatory and quality assurance affairs for 19 years.

Q: Can you tell us what IBA is?

A: IBA is the current market leader in proton beam therapy. As well as working at IBA, I was previously head of the European Commissions’ industry association for medical devices and worked in a regulatory/quality capacity assurance at the IAEA (International Atomic Energy Agency).

Q: So how does your experience benefit AVO and its investors?

A: Having worked on both sides of the regulatory fence I know exactly what AVO must do to meet all regulatory and quality control requirements.

Q: In that regard, what have you been doing so far?

A:We’ve been in dialogue with the major regulatory bodies and have been working through what we, AVO, must do to ensure we meet their requirements in as efficient and timely manner as possible.

Q: Can we expect any newsflow to that effect?

A:Absolutely, although timing is difficult to predict; we have been very busy in this regard and hope to make announcements to this end.

Q: On the LIGHT system itself, can you tell us some of the key features that will differentiate it from its competitors?

A: From a safety perspective, the ability to monitor the exact nature of the proton beam and completely control its transmission i.e. if the beam needs to be shut off, we will be able to ensure the patient receives no dose at all. Another is to vary the energy of the beam and, accordingly, the dose the target tumour receives at very high frequencies, for more accurate tumour targeting.

Q: For any new technology with the potential to disrupt a market, there must be risks associated with the realisation of that technology?

A:The development of LIGHT will be a process and there are challenges ahead. For example, the accelerating modules will contain a vacuum at much lower pressure than is present in existing radiotherapy systems. In addition, the ability to vary the energy of the proton beam with every pulse requires highly sophisticated and robust software control and management.

Q: Are there any other key safety USPs?

A:Yes, the LIGHT system will not suffer from comparable proton losses and, as a result, will not irradiate and physically/chemically alter, otherwise known as activate, the shielding and surrounding materials that any radiotherapy system is housed in. For example, the decommissioning costs of non-Linac proton accelerators can be up to three times as high as the initial cost. So that can be a major headache for hospitals and clinics; LIGHT is the only proton therapy system using a linear particle accelerator.

Q: And given the potential hurdles inherent in LIGHT’s development, what is AVO doing to manage and overcome those risks?

A: Two key approaches adopted by Advanced Oncotherapy have been to hire industry experts, in all relevant fields, and to partner market leading companies, such as Thales. For example, Thales, which will mass produce LIGHT for AVO, has already demonstrated its ability to create a vacuum at the required level that I previously referred to. We have also hired an expert in safety-critical software from Airbus, a market leader in another industry where it is absolutely essential that software, and the systems that that software controls, perform precisely as required.

Q: Is there anything else you’d like to highlight?

A: Just that we, AVO, are doing everything we can to ensure we clear all regulatory and quality control hurdles in all major markets and with all relevant bodies, globally. Michel, thank you for your time.

Advanced Oncotherapy PLC (LON:AVO) subsidiary ADAM S.A. Executive Chairman professor Steve Myers discusses the LIGHT system, its likely impact, its design, the progress being made and its future.

Q: Professor Myers, you became Executive Chairman of ADAM S.A. (ADAM), the CERN spin-off and Advanced Oncotherapy’s (AVO’s) subsidiary, in late 2015, and joined

AVO’s Board earlier this year. Your primary responsibility is overseeing the development of AVO’s proprietary and novel proton beam therapy (PBT) technology, LIGHT?

A: Yes, that’s right. The single most important aspect of LIGHT is that it is based on a fundamentally different design to all other PBT systems. All existing technologies are based on cyclotrons or synchrotrons; LIGHT is the only linear proton accelerator designed for medical application in the treatment of cancer.

Q: Does that matter?

A: It matters a great deal. These differences, in terms of technology and costs, have major implications for LIGHT’s potential disruption of the global radiotherapy market. Its technology provides a paradigm shift in clinical effectiveness: the speed at which the energy and direction of the beam can be modulated, the production of secondary radiation, shielding requirements, beam size, size of magnets along the beam transfer line and, hence, the size of the patient gantry, these are all radically better with a linear accelerator.

Costs, in regards to upfront capital expenditure, ongoing maintenance and decommissioning, have also proven prohibitively high for hospitals and clinics when considering existing technologies. LIGHT will be available at a fraction of the cost of comparable competing systems.

Q: So why aren’t there more linear proton accelerators in hospitals?

A: From a design perspective, it’s because the engineering behind LIGHT is sufficiently challenging that it has taken the expertise within ADAM, and the experience of continually designing, creating and operating next-generation particle accelerators, to build one.

Q: How has that expertise translated into LIGHT’s design; can you highlight some examples?

A: There are a lot, but to pick just one of LIGHT’s components as an example, in February ‘17 we reached a major technical milestone by hitting the desired output energy from the RFQ (Radio Frequency Quadrupole). The RFQ has a number of unique properties: operating at 750 MHz, so it is far smaller than comparable systems, and the energy of the proton beam can be altered 200 times every second, for more accurate tumour targeting and adaptive treatment.

Q: So where are we with LIGHT?

A: We outlined the milestones we’re working towards at the investor evenings in March 2017 and hitting those is very much our focus. We updated the market with the progress we have made on the patient positioning system, ionisation chamber and RFQ on June 12th 2017; we’ll be providing further updates on milestones in due course.

Q: So a major technical event will be generating a proton beam of sufficient energy to treat superficial tumours later in 2018?

A: That’s right.

Q: And then, once the first machine has been produced?

A: There is a huge, unmet medical need for new PBT systems and AVO has been putting the foundations in place to cope with this demand. At the same time, we will keep innovating and continue leveraging LIGHT’s unique capabilities. A potential future addition to LIGHT could be the ability to generate a beam of heavier ions, with higher relative biological effectiveness than even protons. Other enhancements could include enhanced accelerating power and, therefore, a shorter LIGHT system or more efficient radiofrequency generators to reduce already low operating costs. LIGHT’s modular nature lends itself perfectly to the possibility of upgrades and to further improved clinical benefits and/or lower costs.

But, I should stress that the Advanced Oncotherapy PLC LIGHT is already sufficiently different to existing technology to be hugely disruptive in the current market. Getting LIGHT into mass production is what we’ll be concentrating on.

Advanced Oncotherapy PLC (LON:AVO) Chief Executive Officer, Nicolas Serandour, highlights the opportunities ahead, the challenges AVO has faced, what’s been done to overcome those obstacles and what the future might hold for the Company and its shareholders.

Q: Nicolas, you became CEO in October last year; a lot has happened since then, including technical developments, an updated timetable at Harley Street and new financing. You’ve clearly been busy, yes?

A: Yes, that’s right, although the same can be said of the whole team at Advanced Oncotherapy. We reached a number of major milestones in the development of LIGHT, gave a more detailed, and revised timetable for our flagship Harley Street centre and have made considerable progress in the redevelopment of the Harley Street site.

AVO has had challenges as well and some are not uncommon for companies of similar size and maturity. The priority for me, the Board and executive team is managing the transition from an R&D-focused company into one with a clear commercial goal. Some changes have been necessary, as has continuing to capitalise on the world-leading scientific expertise within ADAM, the CERN spin-off and AVO subsidiary.

Q: What have you done to overcome the challenges?

A: The first step was to focus on our priorities. It’s important for smaller companies to have a clear understanding of what really matters and to stick to that, so we’ve focused on what will advance the project as safely, efficiently and cost-effectively as possible.

As a consequence, two key areas in particular have been strengthened: personnel and regulatory engagement. For example, we’ve reorganised teams to work on a functional rather than simply a reporting basis, made a number of key hires and concentrated on accountability and KPIs.

Those hires have included experts in medical device regulation, with a view to ensuring regulatory compliance. As a result, we have had several meetings with regulatory bodies in Europe, the US and in China, which have given us confidence we are pursuing a valid path to regulatory approval.

Q: So where does that leave AVO; how would you describe the opportunity for the Company and its ability to capitalise on it?

A:The opportunity is, unquestionably, enormous. We are uniquely placed to upset the status quo in the global radiotherapy market, by offering a proton therapy system that is radically different to existing machines. In turn, this has major implications for potential costs/ease of installation for hospitals and clinics and for clinical benefits for patients.

Completing the first LIGHT system according to the schedule we outlined in our investor event in March this year will help us to maximise our commercial opportunities. We’re making great progress in this regard and have already reached a number of key milestones.

Terminating discussions in China was obviously disappointing, but was the right thing to do. It is a key market and one we’ll undoubtedly return to given the potential demand there and we’re making great progress in other countries. The opportunity is global.

Opportunities don’t automatically translate into commercial realities, however; the right decisions must be taken to realise potential. That’s why we have entered into partnerships with market leading companies. They bring the commercial know-how that will help us to rapidly reduce operating costs and accelerate the production ramp-up. In addition, the right people are necessary to make AVO the success it will be and I’m fortunate to work with a very talented group. Together, we execute the strategy our Board has set out.

Q: And what next for AVO?

A:We need to continue on the path I set when I became CEO. That means hitting the technical milestones and construction timetable at Harley Street, the site of our flagship project, strengthening our financing platform and pursuing commercial opportunities globally. We will keep the market updated with our progress and I’m convinced that by delivering on each of these steps we will deliver, to the benefit of all shareholders and to cancer sufferers here in the UK and around the world.

To make the most of this opportunity, we need to strive for excellence: “Winning requires a crystal clear vision, relentless passion and complete dedication with no excuses.”

Ed Lee, Chief Operating Officer of Advanced Oncotherapy plc (AVO), talks about his background, what that experience brings to AVO and how that knowledge can translate into shareholder value.

Q: Ed, I understand you joined AVO earlier this year?

A: Yes, I joined AVO in February and have been busy getting to know the company, its culture, personnel, and, of course, the LIGHT system, while helping drive our production priorities forwards.

Q: Is that your background, in production?

A: Yes it is. I worked in senior management production roles with the likes of Meggitt and Northrup Grumman for over 10 years, before joining Optivus Proton Therapy in 2011, where I’ve been since. At Optivus I had dual responsibility for production and for client-facing tasks, such as installation and on-going system servicing.

Q: Can you tell us a little more about this experience and why it is relevant to AVO?

A: One of the key crossovers from my time at companies in the aerospace & defence industry is the critical nature of their systems. Quality has to be guaranteed, given the absolute requirement to avoid failures with potentially catastrophic consequences. The same is true of Optivus and all proton therapy businesses, albeit in a more directly relevant manner where patient care is absolutely paramount.

Q: For those who don’t know, can you explain what Optivus is and does?

A: Of course. Optivus was the pioneer of proton therapy in the 80’s, setting up the first hospital-based proton treatment and research centre at Loma Linda in California. Today, Optivus has two key products: their own proton therapy system, which is analogous to the hardware of LIGHT, although not a linear accelerator, and a treatment planning system i.e. the computer software and hardware that controls all patient treatment (analogous to LIGHT’s patient treatment systems).

That centre has now treated more than 20,000 cancer patients over 27 years, which is more than any other. That experience, through helping to run a 4 treatment room facility, can translate directly into AVO’s commercial operations.

LIGHT itself is a turn-key solution, in that it provides everything a hospital or clinic would require. My background with Optivus gives me insight into every step of the production process and LIGHT’s clinical application.

Q: Can you explain further how that experience can benefit AVO?

A: In driving improvements in manufacturing reliability, such as in on-time delivery, for example. On-time delivery relies on enhancing the strength of the production process to reduce occurrence of faulty goods and by executing project plans on time and on budget. This comes about from working closely alongside different departments, establishing the right work culture and employing great people.

All this should lead to an efficient and reliable production process and an ability to offer excellent customer service.

Q: And is your educational background in a discipline related to manufacturing?

A: It is, yes. I trained as a mechanical engineer.

Q: So your focus is on the design and implementation of new machines and systems?

A: It is to a great extent, but not completely so. For example, I have also worked on the financial analysis and cash flow modelling of new products.

Q: How is that relevant to what you are doing now?

A: It’s essential to maintain a financial perspective on the whole of the manufacturing and client servicing process. AVO’s shareholders are expecting a return on their investment and it is my responsibility to help ensure that that happens.

To put it another way, everything that’s done by our scientists and engineers will be financially sound.

But it’s important not to forget that we’re in the business of treating cancer. Like many others, my own family has had to cope with this disease and we have personally benefited from proton therapy.

Q: And what progress can you flag to AVO’s shareholders?

A: We’ve already hit a number of the key targets in our project timeline: the proton beam through the RFQ, delivery of CCL units, receipt of our unique ionisation chamber and, just recently, successful integration of and beam firing through the first Side Coupled Drift Tube Linac (“SCDTL”) module.

LIGHT has been designed to be the only proton therapy system on the market that can be mass produced, thereby maximising our commercial opportunities. To do that, we have to make sure there is robustness in our design and repeatability in our manufacturing process.

Q: Is that readily achievable?

A: No, it isn’t. But it comes from having an overview of the whole manufacturing and client-servicing process, which I have, and by working with all relevant stakeholders, such as our suppliers, manufacturing partners, customers and, of course, our R&D team.

Q: How much of a benefit is it to AVO to be able to draw on the knowledge of your scientists and engineers in Geneva?

A: It’s hugely beneficial to AVO. My challenge is helping to ensure the intellectual property within AVO gets converted into shareholder value. It’s one I am relishing and am confident we can achieve as a team.

Mike Sinclair, Executive Chairman of Advanced Oncotherapy plc (AVO), provides an insight into his background in healthcare, his vision for AVO and the opportunity the Company has to transform the global radiotherapy market.

Q: Mike, can you tell us a little about your work in the healthcare sector before the creation of AVO?

A: Sure; I’m a physician by training and began my career in the healthcare industry in 1971. Over the next forty-odd years, I founded and built, or had senior roles in, companies in the UK and the US, often working with institutional investors and/or with colleagues from prior ventures. Some of these companies had global markets, others were domestically focused; most became market leaders.

For example, Allied Medical (“AM”), where I was Chief Executive and which I founded, was acquired, grew to be the largest hospital management and healthcare personnel firm in Europe. I was subsequently recruited by Hospital Affiliates International (“HAI”), the losing bidder for AM, to create their international hospital division as President of HAI. HAI’s parent company then merged and had to divest its hospitals division, so I returned to the UK and founded Hospital Capital Corporation, which built and managed hospitals and nursing homes around the UK, many of which were subsequently sold to US-based firms. When Lifetime Corporation, a US home healthcare business I set up in the mid 1980’s and which was listed on the NYSE, was acquired in 1993 it had revenues in excess of $1 billion and was US market leader. Atlantic Medical was a US-domiciled healthcare venture fund, with portfolio companies focusing on IT and telecoms services for healthcare providers; one such company, Quovadx, went on list on NASDAQ at a highly profitable level for our investors. Finally, Care Capital, the forerunner to Advanced Oncotherapy, was originally set up in 1994 to develop, own and lease medical office buildings (“MOBs”) to healthcare operators and listed on AIM in 2006, ahead of its realignment to oncology in 2012.

Q: You must have gained a lot of industry knowledge from those experiences, no?

A: What I’ve learned, aside from how to nurture and run a successful, multinational healthcare business, is an intimate understanding of the nature of hospitals and the healthcare sector as a whole: how hospitals operate, how they are financed, how they provide their services, etc., in both the public and private sectors. That experience is particularly broad here in the UK, in the US, Middle East and in Asia. They are all significant for AVO: the UK is our home market and site of our flagship project in Harley Street, the US is an early adopter of proton therapy, the Middle East is playing catch up with Europe and the US, creating local centres of medical excellence, while Asia is a key growth market.

Q: And in that context, what read through is there for AVO from your background?

A: Value-based care is an imperative for many healthcare providers. This may be obvious in the private sector, where costs are relatively transparent, and might be expected to be critical or to at least feature in the decision making process in the public sector; NHS England produced a discussion paper on this very subject in February of this year.

Lifetime treatment costs would be expected to be lower for proton therapy than X-ray based radiotherapy, due to less chance of developing serious side effects (which need medical care, and represent an additional cost), fewer treatment sessions (hypo-fractionation: less time needed in hospital so lower cost) and a reduced probability of secondary cancers from radiotherapy treatment later in life (particularly relevant in paediatric cases).

AVO’s goal is to reduce the immediate cost of treating each cancer patient, as well as cutting the lifetime cost. The modularity of LIGHT, our unique linear proton accelerator and integrated patient treatment systems, should allow for mass production, physical installation to smaller existing radiotherapy departments/buildings, reduced shielding requirements, more efficient commissioning and high patient throughput, all of which will help lower the immediate cost of treatment to any hospital or clinic. Lifetime costs should be cut further through LIGHT’s designed ability to vary the direction, the dose and the energy of the beam (performing active spot-scanning) hundreds of times per second, thereby targeting tumours accurately in a way that is not currently possible with cyclotron/synchrotron proton therapy systems.

Q: What about the risks facing AVO; how would you describe those?

A: The progress we’ve made recently has greatly reduced any technical risk and those aren’t my words but come from our scientific colleagues. Market risk is minimal as there’s a clear unmet medical need for proton therapy systems and recent advances in immunotherapy are likely to be complementary to proton therapy, as most cancers are treated with a combination of radiotherapy, surgery and/or chemotherapy. Furthermore, precisely targeted ultra high doses of ionising radiation i.e. what LIGHT is designed to be able to deliver, can be used to trigger what’s called the abscopal effect, whereby the body’s own immune response attacks outlying secondary tumours. We’re also doing everything we can to minimise regulatory risk. The main risk relates to AVO’s ability to stick to its plan; this is two-fold with management having to ensure the company remains focused on its priority, installing the first LIGHT system in Harley Street, and that we have sufficient funding to realise that goal.

I am continually humbled by our ability to attract the very best people in their fields to work at AVO. This gives me great confidence that we will achieve our targets. In addition, the Board is continually looking at ways to optimise our capital structure and ensure we are fully funded through to first patient.

Q: And what of the opportunity for AVO?

A: It is notable that some industry experts, such as Professor Jay Loeffler of Harvard Medical School, and who sits on our medical advisory board, expects proton therapy to completely replace X-ray based radiotherapy, if and when costs become similar for both treatments. Others believe the two approaches will be used to treat different types of cancers. Whatever the eventuality, there is a growing body of evidence on proton therapy’s clinical superiority.

I’ve had a long career in healthcare; AVO is, without a doubt, the most exciting project I’ve had the opportunity to be involved with.

AVO has the capacity to disrupt and gain significant market share in not just the proton therapy global market, which is set to break the $1 billion mark in the next few years, but the whole radiotherapy market. Bearing in mind that only around 1% of the world’s population in need of radiotherapy will receive proton therapy, the opportunity for AVO cannot be overstated.