Public Funding for Xerion Healthcare Limited

Although great progress has been made in the treatment of some common cancers there remain many where there has been little improvement over decades. One of these is aggressive brain tumours, which have a median survival time of 14.6 months -- a figure that has not improved over the last four decades. The current best-supported care is surgery, which removes as much of the tumour as possible, followed by radiotherapy and chemotherapy. Cancer regularly reappears in this region and progresses rapidly. A unique nanoparticle loaded hydrogel will be developed which will release nanoparticles in areas of residual cancer. These nanoparticles improve the effectiveness of radiotherapy. This project will bring together Xerion Healthcare Ltd, a SME developing radiotherapy enhancing nanoparticles, and the Medicines Discovery Catapult (MDC), a CRO that specialises in pre-clinical development and imaging to develop a unique product that will enhance the effect of post-surgical radiotherapy on aggressive brain tumours and reduce the prospects of cancer regrowth. This project will enable Xerion to take the product forward to clinical trials. Given the critical clinical need for new treatments for this devastating disease, Xerion expects the rollout and uptake to be rapid.

Although great progress has been made in the treatment of some common cancers there remain many indications where there has been little improvement in care over decades. The most difficult tumours tend to be inoperable with treatment options limited to chemotherapy and radiotherapy. Chemotherapy is administered systemically and a balance between toxicity and tumour dose is hard to achieve. Radiotherapy is more effective as it can be targeted to the tumour. However, it relies on the presence of oxygen to generate cell killing free radicals, meaning that aggressive oxygen deficient (hypoxic) tumours cannot be treated without unacceptable off-target toxicity. Recently, nanoparticles have begun use as radiosensitisers to enhance the efficacy of radiotherapy treatment. Direct intratumoural injection is currently under active investigation as a method of reducing systemic toxicity but presents a threefold challenge for clinicians. Firstly, direct real-time imaging of the needle tip into the tumour is difficult, particularly for deep tumours in, for example, the pancreas. Secondly, it is not known how far from the needle tip the active ingredient disperses into the tumour. Thirdly, conventional injection provides little control of the distribution of the nanoparticles within the tumour. Consequently, it is very difficult for the clinician to devise an effective clinical intervention strategy for intratumoural injection. This project brings together collaborators with broad and deep skills in the area of nanoparticle development, fluid delivery and medical imaging. This programme will develop the basis of a clinical intervention strategy for cancer treatment of human patients using intratumoural injection.

Xerion Healthcare Ltd ("Xerion") have developed a highly innovative and cost-effective nanoparticle technology, Oxilia. This technology is intended to augment standard radiotherapy to provide more effective treatment for patients with inoperable cancers, with the primary focus on head and neck (HNC) and pancreatic cancers. Current therapies are not adequate for effective treatment of such cancers, and this improved treatment regime is likely to offer a significantly better prognosis for patients, extending lives of patients with previously untreatable cancers, while considerably reducing treatment costs. Oxilia is made up of novel titanium dioxide nanoparticles, doped with a rare earth metal, giving it unique properties and allowing the generation of free radicals from water during radiotherapy. This permits treatment of aggressive and challenging hypoxic tumours, which are deficient in the very oxygen required to generate the cancer killing free radicals, during conventional radiotherapy. This innovative approach has shown increased cancer cell death in lab studies, with 1.9x the cell killing capacity of conventional radiotherapy in pancreatic cancer cells. To translate these results obtained from preclinical studies to clinical practice, Xerion have to obtain authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) to commence clinical trials. The main aims of this project are to meet MHRA requirements by: -Completing animal efficacy and dose response studies, and pharmacokinetic, biodistribution and toxicity studies; -Demonstrating that production quality requirements can be met. The defined outcomes of Oxilia project are: -Demonstration that the current process can be scaled 20-fold in a compliant clean production environment, capable of producing up to 8,000 complete treatment kits per annum per reactor, -MHRA authorisation for a pilot clinical trial using the complete treatment kits developed within the project, -Capability to serve 100% of UK and 25% of EU unresectable HNC market, demonstrating feasibility of increasing the manufacturing scale. Successful completion will allow Xerion to undertake clinical tests and commercialise Oxilia for HNC and pancreatic cancers. By 2028, Xerion expect to be treating up to 15,000 HNC patients across the UK and the EU, thereby significantly improving the quality of life for many people suffering from unresectable cancers.

"Application defined by a partnership: the lead applicant has an advanced ultrasound ""driven"" needle that greatly improves the accuracy of delivering medicines to deep tissues (improved tissue penetration and highly visible on ultrasound scanners); the partner has a nanotechnology based agent that generates highly localised free radicals to enhance the effectiveness of cancer radiotherapy. This project enables these two companies to bring these two highly complementary technologies together and explore the possibility of a more accurate system of targeting radiotherapy that is less traumatic, more effective and that may offer a route to a cure. Uniting these two technologies opens up a considerable commercial potential for both parties. The vision is to propel both parties forward by developing a combination system that can drastically enhance the accuracy of treating challenging tumours in the head, neck and pancreas. To bring these two innovations together the feasibility of this approach must be explored. The applicants wish to understand how the combined system would be used to target a pancreatic tumour. The enclosed project will explore: * Configuration of advanced ""Active Needle"" that is suitable for the targeting of pancreatic tumours; * Use the above needle to validate biodistribution of the nanoparticulate radiotherapy enhancement agent in a mouse pancreatic cancer model; * Develop a future pre-clinical study protocol for the combined system validation; * Examine the relevant intellectual property landscape for this innovation and secure IP."

The project will develop nanoparticles of complex semiconductors that will be injected into tumours and act to enhance the effectiveness of radiotherapy treatment of cancer. Radiotherapy treatment is often limited by the toxicity of the treatment to healthy tissues surrounding the tumour, meaning that simply increasing the dose is not an option. Xerion Healthcares novel nanoparticle technology will act to significantly enhance the effects of radiotherapy for the treatment of a range of cancers. The nanoparticles are injected into the tumour and interact with X-rays to generate cell killing free radicals. This project will focus on improving the treatment of pancreatic cancer. Pancreatic cancer is the most deadly of the common cancers with a one year survival rate of 12% and a five year survival rate of only 3%. Over 9400 cases of this devastating disease are diagnosed in the UK alone, over 80% at advanced stages where surgery is impossible and chemotherapy ineffective. This project aims to significantly improve the prognosis of patients with Stage III and IV pancreatic tumours.