Public Funding for Lightox Limited

The management of wounds is a "silent epidemic" that is challenging health services worldwide. The NHS treats 2.2 million patients with a chronic wound, the management of which costs at least £5.6 billion each year. A major factor inhibiting wound healing is infections caused by colonising microbes. Untreated infections prevent healing and often spread; treated infections almost always re-occur and this cycle of infection can necessitate surgery and even amputation. The increasing prevalence of co-morbidities like diabetes and obesity, and limited treatment options for the increasing problem of bacteria resistant to antibiotics means that incidence of chronically infected wounds is rising in all geographies and age groups. Diabetic foot ulcers (DFUs) are a particularly challenging chronic wound, afflicting around 9% of all adult diabetics; chronic infections of DFUs result in loss of mobility and significant pain. As we face the prospect of a world where antibiotics are increasingly less effective, we urgently need new modalities that can inhibit infections that arise in chronic wounds such as DFUs to aid healing and, thus, lower the enormous burden faced by healthcare services. LightOx, based in Newcastle-upon-Tyne, have developed molecules that, when activated by light, cause the destruction of bacteria that colonise wounds through the generation of reactive oxygen species (ROS). We have also shown that these molecules are capable of disrupting and inhibiting the growth of biofilms -- a common complication of infected wounds that can inhibit healing. Uniquely, bacteria are unable to become resistant towards ROS, and hence, LightOx see great potential for their novel light-activated molecules as the next generation of antibacterial technology for the growing burden of infected chronic wounds. In this feasibility project, LightOx will engage Health Innovation North West Coast to access leaders in the NHS, charities, and patient groups to understand the huge challenges that woundcare professionals face on a daily basis, with a particular focus on DFUs. We will determine the unique characteristics of DFU woundcare (and other wound types), gather feedback from patients suffering from these wounds and the nurses and clinicians who treat them, and further develop market access plans for our technology. This information will enable us to co-develop a specification that LightOx can use to progress their novel antibacterial technology into a product that can improve outcomes for sufferers of these painful wounds.

The management of wounds is a "silent epidemic" that is challenging health services worldwide. The NHS treated 3.8 million patients with a wound in 2017/18, translating to a burden of \>£8.3billion. A major factor that influences the healing of a wound is an infection by colonising microbes. Untreated infections prevent healing, but can also spread further, frequently necessitating surgery and even amputation. The increasing prevalence of contributing factors such as diabetes and obesity, and the alarming emergence of bacteria that are resistant to antibiotics means that the number of chronically infected wounds is rising in all geographies and age groups. As we face the prospect of a world where antibiotics are no longer effective, we urgently need new modalities that can lower bioburden in wounds to aid healing and, thus, lower the enormous burden faced by healthcare services. LightOx, based in Newcastle-upon-Tyne, have developed molecules that, when activated by light, cause the destruction of bacteria that colonise wounds through the generation of reactive oxygen species(ROS). We have also shown that these molecules are capable of disrupting and inhibiting the growth of biofilms -- a common complication of infected wounds that can inhibit healing. In this feasibility project, LightOx will develop our lead molecule, LightOx78, into three woundcare product prototypes -- a dressing, a hydrogel and a gel/aqueous solution -- and work with experts at Durham University to demonstrate the capability of these prototypes in the elimination of wound-colonising microbes and biofilms to aid effective wound healing. Concurrently, we will lay out an exploitation and regulatory roadmap to bring this novel technology to market as a woundcare product that augments the current standard of care. This technology could halve the average number of care appointments required to heal wounds and would have enormous benefit for health services and patients alike.

Oral cancers are the 14th most common cancer in the UK. Around 50% of patients die within 5-years of diagnosis, whilst a reliance on invasive surgery (used in 95% of cases) means that survivors are left with severe life-long impacts affecting swallowing, eating and speech. The number of cases of oral cancer is increasing, particularly in those aged 50+, where the rate of incidence is around 10 to 25 times greater than those aged <39 years, and 2 to 5 times greater than those aged 40-49\. Therefore, there is a need to prevent the development of oral cancer in at-risk patients. One such group of patients are those with a condition called "Oral Epithelial Dysplasia", a pre-cancerous condition presenting with red or white patches on the lining of the mouth. LightOx, based in NE England, has developed novel drugs that can be applied to these patches and activated by a light to precisely destroy the oral epithelial dysplasia and, hence, stop progression to oral cancer, eliminating the need for surgery. Patients could even have multiple lesions treated in one visit in an appointment that would be like visiting the dentist. Compared to surgery, our low-cost, non-invasive treatment will eliminate off-target tissue damage, enabling almost immediate recovery (compared to 6--8 weeks healing after surgery) and long-term impacts on swallowing, taste and speech will be avoided. In this project, LightOx will work with expert partners to convert our lead drug into a topical gel that will make it easy for a doctor to apply inside the mouth. We will then evidence how this gel can be applied to dysplasias and activated to destroy them using light sources already in use in health services. In tandem with the development of the technology, we will work with some of the leaders in the field including world renowned oral cancer experts in the NHS at the Liverpool Head and Neck Centre (LHNC). Together, we will map out the pathway needed to bring our unique therapy to the clinic, taking advice from patient and charity groups to ensure we develop a treatment with the patient in mind. Our technology has potential in other areas such as skin, bladder and eye cancers. Hence, success in this project will not only provide a new treatment to reduce the incidence of oral cancer, but also enable LightOx to develop our platform for other clinical areas in the future.

LightOx are a drug development company based in Newcastle upon Tyne that has made its light-activated products, known as LightOx Probes, available to other researchers to enable them to understand biological processes that occur in a cell. LightOx has shown that their Probe molecules are capable of emitting fluorescence when they are activated by light, allowing researchers to see where a Probe is situated inside a cell. However, while fluorescence measurements can show researchers where these molecules are localised, they cannot accurately tell us how much is there. To solve this problem, researchers around the world are beginning to demonstrate a new imaging technique, combined fluorescence and Raman imaging, that incorporates Raman (a form of light scattering) measurements along with light from fluorescence to answer both of these "Where?" and "How much?" questions. One disadvantage to this technique is that it requires specially-designed probes that are capable of both fluorescence and Raman measurements; there is no on-market probe that satisfies these conditions, significantly slowing the advancement of this fascinating technique that promises to help researchers answer complex biological questions. LightOx believe that many of their LightOx Probes exhibit unique structures that are capable of this new imaging technique, but they are a small company (10 employees) and lack the expertise and equipment required to demonstrate their probes' capabilities in these experiments. To solve this, LightOx have partnered with two of the world's leading technology facilities, the Central Laser Facility (CLF) and the National Physical Laboratory (NPL), on this A4I project to characterise the Raman properties of their LightOx probes and use these measurements to demonstrate utility in this new imaging technique. The CLF and NPL are equipped with state-of-the-art instrumentation to measure these properties, and these experiments will enable customers to use LightOx Probes to utilise combined fluorescence and Raman imaging and also allow LightOx to learn more about their novel technology. LightOx already sell LightOx Probes through a market-leading worldwide distributor and have noted that there are no probes currently marketed for combined fluorescence and Raman imaging. Hence, LightOx sees an opportunity to fill an emerging and potentially lucrative market gap, and we have partnered with the CLF and NPL to undertake this ambitious project that aims to establish a new application for LightOx products. These Probes have potential to enable researchers across the world to make new discoveries in fields such as cancer, cell biology and therapeutics.

LightOx are a drug development company based in the North East of England that has made its light-activated products available to other researchers to develop and understand the biological processes that occur in a cell. These "LightOx Probes" act to show biological researchers the importance of specific cell functions and the mechanisms that cells use to survive and grow. LightOx has shown that their Probes are capable of emitting fluorescence when they are activated by short wavelengths of light (violet or blue light), allowing researchers to see where a Probe is situated inside a cell. Short wavelengths of light efficiently activate this fluorescence, but this light only penetrates to short distances and can be damaging to cells. Some of our customers have shown that LightOx Probes can also be activated by much longer wavelength light by a novel technique known as two-photon absorption. This approach has major advantages as longer wavelengths of light (red light) penetrate materials much better and are also non-toxic to cells; thus, two-photon absorption would allow researchers to look at LightOx probes in challenging biological samples such as cancerous tumours. LightOx have partnered with one of the world's leading technology facilities, the Central Laser Facility (CLF) in Didcot, Oxford, on this A4I project to further understand the two-photon absorption properties of LightOx Probes. The CLF is equipped with state-of-the-art laser instrumentation to analyse the two-photon absorption properties of molecules and, together, LightOx and scientists at the CLF will work to undertake precise measurements of LightOx Probes that will enable us to build a picture of the ideal molecule that will provide the best two-photon absorption. Molecules that are more efficiently activated by two-photon absorption will make it easier for researchers to study cells/tissues using this technique. LightOx already sell their LightOx Probes through a global distributor and have noticed that there are very few probes on the market that are capable of two-photon absorption. Hence, LightOx sees that developing LightOx Probes with strong two-photon absorption could fill a gap in the research tools market. However, LightOx are a small company (15 employees) and do not have the equipment/expertise to measure two-photon absorption. Hence, we have partnered with the CLF to undertake this ambitious project that aims to establish a new product line for LightOx that promises to enable researchers across the world to make new discoveries in fields such as cancer, cell biology and therapeutics.

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LightOx looks to advance the scientific field of biological imaging using fluorescence by developing novel agents that have intrinsic chemical properties for targeting cell subtypes and intracellular organelles. The experimental basis of this comes from a background of 15 years of research within university institutes and are now being undertaken by the company and in collaboration with other research institutes. The project has many possible outcomes and a level of uncertainty and risk associated with it. As we are fundamentally changing the chemical structure and electronic nature of these molecules there is no guarantee of success. We have shown this science is both novel and undiscovered through the publications presented this year and the granting of our patent portfolio, and as such we believe we have a niche area of development to work within. By careful experimental design we have planned an over-arching R&D programme spanning the next two years that will allow us to investigate the relationships of our novel imaging agents in a variety of disease states and organisms including cancerous, mammalian, plant, fungal and bacterial species. We have developed over 130 imaging agents to date and have 3 chemical families. As part of this A4i project we will test selected probes from each family as agents for 2 photon biological microscopy. This imaging technique has many benefits over more conventional microscopy, including the use of light that is less toxic to biological samples and that can penetrate more deeply. The data arising from the collaboration between NPL and LightOx is essential to open new markets in this area. We are eager to partner with leading global institutes to investigate and de-risk our work. It is only with this unique mixture of people are we able to achieve our goals, and the fact we are able to publish and patent with peer review processes shows this work to be truly unique to our team.