Periodic Reporting for period 4 - CerISMA (Cerenkov Imaging for Surgical Margin Assessment) Reporting period: 2018-12-01 to 2019-06-30 Summary of the context and overall objectives of the project Cancer is not only a leading public health challenge in Europe, it is also a growing economic challenge. Over three million cases are currently diagnosed each year across the continent. Forecasts show that by 2020 almost half of the population will be diagnosed with the disease in their lifetime. The cost of cancer for the EU is €126 billion per year and rising. The health and economic implications of cancer therefore provide a compelling opportunity for technologies that can improve health outcomes and reduce treatment costs. Surgery remains one of the primary treatments for cancer, yet surgeons lack the tools to identify accurately and remove cancer during an operation, resulting in costly re-operations and negative health ramifications. Lightpoint Medical Ltd has developed a molecular imaging camera (LightPath™) based on a breakthrough imaging modality, Cerenkov Luminescence Imaging (CLI). The technology can provide surgeons with real-time intraoperative analysis of cancerous tissue to ensure the complete removal of cancer in a single operation. The device provides the potential for a dramatic reduction in costly reoperations and follow-up treatments across a wide range of major cancer indications, proving not only an innovative solution for healthcare providers, but also a tool to substantially reduce cancer care costs. The CerISMA project is critical to underpinning the success of Lightpoint Medical Ltd’s ambitious sales and marketing strategy for LightPath™ in mainstream clinics in Europe and North America with a particular focus on initial strategic territories of the UK, France, Germany, Netherlands and the US. The project will consist of a multi-centre, multi-national (EU) clinical trial to comprehensively validate the clinical performance of LightPath™ and provide health economic data. The study will focus on the company’s first target cancer indication, which is breast cancer. Breast cancer is one of Europe’s most common cancer indications and is the leading cancer-related cause of death for women in the EU. The project’s clinical data and results from the CerISMA project will be critical in supporting the commercial exploitation of LightPath™ technology and in understanding the potential impact of the technology on patient outcomes and health service costs. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The project team has completed the study in the fourth year of the grant. 107 patients in total were screened and consented on to the study. Of the total patients consented, 104 completed the study with imaging and histopathology results submitted for analysis. From these patients, a total of 274 images were evaluated. The images were analysed by surgeons at the clinical sites during the procedure and then a central read of the data was performed by independent surgeons. The images were compared to gold-standard histopathology.From the study evaluation, surgical margin assessment using the LightPath® Imaging System was found to be a safe and feasible procedure for breast-conserving surgery. In particular, the methodology was found to be an effective and practical technique. The safety profile was excellent with no device-related adverse events. In general, the image quality was good with few non-evaluable images. The staff radiation exposure was low (39.7±36.7 μSv) and within acceptable limits. The LightPath® Imaging System showed good diagnostic specificity. However, the study results highlighted areas to work on to improve sensitivity. Key learnings for future development of the technique include: 1. Identify patient sub-populations with increased FDG radiotracer uptake, for example, breast cancer patients with high estrogen receptor expression; 2. Investigate the use of alternative radiotracers and/or higher doses to achieve higher sensitivity and signal levels; 3. Further optimize the scintillator material to increase the light yield;4. Improve the site training to increase the agreement between readers;5. Investigate alternative cancer types, in particular, prostate cancer and oral cancer, for which available tracers demonstrate high diagnostic performance and light yield.Overall the study produced useful results that will be instrumental in further development of the technology and disease area strategy.Over the course of the project, the company has made excellent progress on the commercialization of the device, including the continued placement of the LightPath® in leading research institutes in the US and Europe, publication of results, building relationships with key opinion leaders, initiating clinical trials in other cancer indications, securing early adopter sales and building a pipeline of future sales prospects. The company has continued to receive industry recognition and media coverage for the technology. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) LightPath™ promises to dramatically improve detection of cancerous tissue during cancer surgery. It is expected that the device will provide the diagnostic performance comparable to the current gold-standard histopathology whilst, in addition, reducing re-operation rates, reducing critical delays in follow-up treatment and a significant improvement in cosmetic outcomes. The consequent reduction in costs will provide substantial benefits to healthcare providers and society. The CerISMA study, which included 104 patients, produced useful results that will be instrumental in further development of the technology and disease area strategy. The positive outcomes of the study were:1. Proving the safety and feasibility of the methodology;2. Demonstrating a high diagnostic specificity. The project team plans to publish the study results in the following journals and at the following conferences: Journal of Nuclear Medicine (submission Dec 2019), The Breast (submission Dec 2019), Society of Nuclear Medicine and Molecular Imaging Annual Meeting (June 2020), Congress of the European Society of Surgical Oncology (October 2020), European Association of Nuclear Medicine Congress (October 2020).Commercial objectives continue to be advanced, including:- Signature of four distributor contracts in European territories;- 15 Key Opinion Leaders in the US and Europe secured to help market the technology once the clinical data is available;- The first four sales of the device achieved with additional orders pending;- Industry recognition received, including the British Engineering Excellence Awards, The Institution of Engineering and Technology Innovation Awards, The Great British Entrepreneur Awards, The Microsoft Accelerator; The European Venture Contest, The Royal Academy of Engineering, SME Leaders Programme; UK Private Business Award for Technology Innovation of the Year; Medilinks Innovation Award; Mayor of London International Innovation Programme, Lloyds Bank National Business Award Finalist, PRISM Award for Photonics Innovation Finalist, MedTech Insight Awards: Best Technological Innovation Finalist, Co-Investment Deal of the Year Finalist UK Business Angels Association and The Engineer’s Collaborate to Innovate Award Finalist.- Funding secured for two clinical studies in prostate cancer surgery and one in head and neck cancer surgery;- Funding secured for the development of a second product for laparoscopic key-hole cancer surgery, which has now passed preclinical validation and funding has been secured for clinical validation studies.- Funding secured from the European Commission's ACTPHAST programme for photonics innovation. Image of the LightPath Imaging System
