Periodic Reporting for period 2 - INSTAGLOW (Game-changing uPAR-targeting dye for guiding surgical treatment of cancer) Reporting period: 2021-07-01 to 2022-12-31 Summary of the context and overall objectives of the project Surgery is a cornerstone in treatment of cancer. Approximately 80% of patients with cancer will receive surgical treatment once during their disease. In almost half of the patients’ cancer is recurring after the surgery due to incomplete tumour removal. The recurring of cancer leads to patient suffering and causes a huge financial burden on the healthcare system, and it can even cause death of the patient. There is a major unmet need to delineate cancer accurately, sparing healthy tissue, identifying local metastases, and aiding surgeons to precisely remove the entire tumour. FluoGuide develops FG001, a breakthrough, real-time, surgical visualisation solution that lights up cancer and improve surgical precision during surgery. FG001 is the first actively targeting fluorescent tumour marker in development that targets uPAR, a receptor extensively expressed in a wide range (>80%) of solid tumours such as brain (high grade glioma including glioblastoma (GBM)), lung, breast, colorectal and head and neck cancers. FluoGuide’s proprietary FG001 has the potential to revolutionise cancer surgery to improve the surgical outcome of >3 million cancer patients undergoing surgery every year.To realise this huge potential, FluoGuide is working on accelerating the development of FG001. Our initial focus is on high grade glioma including GBM. This disease has poor survival rates, only half of the patients surviving 14 months on average. Moreover, surgical precision is extremely important as removing too much brain tissue can severely disable the patient. FG001 can thus enormously improve surgery of GBM patients. The funding from EIC accelerator pilot has accelerate and substantiate FG001’s clinical phase IIb/III study for GBM, and catapult FluoGuide to become a leader in cancer surgery guidance. We will generate revenues by 1) direct sales, paid for via reimbursement by insurance companies and governments, and 2) through partners, by a combination of revenue generated by selling finished products to partners for distribution to their customers and revenue generated by royalty paid by partners for having rights to our patent portfolio. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Results obtained during and within the project:• Clinical trial with FG001 in high grade glioma (incl. GBM): FG001 has been well tolerated and light up cancer in patients with high grade glioma. The pathology examination confirmed tissue that light up was cancer (specificity on 100%) and that the tissue containing cancer did light up (sensitivity on 79%). • Manufacturing of FG001: The process has been developed for commercial stage needed before phase III studies can be initiated.• Quality Assurance: The quality system in FluoGuide has been established. This is important for many reasons including to support documentation activities and prepare approval of FG001. • Relevance of FG001 in other cancer indications has been established: Clinical data on FG001 supporting it is effective in additional and more prevalent cancer types has been generated; less aggressive brain cancers (Glioma grade III and meningioma) and lung cancer • Market research of FG001 in high grade glioma: The results are feed back into the development.Results obtained outside of the INSTAGLOW project paid for by FluoGuide:• Photothermal therapy (‘PTT’) property of FG001: The fluorophore in FG001 exhibits photothermal therapy potential, whereby excitation of light causes the product to heat up and destroy nearby cells to which it is bound without harming surrounding normal cells. FG001 binds specifically to uPAR (urokinase type plasminogen activator receptor) which is a cancer specific receptor. FG001’s photothermal therapy property can therefore potentially be used for highly targeted destruction of cancer cells, while sparing the surrounding normal cells. This unique property of FG001 is combined with its core objective to vastly improve the outcome of brain cancer surgery. • Relevance of FG001 in other cancer indications has been established: Clinical data on FG001 supporting it is effective in additional and more prevalent cancer types has been generated; Head & neck cancer. 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) The expected result of INSTAGLOW is to develop a product that saves lives of patients with aggressive brain cancer and saves treatment costs for hospitals and society – FG001.Unique Selling Points of FG001:• Unique target: FG001 is the first fluorescent agent in development that targets uPAR, a receptor that is present extensively in most patients with solid tumour indications. uPAR is especially expressed at the invasive front of the tumour, making uPAR an ideal target for fluorescence-guided surgery. • Safety: FG001 is made of a targeting molecule linked to a NIR fluorophore, which is well tolerated by humans, and provides an optical imaging ligand with high receptor affinity in vivo. • Compatible with current workflows: In line with current practice, surgeons will administer FG001 intravenously prior to surgery and can visualise all solid tumours for up to at least 48 hours after injection.• Equipment independent: Surgeons have flexibility in choosing equipment as almost all equipment is compatible with the spectral specifications of FG001.So far, the INSTAGLOW project strongly supported this Unique Selling Points, as planned. In addition, the photothermal therapy has been demonstrated beside INSTAGLOW and gives a significant potential enhancement of the value provided by FG001 to patients. FG001 clearly delineates cancer margins FG001 Summary of the results of the Phase 1/2a Clinical Trial FG001: Simple procedure, profound impact FG001 Light up cancer margins
