Periodic Reporting for period 3 - msGUIDE (Insight into Drug Distribution and Local Concentration using Multispectral Imaging of Fluorescent Drugs in Inflammatory Bowel Diseases)
Reporting period: 2024-08-01 to 2025-11-30
The field of personalized medicine has evolved rapidly since the introduction of expensive novel targeted biological treatment options for a wide variety of diseases, such as inflammatory diseases and multiple cancer types. However, limitations of current technologies do not allow the visualization of the molecular phenotype or heterogeneity within patients, who often only partially respond to a treatment. Surprisingly, even in the current era, it remains completely unknown whether a drug reaches its actual target in the tissue and if a sufficient local concentration is reached for target engagement to achieve treatment response. Thus, treatment and dose administration are empirical, leading to high costs and delays in finding an effective individualized treatment. These inefficiencies are especially crucial in inflammatory bowel diseases (IBD), ulcerative colitis, and Crohn’s disease. These chronic relapsing inflammatory disorders of the gastrointestinal tract affect 2.5Mio patients in Europe. The majority of newly diagnosed patients are in adolescence or early adulthood and in the midst of their family life, career, and social development. Though luckily not life-threatening, the disease comes with significant morbidity and complex treatment strategies and is associated with a high social burden and medical costs of ~€10 billion annually in the EU. This is due to the unpredictable response to expensive biological immunomodulating therapies and is thereby frustrated by high primary non-response (30-60%) and loss of response over time (48-58%). Liquid biomarkers, tissue markers, gene expression signatures, therapeutic drug monitoring of serum levels, and analyses of the microbiome do not yield an adequate prediction of individual responses or dosing. Thus, burning issues to be solved are: 1. Does the drug reach sufficient concentrations at all inflamed areas to block the target? 2. What is the mechanism of action? 3. Can we stratify patients into the specific therapies? 4. How should we dose individual patients?
We are proposing a technology that aims at combining molecular data to stratify individuals based on their probability to respond to treatment taking inter-patient and intra-patient heterogeneity into account. It will allow a more personalized medical treatment that can predict which patients will respond to certain treatments and what the optimal dosage is, eventually resulting in lower non-response rates. In addition, these results will improve our knowledge of existing biological therapy and enable the development of novel therapeutic targets and faster drug development in collaboration with the pharmaceutical industry. Our technology will enable and provide robust precise measurements, required for precision medicine. In the context of msGUIDE, we will develop a groundbreaking technology that, for the first time, will simultaneously visualize and quantify local drug concentrations throughout the whole colonic mucosa in real-time to gain insight into drug distribution of multiple therapeutic agents. This will be achieved by enhancing HD-White light endoscopy (HD-WLE) performance with concurrent highly sensitive Near-Infrared Fluorescence and Reflectance Multispectral Imaging (NIR-FRMI), using fluorescent labeled drugs employed in IBD treatment.
We are proposing a technology that aims at combining molecular data to stratify individuals based on their probability to respond to treatment taking inter-patient and intra-patient heterogeneity into account. It will allow a more personalized medical treatment that can predict which patients will respond to certain treatments and what the optimal dosage is, eventually resulting in lower non-response rates. In addition, these results will improve our knowledge of existing biological therapy and enable the development of novel therapeutic targets and faster drug development in collaboration with the pharmaceutical industry. Our technology will enable and provide robust precise measurements, required for precision medicine. In the context of msGUIDE, we will develop a groundbreaking technology that, for the first time, will simultaneously visualize and quantify local drug concentrations throughout the whole colonic mucosa in real-time to gain insight into drug distribution of multiple therapeutic agents. This will be achieved by enhancing HD-White light endoscopy (HD-WLE) performance with concurrent highly sensitive Near-Infrared Fluorescence and Reflectance Multispectral Imaging (NIR-FRMI), using fluorescent labeled drugs employed in IBD treatment.
The msGUIDE consortium has successfully developed two versions of the endoscope, one based on an integrated endoscope and one based on imaging sensors. Along with this, phantoms were developed as well, which have not only served to test the prototypes, but will also enable standardization of the endoscopic procedures, a crucial step to bring the msGUIDE system into the clinical grounds.
Safety tests have been performed, standardization protocols have been established, and the regulatory work to for a future approval as a medical device is ongoing. All system drivers and managements software have already been developed, allowing data acquisition, analysis and real-time visualise of the readouts. In parallel, two fluorescently labelled drugs have been developed and proved to be safe. Dose-finding studies and ex-vivo analyses have been conducted, and the feasibility to acquire fluorescence and spectroscopy data in vivo has been demonstrated.
With the main technological and scientific innovations successfully developed, the consortium is ready to start the human studies that will ultimately validate the msGUIDE endoscopic system. Towards this end, the protocols and the msGUIDE system have already been approved by the relevant authorities and, hence, the initiation of the clinical studies is imminent.
Safety tests have been performed, standardization protocols have been established, and the regulatory work to for a future approval as a medical device is ongoing. All system drivers and managements software have already been developed, allowing data acquisition, analysis and real-time visualise of the readouts. In parallel, two fluorescently labelled drugs have been developed and proved to be safe. Dose-finding studies and ex-vivo analyses have been conducted, and the feasibility to acquire fluorescence and spectroscopy data in vivo has been demonstrated.
With the main technological and scientific innovations successfully developed, the consortium is ready to start the human studies that will ultimately validate the msGUIDE endoscopic system. Towards this end, the protocols and the msGUIDE system have already been approved by the relevant authorities and, hence, the initiation of the clinical studies is imminent.
The anticipated impact of msGUIDE remains highly significant, as described in the Grant Agreement and previous reports. The project introduces a technological innovation that will enable, for the first time, real-time in vivo visualization of local drug concentrations and distribution at the precise site of action, which is the colon mucosa in patients with inflammatory bowel disease (IBD). This capability addresses a critical and persistent limitation in personalized medicine and drug development, as existing methodologies cannot reliably determine whether therapeutic agents reach their intended targets at sufficient local concentrations to achieve effective target engagement.
By providing this essential information, msGUIDE is expected to accelerate targeted screening and patient stratification during both drug development and clinical implementation. This advancement will facilitate more rational and efficient drug utilization, optimize prescription practices, and inform personalized therapeutic decisions. It will overall improve future drug development strategies and enhance the predictive accuracy of patient responses to specific therapies.
The long-term societal and economic implications are considerable. The outcomes of msGUIDE have the potential to substantially alleviate the burden on patients suffering from IBD while simultaneously reducing healthcare costs associated with treatment and mitigating broader social costs linked to the disease. The introduction of this novel approach is anticipated to exert a profound and enduring positive impact on healthcare systems.
Further uptake and successful implementation will be supported by a comprehensive exploitation strategy, which will be fully developed during the upcoming reporting period. Establishing access to relevant markets, together with a robust plan for commercialization, will be essential to promote future adoption by end-users. In this context, laying the groundwork for the pathway toward CE marking will be a critical step, with initial actions planned for the final project stage.
By providing this essential information, msGUIDE is expected to accelerate targeted screening and patient stratification during both drug development and clinical implementation. This advancement will facilitate more rational and efficient drug utilization, optimize prescription practices, and inform personalized therapeutic decisions. It will overall improve future drug development strategies and enhance the predictive accuracy of patient responses to specific therapies.
The long-term societal and economic implications are considerable. The outcomes of msGUIDE have the potential to substantially alleviate the burden on patients suffering from IBD while simultaneously reducing healthcare costs associated with treatment and mitigating broader social costs linked to the disease. The introduction of this novel approach is anticipated to exert a profound and enduring positive impact on healthcare systems.
Further uptake and successful implementation will be supported by a comprehensive exploitation strategy, which will be fully developed during the upcoming reporting period. Establishing access to relevant markets, together with a robust plan for commercialization, will be essential to promote future adoption by end-users. In this context, laying the groundwork for the pathway toward CE marking will be a critical step, with initial actions planned for the final project stage.