PROBLEM: Today, organ transplant medicine is limited by life-long immunosuppression and vulnerability to infections, malignancies and cardiovascular diseases, and by a 20% rate of long-term graft failure. SOLUTION: PHOENIX reprograms the local immune micro-environment around a graft organ, inducing long-term transplant tolerance without broader systemic immunosuppression. FOUNDATIONS: Our expert teams have already discovered novel peptide-MHC complex-based nanomedicines for the treatment of autoimmune diseases. This project will transform, deploy and validate this nano-technology platform for transplant medicine. We have unique expertise in kidney and liver murine transplant models as well as liver transplantation in pigs and have established a molecular engineering pipeline for immune-protein synthesis to enable future clinical translation. Extensive clinical-trial expertise will enable us to progress efficiently from this project towards the clinic. WORKPLAN: We are designing and building a unique nanomedicine which delivers ubiquitous or self-antigens - common to all humans – that will redirect the host immune response against the graft toward regulation and tolerance development. These medicines will be demonstrated in murine and porcine models, laying the foundation for human clinical trials immediately post-project. SUMMARY: This project combines innovative multi-disciplinary approaches, building on a proven foundation, to deliver a novel therapy which will have a transformative positive effect on organ transplant patients and healthcare.

EUPHORIA will pave the way to establish MSOT (Multispectral Optoacoustic Tomography) technology for the non-invasive assessment of intestinal inflammation in patients. EUPHORIA will enable commercialization of the technology by finalizing technical improvements that will increase diagnostic outcome beyond what has been shown in a first feasibility study, will improve usability, prepare CE marking for the new device and validate clinical results in a large clinical study. Inflammatory bowel disease (IBD) is a chronic condition, posing significant burden to patients and health care systems. Patients suffer from a relapsing course of intestinal inflammation, and to date, there is no satisfying non-invasive diagnostic modality for monitoring disease activity. In a recent clinical study conducted by University Hospital Erlangen, MSOT, a technology developed by iThera Medical (ITM), has proven to be superior in diagnostic performance to other procedures. Imasonic (IMA) and RayFos (RFO) are ideally positioned to drive the technical improvement steps: Imasonic, an expert in ultrasound transducer manufacturing, will develop an ultrasound detector with higher signal-to-noise ratio to enable better sensitivity and detection at depth. RayFos specializes on real-time sensing and image inversion, processing and rendering and has significant experience in optoacoustic tomography algorithms and implementation. iThera Medical will lead the incorporation into the device, CE marking and commercialization. The University Hospital Erlangen is an excellence center in IBD and will drive the clinical validation. Pintail has extensive project management, dissemination and commercialization expertise.

Protecting healthcare staff and preserving key clinical practice is a key WHO priority area for the immediate term in the COVID-19 pandemic, and also after peak crisis in the new practice landscape with population prevalence. Surgery is a key therapy for emergency patients and for cancer care and cardiac disease among others. It also is the hallmark aerosolising intervention, risking viral transmission to many staff, not only during the procedure itself, but also during other interventional procedures including bedside episodic procedures such as intubation for ventilation or nasogastric tube drainage. Recent guidance has suggested abandoning keyhole surgery access, despite its cornerstone role in emergency and cancer therapy, its myriad benefits to patients, and the fact that a whole generation of surgeons would need retraining in open surgery to accomplish this safely. Laparoscopic surgery uses gas to distend a body cavity to make space for a camera and instruments to be inserted and worked by a surgical team. This gas is emptied from the patient by opening valves in the access instrumentation which typically enters the operating room (OR). The risks of venting gas can be addressed technologically by using more sophisticated and emerging insufflation technology. However this does not address leaks during endotracheal tube placement, leaks that occur around the trocar, leaks during endoscopy or leaks from the anus during transanal surgery. This project will a) characterise the nature of these gas leaks using specialized imaging technology, b) develop vacuum devices to entrain and filter such leaks c) validate the effectiveness of the devices clinically, complete CE mark certification and e) deploy to surgery centres worldwide.