Oral delivery of peptide-analogues (a macromolecule) is one of the great challenges in pharmaceutical research. Thus far, only five peptide-analogues have been converted to oral formulations such as tablets/capsules and all face distinct challenges including low bioavailability, dosage control, patient administration inconvenience and restrictions in use (e.g. undesirable food interactions). The BUCCAL-PEP consortium will join hands to develop a multifunctional biomaterial patch which allows, for the first time, buccal (in the cheek) delivery of peptide-analogue therapies, thereby overcoming these challenges through unique integration of a permeation enhancer (SDC) with biomaterials and a peptide-analogue. The novel formulation enables peptides to diffuse across the mucosal multilayer, thereby effectively achieving their intended pharmacological response. The novel approach will result in an improved quality of patient life and increased treatment compliance. Within this project, the consortium will design, select and manufacture a lead product (with Type 2 Diabetes as showcase indication) that will be validated for performance in in vivo large animal studies. Additionally, a Health Technology Assessment will be performed to support the development an evidence-based value proposition and aid in the development of a commercialisation strategy. The final deliverable of the project is a patch that is pre-clinically validated and ready for clinical trials in the desired showcase indication. Overall, the BUCCAL-PEP project will provide a platform technology for oromucosal delivery of peptide-analogues that will be suitable for a broad range of experimental- and approved peptides-analogues therapies across a multitude of disease indications. BUCCAL-PEP will enable novel peptide-based treatments to emerge, which otherwise might not have reached the market due to incompatibility with the currently available administration routes.

Chinese hamster (CHO) ovary cells are the production host for a +50 billion €/yr biopharmaceuticals market. Current CHO production platforms dates to 1980 and are based primarily on media and process optimisation with little consideration to the optimization of the cellular machinery. Fortunately, with the recent sequencing of the CHO genome, an opportunity has opened to significantly advance the CHO platform. The benefit will be advanced production flexibility and a lower production cost. This ITN graduate training programme - eCHO Systems - will blend conventional molecular, cellular, and synthetic biology with genome scale systems biology training in ‘omics data acquisition, biological network modeling, and genome engineering in three interdisciplinary topics: 1) Acquisition of large scale ‘omics data sets and their incorporation into genome-scale mathematical models 2) Development of genome engineering tools, enabling synthetic biology 3) Application of systems and synthetic biology and genome engineering to improve performance of CHO producers The training projects are supported by 15 industrial participants, which will participate in the research and test the results. ESR training will include intense courses focused on computational systems biology, cell biology, business and entrepreneurship. The three universities bring unique complementary skills in systems and synthetic biology, ‘omics technologies, cytometry, and molecular cell biology which will provide depth and breadth to this training. The eCHO Systems will produce four major outputs: General knowledge to improve the productivity, quality, and efficiency of CHO platform cell lines, new systems models for CHO cells, new CHO cell line chassises generated through synthetic biology approaches, high quality education at the graduate level, and a cadre of interdisciplinary graduates poised to transform biopharmaceutical biotechnology.

Randomised controlled trials are the cornerstone of evidence-based medicine. However, the digitisation of real-world data (RWD) including data from devices, wearables, and electronic health records in large national registries provides opportunities to demonstrate efficacy and safety of innovative technologies including drugs, devices, diagnostics, and digital health. These data are particularly relevant to long-term conditions such as diabetes mellitus, where drugs, lifestyle interventions, and digital technologies often work together. To better utilise RWD in diabetes for regulatory decision making, a development of standards, guidance, and an assessment of the efficacy to effectiveness gap is needed. REDDIE (Real-World Evidence for Decisions in Diabetes) aims to explore how RWD can complement RCTs to improve efficacy, safety, and value for money of technologies to prevent and treat diabetes. The overall aim of REDDIE is to support the use of RWD in diabetes and health-related research, which will maximise Europe’s scientific expertise and know-how to benefit people with diabetes, resulting in safer, more efficient, and cost-effective interventions. We thus aim to engage with stakeholders such as regulatory and HTA authorities and co-develop evidentiary standards for the collection, assessment, and acceptability of RWD. We will then develop and validate state-of-the art modelling techniques using synthetic data derived from large national registries to better assess outcomes of interventions using RWD. We will use data from four large national registries to elucidate the gap between outcomes in RCTs and RWD studies, and understand the factors that affect this gap. Finally, we will test the ability of machine learning to facilitate the better use of RWD. REDDIE will generate standards for RWD use for the evaluation of medicines and other interventions by regulatory authorities and HTA bodies.

Carbohydrates are nature’s most abundant and versatile molecules and are involved in several diseases (e.g. diabetes, infection, and cancer metastasis) and other regular processes (e.g. fertilization, immune surveillance and inflammatory responses). Understanding, monitoring and intervening in these processes could be exploited in medicinal therapies, glycobiology, and biomedical research in general. Such applications are predicated on the availability of carbohydrate binding molecules (CBMs) that can selectively and supramolecularly (noncovalently) bind a plethora of carbohydrate molecules ranging from simple monosaccharides to complex oligosaccharides and glycoconjugates. Technologies that can be developed based on CBMs include: the separation and isolation of carbohydrate containing molecules; making carbohydrate sensing and detection devices; enabling selective chemistry on (unprotected) carbohydrates; and a range of bio-functional applications. While the expertise to design, synthesize, study and exploit CBMs is mostly European, the research groups active in this emerging field work independent from each other. With this doctoral network grant, we aim to unite this expertise in the ‘European Network for the Supramolecular Chemistry of Carbohydrates’ (ENSCC). With most of the world’s leading minds on the topic and three companies that are spearheading technologies in the field, our ENSCC will be a European powerhouse that will lead the academic field globally for years to come. This will be achieved by sharing expertise, key-infrastructure, molecular building blocks, and –most importantly– by together training the ten PhDs that this doctoral network grant will fund. This training by a unique network of world-leaders, experts in the field and companies with an interest in CBMs will perfectly position our PhD students to further develop the field by continuing their career in academia and/or industry.