This Action will contribute to the sustainable development of European chemical industries in the coming decades by delivering an ambitious doctoral training programme that draws on expertise from industry and academia across 4 European countries. The research agenda and experiential training will grow the skills base beyond approaches that have relied upon a limited set of molecular scaffolds and a relatively small sub-set of reactions to exploit new reaction paradigms and platforms (e.g. high throughput experimentation, photoredox & electrochemistry) that meet the needs of modern drug discovery science.

Industry is the highest heat consuming sector, and its need for high temperature process heat is on the increase. However, 83% of industrial process heat is still supplied by inefficient and polluting fossil fuel boilers. The Highlift project will develop a next-generation high temperature heat pump (HTHP) based on an innovative 4-cylinder alpha configuration Stirling engine design. Highlift accepts low temperature (30´C) input water drawn from industrial waste heat recapture systems and use electrical energy to generate saturated steam at over 180´C. Such temperature lifts are not possible with any other HTHP today. The Highlift project optimises the industrial design via 1) increased system efficiency, 2) improved reliability, 3) 30% cut on production costs, 4) refined production quality control, and 5) improved Cloud-based operating system. We will pilot the near-market prototype at a single high-profile multinational industrial end user with high demands in terms of constant, intensive operation and high output temperature requirements. The project will simultaneously undertake a market maturation process including up- and downstream supply chain development, in-depth target market analyses, and validation of the business and commercialisation strategy. This will bring the HighLift technology to full commercial readiness at the end of the project. Over 25,000 hours of tests with industry since 2012 have shown that it is feasible to use Highlift to generate hot industrial process steam in an economic and environmentally sustainable way. Highlift reduces energy consumption to supply high temperature process heat by 50-70% and will cut industrial CO2 emissions when producing high temperature steam by 70-96%. Our planned commercial roll-out of 174 Highlift heat pumps by 2025 will save our customers a total of €134.2m, and reduce up to 65,600 tons of CO2 (eq) emissions.

Biological drugs such as peptides, proteins, oligonucleotides and analogs provide the patients with more efficacious and less toxic treatments and have lower attrition rates than chemical drugs since 1 on 9 new biological entities entering clinical trials reaches the market (1 on 16 for chemical drugs). Consequently, 15 on 24 top blockbuster drugs were biotherapeutics in 2020 (world-market share of about 40% of $175 billion of revenue per year). In order to reduce the immunogenicity of biodrugs, to overcome their fragility and to increase their capacity to reach quickly and massively their target, reduced-size biologics are extensively developed. However, radiolabeling of large molecules by grafting bifunctional chelating agents which do not alter significantly their biological activity is thus no longer possible with smaller biodrugs. It is therefore of paramount importance to devise new radiolabeling approaches carried out on tiny quantities in aqueous media and very soft conditions. It is also crucial to train a new generation of radiochemists in order to implement these methods and to meet the needs of the European industry. ISOBIOTICS ambitions: 1) to develop new chemically-benign strategies for the last-stage radiolabeling of large peptides, small/medium-size proteins, oligonucleotides and analogs with deuterium, tritium and carbon-14 (preclinical and phase 0 clinical evaluation), and fluorine-18 (phase I-III clinical trials); 2) to educate a new generation of young talented PhD students specialized in the radiolabeling of biologics through a combination of interdisciplinary lab research, transdisciplinary and intersectorial secondments, technical taught courses, scientific lectures and complementary skills workshops; 3) to ensure the appropriate dissemination, exploitation and communication of all ISOBIOTICS outputs in order to maximize the project’s impact and radiance; 4) to secure the students employment and the sustainability of training structures.

Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling and life-shortening congenital syndrome for which no effective therapies exist. Repurposing of AZD0530 (saracatinib, AstraZeneca) would be an ideal solution for de-risking early clinical studies. Using existing assets and investments, this may allow more affordable pricing once an indication is approved. Ectopic bone is formed in soft tissues due to activating mutations in the bone morphogenetic protein receptor kinase ALK2/ACVR1, leading to progressive contractures and early death. Preclinical studies showed AZD0530, previously unexplored in FOP, to be a potent (5nM) inhibitor of ALK2 kinase and ALK2-R206H-mediated neofunction after activin stimulation. In mice, AZD0530 blocked ectopic bone formation preserving limb movement. Hypothesis: AZD0530 will reduce ectopic bone formation and progressive disability in people with FOP. AIM: to provide proof of concept that AZD0530 is an effective drug in the treatment of patients with FOP. Methods: Based on the rarity of the disease and expected drug efficacy (50% reduction in new bone), a phase 2A proof of concept study including a 6 month randomized placebo controlled study and 12 month open label extension study using historical data, is proposed including 16 adults with active FOP disease. The study will be performed in three European FOP expert Centers (Amsterdam The Netherlands – Lead, London UK, and Garmen Partenkirchen Germany). The study will be performed in collaboration with the expert preclinical teams at the Universities of Oxford and Harvard. FOP expert and patient engagement as well as safety will be ensured by establishing advisory, DSM and stakeholder boards. Early involvement of the regulatory agencies are planned. Expectations: we will develop a roadmap for further studies and regulation of this new treatment option in FOP based on the results.