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.

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.

The European Union has been challenged to contribute to the global aim of providing sustainable solutions to the current and future needs on synthetic compounds and materials in the coming years. In this sense, the development of sustainable chemical processes is one of the most important features in modern chemistry. It has become a key research area worldwide, providing solutions to important societal demands by optimizing the use of natural resources and minimizing waste and environmental impact. Among the relevant methods for achieving this goal, catalysis represents a key and central approach. Both Organocatalysis and Metal Catalysis have emerged as solutions to the problems in this context. Despite the enormous advances made towards both types of catalysis, the development of more efficient and general catalysts, as well as synthetic methods is still a challenge. A very similar research-road has occurred in the Photocatalysis area, using visible-light as mild and sustainable energy source. In this context, the pharmaceutical industry has a great impact in our society. Well-stablished organo- and, especially, metal-catalysis have been largely implemented in the chemical industry, both on a micro and ton scale. However, there are only few timid academic applications of novel photocatalytic visible light methodologies into industrial goals. Therefore, the development of cheaper and straightforward methodologies to the incorporation of key photochemical processes is an important field and has a tremendous impact in the industry field. Therefore, greater blending of academia and industry would be desirable for the implementation of photocatalysis in the chemical industry world. Students who can access this doctoral network will have the opportunity to work in European Funded academic researchers and in three Big Pharma companies in a hot field such as photocatalysis with the aim to develop new real industrial solutions.

Better drugs are one of the most efficient and sustainable ways to improve health care, a key strategic orientation in Horizon Europe. New drug modalities such as macrocycles are expected to be a key enabling technology for this strategic perspective. The goal of MC4DD is to train the next generation of European medicinal chemists in a multidisciplinary environment to promote European drug discovery competitiveness, directly by advancing knowhow on macrocycles and long-term via the skills carried on by the researchers trained in the doctoral network.