Two active ingredients combined in a single crystalline solid, with a potential activity in the treatment of pain superior to both each of the two individual components and to their mixture. This is the result of a chemical, synthesis and process research work carried out in Dompé Pharmaceuticals and become one of the winners of the Eugenio Aringhieri 2021 Award. This represents a pioneering branch of pharmacological science, with a first important result that paves the way for a whole new drug discovery program, looking for further patentable solutions.

From the chemical-physical point of view, these are co-crystals, i.e. multicomponent crystalline solids with exact stoichiometry consisting of at least one active pharmaceutical ingredient and an organic molecule as a 'coformer', to which a further active ingredient can be added, so as to form a crystal containing two different drugs. On the one hand, the co-crystal maintains the intrinsic properties of its components, but on the other hand it has physico-chemical, pharmacokinetic and pharmacodynamic properties that can be regulated through the choice of the 'coformer' and active ingredients. This is a future-oriented area where to date there is only one pharmacological co-crystal on the market.

The one discovered and developed by the Dompé working group exploits the synergistic effect of the two components to obtain a potential activity against pain, already proved in pre-clinical phase and to be confirmed through phase 1 and 2 clinical studies soon to be launched.

The complexity of the research does not only concern the conception of the co-crystal itself, but above all the optimization of the process and the supply chain. A work that involved a highly qualified multidisciplinary team with experience in organic, medicinal and analytical chemistry, composed of Andrea Aramini, Head of Research & Early Development, Gianluca Bianchini, Medical Chemistry Associate Director, Samuele Lillini, Medicinal Chemestry Senior Specialist, Niccolò Pacchiarotti, Intern at University of Nottingham, Mara Tommassetti, Medicinal Chemestry Senior Specialist, and Daniele Canestrari, Research & Early Development Expert. The internal collaboration was then joined by a network of external relations and skills specifically created and which includes, among others, the University of Turin and the University of Campania Luigi Vanvitelli. All in a synergy that ensured an accelerated process despite the additional complexity due to the health emergency, with the need to geographically manage the phases of the study depending on the sites where it was possible to work, including laboratories and pre-clinical trials.

The co-crystal synthesis process enables a complete control of the impurities of the final product, optimizing them until they are substantially untraceable. This last milestone was decisive for scaling the industrial production process, i.e. to move from small to large quantities of co-crystal and start clinical trials.

In addition to the co-crystal, the added value of the research process is having developed a work platform on which to structure the next research. The first clinical candidate was identified in just over a year of research, so the approach has shown that it can quickly reach the clinical development stage, also thanks to the use of cutting-edge technologies. In this new branch of pharmacology, still to be clearly defined in the regulatory field both in Europe and the United States, Dompé is positioned as one of the most advanced companies in the world, being able to further expand to other therapeutic areas and active ingredients.