Phase I clinical trial of a new antifibrinolytic agent, compound CM-352, with an efficient synthesis route, aimed at controlling disabling and lethal bleeding

Project description

Hemostatics was born out of research carried out by the Cardiovascular Diseases Program at the Center for Applied Medical Research (CIMA), which also houses the University of Navarra Clinic (CUN). The goal was to investigate new effective mechanisms of action to improve the therapeutic effect in severe bleeding. The results led to the development of the compound CM-352, which, unlike current treatments, addresses the cessation of bleeding by inhibiting matrix metalloproteinases (MMPs), achieving increased effectiveness and safety compared to standards of care (TXA and EACA). The compound CM-352 has undergone a lengthy process of medical chemistry screening and has achieved an excellent safety profile compared to other MMP inhibitors used in clinical trials in the field of oncology, with lower risks when administered acutely.

Hemostatics has decided to carry out the phase I clinical trial at CUN with technical support from CIMA through subcontracting. However, at the molecular level, the compound presents a series of intrinsic problems that make the generation of enantioselective quaternary carbons an extremely inefficient process. For this reason, Hemostatics wants to collaborate with the Catalan Institute of Chemical Research (ICIQ), an expert institution in catalysis and, in particular, in catalysts for enantioselective synthesis, to address the search for alternative routes for the compound under study. We can conclude that the consortium is based on the development of a new antifibrinolytic agent, the compound CM-352, with an efficient synthesis route aimed at controlling disabling and lethal bleeding through a new pharmacological strategy based on MMP inhibition, which will provide a much more effective and safer therapeutic approach than current treatments. By combining catalyst design with hundreds of reaction screening techniques using automated analysis systems, such as the one available at the ICIQ’s HTE laboratory, once we have the new synthesis route of the compound, we have planned toxicological studies to request approval to test the compound CM 352 in humans, classified into genetic and pharmacological toxicology. Finally, the phase I clinical trial will be carried out in the Department of Orthopedic Surgery in primary total knee replacement (TKR) procedures. The phase I clinical trial will be a blind study aimed at investigating the safety, tolerability, and pharmacokinetics of CM-352 in order to verify the safety and feasibility of acute administration of CM-352 in a total of 21 patients. The beneficial results shown by the compound CM-352 will allow us to move on to a phase II study with a focus on severe bleeding in traumatology, where there is currently no treatment with demonstrated clinical efficacy. Unfortunately, bleeding is a very common complication in different clinical situations, such as surgeries (30% of the 800,000 patients requiring a blood transfusion) or trauma (responsible for 45% of deaths after 24 hours following a traumatic injury). If we confirm our hypotheses and verify the results in the proposed models, we could obtain at least one patent for the development of a new synthesis route. Finally, thanks to the impetus of this help, we will be able to have a product ready for licensing in 2028 in a potential market of more than 11 million cases of severe bleeding in surgical interventions by 2032, which could generate a NPV and IRR of 3 billion and 135.6%, respectively.

Proyecto CPP2022-009643, financiado por MCIU/AEI/10.13039/501100011033 y por la Unión Europea “NextGeneration EU”/PRTR.