The consortium’s objective, which has obtained €2.5 million from the Agencia Estatal de Investigación, is to advance to the clinical phase of the antifibrinolytic agent CM-352

A public-private consortium formed by the biotechnology company Hemostatics, based in the Parc Científic de Barcelona (PCB), the Clínica Universidad de Navarra (CUN), and the Institut Català d’Investigació Química (ICIQ-CERCA), has secured €2.5 million from the Agencia Estatal de Investigación (AEI), under the call for Public-Private Collaboration Projects, to accelerate the development of an innovative treatment aimed at controlling disabling and lethal hemorrhages.

The project, led by Hemostatics – a spin-off from the Cima Universidad de Navarra, affiliated with the CUN – aims at the preclinical and clinical development of the antifibrinolytic agent CM-352, a first-in-class drug representing a pioneering therapeutic approach to control severe bleeding in unmet medical needs, such as those associated with major surgery, trauma, or intracranial hemorrhage (ICH).

The CM-352 compound stems from a lengthy research process led by Dr. Josune Orbe (CSO of Hemostatics) and leader of the Atherothrombosis group at CIMA, and Dr. José Antonio Páramo (CMO), from the Hematology Service of the Clínica de Universidad de Navarra and member of the Spanish Society of Thrombosis and Hemostasis (SETH). Based on a technology transfer agreement and an exclusive patent license, Hemostatics was founded in 2020, promoted by CIMA and a team of experts from the healthcare and business sectors, led by Dr. Orbe, Dr. Páramo, and Nicolas Saglio, CEO of Hemostatics and managing partner of the biomedical innovation consultancy HealthTech180, with over 20 years of experience in strategic consulting and innovation for technology and healthcare companies.

The total capital raised to develop the compound now amounts to €3 million, including the €0.3 million received from the Neotec program of the CDTI in 2022, in addition to other private funds.

A global health and economic problem

Hemorrhages account for up to 50% of deaths from trauma worldwide within 24 hours of traumatic injury, according to the Spanish Society of Intensive Care Medicine, Critical Care, and Coronary Units (SEMICYUC) [Intensive Medicine, 2022. DOI:10.1016/j.medin.2021.04.006], and up to 80% of mortality from intraoperative trauma. It is a common complication in cardiovascular patients, or those with certain rare genetic diseases, as well as in various clinical situations, such as surgeries, or postpartum hemorrhages, which are estimated to affect 14 million women each year and represent the leading global cause of maternal death, according to the WHO, with around 70,000 deaths annually.

Public-private partnership to create a next-generation antifibrinolytic

The CM-352 is a drug with a completely innovative mechanism of action, as it addresses the cessation of bleeding by inhibiting matrix metalloproteinases (MMPs), which represents a revolutionary pharmacological strategy promising to be more effective and safer than current standard antifibrinolytics (TXA and EACA) used clinically to control acute bleeding.

The regulatory preclinical phase will be coordinated by Hemostatics and will involve integrating the efforts of the Atherothrombosis Research Group (CIMA), led by Dr. Josune Orbe, UT Health University of Houston, and the company Vivotecnia.

We already have experimental results indicating that CM-352 is highly effective in major bleeding scenarios, with no signs of toxicity, thrombosis, or secondary adverse effects. Now we will complete efficacy, toxicity, pharmacodynamics, and pharmacokinetics studies in several preclinical models required by regulatory agencies. Obtaining these results will allow us to achieve a key milestone in the project: approval from health authorities to test CM-352 in a Phase I clinical trial. Our initial focus will be the FDA in the United States. Subsequently, we will also go to the EMA in Europe, and everything will be done in close collaboration with the Spanish agency, the AEMPS”.

Nicolas Saglio

Through the Innovation and Valorisation Laboratory and the High Throughput Experimentation (HTE Laboratory), ICIQ will address the identification and optimisation of a synthesis route for CM-352 that improves efficiency and reduces the cost of the molecule’s production process. The team involved in the project will be led by Dr. Fernando Bravo, manager of the Knowledge and Technology Transfer Department (KTT) and Industrial Projects, and Dr. Xisco Caldentey, manager of HTE.

The current synthesis route of CM-352 has enabled obtaining sufficient compound quantities to progress through the preclinical phases, and ICIQ’s involvement will focus on developing a synthetic process with a new optimised synthesis route, which also allows for robust, reproducible scaling with safety guarantees. This objective will be addressed through a combination of intelligent catalyst design and high-performance parallelisation techniques for reaction optimisation. In this regard, techniques involving the screening of hundreds of reactions using automated analysis systems will be applied, such as the one available at ICIQ’s HTE Laboratory, a unique facility in Spain, with few similar models worldwide. The selection of the final synthetic route for obtaining CM-352 will be based on techno-economic criteria (cost/kg), including the relative cost of purification processes, efficiency, safety, and minimization of environmental impact, thereby facilitating its future industrialization and commercialization”.

Dr. Fernando Bravo

Finally, the Phase I trial of CM-352 will involve active participation from CUN, with technical support from CIMA, and will focus on severe hemorrhages in traumatology, where there is no treatment with demonstrated clinical efficacy. The study will be conducted by the Hemostasis and Thrombosis Unit of the Hematology Service and the Department of Orthopedic Surgery, under the coordination of Dr. José-Antonio Páramo.

Our objective will be to evaluate the tolerance and safety of CM-352 in patients undergoing scheduled total knee replacement surgery (total knee arthroplasty) to prevent possible hemorrhagic complications, which constitute a serious associated adverse event. This represents a very important milestone in the compound’s development since, in existing literature, no clinical study has reported the use of MMP inhibitors to treat hemorrhages. The absence of toxicity and secondary effects after treatment with CM-352 will also represent the first time such results are obtained for an MMP inhibitor in humans, allowing us to move to a Phase II focused on severe hemorrhages in traumatology.”

Dr. José-Antonio Páramo

Proyecto CPP2022- 009643 financiado por: