Anticancer approach based on the Metabolic Disruption of Cancer Stem Cells with high effectivity across a wide range of solid tumours

Informazioni relative al progetto

MEDiCS

ID dell’accordo di sovvenzione: 101214053

DOI

10.3030/101214053

Data della firma CE 13 Marzo 2025

Data di avvio 1 Maggio 2025

Data di completamento 30 Aprile 2028

Finanziato da

• The European Innovation Council (EIC)

Costo totale

Nessun dato

Contributo UE

€ 2 498 015,63

Coordinato da

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Spain

Periodic Reporting for period 1 - MEDiCS (Anticancer approach based on the Metabolic Disruption of Cancer Stem Cells with high effectivity across a wide range of solid tumours)

Periodo di rendicontazione: 2025-05-01 al 2026-04-30

Sintesi del contesto e degli obiettivi generali del progetto

Cancer remains one of the leading causes of mortality worldwide, with colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) representing two major unmet clinical challenges. CRC is among the most common cancers globally, while PDAC is one of the deadliest malignancies, characterized by poor prognosis and resistance to existing therapies. Current treatment options are often limited by severe side effects, therapeutic resistance, and relapse, highlighting the urgent need for safer and more effective therapeutic approaches.
The MEDiCS project addresses this challenge through the development of a new anticancer chemotherapy targeting the respiration of cancer stem cells, based on the ruthenium complex IGN116. Unlike conventional metal-based chemotherapeutics that promote cytotoxic effects, IGN116 interferes with aerobic oxidative phosphorylation (OXPHOS), a bioenergetic pathway that is key for cancer stem cells (CSCs), a population associated with metastasis, therapy resistance, and tumor recurrence.
Preclinical studies have shown that IGN116 can inhibit tumor growth within 1–2 days after treatment in patient-derived xenograft (PDX) models of CRC and PDAC. Importantly, the compound exhibits a favorable toxicity profile, primarily targeting CSC metabolism while largely sparing healthy cells. This represents a novel therapeutic strategy among both organometallic drugs and CSC-targeting therapies, with the potential to be used in combination with current standards of care.
The project currently stands at Technology Readiness Level (TRL) 3–4, with demonstrated in vivo efficacy, a validated mechanism-of-action hypothesis, and completed pharmacokinetic and toxicity studies conducted internally and through external contract research organizations. However, several limitations remain that must be addressed to enable further development. MEDiCS aims to overcome these limitations through the development of nanoformulations of IGN116.
To advance the technology towards TRL5 and future clinical translation, MEDiCS will develop a scalable GMP-compatible manufacturing process, conduct GLP-compatible in vitro and in vivo studies, and establish a dedicated spin-out company to support commercialization and industrial uptake. These activities will prepare the pathway for first-in-human clinical testing in patients with CRC and PDAC.
By delivering a safer and more effective CSC-targeted therapy, MEDiCS aims to improve outcomes for patients with difficult-to-treat cancers while reducing the burden associated with highly toxic anticancer treatments. The project has the potential to benefit a large number of patients with CRC and PDAC and strengthen Europe’s position in the development of innovative anticancer therapeutics.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

There has been significant progress in the development of nanoformulations of the ruthenium-based therapeutic candidate IGN116, a compound that had never been included in nanocarrier systems. This work established key scientific, technological, and regulatory foundations for its further development as a therapeutic product.
Several nanoparticle platforms were successfully developed and evaluated, leading to the selection of two types of nanoformulations based on physicochemical characterization, drug incorporation, release behavior, stability, preservation of the active compound, and manufacturing feasibility. Both demonstrated excellent stability after lyophilization and reconstitution and retained key properties required for further development, including suitability for intravenous administration and potential for large-scale manufacturing.
In vitro studies demonstrated that the selected nanoformulations retained the characteristic mitochondrial mechanism of action of IGN116, confirming that encapsulation did not compromise biological activity. Preliminary in vivo studies indicate an absence of acute toxicity, providing an important foundation for future candidate selection and translational development.
A comprehensive assessment demonstrated that the transition towards GMP-like manufacturing is feasible without major technical or regulatory barriers. Manufacturing processes and analytical methods were successfully optimized, and an integrated regulatory roadmap was established to support future clinical translation.
Overall, the project delivered two promising IGN116 nanoformulations that preserved biological activity, present encouraging initial preclinical safety data, and are compatible with future manufacturing and regulatory requirements, significantly strengthening the translational potential of the technology.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

The project has already generated important advances beyond the current state of the art in anticancer nanomedicine through the successful development and characterization of nanoformulations of the ruthenium-based therapeutic candidate IGN116. The developed nanoformulations are based on clinically relevant nanocarrier technologies inspired by systems already used in approved medicines. The use of materials and excipients with established pharmaceutical relevance should facilitate future clinical translation.
Importantly, this work represents the first successful nanoformulation of this class of polypyridyl ruthenium complexes. As no previous formulation strategies were available for this type of compound, substantial original research and technological development were required. The project generated new knowledge through comparative studies covering formulation performance, physicochemical characterization, drug release behavior, stability during storage, and the development and validation of analytical methods. Together, these activities have produced a robust scientific and technical dataset that constitutes an important contribution to the field of metal-based nanomedicines.
The project has also generated valuable know-how in the development, characterization, and manufacturing of complex nanoparticle systems. New analytical and production methodologies were established and optimized, creating a strong technological foundation for future development. In addition, the availability of stable formulations that can be stored, transported, and reconstituted while maintaining their key characteristics represents an important step towards future manufacturing, regulatory development, and clinical application.
The results obtained to date demonstrate the feasibility of combining nanotechnology with innovative metal-based anticancer agents, opening new opportunities for the development of more effective therapies. The project has established a clear pathway for the further development of IGN116 nanoformulations and generated knowledge that may apply to other metal-based therapeutic compounds.
Further research is required to complete the ongoing preclinical evaluation and refine the selection of the lead candidate. Pharmacokinetic and in vivo performance data will support candidate prioritization and guide subsequent regulatory and development activities. These results are also expected to strengthen the intellectual property position of the technology, support future patent applications, and contribute to commercial exploitation opportunities.
Despite the scientific and technical challenges associated with developing the first nanoformulations of this type of ruthenium complex, the project has successfully established the essential scientific, technological, and regulatory foundations required for continued advancement. The work remains on track to deliver a clinically relevant nanoformulated version of IGN116 for colorectal cancer and pancreatic ductal adenocarcinoma, while also creating a platform technology that could be extended to additional cancer indications in the future.