Anticancer approach based on the Metabolic Disruption of Cancer Stem Cells with high effectivity across a wide range of solid tumours (MEDiCS)
By combining advanced synthetic chemistry with cancer biology, we have demonstrated the potential of ruthenium complex IGN116 as an effective and tolerable anticancer agent, inhibiting tumour proliferation as early as 1-2 days post treatment in pre-clinical PDX models. Instead of acting as a cytotoxic agent, IGN116 interferes with the key bioenergetic pathway (aerobic oxidative phosphorylation) utilized by Cancer Stem Cells (CSC), drastically effecting their stemness potential whilst keeping other cells essentially unaffected. This mode of action is novel both among organometallic and CSC-targeting drugs, conferring IGN116s effectivity with unmatched low secondary toxicity. Through its unique mechanism of action, IGN116 provides the opportunity to tackle the specific therapeutic challenges of two particularly concerning cancer types that will be the focus of MEDICS: Therapy resistance in the high incidence CRC (1.9 million new cases and 608,000 deaths/year); and poor prognosis in treatment-refractory PDAC (495,773 cases, 466,003 deaths/year). The current TRL is at 3-4 having demonstrated in vivo efficacy, confirmed mechanism of action, and completed full toxicity pharmacokinetic (PK) studies of the isolated IGN116, both in in-house studies and in external CRO-led validation. In MEDICS, we will further develop IGN116 for CRC and PDAC progressing towards TRL5 through: Development of a scalable manufacturing process amenable to GMP; Advancement towards GLP in-vivo studies; and Creation of a spin-out to take the product development towards commercialization. MEDICS will thus tackle a critical challenge in European healthcare: delivering safe and effective cancer treatments, with the potential of benefitting 43,800 CRC and PDAC patients per year in Europe alone by 2040.