Ruthenium-based photoactivated chemotherapy (PACT) is a new technology where the toxicity and anticancer activity of a chemotherapy drug is tuned down by attaching a molecular “cage” to the chemotherapy molecule. By doing so, the active but toxic chemotherapy drug is transformed into a prodrug that is both inactive and non-toxic for the patient. After giving such a prodrug to the patient, for example intraveinously, the prodrug distributes in the body and, like any other drug, partly penetrates into the tumor where it does not do anything. A light source is then used to shine light onto the tumor, where the molecular “cage” is photochemically removed, thereby recovering the anticancer activity of the chemotherapy drug. Local activation of the prodrug ensures a low systemic toxicity of the treatment for the patient, and hence low side effects, compared to standard chemotherapy that is already active when injected in a patient.
Though in theory applicable to all forms of cancer, PACT is not yet applied in the clinics. The ambition of PACT4EYE is to develop the clinical potential of one particular prodrug of this kind, which has been developed at Leiden University, in the context of uveal melanoma (UM). UM is the most common form of eye cancer but it is a rare disease. It hence represents a challenging target for drug development and for the translation of new molecules to the clinics, as big pharma is typically not interested. On the other hand, special regulations have been developed in Europe to simplify the translation of innovative treatments of rare diseases.
The ambition of PACT4EYE is to use this simplified path to demonstrate to science, to the public, and to investors, that it is possible to develop PACT treatment of UM as an industrially viable product. Our target is to define such a product, and to develop a realistic business plan towards development of this product towards clinical trial. Our consortium will define our clinical target and product, and perform all pre-clinical work necessary to demonstrate the safety and efficacy of our prodrug in animal models using patient-derived tumor models. These tumor models currently represent the method with the best predictive power for the clinical success of new (pro)drugs.
The project includes a chemical part for scaling up synthesis and preparing it for GMP production; a biological part, to study toxicity of our prodrug towards animals, their eyes, and their vision, and the efficacy of our treatment in tumor models; and a business part, to investigate the patent landscape, develop a business plan and the business readiness of our product.
