The focus of the beneficiaries in the project PANACREAS will be on multiple pathways and mechanisms involved in PDAC. We will synthesize new molecules, assess their capacity to effectively block precise cancer-associated mechanisms and determine their anticancer activity in vivo. Compounds with strong PoC activity will be developed up to the stage of IND, and thus put on their way to clinical experimentation.
As a general scheme for this project (see below) we foresee a strong commitment to the synthesis and screening of new targeted inhibitors during the first 12 months of the project. The hit-validation and lead optimization phase is foreseen in the subsequent 12 months. Those compounds that appeared promising in terms of in vitro anticancer activity/potency/specificity will undergo pre-formulation/formulation work and PK/BA studies at the pharmaceutical companies involved in PANACREAS (6-12 months). Thereafter, such compounds will be used for the PoC study in PDAC models at the CIO Cologne-Bonn (UKB) (6 months). Finally, upon recognition that one or more compounds do show PoC activity in these models, in particular those exhibiting an improved efficacy when compared to the current standard-of-care gemcitabine, we are committed to perform an IND-enabling study with such molecules (24 months) in order to deliver by the end of the project a drug that is ready for clinical testing.