MIAT has in place a collaboration agreement with the Italian Fondazione IRCCS Istituto Nazionale dei Tumori of Milan for the development of specific research projects.
One of the projects concerns a Vitamin A derivative as a novel non-toxic chemotherapeutic agent for cancer therapy. The compound is a patented derivative of a well tolerated and clinically tested vitamin A analog, hydroxyphenil-retinamide (fenretinide).
The new compound, a salt of 4-oxo-HPR (s-4-oxo-HPR), has shown a potent in-vitro anti-proliferative activity against highly proliferating tumors. In preclinical studies, s-4-oxo-HPR reduced tumor growth and increased survival in xenografted murine models (lymphoma, breast and ovarian cancer, mesothelioma).
The envisaged clinical application of s-4-oxo-HPR is in the combination treatment with chemotherapeutics to reduce their dose, and toxicity, and improve efficacy.
The chemical synthesis and scale-up of the compound has been successfully completed.
A complete program of non-clinical development has been agreed with the Laboratory of Preclinical Research (LARP) of the University of Ferrara (Italy) and is currently undergoing.
After a preliminary study in Sprague-Dawley rats to acquire information on the toxicokinetic parameters, the development program will continue with an ADME and bioavailability study in rats.
At the completion of the ADME study, a 90-day, GLP regulated, repeated-dose toxicity study will be carried out to establish the safety of the compound.