Proof of concept for superior therapeutic efficacy of nose-to-brain delivery of trastuzumab compared to systemic route for treatment of brain metastase. – N2B

Diseases of the central nervous system (CNS) could be eligible for biodrugs but the blood-brain barrier (BBB) remains the main obstacle for their delivery in the CNS. Metastatic breast cancer is a leading cause of mortality in women and particularly the brain metastases. Although trastuzumab (TZB) has improved patient survival, it cannot cross the intact BBB. Even when injected intrathecally, TZB is rapidly cleared into the blood making it difficult to achieve the concentration of TZB required for therapeutic effect. The various therapeutic approaches to bypass the BBB have proven unsatisfactory for patient survival. The original approach of this project is the Nose To Brain (N2B) pathway by a promising option to bypass the BBB, allowing direct delivery into the brain parenchyma thus limiting the efflux of TZB to the blood by the FcRn present on the BBB and finally to reduce systemic adverse drug effects. N2B project aims at demonstrating the therapeutic efficacy of the trastuzumab (TZB) or its fragment Fab (Fab TZB), targeting the HER2 tyrosine kinase receptor in an appropriate formulation allowing its passage via N2B using the olfactory and trigeminal nerves. This disruptive approach opens the way to treat many brain pathologies eligible for treatment with biodrugs.