Bionure is undertaking a Phase-1 clinical trial of its lead compound BN201
Bionure’s main candidate BN201 promotes nerve and brain natural repair by enhancing remyelination and neuroprotection. This new chemical entity (NCE) is a first-in-class selective SGK2 agonist.
SGK, which is expressed in the nerve tissue, is an intracellular serine/threonine kinase that plays a crucial role in the response of neurons to stress and its survival.
BN201 promotes cell survival and endogenous natural repair through activating SGK-mediated FOXO3 translocation from cell nucleus to cytoplasm. The translocation of protein FOXO3 out of the nucleus shuts-off the transcription of apoptotic genes, therefore promoting survival.
Demyelinated Multiple Sclerosis (MS) and Acute Optic Neuritis (AON) lesions show a lack of mature oligodendrocytes (OL), even though oligodendrocyte progenitor cells (OPCs) can be found, indicating that a differentiation block of OPCs causes remyelination failure in MS/AON.
BN201 promotes remyelination by inducing OPCs differentiation into mature oligodendrocytes and promoting the formation of myelin sheaths around the axons. Our compound also promotes in vivo neuroprotection by preventing axonal loss and preserving retinal ganglion cells, crucial for preventing ganglion cells layer atrophy.
In MS, AON and also Neuromyelitis Optica (NMO), inflammation of the nerves induces significant demyelination and axonal damage. Once inflammation is removed by natural mechanisms or accelerated by the use of corticosteroids, nerve tissue remains damaged. So, a key unmet need in MS, AON and NMO patients is to prevent axonal damage during the attack in order to prevent subsequent disability.
BN201 has been shown to promote neuroprotection by preventing axonal loss and neuronal death in several animal models driven by different mechanisms of damage: demyelination in the lysolecithin-induced demyelination model, inflammation in the experimental autoimmune encephalomyelitis model and hypertension in the hypertensive glaucoma model.
Currently, a Phase 1 clinical trial is studying safety, tolerability and pharmacokinetics of BN201.