Auris Medical is developing AM-111 for the treatment of acute inner ear (sensorineural) hearing loss (ASNHL). AM-111 contains brimapitide, or D-JNKI-1 (D-stereoisomer of c-Jun N-Terminal Kinase Inhibitor 1), an inhibitor of the JNK stress kinase coupled to an intracellular transporter. AM-111 is formulated in a biocompatible and fully biodegradable gel and administered in a single dose intratympanic injection into the middle ear. From there the drug diffuses through the round window membrane into the cochlea.
AM-111 received orphan drug designation from both EMA and FDA for the treatment of ASNHL. AM-111 has the potential to become the first approved pharmaceutical treatment for ASNHL.
JNK is a signal transmitting enzyme that regulates a number of important cellular activities, including activation of genes encoding inflammatory molecules or promoting cell death (apoptosis). JNK is activated following various types of cochlear insults (stress) that may lead to ASNHL. AM-111 enters cells and binds to JNK, thereby inhibiting activation of transcription factors such as c-jun and c-fos. This in turn prevents JNK mediated apoptosis and inflammatory response, which could otherwise result in irreversible loss of hair cells and cochlear neurons. AM-111 supports natural recovery processes and helps to prevent or reduce chronic hearing loss.
AM-111's otoprotective effect has been demonstrated in various animal models of cochlear stress, including acute acoustic trauma, acute labyrinthitis (inflammation), drug ototoxicity (aminoglycosides), bacterial infection, cochlear ischemia and cochlear implantation trauma.
AM-111 is currently in Phase 3 clinical development.