Auris Medical Announces Publications Related to AM-101 in Peer-Reviewed Scientific and Medical Journals

Auris Medical Holding AG

, a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in otolaryngology, today announced publications related to AM-101, the Company's lead product candidate for the treatment of acute inner ear tinnitus, in two peer-reviewed specialist journals. "We are very pleased to see these important additional pre-clinical and clinical data published on our AM-101 program", commented Thomas Meyer, Auris Medical's founder, Chairman and CEO. "They add further to our understanding of the pathogenesis of inner ear tinnitus as well as AM-101's therapeutic effects and potential clinical use." The first of the two articles appeared in Audiology & Neurotology and describes the outcomes from TACTT1, the second randomized, placebo-controlled, double-blind phase 2 clinical trial conducted with AM-101 in the treatment of acute inner ear tinnitus.(1) The primary objective for TACTT1 was the evaluation of appropriate dosing regimens by comparing treatment outcomes between a single intratympanic dose of AM-101 or three doses spread over two weeks. The trial showed a consistent trend for superior tinnitus improvement for AM-101 treatments over placebo that was similar for both dose regimens. The primary endpoint, the change in tinnitus loudness from baseline to the last follow-up visit, did not show a statistically significant difference. The comparison of the primary endpoint effect sizes observed in TACTT1 with the corresponding value in the preceding TACTT0 trial revealed that the best results were achieved with repeated injections over a short treatment cycle. "The TACTT1 trial provided further evidence of AM-101's therapeutic benefits in the treatment of acute inner ear tinnitus and additional support for our choice of dose regimen," commented Bettina Stubinski, Auris Medical's Chief Medical Officer. "The repeated application of AM-101 over a few days is well tolerated and allows for concentrated inhibition of cochlear NMDA receptors, while limiting the procedural impact on the patient." In the currently ongoing phase 3 trials, AM-101 or placebo are administered three times over 3-5 days. The second article was published in Cellular Physiology and Biochemistry and presents the results of a study of AM-101 in an animal model of tinnitus induced by acute noise trauma.(2) The study was conducted by Prof. Marlies Knipper and colleagues at the Tübingen Hearing Research Center in Germany. The researchers sought to further assess the role of aberrant NMDA receptor activation and related auditory nerve excitation in the generation of tinnitus following traumatic injury to the cochlea. They focused on the damage to inner hair cells (IHCs)and in particular loss of ribbon synapses as correlate for deafferentation as well as on its impact on auditory brainstem responses (ABRs). Previous studies had shown that a pattern of severe IHC ribbon loss and reduced ABR wave size after acute noise trauma was linked to high-frequency hearing impairment and tinnitus. In the present study, the researchers administered AM-101 to the inner ear of laboratory rats in single or repeated doses several days after exposure to tinnitus-triggering noise trauma. They found in AM-101 treated animals a significant reduction in trauma-induced loss of IHC ribbons and superior preservation of the centrally generated ABR wave amplitudes. While the IHC ribbon synapses and signal transmission in the auditory nerve were conserved, the treatment had no negative effect on hearing thresholds. The authors concluded that round-window application of AM-101 may be a promising therapeutic intervention for the treatment of synaptopathic tinnitus by counteracting maladaptive auditory patterns in the ascending auditory pathway. (1) Staecker H, Maxwell KS, Morris JR, van de Heyning P, Morawski K, Reintjes F, Meyer T (2015): Selecting appropriate dose regimens for AM-101 in the intratympanic treatment of acute inner ear tinnitus, Audiology & Neurotology 20(3), 172-182. Open access: www.karger.com/Article/Pdf/369608 (2) Bing D, Lee SC, Campanelli D, Xiong H, Matsumoto M, Panford-Walsh R, Wolpert S, Praetorius M, Zimmermann U, Chu H, Knipper M, Rüttiger L, Singer W (2015): Cochlear NMDA receptors as a therapeutic target of noise-induced tinnitus, Cellular Physiology and Biochemistry 35(5), 1905-1923. Open access: www.karger.com/Article/Pdf/374000