AUT-00063: Development and Clinical Evaluation of a Kv3 Channel Modulator for Hearing Disorders

1. Introduction and Overview

AUT-00063 (also designated AUT00063) is an investigational small molecule drug developed by Autifony Therapeutics.[1] It was designed as a positive modulator of voltage-gated potassium channels of the Kv3 subfamily, particularly Kv3.1.[2] These channels play a critical role in regulating neuronal firing patterns, especially in the auditory system. Based on preclinical evidence suggesting that enhancing Kv3 channel function could ameliorate deficits associated with hearing loss and tinnitus, AUT-00063 was advanced into clinical development for these indications.[3] Phase I studies were initiated in 2013 [3], followed by Phase II trials exploring its efficacy in age-related hearing loss (ARHL), subjective tinnitus, and cochlear implant users.[2] Despite demonstrating a favorable safety profile, the Phase II clinical trials ultimately failed to show significant efficacy in these patient populations, leading to the cessation of development for these specific indications around 2019.[1]

2. Mechanism of Action and Preclinical Rationale