AB-14

AB-14 is an autophagy-targeting chimera (AUTOTAC) small molecule degrader developed by Autotac Bio for the treatment of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. It is specifically designed to target and eliminate pathogenic aggregates of the TAR DNA-binding protein 43 (TDP-43), which are found in the majority of ALS cases. The AUTOTAC mechanism involves a bifunctional molecule that binds to misfolded or oligomeric TDP-43 species and simultaneously recruits the autophagy receptor p62 (SQSTM1). This recruitment facilitates the sequestration of the target protein into autophagosomes for subsequent lysosomal degradation, while notably sparing the functional monomeric form of TDP-43. AB-14 (as ATC141) has demonstrated the ability to reduce TDP-43 aggregates and improve neuromuscular and cognitive functions in preclinical models and is currently being evaluated in Phase 1 clinical trials.