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30 Calpain-2, a Protein Involved in Neurofilament Biology, Plays an Essential Role in Axonal Degeneration, a Critical Effector in the Progression of ALS Genetic Support for Calpain-2 NfL is Cleaved by Calpain-2, 1-4 Evidence for Targeting Calpain-2 in ALS as a Target with Increased NfL Fragments Seen in ALS Multiple injury paradigms and hypotheses of axonal degeneration converge on calpain-2 Calpain-2 genetic variant found to be associated with ALS Full-Length NfL Calpain-2 levels are Calpain-2 inhibition Full Length Neurofilament (68 kDa) elevated in people increases overall survival is not observed in ALS or 6 with ALS and delays disease onset Healthy Control in ALS mouse model NfL Fragment ~30K data set (~20K with ALS / 7 ~10K controls) Calpain-2 substrates AMX0114 has shown include neurofilament efficacy in preclinical and TDP-43 ALS models ALS=amyotrophic lateral sclerosis