Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis

Key Inclusion Criteria (Double-Blind Part): * Women of non-childbearing potential and men, aged 21-80 years * Willingness and ability to complete all aspects of the study; participant should be capable of completing assessments either alone or with help of a caregiver * Diagnosis of laboratory-supported probable, probable, or definite (sporadic or familial) ALS according to the El Escorial World Federation of Neurology revised research diagnostic criteria * Less than 3 years since symptom onset * Forced vital capacity (FVC) \>50% predicted measured within 30 days of screening * If subject is taking approved ALS treatments (riluzole and/or edaravone), doses must be stable for ≥2 months prior to screening and subject is expected to stay on a stable regimen throughout the study Key Exclusion Criteria (Double-Blind Part): * History of a clinically significant non-ALS neurologic disorder (other than frontal temporal lobe dementia), including, but not limited to, muscular dystrophy, spinal stenosis, peripheral neuropathy, inherited neuropathies, AD, Parkinson's disease, Lewy body dementia, vascular dementia, Huntington's disease, epilepsy, stroke, multiple sclerosis, brain tumor, or brain infection or abscess * Unstable or poorly controlled comorbid disease process of any organ system currently requiring active treatment or likely to require treatment adjustment during the study Key Inclusion Criteria (Open-Label Extension): * Successful completion of both periods of the the double-blind, crossover part of the study * Continued diagnosis of laboratory-supported probable, probable, or definite (sporadic or familial) ALS according to the El Escorial World Federation of Neurology revised research diagnostic criteria Key Exclusion Criteria (Open-Label Extension): * Presence of laboratory abnormalities, physical examination findings, or AEs determined to be clinically significant by the investigator from the double-blind part of the study that have not resolved by the final follow-up visit as part of the double-blind study period * New diagnosis of clinically significant neurological disorder (other than frontal temporal lobe dementia)