UAMS - Translational Research Institute

For all participants: - Completed 718-CIH-201 (NCT05107128) or 718-CIH-202 (NCT05358821) studies or meet eligibility criteria for the de novo cohort. - Agree to refrain from drugs of abuse for the duration of the study and from alcohol during the 48 hours preceding each study visit. - Be willing to invite a study partner, if available, who is reliable, competent, and at least 18 years of age to participate in the study. - Be able to travel to the study center, and, judged by the investigator, is likely to be able to continue to travel to the study center to complete study visits for the duration of the study. Additional inclusion criteria for the de novo cohort (Cohort 3): - Be at least 25 years old, but not older than 65 years of age at Screening. - Genetically confirmed disease with cytosine-adenine-guanine (CAG) expansion ≥40 - No features of juvenile HD - CAG-Age-Product (CAP) score ≥90, as calculated using the CAP formula: AGE × (CAG - 30) / 6.49. - At screening, scores of either: a) Unified Huntington's Disease Rating Scale (UHDRS) -Total Functional Capacity (TFC)=13 and Montreal Cognitive Assessment (MoCA) ≤25 score, or b) UHDRS-TFC ≤12 and MoCA >25

For all participants - Have a diagnosis of an ongoing neurodegenerative condition other than HD, including but not limited to, Alzheimer's Disease, vascular dementia, dementia with Lewy bodies, or Parkinson's Disease. - Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any related procedures that interfere with gastrointestinal transit. - Is known to be allergic to any of SAGE-718 excipients, including soy lecithin. - Receive any prohibited medications within 30 days of screening and during participation in the study. Additional exclusion criteria for the de novo cohort (Cohort 3): - Have previous exposure to gene therapy, or have participated in any other HD investigational drug, biologic, or device trial within 180 days or a non-HD drug, biologic or device trial within 30 days or 5 half-lives (whichever is longer). Additionally, participants who have received treatment with antisense oligonucleotides or a messenger ribonucleic acid (mRNA) splicing modifier will be excluded. Note: Participants with confirmation of enrolment in the placebo arm of these investigational trials would not be excluded. Additional exclusion criteria for 718-CIH-201/202 completers (Cohorts 1 and 2): - Have one or more ongoing serious adverse events (SAEs) from the parent study. - Have ongoing, unresolved AE(s), which in the opinion of the investigator or sponsor, is likely to interfere with study conduct or compliance.