A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease

Inclusion Criteria:

For all participants:

• Completed 718-CIH-201 (NCT05107128) or 718-CIH-202 (NCT05358821) studies or meeteligibility criteria for the de novo cohort.

• Agree to refrain from drugs of abuse for the duration of the study and from alcoholduring the 48 hours preceding each study visit.

• Be willing to invite a study partner, if available, who is reliable, competent, andat 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 tobe able to continue to travel to the study center to complete study visits for theduration 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) ≤25score, or b) UHDRS-TFC ≤12 and MoCA >25

Exclusion Criteria:

For all participants

• Have a diagnosis of an ongoing neurodegenerative condition other than HD, includingbut not limited to, Alzheimer's Disease, vascular dementia, dementia with Lewybodies, or Parkinson's Disease.

• Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any relatedprocedures 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 duringparticipation 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 HDinvestigational 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 antisenseoligonucleotides or a messenger ribonucleic acid (mRNA) splicing modifier will beexcluded.

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.