GENERATION HD2. A Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen Compared With Placebo in Participants With Prodromal and Early Manifest Huntington's Disease.

Open to people ages 25-50

• Signed study companion consent form. A study companion is required for all participants.

• HD gene expansion mutation carrier status. CAP score of 400-500, inclusive, where CAP is calculated as follows:

  Age x (CAG repeat length -33.66) -Prodromal HD, defined as DCL 2 to 3, Total Motor Score (TMS) >6, Independence Scale (IS) = 100 (broadly equivalent to HD-ISS Stage 2), or early manifest HD, defined as DCL 4, TMS > 6, 100 >IS>/= 70, and TFC >/=8 (broadly equivalent to HD-ISS Stage 3) Companion Inclusion Criteria - HD gene expansion mutation carrier status. CAP score of 400-500, inclusive, where CAP is calculated as follows: Age x (CAG repeat length -33.66)

• Prodromal HD, defined as DCL 2 to 3, Total Motor Score (TMS) >6, Independence Scale (IS) = 100 (broadly equivalent to HD-ISS Stage 2), or early manifest HD, defined as DCL 4, TMS > 6, 100 >IS>/= 70, and TFC >/=8 (broadly equivalent to HD-ISS Stage 3)
• Signed study companion consent form. A study companion is required for all participants.

• Current or previous use of an ASO (including small interfering RNA) or any HTT lowering therapy (including tominersen)
• Anti-platelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the study, including, but not limited to, aspirin (unless </= 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and heparin
• History of gene therapy, cell transplantation, or brain surgery
• Hydrocephalus
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of study drug
• History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening