A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD)

Key Inclusion Criteria:

• Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeatlength from 40 to 50, inclusive

Eligibility for HD-ISS Stage 2 Group (Parts A, B, and C):

• A Unified Huntington's Disease Rating Scale (UHDRS)-Independence Scale (IS) score of 100

• A UHDRS Total Functional Capacity (TFC) score of 13

• A score between 0.18 and 4.93 inclusive on the normed version of the HD prognosticindex (PINHD)

Eligibility for HD-ISS Mild Stage 3 Group (Parts D, E, and F):

• A UHDRS Total Functional Capacity (TFC) score of 11 or 12, or a UHDRS TFC score of 13 with an UHDRS IS score of <100

Key Exclusion Criteria:

• Receipt of an experimental agent within 90 days or 5 half-lives prior to Screeningor anytime over the duration of this study, ribonucleic acid (RNA)- ordeoxyribonucleic acid (DNA)-targeted HD-specific investigational agents such asantisense oligonucleotides, cell transplantation, or any other experimental brainsurgery

• Any history of gene therapy exposure for the treatment of HD

• Participation in an investigational study or investigational paradigm (such asexercise/physical activity, cognitive therapy, brain stimulation, etc) within 90days prior to Screening or anytime over the duration of this study

• Any medical history of brain or spinal disease that would interfere with the lumbarpuncture process safety assessments

• Any medical history or condition that would interfere with the ability to completethe protocol-specified assessments (for example, implanted shunt, conditionsprecluding magnetic resonance imaging [MRI] scans)

• Pregnancy, planning on becoming pregnant during the course of the study or within 6months of end of treatment, or currently breastfeeding

Note: Other inclusion and exclusion criteria may apply.