Prescreening Study to Identify Potential Wilson Disease Participants for Gene-Editing Clinical Trial

This will be a multi-region, multi-site, prescreening study for individuals with WD. Eligible participants must have a clinical history consistent with WD. p.H1069Q or p.R778L mutation are eligible for this study. Participants who do not have a known genotype at enrollment may have their ATP7B gene sequenced while on study, with the approval of the study Medical Monitor. Participants who have previously received liver transplant or gene therapy for WD are excluded.

This study will enroll up to approximately 30 participants aged 18 and above, at least 15 of whom must have at least 1 ATP7B p.H1069Q allele. Participants must meet all inclusion criteria and none of the exclusion criteria to be eligible for the study. Each participant will have a blood sample collected to evaluate total serum ceruloplasmin and ceruloplasmin oxidase. For participants who have at least 1 ATP7B allele with the p.H1069Q or p.R778L mutation, chart review will be conducted to collect relevant medical history information, and the participant will be asked to complete a survey to evaluate their interest in and attitudes towards gene editing for WD. Study participants will receive no study mandated therapeutic interventions but will continue to receive standard of care (SOC) for the treatment of WD. The expected duration of participation for each participant is approximately 90 days.

Inclusion criteria

• Confirmed Wilson Disease (WD) as determined by the following criteria:

• An established clinical diagnosis of WD
• Genetic analysis confirming the presence of biallelic pathogenic variants at ATP7B, at least one of which is EITHER p.H1069Q OR p.R778L OR Participants without a confirmed genetic diagnosis may enroll only with explicit approval from the Medical Monitor

Exclusion criteria

• Prior history of gene therapy, liver transplantation, hepatocyte (cellular) transplantation, or active listing for liver transplantation
• For individuals with known ATP7B genotype: individual does not have at least 1 ATP7B allele with either the p.H1069Q or p.R778L mutation.
• Significant neurological conditions within the prior 12 months which may impact participant safety or participation in the study, including ability to complete study requirements or procedures as outlined in the clinical study protocol.
• In patients with psychiatric involvement, current or fluctuant clinical instability with new or changing diagnoses or substantial medication regimen changes in the past 12 months that could limit their participation, in the opinion of the Investigator.
• History of cirrhotic decompensation within the past year.
• Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the participant or would preclude the participant from successful study completion, including participant unable or unwilling to comply with the protocol requirements.
• Current participation in an investigational study for the treatment of WD.
• Prior or active malignancy or myeloproliferative disorder (excluding Stage 1 or lower, fully treated/excised malignant and pre-malignant disease of the skin, cervix or colon. Additionally, any other malignant and pre-malignant disease that the Investigator in consultation with the treating oncologist and study Medical Monitor deem has been fully treated/excised for > 5 years).