Efficacy and Safety of WTX101 Administered for 48 Weeks Versus Standard of Care in Wilson Disease Subjects

This study is a randomized, rater-blinded, multi-center study assessing the efficacy and
safety of an individualized WTX101 dosing regimen administered for 48 weeks, compared to SoC,
in WD subjects aged 18 and older. Approximately 100 subjects will be enrolled at
approximately 5 to 10 North American sites and 15 to 25 sites in the rest of the world.
Subjects who complete the 48-week treatment period will be offered to participate in an
Extension Phase of the study to evaluate the long-term safety and durability of treatment
effect of WTX101.

The primary objective is to evaluate the efficacy of WTX101 administered for 48 weeks,
compared to SOC, on Cu control in WD subjects aged 18 and older. Copper control will be
assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in
non-ceruloplasmin-bound copper (NCC) levels. For WTX101-treated subjects, the NCC level will
be corrected for the amount of Cu bound to the WTX101 tripartite complex (TPC)
(NCCcorrected).

Inclusion Criteria:

Subjects who meet all of the following criteria will be eligible to participate in the
study:

- Established diagnosis of WD by Leipzig-Score ≥4 documented by testing as outlined in
the 2012 European Association for the Study of Liver WD Clinical Practice Guidelines;

- Treatment for >28 days for WD with chelation therapy (ie, penicillamine, trientine
hydrochloride), Zn therapy, or a combination of a chelator and Zn; OR Treatment naïve
or treatment for ≤28 days for WD with chelation therapy (ie, penicillamine, trientine
hydrochloride), Zn therapy, or a combination of a chelator and Zn;

- Willing and able to give informed consent for participation in the study;

- Male or female subjects, aged 18 years or older as of signing the informed consent
form (ICF);

- Able to understand and willing to comply with study procedures, restrictions, and
requirements, as judged by the Investigator;

- Willing to undergo ≥48-hour washout from current WD treatment;

- Adequate venous access to allow collection of required blood samples;

- Willing to avoid use of vitamins and/or minerals containing Cu, Zn, or Mo throughout
the study duration;

- Willing to avoid intake of foods and drinks with high contents of Cu throughout the
study duration;

- Females of childbearing potential will be included if they are either sexually
inactive (abstinent) for 14 days prior to the first WTX101 dose and continuing through
28 days after the last WTX101 dose, or using 1 of the following highly effective birth
control methods (ie, results in <1% failure rate when used consistently and
correctly):

1. Intrauterine device (without Cu) in place for at least 3 months prior to the
first WTX101 dose and throughout the study;

2. Surgical sterilization of the partner (vasectomy for 6 months minimum);

3. Combined (estrogen or progestogen containing) hormonal contraception associated
with the inhibition of ovulation (either oral, intravaginal, or transdermal) for
at least 3 months prior to the first WTX101 dose and throughout the study;

4. Progestogen only hormonal contraception associated with the inhibition of
ovulation (either oral, injectable, or implantable) for at least 3 months prior
to the first WTX101 dose and throughout the study;

5. Intrauterine hormone releasing system for at least 3 months prior to the first
WTX101 dose and throughout the study; or

6. Bilateral tubal occlusion for at least 6 months prior to the first WTX101 dose;

- Note: Sexual abstinence is considered a highly effective method only if
defined as refraining from heterosexual intercourse during the entire period
of risk associated with the study treatments. In this trial, abstinence is
only acceptable if in line with the subject's preferred and usual lifestyle;
and

- Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods),
withdrawal (coitus interruptus), spermicides only, and lactational
amenorrhoea method are not acceptable methods of contraception. As well,
female condom and male condom should not be used together;

- Females of childbearing potential agree to remain sexually inactive or to keep the
same birth control method for at least 28 days following the last dose;

- A female of non-childbearing potential must have undergone 1 of the following
sterilization procedures at least 6 months prior to the first WTX101 dose:

1. Hysteroscopic sterilization;

2. Bilateral tubal ligation or bilateral salpingectomy;

3. Hysterectomy; or

4. Bilateral oophorectomy; OR be postmenopausal with amenorrhoea for at least 1 year
prior to the first WTX101 dose and follicle stimulating hormone serum levels
consistent with postmenopausal status;

- A non-vasectomized male subject agrees to use a condom with spermicide or abstain from
sexual intercourse during the study until 90 days beyond the last dose of study drug.
For a vasectomized male who has had his vasectomy 6 months or more prior to study
start, it is required that they use a condom during sexual intercourse. A male who has
been vasectomized less than 6 months prior to study start must follow the same
restrictions as a non-vasectomized male;

- Note: Sexual abstinence is considered a highly effective method only if defined
as refraining from heterosexual intercourse during the entire period of risk
associated with the study treatments. In this trial, abstinence is only
acceptable if in line with the subject's preferred and usual lifestyle; and

- Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods),
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea
method are not acceptable methods of contraception. As well, female condom and
male condom should not be used together; and

- If male, agrees not to donate sperm from the first WTX101 dose until 90 days after
dosing.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participation in the
study:

- Decompensated hepatic cirrhosis;

- MELD score >13;

- Modified Nazer score >7;

- Clinically significant gastrointestinal bleed within past 3 months;

- Alanine aminotransferase >2 × upper limit of normal (ULN) for subjects treated for >28
days with WD therapy (Cohort 1);

- Alanine aminotransferase >5 × ULN for treatment naïve subjects or subjects who have
been treated for ≤28 days (Cohort 2);

- Marked neurological disease requiring either nasogastric feeding or intensive
inpatient medical care;

- Severe anaemia with a hemoglobin <9 g/dL;

- Participation in a clinical study of an experimental or unapproved/unlicensed therapy
at the same time or within the 4 weeks prior to this Screening Visit;

- History of seizure activity within 6 months of study start;

- Pregnant (or women who are planning to become pregnant) or lactating women;

- Known sensitivity to WTX101, WTX101 excipients (anhydrous di-calcium phosphate,
anhydrous sodium carbonate), or any of the ingredients contained in WTX101 or related
compounds;

- Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C
virus (subjects with positive hepatitis C antibody result would require confirmation
of active disease with a positive hepatitis C polymerase chain reaction test), or
seropositivity for human immunodeficiency virus;

- Any disability acquired from trauma or another illness that, in the opinion of the
Investigator, could interfere with evaluation of disability due to WD;

- Previous treatment with tetrathiomolybdate;

- Major systemic disease or other illness that would, in the opinion of the
Investigator, compromise subject safety or interfere with the collection or
interpretation of study results;

- In the opinion of the Investigator, the subject is likely to be non-compliant or
uncooperative during the study; or

- Any deviation in laboratory values that are confirmed on re-examination to be
clinically significant by the Investigator that would jeopardize the safety of the
subject or impact the validity of the study results.