An Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With TK2

This is a Phase 2 prospective, open-label treatment study of the safety and efficacy of
MT1621 in TK2 deficient patients who participated in the retrospective Study MT-1621-101.
Patients who are being treated with dC/dT and did not participate in MT-1621-101 may also be
allowed to enroll with Sponsor approval. For all patients, it is important to ensure that
collection of clinical and functional measurements prior to treatment with dC/dT are
sufficient to serve as baseline assessments for purposes of evaluating safety and efficacy.

After enrollment into this study, patients will transition from their current chemical-grade
dC/dT or dCMP/dTMP to the same dose of MT1621, or continue use of MT1621 at their current
dose (by weight), up to a maximum of 400 mg/kg/day. Patients who are on a dose <400 mg/kg/day
dC/dT or dCMP/dTMP will initiate treatment with MT1621 at the same dose (by weight), and the
Investigator will have the options of continuing at this dose or escalating to a higher dose,
with the highest dose being 400 mg/kg/day MT1621. The dose may be reduced for tolerability
reasons.

Safety and efficacy will be assessed upon enrollment, at 1 month, every 3 months through 18
months, every 6 months through 36 months, then annually thereafter, and at end of study
participation. For patients who did not participate in Study MT-1621-101, specific
assessments for each patient will be determined by the Sponsor in discussion with the
Investigator based on data collected as baseline assessments for purposes of evaluating
safety and efficacy.

The study will include sparse PK sampling.

Inclusion Criteria:

1. Signed informed consent by the parent(s) or legally authorized representative (LAR)
and/or assent by the patient (when applicable).

2. Confirmed genetic mutation in the TK2 gene.

3. Absence of other genetic disease or polygenic disease.

4. Current treatment with nucleos(t)ides for TK2 deficiency. Patients who were not
previously enrolled in MT 1621 101 will require Sponsor approval to ensure that
collection of clinical and functional measurements prior to treatment are sufficient
to serve as baseline assessments for purposes of evaluating safety and efficacy.

5. Female patients must not be breastfeeding, have a negative pregnancy test at screening
(females ≥10 years old), and have no intention to become pregnant during the course of
the study. Female patients who are of childbearing potential (ie, following menarche
until ≥1 year post-menopausal if not anatomically and physiologically incapable of
becoming pregnant) must agree and commit to the use of highly effective methods of
birth control for the duration of the study and for 30 days after the end of the
study. Acceptable methods are defined as those that result, alone or in combination,
in a low failure rate (ie, <1% per year) when used consistently and correctly, such as
surgical sterilization, an intrauterine device, or hormonal contraception in
combination with a barrier method. In certain countries (if permitted by law), women
of childbearing potential may instead agree to abide by heterosexual sexual abstinence
during the study and for 30 days after the end of the study.

6. Willingness to maintain current treatment regimen and current exercise regimen for the
duration of the clinical study.

7. Willingness to comply with the study protocol, including but not limited to, all study
procedures, study visits, and study drug compliance.

Exclusion Criteria:

1. History of liver disease, or liver function test results (ALT, AST, or total
bilirubin) ≥2× upper limit of normal without prior Sponsor approval.

2. Other significant medical condition that, in the opinion of the Investigator or Study
Sponsor, may confound interpretation of the clinical course of TK2 deficiency.