A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease

Patients with inherited mitochondrial diseases associated with nuclear or mitochondrial
deoxyribonucleic acid (DNA) mutations that impair the respiratory chain. These include, but
are not limited to the following clinical syndromes: Leber's hereditary optic neuropathy;
myoclonic epilepsy and ragged-red fibers (MERFF); mitochondrial encephalomyopathy, lactic
acidosis, and stroke-like syndrome (MELAS); Kearn-Sayre syndrome; subacute necrotizing
encephalopathy (Leigh Syndrome); polymerase gamma (POLG)-related disorders
(Alpers-Huttenlocher Syndrome, Autosomal Dominant Progressive External Ophthalmoplegia,
Autosomal Recessive Progressive External Ophthalmoplegia, Childhood Myocerebrohepatopathy
Spectrum Disorders, Myoclonic Epilepsy Myopathy Sensory Ataxia, POLG-Related Ataxia
Neuropathy Spectrum Disorders); Mitochondrial neurogastrointestinal encephalopathy syndrome
(MNGIE), also called myoneurogastrointestinal encephalopathy syndrome or
polyneuropathy-ophthalmoplegia-leukoencephalopathy- Intestinal pseudoobstruction (POLIP)
syndrome; others, e.g., mitochondrial cardiomyopathies and other syndromes due to multiple
mitochondrial DNA deletions.

Patients completing study RP103-MITO-001 (NCT02023866) are eligible for enrollment into the
extension study RP103-MITO-002 if all inclusion and exclusion criteria are fulfilled.
Subjects continue on the last total daily dose of cysteamine bitartrate delayed-release
capsules taken during RP103-MITO-001. Dose-adjustments are permitted.

Inclusion Criteria:

1. Completed all visits in Study RP103-MITO-001 (NCT02023866).

2. Body weight ≥ 5 kg.

3. The subject must be willing to abstain from initiating dietary supplements and
non-prescribed medications except as allowed by the Investigator, throughout the study
(from Day 1 to Study Exit).

4. Willing and able to comply with study drug dosing requirements, i.e. ingest the RP103
capsules intact, or sprinkled in liquid or soft food, or using a G-tube.

5. Sexually active female subjects of childbearing potential (i.e., not surgically
sterile [tubal ligation, hysterectomy, or bilateral oophorectomy]) must agree to
utilize two of the following acceptable forms of contraception throughout the study
(from Day 1 to Study Exit):

- Hormonal contraception: birth control pills, injection, patch, vaginal ring or
implant;

- Condom or diaphragm, with spermicide;

- Intrauterine device (IUD);

- Sterile male partner (vasectomy performed at least 6 months prior to the study).

6. Patient's legally authorized representative must provide written informed consent;
Patient must provide assent, if required by local/institutional requirements.

Exclusion Criteria:

1. Documented diagnosis of concurrent inborn errors of metabolism.

2. Platelet count, lymphocyte count or hemoglobin below the lower limit of normal (LLN)
at the Baseline visit.

3. Hepatic insufficiency with liver enzyme tests (alkaline phosphatase, aspartate
aminotransferase [AST] or alanine aminotransferase [ALT]) greater than 2.5 times the
upper limit of normal (ULN) at the Baseline Visit.

4. Bilirubin > 1.2 g/dL at the Baseline Visit.

5. Inability to complete the elements of the study, e.g., coma, hemodynamic instability
or requiring continuous ventilator support.

6. Malabsorption requiring total parenteral nutrition (TPN), chronic diarrhea, bouts of
pseudo obstruction.

7. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in
lactic acidosis.

8. Patients with suspected elevated intracranial pressure, pseudotumor cerebri (PTC)
and/or papilledema.

9. Severe gastrointestinal disease including gastroparesis.

10. History of drug or alcohol abuse.

11. History of pancreatitis.

12. Participated in an investigational drug trial (except the RP103-MITO-001 study) within
30 days or, within 90 days for a biologic, device, or surgical treatment, for
inherited mitochondrial diseases prior to the Baseline Visit.

13. Known or suspected hypersensitivity to cysteamine and penicillamine.

14. Female subjects who are nursing, planning a pregnancy, known or suspected to be
pregnant, or with a positive serum pregnancy test at the Baseline visit.

15. Patients who, in the opinion of the Investigator, are not able or willing to comply
with the protocol.