An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead)

Inclusion Criteria:

• mtDNA-PMM subjects: Completed treatment in STRIDE or was participating in StudyREN001-101 when the study stopped due to the COVID-19 pandemic, and in the opinionof the Investigator and Sponsor had been compliant with the study requirements ORnDNA-PMM subjects: Subjects aged 18 years or older with known nuclear (nDNA)pathogenic variants with a major muscle phenotype consisting of objective myopathywith poor exercise tolerance. Proof of pathogenicity must be provided. Must be ableto walk at least 100m in the screening 12MWT and the limitations in walk test mustbe primarily due to the energy deficit and not due to ataxia or any other condition.For subjects under 25 years old only: confirmation of bone growth plate closure bywrist radiograph.

• Have PMM which continues to be primarily characterized by exercise intolerance oractive muscle pain.

• Willing and able to swallow the REN001 gelatin capsules.

• Concomitant medications (including supplements) intended for the treatment of PMM orother co-morbidities likely to remain stable throughout participation in the studywhere clinically possible.

• Signed and dated informed consent document indicating that the subject has beeninformed of all pertinent aspects of the study.

• Females should be either of non-child-bearing potential or must agree to use highlyeffective methods of contraception from baseline through to approximately 30 daysafter the last dose of study drug. Males with partners who are women of childbearingpotential (WOCBP) must also use contraception from baseline through to 14 weeksafter the last dose of study drug.

Exclusion Criteria:

• Anticipated to need a peroxisome proliferator-activated receptor (PPAR) agonistother than REN001 during the study.

• Intent to donate blood, or blood components during the study or within one monthafter completion of the study.

• Current drug dependency. Use of opiates/cannabis for medical reasons is acceptablewith prescription evidence or at the Investigator's discretion.

• Current alcohol dependency.

• Any medical, psychiatric or laboratory condition that may increase the riskassociated with study participation or interfere with the interpretation of studyresults and, in the judgment of the Investigator and Medical Monitor, would make thesubject inappropriate for entry into this study.

• Pregnant or nursing female

Subjects with mtDNA mutations can enroll at STRIDE Week 24 visit, STRIDE-FU visit, after exiting from STRIDE or after exiting REN001-101 (UK only). Subjects enrolling after exiting from either of the 2 feeder mtDNA studies and all subjects with nDNA mutations will be required to fulfill additional exclusion criteria during their additional screening visit. This is required for the mtDNA-PMM subjects due to the gap in study drug treatment and period of time without study assessments. The additional exclusion criteria are:

1. Clinically significant kidney disease or impairment calculated as eGFR Grade 2 orabove <60ml/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation at Screening.

2. Clinically significant liver disease or impairment of AST or ALT Grade 2 or above (>2.5 x ULN), or Total bilirubin > 1.6 x ULN or >ULN with other signs and symptomsof hepatotoxicity at Screening.

3. Subjects with uncontrolled diabetes and/or a Screening HbA1c of ≥11%.

4. Evidence of significant concomitant clinical disease that may need a change inmanagement during the study or could interfere with the conduct or safety of thisstudy. (Stable well-controlled chronic conditions such hypercholesterolemia,gastroesophageal reflux, or depression under control with medication (other thantricyclic antidepressants), are acceptable provided the symptoms and medicationswould not be predicted to compromise safety or interfere with the tests andinterpretations of this study.)

5. Subjects with a history of cancer. A history of in situ basal cell carcinoma in theskin is allowed.

6. Clinically significant cardiac disease and/or clinically significant ECGabnormalities such as 2nd degree heart block, symptomatic tachyarrhythmia orunstable arrhythmia (right bundle branch block, left fascicular block and long PRinterval are not excluded) that in the opinion of the Investigator should excludethe subject from completing exercise tests.