Sponsor Decision

This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study of the efficacy and safety of MT1621 in pediatric and adolescent patients with thymidine kinase 2 deficiency (TK2d). In order to be eligible for this study, participants must have genetic confirmation of TK2d and must not have ever received MT1621 or nucleos(t)ides before entering the study.

Thymidine kinase 2 (TK2) is a protein involved in the normal function of mitochondria. Thymidine kinase 2 deficiency (TK2d) is a form of mitochondrial DNA depletion syndrome and is a very rare inherited genetic disorder. TK2d leads to abnormally low amounts of DNA in mitochondria and because of this defect, the mitochondria are not able to provide the energy that cells need to function properly, which causes severe muscle weakness, along with host of additional symptoms that may involve the respiration, feeding, and ambulation, and can progress until patients lose many of these abilities. There are no FDA-approved medicines to treat TK2d.

MT1621 is a therapy that targets the underlying pathophysiology of TK2d by restoring mitochondrial DNA (mtDNA) replication fidelity. MT1621 consists of a combination of deoxynucleosides (the building blocks of mtDNA) given orally. Deoxynucleoside combination therapy improves nucleotide balance, increases mtDNA copy number, improves cell function, and prolongs life in preclinical models of TK2d.

This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study to assess the efficacy and safety of MT1621 in treatment naïve pediatric and adolescent subjects <18 years of age with TK2d. The study seeks to enroll approximately 16 subjects globally in this ultra rare disease.

Inclusion Criteria:

• Subject must be aged birth to <18 years of age on the day of consent.
• Diagnosis of TK2 deficiency based on confirmed disease-causing mutation(s) in the TK2 gene.
• Onset of TK2d at ≤12 years of age as defined as the age at which the first TK2d symptom occurred.

Exclusion Criteria:

• Documented clinically significant central nervous system involvement.
• ALT or AST >3 x upper limit of normal and total bilirubin > 2 x ULN or International Normalized Ratio (INR) >1.5.
• EtCO2>45 mmHg if not on ventilatory support
• Current or prior treatment with nucleos(t)ides for TK2d.