ATR 1072 in Participants With PRKAG2 Syndrome

ATR 1072 is an antibody-oligonucleotide conjugate (AOC) designed to reduce expression of PRKAG2 through targeted delivery of siRNA to cardiac tissue. This first-in-human, Phase 1/2, open-label, multicenter study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of multiple doses of ATR 1072 in adults with PRKAG2 Syndrome. The study consists of a multiple ascending dose portion (Part A) followed by a dose-expansion cohort at the dose selected in (Part A). After completion of a 48-week treatment period, participants in Parts A and B enter a 42-week extension period followed by a post-treatment follow-up of up to 18 weeks. Approximately 37 participants will be enrolled globally.

Inclusion criteria

• Adults 18 to 65 years of age.
• Pathogenic, likely pathogenic, or variant of uncertain significance (VUS) in PRKAG2 confirmed by genetic testing.
• Clinical manifestations consistent with PRKAG2 Syndrome.
• Able and willing to comply with study procedures.
• Able and willing to undergo endomyocardial biopsy procedures (Part A)

Exclusion criteria

• Pregnancy or breastfeeding.
• Significant hepatic, renal, hematologic, or cardiovascular abnormalities that may increase study risk.
• NYHA Class IV heart failure or left ventricular ejection fraction <45%.
• Recent clinically significant cardiovascular events or procedures.
• Prior treatment with prohibited investigational therapies or oligonucleotide therapies within protocol-defined washout periods.
• Any condition that, in the investigator's