VP55 Topline data analysis of the phase 1/2 clinical trial evaluating AOC 1001 in adult patients with myotonic dystrophy type 1: MARINA

The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 in adults with myotonic dystrophy type 1 (DM1). DM1 is a rare, dominantly inherited, progressive neuromuscular disease caused by a toxic gain-of-function mutation in the DM1 protein kinase (DMPK) gene. Currently, no disease-modifying therapies exist. AOC 1001 is an antibody oligonucleotide conjugate (AOC™) comprised of a DMPK siRNA conjugated to a humanized antibody targeting human transferrin receptor 1 (TfR1), designed for functional delivery to muscle cells, where it can reduce the toxic mutant DMPK mRNA. This phase 1/2 study (NCT05027269) is a randomized, placebo-controlled, double-blind trial in two parts. Part A was a single dose design. Part B is a multiple-ascending dose design with 3 cohorts (dose levels), with quarterly doses and 1 booster after the first 6 weeks. The cohorts were initiated in a staggered fashion based on a safety data review of the preceding cohort(s). The primary objective is safety and tolerability. Secondary objectives include spliceopathy, pharmacokinetics, and pharmacodynamics (DMPK mRNA knockdown). Exploratory objectives include efficacy measures (myotonia, mobility, muscle strength, and muscle function), and patient-reported outcomes. The study has enrolled 38 adults aged 18 to 65 years with a genetic diagnosis of DM1: eight in Part A and 30 in Part B. After completing MARINA, all patients may enroll in an open-label extension study and receive AOC 1001 for a 24-month treatment period. MARINA-OLE has commenced enrolling patients. The MARINA study is the first complete trial in the development of AOC 1001. This topline data analysis will include safety and tolerability, pharmacokinetics, pharmacodynamics, and the changes in RNA splicing from all cohorts. AOC 1001 represents a novel potential therapy addressing the underlying cause of DM1. The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 in adults with myotonic dystrophy type 1 (DM1). DM1 is a rare, dominantly inherited, progressive neuromuscular disease caused by a toxic gain-of-function mutation in the DM1 protein kinase (DMPK) gene. Currently, no disease-modifying therapies exist. AOC 1001 is an antibody oligonucleotide conjugate (AOC™) comprised of a DMPK siRNA conjugated to a humanized antibody targeting human transferrin receptor 1 (TfR1), designed for functional delivery to muscle cells, where it can reduce the toxic mutant DMPK mRNA. This phase 1/2 study (NCT05027269) is a randomized, placebo-controlled, double-blind trial in two parts. Part A was a single dose design. Part B is a multiple-ascending dose design with 3 cohorts (dose levels), with quarterly doses and 1 booster after the first 6 weeks. The cohorts were initiated in a staggered fashion based on a safety data review of the preceding cohort(s). The primary objective is safety and tolerability. Secondary objectives include spliceopathy, pharmacokinetics, and pharmacodynamics (DMPK mRNA knockdown). Exploratory objectives include efficacy measures (myotonia, mobility, muscle strength, and muscle function), and patient-reported outcomes. The study has enrolled 38 adults aged 18 to 65 years with a genetic diagnosis of DM1: eight in Part A and 30 in Part B. After completing MARINA, all patients may enroll in an open-label extension study and receive AOC 1001 for a 24-month treatment period. MARINA-OLE has commenced enrolling patients. The MARINA study is the first complete trial in the development of AOC 1001. This topline data analysis will include safety and tolerability, pharmacokinetics, pharmacodynamics, and the changes in RNA splicing from all cohorts. AOC 1001 represents a novel potential therapy addressing the underlying cause of DM1.