delpacibart etedesiran (AOC 1001) / Avidity Biosci - LARVOL DELTA

Avidity Biosciences Receives Orphan Drug Designation in Japan for Delpacibart Etedesiran (del-desiran) for Treatment of Myotonic Dystrophy Type 1 (PRNewswire) - "Avidity has aligned with global regulators on the registrational path for del-desiran for the treatment of DM1, which informed the design of the ongoing Phase 3 HARBOR study. Avidity expects to complete participant enrollment in the Phase 3 HARBOR study in mid-2025 and submit marketing applications starting 2026 in the U.S., European Union and Japan."

EMA filing • Enrollment status • FDA filing • Japan filing • Myotonic Dystrophy

Avidity Biosciences Receives Orphan Drug Designation in Japan for Delpacibart Etedesiran (del-desiran) for Treatment of Myotonic Dystrophy Type 1 (PRNewswire) - "Avidity Biosciences...today announced that the Japan Ministry of Health, Labour and Welfare (MHLW) has granted Orphan Drug designation (ODD) to delpacibart etedesiran (del-desiran) for the treatment of myotonic dystrophy type 1 (DM1), an investigational treatment designed to address the root cause of DM1, an underrecognized, progressive and often fatal neuromuscular disease with no approved therapies. Del-desiran is the first investigational treatment for DM1 to receive Orphan Drug designation in Japan."

Orphan drug • Myotonic Dystrophy

Avidity Biosciences Announces Upcoming Presentations at the Muscular Dystrophy Association (MDA) Clinical & Scientific Conference (PRNewswire) - "Avidity Biosciences, Inc...today announced that the company will be presenting one oral and two poster presentations at the 2025 MDA Clinical & Scientific Conference (MDA) in Dallas, Texas, being held March 16-19, 2025 and will host an investor and analyst webcast event on March 17, 2025....Aravindhan Veerapandiyan, MD, Associate Professor of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital and EXPLORE44 trial investigator, will present topline del-zota data from Phase 1/2 EXPLORE44 trial at 2025 MDA Clinical & Scientific Conference in Dallas, Texas."

Clinical protocol • P1/2 data • Duchenne Muscular Dystrophy • Myotonic Dystrophy

Avidity Biosciences Reports Fourth Quarter 2024 Financial Results and Recent Highlights (PRNewswire) - "Delpacibart zotadirsen (del-zota) for the treatment of DMD44: Planned BLA submission year end 2025....Presentation of topline data from the EXPLORE44 trial (Q1). Presentation of topline data from the ongoing EXPLORE44-OLE trial (Q4). Delpacibart etedesiran (del-desiran) for the treatment of myotonic dystrophy type 1 (DM1)...Publication of data analyses from the completed Phase 1/2 MARINA trial (2025)....Research and Development (R&D) Expenses: These expenses were $95.6 million for the fourth quarter of 2024 compared with $52.8 million for the fourth quarter of 2023, and $303.6 million for the year ended 2024 compared with $191.0 million for the year ended 2023. The increases were primarily driven by the advancement of del-desiran, del-brax and del-zota, as well as internal and external costs related to the expansion of the company's overall research capabilities."

Commercial • FDA filing • P1/2 data • P2 data • Duchenne Muscular Dystrophy • Muscular Dystrophy • Myotonic Dystrophy

2025 Upcoming Clinical and Regulatory Highlights (PRNewswire) - "Delpacibart etedesiran (del-desiran) for the treatment of DM1...Presentation of additional data analyses from the Phase 1/2 MARINA trial (Q1); Completion of enrollment of the ongoing Phase 3 HARBOR trial (mid-2025); Update from the ongoing MARINA-OLE trial including long-term 4mg/kg and safety data (Q4); Planned marketing application submissions in 2026, including in the U.S. and European Union"

EMA filing • FDA filing • P1/2 data • Trial status • Myotonic Dystrophy

Avidity Biosciences Plans First BLA Submission and Accelerates Commercialization Preparations (PRNewswire) - "Delpacibart zotadirsen (del-zota) for the treatment of DMD44: Planned BLA submission year end 2025...The U.S. Food and Drug Administration (FDA) confirmed the accelerated approval path is available for del-zota and that the clinical data package from the EXPLORE44 program could support a BLA filing; Presentation of topline data from the EXPLORE44 trial (Q1); Presentation of topline data from the ongoing EXPLORE44-OLE trial (Q4)"

FDA filing • P1/2 data • P2 data • Muscular Dystrophy

MARINA-OLE: Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients (clinicaltrials.gov) - P2 | N=37 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jun 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • CNS Disorders • Genetic Disorders • Muscular Atrophy • Muscular Dystrophy • Musculoskeletal Diseases • Myotonic Dystrophy

HARBOR: Global Study of Del-desiran for the Treatment of DM1 (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Avidity Biosciences, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

HARBOR: Global Study of Del-desiran for the Treatment of DM1 (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Avidity Biosciences, Inc.

New P3 trial • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Avidity Biosciences Receives FDA Breakthrough Therapy Designation for Delpacibart Etedesiran (AOC 1001) for Treatment of Myotonic Dystrophy Type 1 (PRNewswire) - "Avidity Biosciences...today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to delpacibart etedesiran (AOC 1001), the company's lead clinical development program, for the treatment of myotonic dystrophy type 1 (DM1)....Avidity is initiating the global pivotal HARBOR™ study of del-desiran this quarter."

Breakthrough therapy designation • New trial • Myotonic Dystrophy

AOC 1001-mediated Reduction of DMPK Leads to Increase in Functional MBNL Levels, Improving Muscle Function in Patients with DM1 (MDA 2024) - P1/2 | "As anticipated, DM1 participants in MARINA had spliceopathy and reduced [MBNL]inferred in muscle compared to healthy muscle. The reduced levels of [MBNL]inferred were associated with deficits in multiple functional measurements in DM1 participants. Treatment with AOC 1001 produced robust reduction of DMPK mRNA expression and a substantial dose-dependent increase in [MBNL]inferred levels in DM1 patients (2 mg/kg: 20% increase; 4 mg/kg: 34% increase), reflecting the correction of aberrant RNA splicing."

Clinical • CNS Disorders • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Initial Results of the Phase 2 Open-Label Extension Study of AOC 1001 in Adults with Myotonic Dystrophy Type 1: MARINA-OLE (MDA 2024) - P1/2, P2 | "Long-term safety and efficacy data of AOC 1001 continue to support the findings in MARINA. AOC 1001 represents a novel potential therapy addressing the underlying cause of DM1."

Clinical • P2 data • CNS Disorders • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

Topline data analysis of the phase 1/2 clinical trial evaluating AOC 1001 in adult Patients with Myotonic dystrophy type 1: MARINA (WMS 2023) - No abstract available

Clinical • P1/2 data • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

AOC 1001 demonstrates DMPK reduction and spliceopathy improvement in a phase 1/2 study in myotonic dystrophy type 1 (DM1) (MARINA) (WMS 2023) - No abstract available

P1/2 data • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

AOC 1001-CS1 (MARINA) (WMS 2023) - No abstract available

MARINA-OLE: Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients (clinicaltrials.gov) - P2 | N=37 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Genetic Disorders • Muscular Atrophy • Muscular Dystrophy • Musculoskeletal Diseases • Myotonic Dystrophy

MARINA: Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients (clinicaltrials.gov) - P1/2 | N=38 | Completed | Sponsor: Avidity Biosciences, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2023 ➔ Feb 2023 | Trial primary completion date: Sep 2023 ➔ Feb 2023

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Antibody oligonucleotide conjugates: Development of AOC 1001 for the treatment of myotonic dystrophy (ACS-Fall 2023) - "Introduction to oligonucleotides and AOC 1001AOC 1001 preclinical and Phase-1 clinical data"

Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Preliminary Assessment of the Phase 1/2 Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AOC 1001 Administered Intravenously to Adult Patients with Myotonic Dystrophy Type 1 (DM1) (MARINA) (AAN 2023) - P1/2 | "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 DMPK-specific mRNA that is responsible for DM1 pathogenesis. These results will be presented. Conclusions AOC 1001 represents a novel potential therapy addressing the underlying cause of DM1."

Clinical • P1/2 data • PK/PD data • CNS Disorders • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

The myotonic dystrophy type 1 drug development pipeline: 2022 edition. (PubMed, Drug Discov Today) - "Three interventional first-in-human clinical trials got underway with distinct drug classes, namely AOC 1001 and DYNE-101 nucleic acid-based therapies, and the small molecule pitolisant, which joins the race toward market authorization with other repurposed drugs, including tideglusib, metformin, or mexiletine, already in clinical evaluation. Furthermore, newly disclosed promising preclinical data for several additional nucleic-acid therapeutic candidates and a CRISPR-based approach, as well as the advent into the pipeline of novel therapeutic programs, increase the plausibility of success in the demanding task of providing valid treatments to patients with DM1."

Journal • Review • Gene Therapies • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

A phase 1/2 clinical trial evaluating the safety and pharmacokinetics of AOC 1001 in adults with myotonic dystrophy type 1: MARINA study design (WMS 2022) - P1/2 | "The study will enroll 44 symptomatic adults aged 18 to 65 years with genetically confirmed DM1 (CTG repeat length ≥ 100). Eligible participants from parts A and B will have the option to participate in an open-label extension study."

Clinical • P1/2 data • PK/PD data • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

MARINA: Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients (clinicaltrials.gov) - P1/2 | N=44 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

MARINA-OLE: Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients (clinicaltrials.gov) - P2 | N=44 | Enrolling by invitation | Sponsor: Avidity Biosciences, Inc.

New P2 trial • CNS Disorders • Genetic Disorders • Muscular Atrophy • Muscular Dystrophy • Musculoskeletal Diseases • Myotonic Dystrophy

Study Design of AOC 1001-CS1, a Phase 1/2 Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AOC 1001 Administered Intravenously to Adult Patients with Myotonic Dystrophy Type 1 (DM1) (MARINA) (AAN 2022) - P1/2 | "NA"

Clinical • P1/2 data • PK/PD data • CNS Disorders • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

MARINA: Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients (clinicaltrials.gov) - P1/2; N=44; Recruiting; Sponsor: Avidity Biosciences, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy