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

A translational and quantitative modeling framework for TfR-mediated delivery of gene silencing therapies for myotonic dystrophy type 1 (Neuroscience 2025) - "Parameters were translationally adjusted using physiological values and allometric scaling, and the model was used to predict PK/PD in DM1 patients participating in the AOC-1001 Phase 1/2 trial (MARINA). The same framework was applied in a reverse-translational manner, by calibrating to PK/PD data from patients receiving DYNE-101, a DMPK-targeting ASO conjugated to a Fab, in a Phase 1/2 trial (ACHIEVE), then predicting available NHP PD response...Lancet Neurol 2023, 22: 218-28 [2] www.aviditybiosciences.com/platform/publications [3] www.dyne-tx.com/our-forcetm-publications [4] Provenzano et al. J Clin Invest 2025, 135(4):e185426"

CNS Disorders • Myotonic Dystrophy

From molecular convergence to clinical divergence: Comparative pathogenic mechanisms and therapeutic trajectories in C9orf72-ALS/FTD and myotonic dystrophy. (PubMed, Neurobiol Dis) - "In contrast, RNA-targeting conjugates for DM1 (delpacibart etedesiran and DYNE-101) received FDA Breakthrough Therapy designation. Therapeutic success depends on tissue accessibility and addressing both shared and circuit-specific pathogenic cascades. While nuclear RNA targets appear druggable in myotonic dystrophy, the bidirectional transcription and compartmentalized pathology of C9orf72 ALS/FTD may require multi-targeted approaches for precision medicine."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Genetic Disorders • Metabolic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TARDBP

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

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

HARBOR-OLE: Global Open-Label Extension Study of Del-desiran for the Treatment of DM1 (clinicaltrials.gov) - P3 | N=217 | Enrolling by invitation | Sponsor: Avidity Biosciences, Inc. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

HARBOR: Global Study of Del-desiran for the Treatment of DM1 (clinicaltrials.gov) - P3 | N=159 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2027 ➔ Sep 2026 | Trial primary completion date: Oct 2026 ➔ Mar 2026

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

Avidity Biosciences Announces Completion of Enrollment for HARBOR, the First Global Phase 3 Trial of Delpacibart Etedesiran (del-desiran) for Treatment of DM1 and Provides Guidance on Regulatory Submission (PRNewswire) - "On track to share updates from ongoing MARINA-OLE trial of del-desiran including long-term 4 mg/kg efficacy and safety data in Q4 2025...Avidity Biosciences...announced the completion of enrollment in the ongoing global Phase 3 HARBOR clinical trial of delpacibart etedesiran (del-desiran) for people living with myotonic dystrophy type 1 (DM1). Topline data from HARBOR, the first global Phase 3 clinical trial in DM1, are anticipated in the second quarter of 2026...Prior to initiation of the HARBOR trial, Avidity aligned with global regulators, including FDA, on the registrational path for del-desiran. The Company plans to submit marketing applications beginning in the second half of 2026 including in the United States, European Union and Japan."

Enrollment closed • Filing • P3 data: top line • Trial status • Myotonic Dystrophy

HARBOR-OLE: Global Open-Label Extension Study of Del-desiran for the Treatment of DM1 (clinicaltrials.gov) - P3 | N=217 | Not yet recruiting | Sponsor: Avidity Biosciences, Inc.

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

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