delpacibart etedesiran (EWF980) / Avidity Biosci, Novartis - LARVOL DELTA

Novartis provides update on delpacibart etedesiran (del-desiran) Phase III HARBOR study for the treatment of myotonic dystrophy type 1 (DM1) (The Manila Times) - "Novartis...announced that the global Phase III HARBOR study evaluating del-desiran in people living with myotonic dystrophy type 1 (DM1) did not demonstrate statistically significant improvement versus placebo on the primary endpoint of video hand opening time (vHOT)...Evidence of clinical activity in secondary endpoints and exploratory analyses were observed. Safety findings from HARBOR were generally consistent with previously reported data...Novartis is evaluating the full HARBOR dataset and will engage with health authorities to determine the most appropriate development path for del-desiran.”"

P3 data • Muscular Dystrophy

HARBOR: Global Study of Del-desiran for the Treatment of DM1 (clinicaltrials.gov) - P3 | N=159 | Completed | Sponsor: Avidity Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Long-Term Safety and Tolerability of Del-Desiran in Myotonic Dystrophy Type 1: Final Results from MARINA-OLE™ (EAN 2026) - "Delpacibart etedesiran (del-desiran; AOC 1001) is an investigational antibody oligonucleotide conjugate comprised of a monoclonal antibody targeting transferrin receptor 1 for muscle delivery and an siRNA that induces degradation of DMPK mRNA to treat the underlying cause of DM1. Del-desiran showed favorable long-term safety and tolerability in adults with DM1. These data represent the longest safety results for a DMPK-targeted therapy and highlight potential of del-desiran to drive a new treatment paradigm for DM1. NEJ has received grant funding from NINDS (R01NS104010, U01NS124974), NCATS (R21TR003184), CDC (U01DD001242), and the FDA (2R01FD006071); receives royalties from the CCMDHI and the CMTHI, and research funds from Avidity Biosciences, A Novartis Company, Takeda, Sanofi Genzyme, Dyne, Novartis, Vertex Pharmaceuticals, Fulcrum Therapeutics, ML Bio, and Sarepta; provided consultation for Arthex, Novartis, AMO Pharma, Takeda."

Clinical • Late-breaking abstract • Genetic Disorders • Hematological Disorders • Muscular Dystrophy • Myotonic Dystrophy

Experiences With Myotonic Dystrophy Type 1 (DM1) and Treatment With Del-desiran: Interviews With Participants in MARINA-OLE™ and Their Caregivers (EAN 2026) - No abstract available

Interview • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

HARBOR-OLE: Global Open-Label Extension Study of Del-desiran for the Treatment of DM1 (clinicaltrials.gov) - P3 | N=230 | Enrolling by invitation | Sponsor: Avidity Biosciences, Inc.

Trial initiation date • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Delpacibart Etedesiran Improves the Molecular Pathology of Myotonic Dystrophy Type 1 in the Phase 1/2 MARINA® Study. (PubMed, Mol Ther) - "We designed an antibody-oligonucleotide conjugate (AOC™), delpacibart etedesiran (del-desiran), to deliver a DMPK-targeting small interfering RNA to muscle via transferrin receptor 1-mediated cell internalization. The extent of increase in functional MBNL was associated with consistent trends towards muscle function improvement, confirming del-desiran's mechanism of action and supporting its development as a treatment for DM1. The translation of its pharmacodynamic activity from preclinical models (patient-derived myotubes and Macaca fascicularis (Cynomolgus monkeys)) to patients with DM1 demonstrates del-desiran's consistency across species and reveals the potential broad utility of the AOC™ platform in further neuromuscular diseases."

Journal • P1/2 data • CNS Disorders • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • ACACA

Antibodies to watch in 2026. (PubMed, MAbs) - "In this installment of the series, we recap first marketing approvals granted to 19 antibody therapeutics in 2025, discuss 26 molecules currently in regulatory review, including the bispecific antibody-drug conjugate izalontamab brengitecan, and predict which molecules of the 209 currently in the commercial late-stage pipeline might transition to regulatory review by the end of 2026. Most antibody therapeutics in the latter category are for non-cancer indications (16/21, 76%) and have a conventional format (13/21, 62%), but the category also includes numerous antibody-oligo or -drug conjugates, such as delpacibart etedesiran, delpacibart zotadirsen, zeleciment rostudirsen, sonesitatug vedotin, trastuzumab pamirtecan, and ifinatamab deruxtecan, as well as the bispecific petosemtamab...Finally, to benchmark the time typically required for clinical development and regulatory review, we calculated this period for recently approved antibody therapeutic products stratified by..."

Journal • Review • Oncology

AOC 1001-CS4: A Global Phase 3 Open-Label Extension Study to Assess AOC 1001 in Patients with DM1 (clinicaltrialsregister.eu) - P2/3 | N=46 | Not yet recruiting | Sponsor: Avidity Biosciences Inc.

New P2/3 trial • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

An Antibody-Oligonucleotide Conjugate for Myotonic Dystrophy Type 1. (PubMed, N Engl J Med) - P1/2 | "Our results are consistent with delivery of del-desiran to muscle and amelioration of aberrant alternative splicing in some patients with myotonic dystrophy type 1; two serious adverse events occurred. These data support further clinical investigation. (Funded by Avidity Biosciences; ClinicalTrials.gov number, NCT05027269.)."

Clinical • Journal • CNS Disorders • 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. | Trial primary completion date: Mar 2026 ➔ Aug 2026

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

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