delpacibart zotadirsen (KPE179) / Eli Lilly, Avidity Biosci - LARVOL DELTA

SAFARI44: A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: Avidity Biosciences, Inc. | Not yet recruiting ➔ Recruiting

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

EXPLORE44OLE: Ph2 Open-label Study of AOC 1044 in Duchenne Muscular Dystrophy Participants With Mutations Amenable to Exon44 Skipping (clinicaltrials.gov) - P2 | N=39 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Trial completion date: Jul 2027 ➔ Apr 2027

Trial completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

AOC 1044-CS3: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study with an Open-Label Extension to Evaluate the Efficacy and Safety of Intravenous AOC 1044 (delpacibart zotadirsen) for the Treatment of DMD with Gene Mutations Amenable to Exon 44 Skipping (clinicaltrialsregister.eu) - P2/3 | N=42 | Not yet recruiting | Sponsor: Avidity Biosciences Inc. | N=30 ➔ 42

Enrollment change • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

AOC 1044-CS3: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study with an Open-Label Extension to Evaluate the Efficacy and Safety of Intravenous AOC 1044 (delpacibart zotadirsen) for the Treatment of DMD with Gene Mutations Amenable to Exon 44 Skipping (clinicaltrialsregister.eu) - P2/3 | N=26 | Not yet recruiting | Sponsor: Avidity Biosciences Inc.

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

SAFARI44: A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping (clinicaltrials.gov) - P3 | N=70 | Not yet recruiting | Sponsor: Avidity Biosciences, Inc.

New P3 trial • CNS Disorders • Genetic Disorders • Muscular Atrophy • Muscular Dystrophy • Musculoskeletal Diseases • Myotonic Dystrophy

EXPERT CONSENSUS ON TREATMENT GUIDANCE FOR FDA-APPROVED AND SECOND-GENERATION EXON-SKIPPING THERAPIES IN DUCHENE MUSCULAR DYSTROPHY (DMD): A RAND/UCLA MODIFIED DELPHI PANEL (ISPOR 2026) - "We aimed to characterize the current therapeutic landscape for DMD, including exon-skipping therapies, gene therapy, and givinostat, as well as emerging second-generation exon-skipping agents. Using the RAND/UCLA modified Delphi panel method, nine US experts (seven pediatric neurologists, two physical therapists) rated the likelihood of recommending FDA-approved therapies (eteplirsen, golodirsen, viltolarsen, casimersen, GT, givinostat) and the anticipated clinical value of investigational therapies with Phase 1/2 data (delpacibart zotadirsen, DYNE-251, WVE-N531, and NS-089/NCNP-02)... The panel reached consensus that approved exon-skipping therapies provide modest benefit, particularly in earlier stages, while early data suggest that second-generation exon-skippers may have the potential to offer greater functional improvement. However, trials remain in early stages, and the full risks and benefits of these therapies are not yet known. The findings highlight the rapidly..."

Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

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

Managed Access Program for Del-zota in Participants With DMD Mutations Amenable to Exon 44 Skipping (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Avidity Biosciences, Inc.

New trial • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Atrophy • Muscular Dystrophy • Musculoskeletal Diseases

Avidity Biosciences Receives FDA Breakthrough Therapy Designation for Delpacibart Zotadirsen (del-zota) for the Treatment of DMD in People with Mutations Amenable to Exon 44 Skipping (PRNewswire) - "Avidity Biosciences, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to delpacibart zotadirsen (del-zota) for the treatment of Duchenne muscular dystrophy (DMD) in people living with mutations amenable to exon 44 skipping (DMD44)...Avidity plans to present topline and functional data from the ongoing, fully enrolled Phase 2 EXPLORE44-OLE trial in the fourth quarter of 2025....The company remains on track for a planned BLA submission at year end 2025."

Breakthrough therapy • FDA filing • P2 data • Duchenne Muscular Dystrophy

EXPLORE44OLE: Ph2 Open-label Study of AOC 1044 in Duchenne Muscular Dystrophy Participants With Mutations Amenable to Exon44 Skipping (clinicaltrials.gov) - P2 | N=39 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Trial completion date: Dec 2026 ➔ Jul 2027 | Trial primary completion date: Dec 2025 ➔ Apr 2027

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

AOC 1044 induces exon 44 skipping and restores dystrophin protein in preclinical models of Duchenne muscular dystrophy. (PubMed, Nucleic Acids Res) - "We developed AOC 1044, an antibody-oligonucleotide conjugate (AOC) that combines a PMO-targeting exon 44 with an antibody against the transferrin receptor (TfR1), enhancing delivery to muscle tissues for patients with DMD amenable to exon 44 skipping (DMD44)...In nonhuman primates, single or repeated AOC 1044 doses resulted in dose-dependent increases in PMO concentration and exon 44 skipping across a range of muscle tissues, including the heart. Collectively, these findings highlight AOC 1044 as a promising therapeutic candidate for patients with DMD44, offering improved muscle targeting and meaningful dystrophin restoration, with potential clinical benefits in reducing muscle degeneration."

Journal • Preclinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • TFRC

Avidity Biosciences Announces Positive Topline Del-zota Data Demonstrating Consistent, Statistically Significant Improvements in Dystrophin, Exon Skipping and Creatine Kinase in People Living with Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping in Phase 1/2 EXPLORE44 Trial (PRNewswire) - P1/2 | N=70 | EXPLORE44 (NCT05670730) | P2 | N=35 | EXPLORE44OLE (NCT06244082) | Sponsor: Avidity Biosciences, Inc. | "'...we believe dystrophin data from EXPLORE44 combined with the safety data from our fully enrolled EXPLORE44-OLE trial will support our planned BLA submission at the end of this year.'...Safety and tolerability data were assessed from 26 participants in the completed Phase 1/2 EXPLORE44 trial and 38 participants in the ongoing EXPLORE44 Open-Label Extension (OLE) trial...Targeted delivery of PMOs resulting in tissue concentrations of approximately 200nM in skeletal muscle; Statistically significant increases of approximately 40% in exon 44 skipping; Statistically significant increase of approximately 25% of normal in dystrophin production and restored total dystrophin up to 58% of normal...Significant reductions in creatine kinase levels were sustained in the EXPLORE44-OLE trial with continued treatment up to one year."

P1/2 data • P2 data • Duchenne Muscular 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

EXPLORE44: Study of AOC 1044 in Healthy Adult Volunteers and Participants with Duchenne Muscular Dystrophy (DMD) Mutations Amenable to Exon 44 Skipping (clinicaltrials.gov) - P1/2 | N=70 | Completed | Sponsor: Avidity Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular 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

EXPLORE44OLE: Ph2 Open-label Study of AOC 1044 in Duchenne Muscular Dystrophy Participants with Mutations Amenable to Exon44 Skipping (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

EXPLORE44OLE: Ph2 Open-label Study of AOC 1044 in Duchenne Muscular Dystrophy Participants with Mutations Amenable to Exon44 Skipping (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Avidity Biosciences, Inc. | Enrolling by invitation ➔ Recruiting | N=24 ➔ 35

Enrollment change • Enrollment status • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

EXPLORE44: Study of AOC 1044 in Healthy Adult Volunteers and Participants with Duchenne Muscular Dystrophy (DMD) Mutations Amenable to Exon 44 Skipping (clinicaltrials.gov) - P1/2 | N=64 | Active, not recruiting | Sponsor: Avidity Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Phase 1/2 Trial Evaluating AOC 1044 in Healthy Volunteers and Participants with DMD Mutations Amenable to Exon 44 Skipping (DMD44): EXPLORE44 Trial Design (AAN 2024) - P1/2 | "AOC 1044 is an antibody-oligonucleotide conjugate (AOCTM) comprised of a humanized anti-transferrin receptor 1 (TfR1) antibody conjugated to multiple copies of a phosphorodiamidate morpholino oligomer (PMO) targeting DMD44 mRNA to produce truncated but functional dystrophin protein.Design/EXPLORE44TM (NCT05670730) is a randomized, placebo-controlled, double-blind phase 1/2 trial conducted in two parts...N/A"

Clinical • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • TFRC

Avidity Biosciences Receives FDA Rare Pediatric Disease Designation for AOC 1044 for Treatment of Duchenne Muscular Dystrophy in People with Mutations Amenable to Exon 44 Skipping (PRNewswire) - "Avidity Biosciences, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease designation to AOC 1044, the company's investigational therapy for the treatment of Duchenne muscular dystrophy (DMD) in people living with mutations amenable to exon 44 skipping (DMD44). AOC 1044 is being assessed in the Phase 1/2 EXPLORE44 trial for people living with DMD44 and is the first of multiple AOCs the company is developing for DMD."

FDA event • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

AOC 1044 as a Novel Therapeutic Approach for DMD Patients Amenable to Exon 44 Skipping: EXPLORE44 Phase 1/2 Healthy Volunteer Data (MDA 2024) - P1/2 | "These data represent the first-in-human experience using an AOC to deliver PMOs to muscle. Persistently high levels of PMO and exon skipping on Day 29 support the potential for AOC 1044 to result in accumulation of exon 44-skipped transcripts and dystrophin protein in DMD patients over an extended dosing interval. These results are supported by nonclinical data in humanized exon 44 skip-amenable DMD/mdx mice demonstrating dose-dependent exon skipping and dystrophin restoration in skeletal and cardiac muscle as well as efficient PMO delivery and exon 44 skipping in non-human primates."

Clinical • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • TFRC

EXPLORE44OLE: Ph2 Open-label Study of AOC 1044 in Duchenne Muscular Dystrophy Participants With Mutations Amenable to Exon44 Skipping (clinicaltrials.gov) - P2 | N=24 | Enrolling by invitation | Sponsor: Avidity Biosciences, Inc.

New P2 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Avidity Biosciences Receives FDA Orphan Drug Designation for AOC 1044 for Treatment of Duchenne Muscular Dystrophy in People with Mutations Amenable to Exon 44 Skipping (PRNewswire) - "Avidity Biosciences, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to AOC 1044, the company's investigational therapy in development for the treatment of Duchenne muscular dystrophy (DMD) in people with mutations amenable to exon 44 skipping (DMD44)."

Orphan drug • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Phase 1/2 trial evaluating AOC 1044 in healthy volunteers and participants with DMD mutations amenable to exon 44 Skipping: EXPLORE44 Trial Design (WMS 2023) - No abstract available

Clinical • P1/2 data

EXPLORE44: Study of AOC 1044 in Healthy Adult Volunteers and Participants With Duchenne Muscular Dystrophy (DMD) Mutations Amenable to Exon 44 Skipping (clinicaltrials.gov) - P1/2 | N=64 | Recruiting | Sponsor: Avidity Biosciences, Inc.

New P1/2 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy