AOC 1044 induces exon 44 skipping and restores dystrophin protein in preclinical models of Duchenne muscular dystrophy

Usue Etxaniz, Isaac Marks, Tyler Albin, Matthew Diaz, Raghav Bhardwaj, Aaron Anderson, Olecya Tyaglo, Tiffany Hoang, Maria Azzurra Missinato, Kristoffer Svensson, Ben Badillo, Philip R Kovach, Laura Leung, Michael Cochran, Hae Won Kwon, Md Nur Ahad Shah, Rika Maruyama, Toshifumi Yokota, Venkata R Doppalapudi, Beatrice Darimont, Husam S Younis, W Michael Flanagan, Arthur A Levin, Hanhua Huang, Georgios Karamanlidis
Nucleic Acids Research, Volume 53, Issue 6, 11 April 2025, gkaf241, https://doi.org/10.1093/nar/gkaf241

Structure–Activity Relationship of Antibody–Oligonucleotide Conjugates: Evaluating Bioconjugation Strategies for Antibody–Phosphorodiamidate Morpholino Oligomer Conjugates for Drug Development

Journal of Medicinal Chemistry
Michael Cochran, Isaac Marks, Tyler Albin, Danny Arias, Philip Kovach, Beatrice Darimont, Hanhua Huang, Usue Etxaniz, Hae Won Kwon, Yunyu Shi, Matthew Diaz, Olecya Tyaglo, Arthur Levin, and Venkata Ramana Doppalapudi. Journal of Medicinal Chemistry 2024 67 (17), 14868-14884. DOI: 10.1021/acs.jmedchem.4c00803

Structure–Activity Relationship of Antibody–Oligonucleotide Conjugates: Evaluating Bioconjugation Strategies for Antibody–siRNA Conjugates for Drug Development

Journal of Medicinal Chemistry
Michael Cochran, Danny Arias, Rob Burke, David Chu, Gulin Erdogan, Michael Hood, Philip Kovach, Hae Won Kwon, Yanling Chen, Michael Moon, Christopher D. Miller, Hanhua Huang, Arthur Levin, and Venkata Ramana Doppalapudi. Journal of Medicinal Chemistry 2024 67 (17), 14852-14867. DOI: 10.1021/acs.jmedchem.4c00802

Targeted Tissue Delivery of RNA Therapeutics Using Antibody–Oligonucleotide Conjugates (AOCs)

Nucleic Acids Research
Barbora Malecova, Rob S Burke, Michael Cochran, Michael D Hood, Rachel Johns, Philip R Kovach, Venkata R Doppalapudi, Gulin Erdogan, J Danny Arias, Beatrice Darimont, Christopher D Miller, Hanhua Huang, Andrew Geall, Husam S Younis, Arthur A Levin. Nucleic Acids Research, 2023;, gkad415, https://doi.org/10.1093/nar/gkad415

Targeting Therapeutic Oligonucleotides

The New England Journal of Medicine
Levin, AA. N Engl J Med 2017;376:1DOI 10.1056/NEJMcibr1613559

Treating Disease at the RNA Level with Oligonucleotides

The New England Journal of Medicine
Levin, AA. N Engl J Med 2019;380:1DOI: 10.1056/NEJMra1705346

2025 MDA Clinical and Scientific Conference

Del-zota (delpacibart zotadirsen) produced statistically significant increases in exon skipping and dystrophin levels in EXPLORE44®, a Phase 1/2 study in individuals with DMD44

Phase 3, Randomized, Global Study Assessing Efficacy and Safety of Del-desiran™ for the Treatment of Myotonic Dystrophy Type 1: HARBOR™ Trial Design

AHA Scientific Sessions 2024

Novel Precision Cardiology Treatment for PRKAG2 Cardiomyopathy, a Subset of Patients with Wolff-Parkinson-White Syndrome

2024 World Muscle Society Congress

Phase 3, Randomized, Global Study Assessing Efficacy and Safety of Del-desiran™ for the Treatment of Myotonic Dystrophy Type 1: HARBOR™ Trial Design

2024 NMSG 25TH Annual Scientific Meeting

Interim Results from FORTITUDE™, a Randomized Phase 1/2 Trial Evaluating AOC 1020 in Adults with FSHD

2024 FSHD Society International Research Congress

Interim results from FORTITUDE™, a randomized Phase 1/2 trial evaluating AOC 1020 in adults with FSHD

Increasing Diversity in Clinical Trial Participation: An Exploration of Clinical Trial Site Engagement

2024 International Myotonic Dystrophy Consortium Meeting

Effect of Long-Term Treatment of AOC 1001 in Adults with Myotonic Dystrophy Type 1: from MARINA® to MARINA-OLE™

AOC 1001-Mediated Reduction of DMPK Leads to Increase in Functional MBNL Levels, Improving Muscle Function in Patients with DM1

2024 MDA Clinical and Scientific Conference

Initial results of the Phase 2 Open-Label Extension Study of AOC 1001 in Adults with Myotonic Dystrophy Type 1: MARINA-OLE™

AOC 1001-mediated Reduction of DMPK Leads to Increase in Functional MBNL Levels, Improving Muscle Function in Patients with DM1

AOC 1044 as a Novel Therapeutic Approach for DMD Patients Amenable to Exon 44 Skipping: EXPLORE44 Phase 1/2 Healthy Volunteer Data

Targeting DUX4 for Silencing with AOC for the Treatment of FSHD

Increasing Diversity in Clinical Trial Participation: An Exploration of Clinical Trial Site Engagement

2023 World Muscle Society Congress

Topline Safety and Efficacy Data Analysis of Phase 1/2 Clinical Trial Evaluating AOC 1001 in Adults with Myotonic Dystrophy Type 1: MARINA™

AOC 1001 Demonstrates DMPK Reduction and Spliceopathy Improvement in a Phase 1/2 study in Myotonic Dystrophy Type 1 (DM1) (MARINA™️️️)

Topline Data Analysis of the Phase 1/2 Clinical Trial Evaluating AOC 1001 in Adult Patients with Myotonic Dystrophy Type 1: MARINA™️️️

Phase 1/2 Trial Evaluating AOC 1044 in Healthy Volunteers and Participants with DMD Mutations Amenable to Exon 44 Skipping: EXPLORE44™️️️ Trial Design

Phase 1/2 Study to Evaluate AOC 1020 for Adult Patients with Facioscapulohumeral Muscular Dystrophy: FORTITUDE™️️️ Trial Design

Sex-related Utilization Differences in the 12-months After a Diagnosis of Facioscapulohumeral Muscular Dystrophy (FSHD)

More Prevalent Comorbidities, Healthcare Costs, and Service Utilization in Male Myotonic Dystrophy (DM) Patients and Female Patients

2023 NMSG 24TH Annual Scientific Meeting

Phase 1/2 Trial Evaluating AOC 1044 in Healthy Volunteers and Participants with DMD Mutations Amenable to Exon 44 Skipping (DMD44): EXPLORE44™️ Trial Design

Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of AOC 1020 Administered Intravenously to Adult Patients with Facioscapulohumeral Muscular Dystrophy (FORTITUDE™️) Trial Design

2023 Myotonic Dystrophy Foundation Annual Conference

From Myotube to Patient: AOC 1001 Demonstrates DMPK Reduction and Spliceopathy Improvement in a Phase 1/2 Study in Myotonic Dystrophy Type 1 (DM1) (MARINA™️️️)

Topline Data Analysis of the Phase 1/2 Clinical Trial Evaluating AOC 1001 in Adult Patients with Myotonic Dystrophy Type 1: MARINA™️️️

2023 FSHD Society International Research Congress

Facioscapulohumeral Muscular Dystrophy (FSHD) Surgeries, Cardiovascular Testing, Mobility Aids and Healthcare Utilization After Diagnosis from a Real-World Data Analysis

Phase 1/2 Trial Evaluating AOC 1020 in Adults with FSHD: FORTITUDE Trial Design

AOC 1020: An Antibody Oligonucleotide Conjugate (AOC) in Development for the Treatment of FSHD

Facioscapulohumeral Muscular Dystrophy (FSHD) Age-related Differences in Symptoms Among Patients Over and Under 40-Years

2023 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Conference

Comparative Real‐World Retrospective Data Analysis of Comorbid Conditions and Healthcare Utilization for Patients with Myotonic Dystrophy Over a 5‐Year Timeframe

2023 75th AAN Annual Meeting

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)

Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of AOC 1020 Administered Intravenously to Adult Patients with Facioscapulohumeral Muscular Dystrophy (FORTITUDE) Trial Design

2023 MDA Clinical and Scientific Conference

Phase 1/2 Clinical Trial Evaluating the Safety and Pharmacokinetics of AOC 1001 in Adults with Myotonic Dystrophy Type 1: MARINA Trial in Progress

AOC 1020: An Antibody Oligonucleotide Conjugate (AOC) in Development for the Treatment of FSHD

Myotonic Dystrophy, Comorbid Conditions and Healthcare Utilization Based on a 5-Year Comparative Real-World Data Analysis

AOC 1044: An Antibody Oligonucleotide Conjugate as a Novel Therapeutic Approach for DMD Patients Amenable to Exon 44 Skipping

Burden of Duchenne Muscular Dystrophy in Patients with Mutations Amenable to Exon 44 Skipping (DMD44)

Phase 1/2 Trial Evaluating AOC 1020 Safety and Pharmacokinetics in Adults with Facioscapulohumeral Muscular Dystrophy (FSHD): FORTITUDE Trial Design

2023 AMCP Annual Meeting

Specialty Pharmacy Products Used by Patients with Myotonic Dystrophy 2-Years Pre- and Post-Diagnosis

Prescription Medication Use Prior to and Following a Diagnosis of Facioscapulohumeral Muscular Dystrophy (FSHD): Learnings from the Patient Journey

2022 World Muscle Society Congress

A Phase 1/2 Clinical Trial Evaluating the Safety and Pharmacokinetics of AOC 1001 in Adults with Myotonic Dystrophy Type 1: MARINA Study Design

AOC 1020: An Antibody Oligonucleotide Conjugate (AOC) in Development for the Treatment of FSHD

Durable AOC Mediated Exon 44 Skipping In Non-Human Primate Muscle Tissue And Dystrophin Protein Restoration In DMD Patient Derived Skeletal Muscle Cells

Prevalence of Healthcare Conditions and Services Used by Patients with Myotonic Dystrophy (DM) Pre- and Post-Diagnosis: A Real-World Data Analysis

Understanding the Patients’ Journey Pre- and Post-Diagnosis of Facioscapulohumeral Muscular Dystrophy (FSHD): A Real-World Retrospective Data Analysis

2022 FSHD Society International Research Congress

AOC 1020: An Antibody Oligonucleotide Conjugate (AOC) in Development for the Treatment of FSHD

Inpatient Admissions and Emergency Department Visits for Patients with Facioscapulohumeral Muscular Dystrophy (FSHD): A Real-World Retrospective Data Analysis of Pre- and Post-Diagnosis Events

2022 74th AAN Annual Meeting

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™) 

Antibody-Oligonucleotide Conjugates (AOCs) Demonstrate Potent and Durable Exon Skipping and Dystrophin Restoration in a Mouse Model of Duchenne Muscular Dystrophy

Prevalence of healthcare conditions and services used by patients with myotonic dystrophy (DM1 and DM2) prior to diagnosis; a real-world data analysis

Understanding the patients’ journey to the diagnosis of Facioscapulohumeral Muscular Dystrophy (FSHD): a real-world retrospective data analysis

DUX4 siRNA Optimization for the Development of an Antibody-Oligonucleotide Conjugate (AOC™) for the Treatment of FSHD

2022 MDA Clinical and Scientific Conference

DUX4 siRNA Optimization for the Development of an Antibody-Oligonucleotide Conjugate (AOC^TM) for the Treatment of FSHD

A Phase 1/2 Clinical Trial Evaluating the Safety and Pharmacokinetics of AOC 1001 in Adults with Myotonic Dystrophy Type 1 (DM1): MARINA Study Design

Understanding the patients’ journey pre- and post-diagnosis of Facioscapulohumeral Muscular Dystrophy (FSHD): a real-world retrospective data analysis 

Prevalence of healthcare conditions and services used by patients with myotonic dystrophy pre-and post-diagnosis, a real-world data analysis 

2021 MDA Virtual Clinical and Scientific Conference

DUX4 siRNA Optimization for the Development of an Antibody-Oligonucleotide Conjugate (AOC^™) for the Treatment of FSHD

2021 AAN Annual Meeting

Optimization of AOC 1001, an antibody-oligonucleotide conjugate targeting the underlying cause of myotonic dystrophy type 1

2021 FSHD Society IRC Annual Meeting

DUX4 siRNA Optimization for the Development of an Antibody Oligonucleotide Conjugate (AOC^™) for the Treatment of FSHD