Del-zota produced statistically significant increases in exon skipping and dystrophin levels in EXPLORE44, a Phase 1/2 study in patients with DMD44

Topic:

Clinical Trials

Poster Number: O72

Author(s):

Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Jamie Eskuri, MD, Gillette Children’s Hospital, Kevin Flanigan, MD, Nationwide Children's Hospital, Columbus, Chamindra Laverty, MD, University of California, Han Phan, MD, Rare Disease Research, Atlanta, Georgia, USA, Edward Smith, MD, Rare Disease Research, Carolina Tesi Rocha, MD, Stanford University, Brenda Wong, MD, UMass Medical Center, Worcester, Massachusetts, USA, Marc Morris, MD, JD, Avidity Biosciences, Yvonne Tami, BS, Avidity Biosciences, Tara Carmack, MS, Avidity Biosciences, Philip Kovach, MS, Avidity Biosciences, Josiah Herzog, PhD, Avidity Biosciences, Steve Hughes, MD, Avidity Biosciences, Yiming Zhu, PhD, Avidity Biosciences, Elizabeth Ackermann, PhD, Avidity Biosciences

Background: Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Delpacibart zotadirsen, or del-zota (AOC 1044), is an antibody-oligonucleotide conjugate (AOC) comprised of an anti-transferrin receptor 1 (TfR1) antibody conjugated to an exon 44-skipping phosphorodiamidate morpholino oligomer (PMO). Del-zota is designed to restore the dystrophin reading frame and produce functional, internally truncated dystrophin protein in individuals with mutations amenable to exon 44 skipping (DMD44).

Design: Part B of the Phase 1/2 EXPLORE44TM trial (NCT05670730) is a randomized, placebo-controlled, double-blind study assessing safety, tolerability, pharmacokinetics, and exon skipping efficacy of multiple-ascending doses of del-zota. EXPLORE44 enrolled 24 ambulatory and non-ambulatory individuals aged 7 – 27 years with DMD44. (Part A healthy volunteer data has been reported previously).

Results: Treatment with del-zota produced statistically significant increases in exon skipping and dystrophin production in skeletal muscle and significant reductions in blood creatine kinase (CK) to near normal levels. Del-zota produced favorable safety and tolerability results.

Conclusion: The EXPLORE44 trial represents the first in-patient experience using Avidity Biosciences’ proprietary AOCTM technology to deliver PMOs to muscle. Del-zota’s ability to increase dystrophin production and exon skipping and reduce CK levels highlights its potential to improve the lives of patients with DMD44. These data support the continued evaluation of del-zota in the Phase 2 EXPLORE44-OLETM trial (NCT06244082).