Avidity Biosciences Announces Positive AOC 1044 Data

Avidity Biosciences, which received early funding from CureDuchenne, announced positive initial data from their EXPLORE44 Trial for individuals with Duchenne amenable to skipping exon 44.  Their experimental exon-skipping agent, AOC 1044 (del-zota), at 5 mg/kg increased exon 44 skipping by an average of 37% (from 7% at baseline to 44%) and increased average dystrophin levels by 25% (from 7% of normal at baseline to 32%) after 3 doses received once every 6 weeks. Creatine kinases levels were reduced to near normal levels. Watch the webinar here.

LETTER TO THE COMMUNITY

We are very pleased to share with you that today we announced positive initial data from our EXPLORE44™ clinical trial, that is assessing the safety and efficacy of our investigational therapy, AOC 1044 in people living with Duchenne muscular dystrophy mutations amenable to exon 44 skipping (DMD44). EXPLORE44 is a placebo-controlled study that enrolled 40 healthy volunteers and 24 participants with DMD44, ages seven to 27 years old.  AOC 1044 is designed to specifically skip exon 44 of the dystrophin gene to enable dystrophin production in people living with DMD44.

Data from the 5mg/kg cohort of AOC 1044 at four months demonstrated statistically significant increase of 25% of normal in dystrophin production, statistically significant increase of 37% in exon 44 skipping and reduced creatine kinase levels to near normal with greater than 80% reduction compared to baseline. AOC 1044 demonstrated favorable safety and tolerability in people living with DMD44.

We also shared today that delpacibart zotadirsen is the approved international nonproprietary name of AOC 1044, abbreviated as del-zota.

Full PRESS RELEASE announcing today’s DMD44 news here:

Avidity Biosciences Announces Positive AOC 1044 Data Demonstrated Significant Increase of 25% in Dystrophin Production and Reduction of Creatine Kinase Levels to Near Normal in People Living with Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping in the Phase 1/2 EXPLORE44™ Trial

In EXPLORE44 study, del-zota demonstrated:

• Consistent delivery of PMO of 200 nM in skeletal muscle
• Statistically significant 37% increase in exon 44 skipping and up to 66%  skipping
• Statistically significant increase of 25% of normal in dystrophin production and restored total dystrophin up to 54% of normal
• Creatine kinase levels were reduced to near normal with greater than 80% reduction compared to baseline
• Favorable safety and tolerability with most treatment emergent adverse events (AEs) mild or moderate in participants with DMD44.

We would like to thank each participant in the trial, their families, our advocacy partners and the investigators and their teams for their time, commitment, and continued contributions.

WEBINAR

We invite you to watch the webinar in partnership with Cure Duchenne to learn more about these findings. The Avidity team, joined by Dr. Diana Castro, Pediatric Neurologist, Neurology and Neuromuscular Care Center and Founder and Director, Neurology and Neuromuscular Care Center/Neurology Rare Disease Center, will review the EXPLORE44 trial initial findings and provide insights on what these results mean for this development program and for the DMD44 community.

With this encouraging data, we will focus on regulatory discussions with FDA as we work to complete both our EXPLORE44 and EXPLORE44-OLE (Open-Label Extension) studies. While the EXPLORE44 trial is fully enrolled, it is important that participants complete participation. Our plan is to enroll an additional 10-15 patients in the EXPLORE44-OLE study.

We share the sense of urgency and the desire to bring new therapies to the DMD community  as quickly as possible. Our most important mission is to complete both of these studies and seek out a pathway toward approval. We anticipate we will have requests for access including a Managed Access Pathway (known as Expanded Access or Compassionate Use in the US) which provides access to investigational therapies outside of a formal clinical trial setting. We will be discussing a potential MAP after we conclude our initial regulatory conversations. Del-zota is currently not available outside of the EXPLORE44 and EXPLORE44 OLE studies. If you have questions, please contact patients@aviditybio.com.

We encourage you to contact your doctor if you have any questions about del-zota or the EXPLORE44 trial.

Sincerely,

The Avidity Team